PaperBLAST

PaperBLAST Hits for NP_001257891.1 potassium voltage-gated channel subfamily D member 3 isoform 1 (Rattus norvegicus) (655 a.a., MAAGVAAWLP...)

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>NP_001257891.1 potassium voltage-gated channel subfamily D member 3 isoform 1 (Rattus norvegicus)
MAAGVAAWLPFARAAAIGWMPVANCPMPLAPADKNKRQDELIVLNVSGRRFQTWRTTLER
YPDTLLGSTEKEFFFNEDTKEYFFDRDPEVFRCVLNFYRTGKLHYPRYECISAYDDELAF
YGILPEIIGDCCYEEYKDRKRENAERLMDDNESENNQESMPSLSFRQTMWRAFENPHTST
LALVFYYVTGFFIAVSVITNVVETVPCGTVPGSKELPCGERYSVAFFCLDTACVMIFTVE
YLLRLFAAPSRYRFIRSVMSIIDVVAIMPYYIGLVMTNNEDVSGAFVTLRVFRVFRIFKF
SRHSQGLRILGYTLKSCASELGFLLFSLTMAIIIFATVMFYAEKGSSASKFTSIPASFWY
TIVTMTTLGYGDMVPKTIAGKIFGSICSLSGVLVIALPVPVIVSNFSRIYHQNQRADKRR
AQKKARLARIRVAKTGSSNAYLHSKRNGLLNEALELTGTPEEEHMGKTTSLIESQHHHLL
HCLEKTTGLSYLVDDPLLSVRTSTIKNHEFIDEQMFEQNCMESSMQNYPSTRSPSLSSHS
GLTTTCCSRRSKKTTHLPNSNLPATRLRSMQELSTIHIQGSEQPSLTTSRSSLNLKADDG
LRPNCKTSQITTAIISIPTPPALTPEGESRPPPASPGPNTNIPSITSNVVKVSAL

Running BLASTp...

Found 252 similar proteins in the literature:

NP_001257891 potassium voltage-gated channel subfamily D member 3 isoform 1 from Rattus norvegicus
100% identity, 100% coverage

• Kv4.3 Channel Dysfunction Contributes to Trigeminal Neuropathic Pain Manifested with Orofacial Cold Hypersensitivity in Rats.
  Kanda, The Journal of neuroscience : the official journal of the Society for Neuroscience 2021
  • GeneRIF: Kv4.3 Channel Dysfunction Contributes to Trigeminal Neuropathic Pain Manifested with Orofacial Cold Hypersensitivity in Rats.
• CaMKII Modulates the Cardiac Transient Outward K+ Current through its Association with Kv4 Channels in Non-Caveolar Membrane Rafts.
  Alday, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2020 (PubMed)
  • GeneRIF: Immunogold staining and electron microscopy of heart vibrosections was performed to localize Kv4.2/Kv4.3 and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) proteins. Patch-Clamp recordings in control conditions and after lipid raft or caveolae disruption show that the CaMKII-Kv4 channel complex must associate in non-caveolar lipid rafts to be functional.
• Over-expression of Kv4.3 gene reverses cardiac remodeling and transient-outward K+ current (Ito) reduction via CaMKII inhibition in myocardial infarction.
  Tao, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2020 (PubMed)
  • GeneRIF: Over-expression of Kv4.3 gene reverses cardiac remodeling and transient-outward K(+) current (Ito) reduction via CaMKII inhibition in myocardial infarction.
• Kv4.3 expression abrogates and reverses norepinephrine-induced myocyte hypertrophy by CaMKII inhibition.
  Wang, Journal of molecular and cellular cardiology 2019
  • GeneRIF: Kv4.3 reduction is an important mediator in cardiac hypertrophy development via excessive CaMKII activation.
• The activation of N-methyl-d-aspartate receptors downregulates transient outward potassium and L-type calcium currents in rat models of depression.
  Liu, American journal of physiology. Cell physiology 2017 (PubMed)
  • GeneRIF: NMDA reduced both currents in a concentration-dependent manner, whereas there was no significant impact on the currents when perfused with MK-801. MDD rats exhibited significantly more fibrosis areas in heart tissue and reduced expression of Kv4.2, Kv4.3, and Cav1.2.
• Role of Kv4.3 in Vibration-Induced Muscle Pain in the Rat.
  Conner, The journal of pain 2016
  • GeneRIF: This study demonstated that that Kv4.3 is involved in vibration-induced muscle pain and explored whether changes in Kv4.3 expression in nociceptors contributes to the mechanical hyperalgesia in a model of hand-arm vibration syndrome in the rat.
• Neuroprotective or neurotoxic effects of 4-aminopyridine mediated by KChIP1 regulation through adjustment of Kv 4.3 potassium channels expression and GABA-mediated transmission in primary hippocampal cells.
  Del, Toxicology 2015 (PubMed)
  • GeneRIF: KChIP1 plays a neuroprotective role against 4-AP acute induced cell death in primary hippocampal cells through regulation of Kv 4.3 and GABA transmission but this is lost after long term exposure.
• Distribution and functional expression of Kv4 family α subunits and associated KChIP β subunits in the bed nucleus of the stria terminalis.
  Rainnie, The Journal of comparative neurology 2014
  • GeneRIF: This study demonistrared that the expression and function of Kv4.3 channels in neurons of the rat bed nucleus of the stria terminalis.
• More

KCND3_RAT / Q62897 A-type voltage-gated potassium channel KCND3; Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Rattus norvegicus (Rat) (see 10 papers)
100% identity, 100% coverage

• function: Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:17057713, PubMed:8734615, PubMed:8831489, PubMed:9001401, PubMed:9450548). In cardiomyocytes, may generate the transient outward potassium current I(To) (Probable). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (Probable). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:17057713, PubMed:8734615, PubMed:8831489, PubMed:9001401, PubMed:9450548). Channel properties are modulated by interactions with regulatory subunits (PubMed:10676964, PubMed:17057713). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:10676964, PubMed:17057713). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (By similarity). Heterotetramer with KCND2 (By similarity). Associates with the regulatory subunits KCNIP3 and KCNIP4 (PubMed:10676964, PubMed:11805342). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1 (By similarity). Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). Interacts with KCNIP1; each KCNIP1 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction stabilizes the tetrameric form and modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:10676964, PubMed:17057713). Interacts with DPP6; this interaction modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (By similarity). Interacts with KCNIP2; each KCNIP2 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C- terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction modulates the channel gating kinetics (PubMed:10676964).

KCND3_MOUSE / Q9Z0V1 A-type voltage-gated potassium channel KCND3; Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Mus musculus (Mouse) (see 3 papers)
100% identity, 100% coverage

• function: Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (By similarity). In cardiomyocytes, may generate the transient outward potassium current I(To). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation. Channel properties are modulated by interactions with regulatory subunits. Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation. Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (By similarity). Heterotetramer with KCND2 (PubMed:11909823). Associates with the regulatory subunit KCNIP3 (PubMed:11598014). Associates with the regulatory subunit KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1 (By similarity). Component of heteromultimeric potassium channels (PubMed:19713751). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). Interacts with KCNIP1; each KCNIP1 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction stabilizes the tetrameric form and modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation. Interacts with DPP6; this interaction modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (By similarity). Interacts with KCNIP2; each KCNIP2 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction modulates the channel gating kinetics (PubMed:11909823).
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...Q9Z0V2 M: Q9Z0V2 T: Q9Z0V2 N-term T154 C-term S548 S548 C-term S552 S552 Kv4.3/KCND3 W: Q9Z0V1 N-term S153 Kv5.1/KCNF1 W: Q7TSH7 C-term S444 C-term S470 C-term S472 Kv7.2/KCNQ2 W: NP_034741 Tr: NP_034741 M: NP_034741 T: NP_034741 N-term S52 C-term S352 S352 C-term S457 C-term T462 C-term...”

KCND3_HUMAN / Q9UK17 A-type voltage-gated potassium channel KCND3; Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Homo sapiens (Human) (see 13 papers)
TC 1.A.1.2.19 / Q9UK17 The voltage-gated K+ channel subfamily D member 3, KCND3 or Kv4.3 from Homo sapiens
NP_004971 A-type voltage-gated potassium channel KCND3 isoform 1 from Homo sapiens
100% identity, 100% coverage

• function: Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). In cardiomyocytes, may generate the transient outward potassium current I(To) (By similarity). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). Channel properties are modulated by interactions with regulatory subunits (PubMed:17187064, PubMed:34997220). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:17187064, PubMed:34997220). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (PubMed:34997220).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (PubMed:17187064, PubMed:34997220). Heterotetramer with KCND2 (By similarity). Associates with the regulatory subunits KCNIP3 and KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1 (PubMed:12297301, PubMed:19213956). Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). Interacts with KCNIP1; each KCNIP1 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction stabilizes the tetrameric form and modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:14980207, PubMed:17187064, PubMed:34997220). Interacts with DPP6; this interaction modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:34997220). Interacts with KCNIP2; each KCNIP2 monomer interacts with two adjacent KCND3 subunits, through both the N- terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction modulates the channel gating kinetics (PubMed:12297301, PubMed:34997220).
• substrates: K+
  tcdb comment: Mutations cause spinocerebellar ataxia type 19 (Duarri et al. 2012). Positively charged residues in S4 contribute to channel inactivation and recovery (Skerritt and Campbell 2007). The crystal structure of Kv4.3 with its regulatory subunit, Kchip1, has been solved (2NZ0) (Wang et al. 2007)
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v 7.2 (NP_742105), K v...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 4.2 K v 4.3 HGNC, UniProt KCND1 , Q9NSA2 KCND2 , Q9NZV8 KCND3 , Q9UK17 Associated subunits KChIP 1-4, DP66, DPP10 KChIP 1-4, DPP6, DPP10, K v 1, NCS-1, Na v 1 KChIP 1-4, DPP6 and DPP10, MinK, MiRPs Channel blockers fampridine (pIC 50 2)...”
• Impact of rs1805127 and rs55742440 Variants on Atrial Remodeling in Hypertrophic Cardiomyopathy Patients with Atrial Fibrillation: A Romanian Cohort Study.
  Popa-Fotea, International journal of molecular sciences 2023
  • “...A member 5 (P22460) [ 17 ] KCND3 Potassium voltage-gated channel subfamily D member 3 (Q9UK17) [ 18 ] KCNE1 Potassium voltage-gated channel subfamily E member 1 (P15382) [ 19 ] KCNE2 Potassium voltage-gated channel subfamily E member 2 (Q9Y6J6) [ 20 ] KCNE3 Potassium voltage-gated...”
• Mechanism of Sanhua Decoction in the Treatment of Ischemic Stroke Based on Network Pharmacology Methods and Experimental Verification
  YingHuang,, BioMed research international 2022
  • “...reductase P04035 JUN Transcription factor AP-1 P05412 KCND3 Potassium voltage-gated channel subfamily D member 3 Q9UK17 KCNH2 Potassium voltage-gated channel subfamily H member 2 Q12809 LCN2 Neutrophil gelatinase-associated lipocalin P80188 MAPK14 Mitogen-activated protein kinase 14 Q16539 MAPT Microtubule-associated protein tau P10636 MMP2 Matrix metalloproteinase-2 P08253 MMP9...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 4.2 K v 4.3 HGNC, UniProt KCND1 , Q9NSA2 KCND2 , Q9NZV8 KCND3 , Q9UK17 Associated subunits KChIP 14, DP66, DPP10 KChIP 14, DPP6, DPP10, K v 1, NCS1, Na v 1 KChIP 14, DPP6 and DPP10, MinK, MiRPs Channel blockers fampridine (pIC 50 2)...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 6.2 K v 6.3 K v 6.4 HGNC, UniProt KCND2 , Q9NZV8 KCND3 , Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A K A Nomenclature...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809; KCNH6, Q9H252; KCNH7, Q9NS40; KCNH8, Q96L42; KCNH3, Q9ULD8; KCNH4, Q9UQ05 KCNMA1, Q12791; KCNT1, Q5JUK3;...”

KCND3_RABIT / Q9TTT5 A-type voltage-gated potassium channel KCND3; Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Oryctolagus cuniculus (Rabbit) (see paper)
99% identity, 100% coverage

• function: Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:12122138). In cardiomyocytes, may generate the transient outward potassium current I(To). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation. Channel properties are modulated by interactions with regulatory subunits. Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation. Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (By similarity). Heterotetramer with KCND2 (By similarity). Associates with the regulatory subunits KCNIP3 and KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1 (By similarity). Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). Interacts with KCNIP1; each KCNIP1 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction stabilizes the tetrameric form and modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation. Interacts with DPP6; this interaction modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation. Interacts with KCNIP2; each KCNIP2 monomer interacts with two adjacent KCND3 subunits, through both the N-terminal inactivation ball of a KCND3 subunit and a C-terminal helix from the adjacent KCND3 subunit, clamping them together; this interaction modulates the channel gating kinetics (By similarity).

XP_005630924 potassium voltage-gated channel subfamily D member 3 isoform X1 from Canis lupus familiaris
95% identity, 96% coverage

• Transmural expression of transient outward potassium current subunits in normal and failing canine and human hearts.
  Zicha, The Journal of physiology 2004
  • GeneRIF: Both Kv4.3 and KChIP2 may contribute to epicardial-endocardial gradients in the transient outward current in normal and failing hearts. [Kv4.3]

XP_018100233 potassium channel, voltage gated Shal related subfamily D, member 3 L homeolog isoform X1 from Xenopus laevis
91% identity, 100% coverage

• Closed-state inactivation in Kv4.3 isoforms is differentially modulated by protein kinase C.
  Xie, American journal of physiology. Cell physiology 2009
  • GeneRIF: Our data demonstrate isoform-specific regulation of closed-state inactivation by protein kinase C in Kv4.3
• Time- and voltage-dependent components of Kv4.3 inactivation.
  Wang, Biophysical journal 2005
  • GeneRIF: biophysical 11-state Markov model of Kv4.3 gating incorporating a direct transition from the open-inactivated state to the closed-inactivated state

XP_015132111 potassium voltage-gated channel subfamily D member 2 isoform X1 from Gallus gallus
74% identity, 100% coverage

• Identification and localization of an arachidonic acid-sensitive potassium channel in the cochlea.
  Sokolowski, The Journal of neuroscience : the official journal of the Society for Neuroscience 2004
  • GeneRIF: An arachidonic acid-sensitive A-type channel in the short (outer) hair cells of the chicken cochlea is encoded by Kv4.2.

KCND2_MOUSE / Q9Z0V2 A-type voltage-gated potassium channel KCND2; Potassium voltage-gated channel subfamily D member 2; Voltage-gated potassium channel subunit Kv4.2 from Mus musculus (Mouse) (see 22 papers)
NP_062671 potassium voltage-gated channel subfamily D member 2 precursor from Mus musculus
74% identity, 100% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (PubMed:10818150, PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites (PubMed:10818150, PubMed:17122039, PubMed:22815518). Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (PubMed:22815518). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (PubMed:18045912). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member (PubMed:10601491, PubMed:11909823, PubMed:23713033, PubMed:9734479). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:22311982, PubMed:9734479). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel (PubMed:11909823). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:11909823). Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (By similarity). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:22311982). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCND3 or KCND1 (PubMed:11909823, PubMed:19713751, PubMed:20943905, PubMed:9734479). Associates with the regulatory subunits KCNIP2, KCNIP3 and KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905). Interacts with the regulatory subunit KCNIP1; this interaction mediates the capture of both the N- and C-terminus of KCND2, preventing N-type inactivation and stabilizing the S6 conformation, thereby accelerating closed state inactivation and recovery (By similarity). In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Interacts with DLG1 (By similarity). Interacts with DLG4 (By similarity). Interacts with NCS1/FREQ (PubMed:11606724). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity). Interacts with FLNA and FLNC (By similarity). Interacts with DPP10 (PubMed:22311982). Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity). Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery (PubMed:22311982).
  disruption phenotype: Mice are viable, fertile and appear to be in good health (PubMed:16293790, PubMed:22738428). The loss of KCND2 has only minor functional consequences, probably due to an increase of the activity of other potassium channels, even though there is no visible change of their expression levels (PubMed:20371829). Mutant mice show no sign of heart dysfunction, but the fast component of the rapidly inactivating and rapidly recovering potassium current I(to) is lost in their ventricular myocytes (PubMed:16293790). Instead, a slowly inactivating current is expressed that is not observed in wild-type (PubMed:16293790). Electrocardiograms of mutant hearts display no significant differences relative to wild-type regarding their QT, PR, QRS and RR intervals (PubMed:16293790). The neuronal A-type current is reduced by about 80% in brain cortex and hippocampus CA1 pyramidal neurons, by about 50% in suprachiasmatic nucleus neurons and by about 60% in dorsal horn neurons (PubMed:17122039, PubMed:18045912, PubMed:18187474, PubMed:20371829, PubMed:22815518). The dendritic A- type current is abolished in pyramidal neurons from the hippocampus CA1 layer (PubMed:17122039). Concomitantly, the back-propagation of action potential in dendrites is increased (PubMed:17122039). This may lower the treshold for neuronal long-term potentiation (LTP) (PubMed:17122039). Loss of KCND2 does not influence the levels of KCND3 or KCNA4, but leads to reduced KCNIP1, KCNIP2 and KCNIP3 protein levels (PubMed:17122039, PubMed:18187474, PubMed:22612819). Mutant mice show only minor differences in their behavior when compared to wild-type; they display hyperactivity to some, but not all, novel stimuli (PubMed:22738428). Mutant mice show subtle spatial learning deficits (PubMed:20857488). Mutant mice display shorter periods of locomotor activity that wild-type littermates, due to a corresponding change in the circadian rhythm of repetitive firing in suprachiasmatic nucleus neurons (PubMed:22815518). Mutant mice display loss of spontaneous nociceptive behavior that is caused by the activation of GRM5 (PubMed:18045912).
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...S755 Kv3.4/KCNC4 W: Q8R1C0 C-term S555 Kv4.1/KCND1 W: Q03719 C-term S460 C-term S555 Kv4.2/KCND2 W: Q9Z0V2 M: Q9Z0V2 T: Q9Z0V2 N-term T154 C-term S548 S548 C-term S552 S552 Kv4.3/KCND3 W: Q9Z0V1 N-term S153 Kv5.1/KCNF1 W: Q7TSH7 C-term S444 C-term S470 C-term S472 Kv7.2/KCNQ2 W: NP_034741 Tr:...”
• Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis.
  Xiao, Neurochemistry international 2021 (PubMed)
  • GeneRIF: Voltage-dependent potassium channel Kv4.2 alleviates the ischemic stroke impairments through activating neurogenesis.
• Chronic mild stress alters synaptic plasticity in the nucleus accumbens through GSK3β-dependent modulation of Kv4.2 channels.
  Aceto, Proceedings of the National Academy of Sciences of the United States of America 2020
  • GeneRIF: Study uncovers increased levels of active GSK3beta in the nucleus accumbens (NAc) of mice with a depressive-like phenotype induced by chronic stress. Increased levels of active GSK3beta within the NAc of these mice lead to altered synaptic plasticity in medium spiny neurons through phosphorylation of the Kv4.2 subunit uncovering molecular mechanism of underlying depression-like behaviors.
• Activity-dependent isomerization of Kv4.2 by Pin1 regulates cognitive flexibility.
  Hu, Nature communications 2020
  • GeneRIF: activity-induced Kv4.2 phosphorylation triggers Pin1 binding to, and isomerization of, Kv4.2 at the pThr(607)-Pro motif, leading to the dissociation of the Kv4.2-DPP6 complex.
• The potassium channel Kv4.2 regulates dendritic spine morphology, electroencephalographic characteristics and seizure susceptibility in mice.
  Tiwari, Experimental neurology 2020
  • GeneRIF: The potassium channel Kv4.2 regulates dendritic spine morphology, electroencephalographic characteristics and seizure susceptibility in mice.
• GSK3β Modulates Timing-Dependent Long-Term Depression Through Direct Phosphorylation of Kv4.2 Channels.
  Aceto, Cerebral cortex (New York, N.Y. : 1991) 2019
  • GeneRIF: Results identify the functional interaction between GSK3beta and Kv4.2 channel as a novel mechanism for long-term depression modulation providing exciting insight into the understanding of GSK3beta role in synaptic plasticity.
• Elevated potassium outward currents in hyperoxia treated atrial cardiomyocytes.
  Vysotskaya, Journal of cellular physiology 2018 (PubMed)
  • GeneRIF: we are investigating the effects of hyperoxia on atrial electrophysiology using whole-cell patch-clamp electrophysiology experiments along with assessment of Kv1.5, Kv4.2, and KChIP2 transcripts and protein profiles using real-time quantitative RT-PCR and Western blotting.
• Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons.
  Mendonça, The Journal of physiology 2018
  • GeneRIF: Kv4 interacting dynamically with persistent sodium currents is a key determinant of the irregular firing behaviour of Kiss1(Arc) neurons.
• Phosphorylation of K+ channels at single residues regulates memory formation.
  Vernon, Learning & memory (Cold Spring Harbor, N.Y.) 2016
  • GeneRIF: Result suggests that the memory type supported by neurons may depend critically on the phosphorylation of specific K+ channels at single residues.
• More

KCND2_RABIT / P59995 A-type voltage-gated potassium channel KCND2; Potassium voltage-gated channel subfamily D member 2; Voltage-gated potassium channel subunit Kv4.2 from Oryctolagus cuniculus (Rabbit) (see paper)
74% identity, 100% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (By similarity). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (By similarity). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCND1 or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DPP6, DPP10, DLG4 and DLG1. In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with KCNIP3 promotes tetramerization and formation of a functional potassium channel (By similarity). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity). Interacts with FLNA and FLNC (By similarity). Interacts with NCS1/FREQ (By similarity). Identified in a complex with cAMP- dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity). Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery (By similarity).

NP_113918 potassium voltage-gated channel subfamily D member 2 from Rattus norvegicus
74% identity, 100% coverage

• CaMKII Modulates the Cardiac Transient Outward K+ Current through its Association with Kv4 Channels in Non-Caveolar Membrane Rafts.
  Alday, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2020 (PubMed)
  • GeneRIF: Immunogold staining and electron microscopy of heart vibrosections was performed to localize Kv4.2/Kv4.3 and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) proteins. Patch-Clamp recordings in control conditions and after lipid raft or caveolae disruption show that the CaMKII-Kv4 channel complex must associate in non-caveolar lipid rafts to be functional.
• Magnesium Deficiency Causes Transcriptional Downregulation of Kir2.1 and Kv4.2 Channels in Cardiomyocytes Resulting in QT Interval Prolongation.
  Shimaoka, Circulation journal : official journal of the Japanese Circulation Society 2020 (PubMed)
  • GeneRIF: Magnesium Deficiency Causes Transcriptional Downregulation of Kir2.1 and Kv4.2 Channels in Cardiomyocytes Resulting in QT Interval Prolongation.
• ERK5 Phosphorylates Kv4.2 and Inhibits Inactivation of the A-Type Current in PC12 Cells.
  Kashino, International journal of molecular sciences 2018
  • GeneRIF: Study revealed that ERK5 signaling promotes phosphorylation of Kv4.2 and inhibits the inactivation of the A-type current for the enhancement of membrane excitability in PC12 cells.
• The activation of N-methyl-d-aspartate receptors downregulates transient outward potassium and L-type calcium currents in rat models of depression.
  Liu, American journal of physiology. Cell physiology 2017 (PubMed)
  • GeneRIF: NMDA reduced both currents in a concentration-dependent manner, whereas there was no significant impact on the currents when perfused with MK-801. MDD rats exhibited significantly more fibrosis areas in heart tissue and reduced expression of Kv4.2, Kv4.3, and Cav1.2.
• Reduced expression of IA channels is associated with post-ischemic seizures.
  Lei, Epilepsy research 2016
  • GeneRIF: Results showed: (i) seizures are associated with more brain damage and neuronal damage is not the major contributor of seizure generation in ischemic rats; (ii) the expression of IA channel subunit Kv4.2 is selectively reduced in ischemic rats with spontaneous behavioral seizures; (iii) The reduction of Kv4.2 may be associated with the long-term increased seizure susceptibility of ischemic rats.
• MiR-223-3p as a Novel MicroRNA Regulator of Expression of Voltage-Gated K+ Channel Kv4.2 in Acute Myocardial Infarction.
  Liu, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2016 (PubMed)
  • GeneRIF: Data show that voltage-gated K+ channel Kv4.2 as a target gene of microRNA miR-223-3p.
• Hydrogen Sulfide Targets the Cys320/Cys529 Motif in Kv4.2 to Inhibit the Ito Potassium Channels in Cardiomyocytes and Regularizes Fatal Arrhythmia in Myocardial Infarction.
  Ma, Antioxidants & redox signaling 2015
  • GeneRIF: The study provides the first piece of evidence for the role of H2S in regulating Ito potassium channels and also the specific motif in an ion channel labile for H2S regulation.
• Estrogen suppresses epileptiform activity by enhancing Kv4.2-mediated transient outward potassium currents in primary hippocampal neurons.
  Zhang, International journal of molecular medicine 2015 (PubMed)
  • GeneRIF: 17betaestradiol suppresses epileptiform activity by enhancing Kv4.2-mediated transient outward potassium currents in primary hippocampal neurons.
• More

KCND2_HUMAN / Q9NZV8 A-type voltage-gated potassium channel KCND2; Potassium voltage-gated channel subfamily D member 2; Voltage-gated potassium channel subunit Kv4.2 from Homo sapiens (Human) (see 23 papers)
TC 1.A.1.2.5 / Q9NZV8 Voltage-gated K+ channel subfamily D, member 2, Kv4.2 or KCND2, in neurons and muscle; forms complexes with auxiliary subunits and scaffolding proteins via its N-terminus, influencing trafficking, temperature-sensitivity and gating (Radicke et al. 2013).These subunits are (1) dipeptidyl-peptidase-like type II transmembrane proteins typified by DPPX-S (e.g., protein 6, P42658; 865 aas), and (2) cytoplasmic Ca2+ binding proteins known as K+ channel interacting proteins (KChIPs; TC#5.B.1.1.7; Q6PIL6) from Homo sapiens (Human) (see 17 papers)
KCND2 / RF|NP_036413.1 potassium voltage-gated channel subfamily D member 2 from Homo sapiens (see paper)
NP_036413 A-type voltage-gated potassium channel KCND2 from Homo sapiens
74% identity, 100% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:11507158, PubMed:14623880, PubMed:14695263, PubMed:14980201, PubMed:15454437, PubMed:16934482, PubMed:19171772, PubMed:24501278, PubMed:24811166, PubMed:34552243, PubMed:35597238). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:14623880, PubMed:14980201, PubMed:15454437, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (PubMed:35597238).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCND1 or KCND3 (PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:34552243, PubMed:35597238). Associates with the regulatory subunits KCNIP2, KCNIP3 and KCNIP4 (PubMed:11287421, PubMed:11847232, PubMed:12451113, PubMed:14623880, PubMed:14980201, PubMed:15358149, PubMed:24811166, PubMed:35597238). Interacts with the regulatory subunit KCNIP1; this interaction mediates the capture of both the N- and C-terminus of KCND2, preventing N-type inactivation and stabilizing the S6 conformation, thereby accelerating closed state inactivation and recovery (PubMed:10676964, PubMed:14980207, PubMed:15358149, PubMed:34552243). In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19171772). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (PubMed:14623880, PubMed:14980201, PubMed:24811166). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (PubMed:24811166). Interacts with DLG4 and NCS1/FREQ (By similarity). Interacts with DLG1 (PubMed:19213956). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (PubMed:15358149). Interacts with FLNA, FLNC and DPP10 (PubMed:11102480, PubMed:15454437). Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery (PubMed:15454437, PubMed:34552243, PubMed:35597238).
• substrates: K+
  tcdb comment: The C-terminus interacts with KChIP2 to influence gating, surface trafficking and gene expression (Han et al., 2006; Schwenk et al., 2008). KChIPs (250 aas for mouse KChIP4a; Q6PHZ8) are homologous to domains in NADPH oxidases (5.B.1).Heteropoda toxin 2 (P58426; PDB 1EMX; TC#8.B.5.2.2) interactions with Kv4.3 and Kv4.1 give rise to differences in gating modifications (DeSimone et al., 2011). Mutations cause autism and seizures due to a slowing of channel inactivation (Lee et al. 2014). The stoichiometry of Kv4.2 and DPP6 is 4:4 (Soh and Goldstein 2008). Neferine, an isoquinoline alkaloid from plants, inhibits Kv4.3 channels, probably by blocking the open state (Wang et al. 2015). SUMOylating (derivatizing with small ubiquitin-like modifier) two distinct sites on Kv4.2, increases surface expression and decreases current amplitude (Welch et al. 2019)
• Age-related changes in Kv4/Shal and Kv1/Shaker expression in Drosophila and a role for reactive oxygen species.
  Vallejos, PloS one 2021
  • “...4.1 (NP_032449.1), K v 4.2 (NP_062671.1), K v 4.3 (NP_001034436), or human K v 4.2 (NP_036413.1); [ 30 ]). As such, we set out to examine if age also affects levels of K v 4 channel proteins in the mouse brain. We measured steady-state levels of...”
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 4.1 K v 4.2 K v 4.3 HGNC, UniProt KCND1 , Q9NSA2 KCND2 , Q9NZV8 KCND3 , Q9UK17 Associated subunits KChIP 1-4, DP66, DPP10 KChIP 1-4, DPP6, DPP10, K v 1, NCS-1, Na v 1 KChIP 1-4, DPP6 and DPP10, MinK, MiRPs Channel blockers fampridine...”
• An Analysis of the Anti-Neuropathic Effects of Qi She Pill Based on Network Pharmacology
  Song, Evidence-based complementary and alternative medicine : eCAM 2020
  • “...33 HTR7 5-Hydroxytryptamine receptor 7 P34969 34 KCNH2 Potassium voltage-gated channel subfamily D member 2 Q9NZV8 35 MAOB Amine oxidase [flavin-containing] B P27338 36 OPRD1 Delta-type opioid receptor P41143 37 OPRK1 Opioid receptor kappa 1 P41145 38 OPRM1 Opioid receptor mu 1 P35372 39 PTGS1 Prostaglandin...”
• Bioinformatics characterisation of the (mutated) proteins related to Andersen-Tawil syndrome.
  Polanco, Mathematical biosciences and engineering : MBE 2019 (PubMed)
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 4.1 K v 4.2 K v 4.3 HGNC, UniProt KCND1 , Q9NSA2 KCND2 , Q9NZV8 KCND3 , Q9UK17 Associated subunits KChIP 14, DP66, DPP10 KChIP 14, DPP6, DPP10, K v 1, NCS1, Na v 1 KChIP 14, DPP6 and DPP10, MinK, MiRPs Channel blockers fampridine...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 6.1 K v 6.2 K v 6.3 K v 6.4 HGNC, UniProt KCND2 , Q9NZV8 KCND3 , Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809; KCNH6, Q9H252; KCNH7, Q9NS40; KCNH8, Q96L42; KCNH3, Q9ULD8; KCNH4, Q9UQ05 KCNMA1, Q12791;...”

KCND2_RAT / Q63881 A-type voltage-gated potassium channel KCND2; Potassium voltage-gated channel subfamily D member 2; RK5; Shal1; Voltage-gated potassium channel subunit Kv4.2 from Rattus norvegicus (Rat) (see 46 papers)
74% identity, 100% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart (PubMed:10676964, PubMed:12592409, PubMed:12754210, PubMed:14980206, PubMed:16123112, PubMed:16207878, PubMed:1722463, PubMed:1840649, PubMed:19279261, PubMed:25352783, PubMed:9058605, PubMed:9093524). Mediates the major part of the dendritic A-type current I(SA) in brain neurons (PubMed:16207878, PubMed:17026528). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member (PubMed:9058605, PubMed:9093524). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:10676964, PubMed:12451113, PubMed:12592409, PubMed:12754210, PubMed:14980206, PubMed:15452711, PubMed:16207878, PubMed:16820361, PubMed:1722463, PubMed:1840649, PubMed:25352783, PubMed:9093524). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel (PubMed:25352783). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes (PubMed:12451113, PubMed:16123112). Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:12451113, PubMed:14980206, PubMed:15452711, PubMed:16123112, PubMed:16820361, PubMed:20045463). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:15671030, PubMed:16123112, PubMed:19279261, PubMed:19441798, PubMed:19901547). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCND1 or KCND3 (PubMed:12754210, PubMed:15485870, PubMed:20224290, PubMed:25352783). Associates with the regulatory subunits KCNIP2, KCNIP3 and KCNIP4 (PubMed:10676964, PubMed:11805342, PubMed:11847232, PubMed:12451113, PubMed:14980206, PubMed:15356203, PubMed:15452711, PubMed:15485870, PubMed:16820361, PubMed:20045463, PubMed:24811166). Interacts with the regulatory subunit KCNIP1; this interaction mediates the capture of both the N- and C-terminus of KCND2, preventing N-type inactivation and stabilizing the S6 conformation, thereby accelerating closed state inactivation and recovery (PubMed:14980206, PubMed:14980207, PubMed:15356203). Interacts with DPP10, DLG4 and DLG1 (PubMed:11923279, PubMed:14559911, PubMed:15671030, PubMed:19213956). In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:16123112, PubMed:19901547). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with KCNIP3 promotes tetramerization and formation of a functional potassium channel (PubMed:15485870). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity). Interacts with FLNA and FLNC (PubMed:11102480). Interacts with NCS1/FREQ (By similarity). Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (PubMed:20224290). Interacts (via S1 and S2 helices) with DPP6; this interaction stabilizes the conformation of the S1-S2 helices and facilitates S4 conformational change, including S4 sliding up and down, thereby accelerating activation, inactivation, and recovery (PubMed:12575952, PubMed:15671030).
• Space Radiation-Induced Alterations in the Hippocampal Ubiquitin-Proteome System
  Tidmore, International journal of molecular sciences 2021
  • “...P84586 * Q63100 Q6MG60 Q9WU70 O35274 P26817 P86182 * Q63633 Q6P7S1 Q9Z1C7 O54701 P29411 Q01066 Q63881 Q78P75 Q9Z269 * P00564 P31422 Q02356 Q64232 Q7M6Z5 Q9Z2 5 P01026 P31424 Q1WIM2 Q64640 Q80W83 * P04256 * P31977 Q4FZT0 Q66H20 Q811X6 Fully mapped and annotated in UniProt. * Denotes...”
• Impact of intracellular hemin on N-type inactivation of voltage-gated K⁺ channels
  Coburger, Pflugers Archiv : European journal of physiology 2020
  • “...Kv3.1 (KCNAB3, O43448), and DPP6a from Homo sapiens and Kv1.1 (Kcna1, P10499) and Kv4.2 (Kcnd2, Q63881) from Rattus norvegicus were subcloned into pcDNA3.1. Accession numbers refer to the UniProt database. Mutations were generated using the QuikChange Site-Directed Mutagenesis Kit (Agilent, Waldbronn, Germany) or an overlap-extension mutagenesis...”
• A PIP2 substitute mediates voltage sensor-pore coupling in KCNQ activation.
  Liu, Communications biology 2020
  • “...no. P51787), KCNQ2 (O43526), KCNQ3 (O43525), KCNE1 (P15382), Kir1.1 (P48048), hERG (Q12809), K V 4.2 (Q63881), Na V 1.5 (Q14524), Na V 1 (Q07699), Ca V 1.2 (Q13936), Ca V 1a (Q02641), Ca V 2/ 1 (P54289), and HCN4 (Q9Y3Q4) were subcloned into oocyte expression vectors,...”
• Q/R site interactions with the M3 helix in GluK2 kainate receptor channels revealed by thermodynamic mutant cycles.
  Lopez, The Journal of general physiology 2013
  • “...and GluN2A (Q00959), and subunits of five potassium channels including Kir2.1 (35561), Kir3.4 (P48544), Kv4.2 (Q63881), Kv1.5 (P22460), and KcsA (P0A334). Presumed helical segments are underlined. Colors indicate interactions between locations in the pore loop (orange) and inner helix (red) of homomeric channels, between the pore...”

KCND1_RABIT / P59994 A-type voltage-gated potassium channel KCND1; Potassium voltage-gated channel subfamily D member 1; Voltage-gated potassium channel subunit Kv4.1 from Oryctolagus cuniculus (Rabbit) (see paper)
65% identity, 99% coverage

• function: A-type voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes in the brain. Mediates A-type current I(SA) in suprachiasmatic nucleus (SCN) neurons. Exhibits a low-threshold A-type current with a hyperpolarized steady- state inactivation midpoint and the recovery process was steeply voltage-dependent, with recovery being markedly faster at more negative potentials. May regulates repetitive firing rates in the suprachiasmatic nucleus (SCN) neurons and circadian rhythms in neuronal excitability and behavior. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity. The regulatory subunit KCNIP1 modulates the kinetics of channel inactivation, increases the current amplitudes and accelerates recovery from inactivation, shifts activation in a depolarizing direction (By similarity). The regulatory subunit DPP10 decreases the voltage sensitivity of the inactivation channel gating (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10.

KCND1_HUMAN / Q9NSA2 A-type voltage-gated potassium channel KCND1; Potassium voltage-gated channel subfamily D member 1; Shal-type potassium channel KCND1; Voltage-gated potassium channel subunit Kv4.1 from Homo sapiens (Human) (see 2 papers)
NP_004970 A-type voltage-gated potassium channel KCND1 from Homo sapiens
65% identity, 99% coverage

• function: A-type voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes in the brain (PubMed:15454437). Mediates A-type current I(SA) in suprachiasmatic nucleus (SCN) neurons. Exhibits a low-threshold A-type current with a hyperpolarized steady-state inactivation midpoint and the recovery process was steeply voltage-dependent, with recovery being markedly faster at more negative potentials. May regulates repetitive firing rates in the suprachiasmatic nucleus (SCN) neurons and circadian rhythms in neuronal excitability and behavior. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity. The regulatory subunit KCNIP1 modulates the kinetics of channel inactivation, increases the current amplitudes and accelerates recovery from inactivation, shifts activation in a depolarizing direction (By similarity). The regulatory subunit DPP10 decreases the voltage sensitivity of the inactivation channel gating (PubMed:15454437).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Component of heteromultimeric potassium channels. Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10.
• Comparative Bioinformatic Analysis of the Proteomes of Rabbit and Human Sex Chromosomes
  Pinto-Pinho, Animals : an open access journal from MDPI 2024
  • “...receptor accessory protein-like 2 95.4 X XP_047298053 XP_051693453 IRAK1 interleukin-1 receptor-associated kinase 1 82.7 Unplaced NP_004970 XP_002719951 KCND1 potassium voltage-gated channel subfamily D member 1 97.1 X NP_000416 XP_051693407 L1CAM neural cell adhesion molecule L1 91.3 Unplaced NP_001116078 XP_008271376 LAMP2 lysosome-associated membrane glycoprotein 2 84.2 X...”
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v...”
• Comparative Bioinformatic Analysis of the Proteomes of Rabbit and Human Sex Chromosomes
  Pinto-Pinho, Animals : an open access journal from MDPI 2024
  • “...Interleukin-1 receptor-associated kinase 1 GLOB CS, PM O43736 ITM2A Integral membrane protein 2A TM PM Q9NSA2 KCND1 Potassium voltage-gated channel subfamily D member 1 TM PM Q9UJ90 KCNE5 Potassium voltage-gated channel subfamily E regulatory beta subunit 5 TM PM, ICPM P32004 L1CAM Neural cell adhesion molecule...”
• Etiological involvement of KCND1 variants in an X-linked neurodevelopmental disorder with variable expressivity.
  Kalm, American journal of human genetics 2024
  • “...in Xenopus oocytes The human KCND1 cDNA (GenBank: NM_004979.6) encoding full-length Kv4.1 (GenBank: NP_004970.3, UniProtKB Q9NSA2) 34 was inserted into pGEM-HE to generate pGEM-OK-hKCND1, which carries an optimized Kozak sequence. Variant-specific mutations were introduced utilizing the Quick-Change II site-directed mutagenesis kit (Agilent), and resulting constructs were...”
• Computational engineering of water-soluble human potassium ion channels through QTY transformation.
  Smorodina, Scientific reports 2024
  • “...Uniprot ( https://www.uniprot.org ) 46 including KCNA1 (Q09470), KCNA3 (P22001), KCNA5 (P22460), KCNC4 (Q03721), KCND1 (Q9NSA2), KCNH2 (Q12809), KCNH5 (Q8NCM2), KCNJ3 (P48549), KCNJ8 (Q15842), KCNJ10 (P78508), KCNJ11 (Q14654), KCNJ12 (Q14500), KCNK2 (O95069), KCNK5 (O95279), KCNK9 (Q9NPC2), KCNMA1 (Q12791), KCNN3 (Q9UGI6), and KCNN4 (O15554).Native and QTY sequences...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...A Nomenclature K v 4.1 K v 4.2 K v 4.3 HGNC, UniProt KCND1 , Q9NSA2 KCND2 , Q9NZV8 KCND3 , Q9UK17 Associated subunits KChIP 1-4, DP66, DPP10 KChIP 1-4, DPP6, DPP10, K v 1, NCS-1, Na v 1 KChIP 1-4, DPP6 and DPP10, MinK, MiRPs...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...A Nomenclature K v 4.1 K v 4.2 K v 4.3 HGNC, UniProt KCND1 , Q9NSA2 KCND2 , Q9NZV8 KCND3 , Q9UK17 Associated subunits KChIP 14, DP66, DPP10 KChIP 14, DPP6, DPP10, K v 1, NCS1, Na v 1 KChIP 14, DPP6 and DPP10, MinK, MiRPs...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...UniProt KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 KCND1 , Q9NSA2 Associated subunits MiRP2 is an associated subunit for K v 3.4 KChIP and KChAP Functional Characteristics K V K V K A K A K A Channel blockers fampridine (pIC...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809; KCNH6, Q9H252; KCNH7, Q9NS40; KCNH8, Q96L42; KCNH3, Q9ULD8; KCNH4, Q9UQ05...”

NP_001099218 potassium voltage-gated channel subfamily D member 1 precursor from Rattus norvegicus
66% identity, 96% coverage

• K+ channel Kv4.1 is expressed in the nociceptors/secondary nociceptive neurons and participates in pain regulation.
  Chiu, European journal of pain (London, England) 2022 (PubMed)
  • GeneRIF: K(+) channel Kv4.1 is expressed in the nociceptors/secondary nociceptive neurons and participates in pain regulation.

KCND1_MOUSE / Q03719 A-type voltage-gated potassium channel KCND1; Potassium voltage-gated channel subfamily D member 1; Voltage-gated potassium channel subunit Kv4.1; mShal from Mus musculus (Mouse) (see 4 papers)
NP_032449 potassium voltage-gated channel subfamily D member 1 precursor from Mus musculus
66% identity, 96% coverage

• function: A-type voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes in the brain (PubMed:28560311). Mediates A-type current I(SA) in suprachiasmatic nucleus (SCN) neurons (PubMed:28560311). Exhibits a low-threshold A- type current with a hyperpolarized steady-state inactivation midpoint and the recovery process was steeply voltage-dependent, with recovery being markedly faster at more negative potentials (PubMed:2034678). May regulates repetitive firing rates in the suprachiasmatic nucleus (SCN) neurons and circadian rhythms in neuronal excitability and behavior (PubMed:28560311). Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (PubMed:28560311). The regulatory subunit KCNIP1 modulates the kinetics of channel inactivation, increases the current amplitudes and accelerates recovery from inactivation, shifts activation in a depolarizing direction (PubMed:11423117). The regulatory subunit DPP10 decreases the voltage sensitivity of the inactivation channel gating (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Component of heteromultimeric potassium channels (PubMed:19713751). Identified in potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (PubMed:19713751).
• Impaired pattern separation in Tg2576 mice is associated with hyperexcitable dentate gyrus caused by Kv4.1 downregulation.
  Kim, Molecular brain 2021
  • GeneRIF: Impaired pattern separation in Tg2576 mice is associated with hyperexcitable dentate gyrus caused by Kv4.1 downregulation.
• Calbindin regulates Kv4.1 trafficking and excitability in dentate granule cells via CaMKII-dependent phosphorylation.
  Kim, Experimental & molecular medicine 2021
  • GeneRIF: Calbindin regulates Kv4.1 trafficking and excitability in dentate granule cells via CaMKII-dependent phosphorylation.
• Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.
  Kim, The Journal of neuroscience : the official journal of the Society for Neuroscience 2020
  • GeneRIF: Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.
• Voltage-dependent gating rearrangements in the intracellular T1-T1 interface of a K+ channel.
  Wang, The Journal of general physiology 2006
  • GeneRIF: The complex voltage-dependent gating rearrangements of eukaryotic Kv channels are not limited to the membrane-spanning core but must include the intracellular T1-T1 interface.
• Acute Knockdown of Kv4.1 Regulates Repetitive Firing Rates and Clock Gene Expression in the Suprachiasmatic Nucleus and Daily Rhythms in Locomotor Behavior.
  Hermanstyne, eNeuro
  • GeneRIF: Expression of the Kv4.1-targeted shRNA significantly decreased interspike intervals and increased repetitive firing rates in suprachiasmatic nucleus (SCN) neurons during the day and at night. results presented here also revealed that the acute knockdown of Kv4.1 had differential effects on the daytime and nighttime input resistance and repetitive firing rates in SCN neurons.
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...C-term S732 C-term S740 C-term T751 C-term S755 Kv3.4/KCNC4 W: Q8R1C0 C-term S555 Kv4.1/KCND1 W: Q03719 C-term S460 C-term S555 Kv4.2/KCND2 W: Q9Z0V2 M: Q9Z0V2 T: Q9Z0V2 N-term T154 C-term S548 S548 C-term S552 S552 Kv4.3/KCND3 W: Q9Z0V1 N-term S153 Kv5.1/KCNF1 W: Q7TSH7 C-term S444 C-term...”

7e8eD / Q9NZV8 Cryoem structure of human kv4.2-dpp6s-kchip1 complex, transmembrane and intracellular region (see paper)
77% identity, 78% coverage

• Ligand: peptide (7e8eD)

KCNAL_DROME / P17971 Potassium voltage-gated channel protein Shal; Shaker cognate l; Shal2 from Drosophila melanogaster (Fruit fly) (see paper)
NP_001097646 shaker cognate l, isoform B from Drosophila melanogaster
65% identity, 86% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. May play a role in the nervous system and in the regulation of beating frequency in pacemaker cells
  subunit: Heterotetramer of potassium channel proteins (By similarity). Interacts (via C-terminal dendritic targeting motif) with SIDL.
• Control of Sleep Onset by Shal/Kv4 Channels in Drosophila Circadian Neurons.
  Feng, The Journal of neuroscience : the official journal of the Society for Neuroscience 2018
  • GeneRIF: Study identified that Shal/Kv4, a well known voltage-gated K+ channel, acts as a controller of wake-sleep transition at dusk in Drosophila circadian neurons.
• Bilaterian Giant Ankyrins Have a Common Evolutionary Origin and Play a Conserved Role in Patterning the Axon Initial Segment.
  Jegla, PLoS genetics 2016
  • GeneRIF: We found that ddaE neurons have an axonal diffusion barrier proximal to the cell body that requires a giant isoform of the neuronal ankyrin Ank2. Furthermore, the potassium channel shal concentrates in the proximal axon in an Ank2-dependent manner
• Krüppel mediates the selective rebalancing of ion channel expression.
  Parrish, Neuron 2014
  • GeneRIF: The loss of Shal potassium channel induces compensatory rebalancing of ion channel expression.
• Shal/K(v)4 channels are required for maintaining excitability during repetitive firing and normal locomotion in Drosophila.
  Ping, PloS one 2011
  • GeneRIF: In Drosophila, the single Shal/K(v)4 gene encodes the predominant I(A) current in many neuronal cell bodies.
• SIDL interacts with the dendritic targeting motif of Shal (K(v)4) K+ channels in Drosophila.
  Diao, Molecular and cellular neurosciences 2010
  • GeneRIF: Data show that SIDL is expressed primarily in the nervous system, co-localizes with GFP-Shal channels in neurons, and interacts specifically with the LL-motif of Drosophila and mouse Shal channels.
• The complexity, challenges and benefits of comparing two transporter classification systems in TCDB and Pfam.
  Chiang, Briefings in bioinformatics 2015
  • “...relationships between TCDB and Pfam. Still another example, the potassium voltage-gated channel protein Shal (UniProtKB P17971, TC# 1.A.1.2.3), part of the TCDB VIC superfamily [ 30 , 31 ], maps to four families in Pfam: Shal-type (PF11601), BTB/POZ (PF02214), Ion_trans (PF00520) and DUF3399 (PF11879) ( Figure...”
• Comparison of K+-channel genes within the genomes of Anopheles gambiae and Drosophila melanogaster
  McCormack, Genome biology 2003
  • “...Shal (Kv1, Kv2, Kv3, and Kv4) K + -channel pore region (from SwissProt P08510, P17970, P17971, P17972) as the query sequence against the DNA of the Anopheles genome. In addition, a probabilistic ancestral sequence (the most recent ancestor of the four major K + -channel families)...”
  • “...8,000 nucleotides and comprises at least 10 exons. The Shal K + -channel sequence (SwissProt P17971) from Drosophila was next used as a query sequence against both the Anopheles and Drosophila genomes. The Shal gene in Drosophila is located at chromosome 3L:76B. The Shal ortholog was...”
• Whole-genome analysis of transporters in the plant pathogen Xylella fastidiosa
  Meidanis, Microbiology and molecular biology reviews : MMBR 2002
  • “...potassium channel from Drosophila melanogaster (1.A.1.2.3, P17971), a member of the voltageregulated ion transport family (pfam 00520) (http://pfam.wustl...”
• Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus
  Wallner, Proceedings of the National Academy of Sciences of the United States of America 1996
  • “...Shab, P17970; Kv3.1, P15388; Shaw, P17972; Kv4, A39372; Shal, P17971. In Vitro Translation. H-S0 and D-S0 clones were made by introducing a stop codon after...”

TC 1.A.1.2.3 / P17971 Voltage-sensitive fast transient outward current K+ channel in neurons and muscle of flies and worms from Drosophila melanogaster (Fruit fly) (see 4 papers)
Shal / GB|ABC86265.1 potassium voltage-gated channel protein Shal from Drosophila melanogaster (see paper)
74% identity, 74% coverage

• substrates: K+

XP_026693459 potassium voltage-gated channel protein Shal from Ciona intestinalis
72% identity, 61% coverage

• A potassium channel (Kv4) cloned from the heart of the tunicate Ciona intestinalis and its modulation by a KChIP subunit.
  Salvador-Recatalà, The Journal of experimental biology 2006 (PubMed)
  • GeneRIF: cloning and characterization of a tunicate Kv4 channel, CionaKv4, and a tunicate KChIP subunit, CionaKChIP

TC 1.A.1.2.21 / Q95XD1 Shal (SHL-1, Kv4) K+ channels of 578 aas and 6 TMSs are the predominant transient outward current in C. elegans muscle. SHL-1 expression occurs in a subset of neurons, body wall muscle and in male-specific diagonal muscles (Fawcett et al. 2006) and control the excitability of neurons and cardiac myocytes by conducting rapidly activating-inactivating currents. Activity is modulated by three K+ channel interacting (KChIP) soluble auxiliary subunits, NCS-4, NCS-5, and NCS-7. All three ceKChIPs alter electrical characteristics of SHL-1 currents by slowing down inactivation kinetics and shifting voltage dependence of activation to more hyperpolarizing potentials. Native SHL-1 current is completely abolished in cultured myocytes of Triple KO worms in which all three KChIP genes are deleted from Caenorhabditis elegans
65% identity, 75% coverage

• substrates: K+

EGR_03099 Potassium voltage-gated channel protein Shal from Echinococcus granulosus
61% identity, 67% coverage

• Antigen discovery by bioinformatics analysis and peptide microarray for the diagnosis of cystic echinococcosis
  Batisti, PLoS neglected tropical diseases 2023
  • “...cellulosae specific antigen EGR_03286 SMTVELEEDFVEDLFDACKD 60% 84% 0.78 CE vs controls V-type proton ATPase subunit EGR_03099 RGVLEPIQEELEDAPPLLSQ 72% 78% 0.77 CE vs controls Potassium voltage-gated channel protein Shal EGR_10786 LEEHSRLSNLPPNLVIQVDP 80% 76% 0.80 CE vs controls Nitrogen permease regulator EGR_08586 CRTHAEYMNYEKRLENVRRS 70% 73% 0.73 Active vs...”
  • “...examination of the microarray results and promising for the diagnosis of CE infection (EGR_08002; EGR_03286; EGR_03099; EGR_10786) or for discriminating between active and inactive CE cysts (EGR_08586; EGR_06311; EGR_03965; EGR_06271) were analyzed comparing CE and controls. OD values were subtracted of the background. Horizontal lines represent...”

2i2rL / Q62897 Crystal structure of the kchip1/kv4.3 t1 complex (see paper)
100% identity, 21% coverage

• Ligand: zinc ion (2i2rL)

KCNB2_RAT / Q63099 Potassium voltage-gated channel subfamily B member 2; CDRK; Voltage-gated potassium channel subunit Kv2.2 from Rattus norvegicus (Rat) (see 4 papers)
37% identity, 45% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells (PubMed:1550672). Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:1550672, PubMed:20202934, PubMed:9305895). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20202934). Can also form functional heterotetrameric channels with other alpha subunits that are non- conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes (PubMed:9305895). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells (PubMed:1550672, PubMed:20202934).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCNB1 (PubMed:20202934). Heterotetramer with KCNS1 and KCNS2 (PubMed:9305895). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).

A6H8H5 Potassium voltage-gated channel subfamily B member 2 from Mus musculus
36% identity, 45% coverage

• Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling.
  Vierra, Nature communications 2023
  • “...accession Mean s.e.m. 1 Kv2.1 Q03717 100.0 NA 2 SPHKAP E9PUC4 32.2 1.0 3 Kv2.2 A6H8H5 31.6 0.5 5 VAPA Q9WV55 25.3 1.7 8 PKA RI Q9DBC7 15.3 1.5 9 PKA RI P12849 12.9 0.6 15 VAPB Q8BH80 7.6 1.4 16 Junctophilin-3 Q9ET77 6.3 1.3 17...”
• Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.
  Schulien, Science advances 2020
  • “...are also conserved for both Kv2.1 and Kv2.2 channels in mouse (UniProt Q03717 and UniProt A6H8H5, respectively) and human (UniProt Q14721 and UniProt Q92953, respectively). With this information, we hypothesized that the region encompassing amino acids 602 to 608 within Kv2.2 CT was most likely to...”
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...C-term S655 S655 S655 S655 C-term S782 C-term T803 T803 C-term S804 S804 Kv2.2/KCNB2 W: A6H8H5 C-term T478 C-term S481 C-term S488 C-term S490 C-term S503 C-term S507 C-term S530 Kv3.1/KCNC1 W: P15388 Tr: Q3TR92 T: P15388 N-term S158 N-term S160 S160 C-term T421 C-term S468...”

NP_001075606 potassium voltage-gated channel subfamily B member 2 from Oryctolagus cuniculus
36% identity, 45% coverage

• MicroRNA-1 accelerates the shortening of atrial effective refractory period by regulating KCNE1 and KCNB2 expression: an atrial tachypacing rabbit model.
  Jia, PloS one 2013
  • GeneRIF: miR-1 by anti-miR-1 inhibitor oligonucleotides alleviated the downregulation of KCNE1 and KCNB2, the shortening of AERP, and the increase in the IKs

KCNB2_HUMAN / Q92953 Potassium voltage-gated channel subfamily B member 2; Voltage-gated potassium channel subunit Kv2.2 from Homo sapiens (Human) (see paper)
NP_004761 potassium voltage-gated channel subfamily B member 2 from Homo sapiens
36% identity, 45% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCNB1. Heterotetramer with KCNS1 and KCNS2. Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (PubMed:33124732).
• Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity.
  Li, Neuroscience bulletin 2022
  • GeneRIF: Protein Kinase C Controls the Excitability of Cortical Pyramidal Neurons by Regulating Kv2.2 Channel Activity.
• Kv2 channel-AMIGO β-subunit assembly modulates both channel function and cell adhesion molecule surface trafficking.
  Maverick, Journal of cell science 2021
  • GeneRIF: Kv2 channel-AMIGO beta-subunit assembly modulates both channel function and cell adhesion molecule surface trafficking.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 1.7 (NP_114092), K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v...”
• Kv2.1 Clustering Contributes to Insulin Exocytosis and Rescues Human β-Cell Dysfunction.
  Fu, Diabetes 2017
  • GeneRIF: Kv2.1, but not Kv2.2 (KCNB2), forms clusters of 6-12 tetrameric channels at the plasma membrane and facilitates insulin exocytosis
• Disease-targeted sequencing of ion channel genes identifies de novo mutations in patients with non-familial Brugada syndrome.
  Juang, Scientific reports 2014
  • GeneRIF: Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three Brugada syndrome patients
• Genome-wide association studies of maximum number of drinks.
  Pan, Journal of psychiatric research 2013
  • GeneRIF: The rs2128158 in KCNB2 showed significant associations with MaxDrinks.
• Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.
  Hristov, American journal of physiology. Cell physiology 2012
  • GeneRIF: stromatoxin-1 -sensitive KV2-containing channels are expressed in detrusor smooth muscle (DSM); they control DSM excitability, intracellular Ca2+ levels, and myogenic and nerve-evoked contractions
• A high-density association screen of 155 ion transport genes for involvement with common migraine.
  Nyholt, Human molecular genetics 2008
  • GeneRIF: Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
• More
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 3.3 K v 3.4 HGNC, UniProt KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1, K v 6.1-6.4, K v 8.1-8.2...”
• Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.
  Schulien, Science advances 2020
  • “...channels in mouse (UniProt Q03717 and UniProt A6H8H5, respectively) and human (UniProt Q14721 and UniProt Q92953, respectively). With this information, we hypothesized that the region encompassing amino acids 602 to 608 within Kv2.2 CT was most likely to be responsible for disrupting Kv2.1 clusters, likely by...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 3.2 K v 3.3 K v 3.4 HGNC, UniProt KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3 K v 5.1,...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...UniProt KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v 1 and K v 2 K v 5.1, K v 6.16.4, K...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNA3, P22001; KCNA4, P22459; KCNA5, P22460; KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809;...”

XP_018124040 potassium channel, voltage gated Shab related subfamily B, member 2 S homeolog isoform X1 from Xenopus laevis
37% identity, 44% coverage

• Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation.
  Bhat, American journal of human genetics 2024
  • GeneRIF: Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation.

NP_001079257 potassium channel, voltage gated Shab related subfamily B, member 1 S homeolog from Xenopus laevis
35% identity, 48% coverage

• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...(AAA36156.1, NP_004761.2); Xla: Xenopus laevis (NP_001079257; NP_001079256); Dre: Danio rerio (XP_001332654.1; XP_001332827.1); Hro: H. roretzi (AB018545.1);...”
• Characterization of the heteromeric potassium channel formed by kv2.1 and the retinal subunit kv8.2 in Xenopus oocytes.
  Czirják, Journal of neurophysiology 2007 (PubMed)
  • GeneRIF: Custom-tailored current of Kv2.1/Kv8.2 functionally contributes to photoreception, which why mutations of Kv8.2 lead to a genetic visual disorder.

XP_021332945 potassium voltage-gated channel subfamily B member 1 from Danio rerio
36% identity, 47% coverage

• Kcnb1 plays a role in development of the inner ear.
  Jedrychowska, Developmental biology 2021 (PubMed)
  • GeneRIF: Kcnb1 plays a role in development of the inner ear.
• Functional antagonism of voltage-gated K+ channel α-subunits in the developing brain ventricular system.
  Shen, Development (Cambridge, England) 2016 (PubMed)
  • GeneRIF: Mutation of kcnb1 reduces the size of the ventricular system and its gain of function causes hydrocephalus, which is opposite to the function of Kcng4b. This demonstrates the dynamic interplay between potassium channel subunits in the neuroepithelium as a novel and crucial regulator of ventricular development in the vertebrate brain.

KCNB1_HUMAN / Q14721 Potassium voltage-gated channel subfamily B member 1; Delayed rectifier potassium channel 1; DRK1; h-DRK1; Voltage-gated potassium channel subunit Kv2.1 from Homo sapiens (Human) (see 21 papers)
TC 1.A.1.2.11 / Q14721 Voltage-gated K+ channel, Shab-related, Kv2.1 or KCNB1 (858aas) The crystal structure is known (Long et al., 2007). Rat Kv2.1 and Kv2.2 (long) are colocalized in the somata and proximal dendrites of cortical pyramidal neurons and are capable of forming functional heteromeric delayed rectifier channels. The delayed rectifer currents, which regulate action potential firing, are encoded by heteromeric Kv2 channels in cortical neurons (Kihira et al., 2010). Phosphorylation by AMP-activated protein kinase regulates membrane excitability from Homo sapiens (Human) (see 3 papers)
KCNB1 / RF|NP_004966.1 potassium voltage-gated channel subfamily B member 1 from Homo sapiens (see paper)
NP_004966 potassium voltage-gated channel subfamily B member 1 from Homo sapiens
34% identity, 51% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:10484328, PubMed:12560340, PubMed:1283219, PubMed:19074135, PubMed:19717558, PubMed:24901643, PubMed:8081723). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic- treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the slowly inactivating delayed- rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCNB2 (PubMed:1283219, PubMed:8081723). Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19357235, PubMed:19717558, PubMed:24901643). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (By similarity). Interacts with KCNV2 (PubMed:34535971). Self-associates (via N-terminus and C-terminus) (PubMed:12560340, PubMed:24901643); self-association is required to regulate trafficking, gating and C- terminal phosphorylation-dependent modulation of the channel (By similarity). Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons. Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D- aspartate receptor (NMDAR)-dependent manner. Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate. Interacts with CREB1; this promotes channel acetylation in response to stimulation of incretin hormones. Interacts (via N-terminus and C-terminus) with MYL12B. Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface (By similarity). Interacts with SUMO1 (PubMed:19223394). Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells (By similarity). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (PubMed:33124732).
• substrates: K+
  tcdb comment: Functional interactions between residues in the S1, S4, and S5 domains of Kv2.1 have been identified (Bocksteins et al., 2011). Missense variants in the ion channel domain and loss-of-function variants in this domain and the C-terminus cause neurodevelopmental disorders, sometimes with seizures (de Kovel et al. 2017). Kv2.1 channels consist of two types of alpha-subunits: (1) electrically-active Kcnb1 alpha-subunits and (2) silent or modulatory alpha-subunits plus beta-subunits that, similar to silent alpha-subunits, regulate electrically-active subunits (Jędrychowska and Korzh 2019). It plays a role in neurodevelopmental disorders, such as epileptic encephalopathy. The N- and C-terminal domains of the alpha-subunits interact to form the cytoplasmic subunit of hetero-tetrameric potassium channels. Kcnb1-containing channels are involved in brain development and reproduction
• KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.
  Lacroix, International journal of molecular sciences 2024
  • GeneRIF: KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.
• Inactivation of the Kv2.1 channel through electromechanical coupling.
  Fernández-Mariño, Nature 2023
  • GeneRIF: Inactivation of the Kv2.1 channel through electromechanical coupling.
• Adaptive behavior and psychiatric comorbidities in KCNB1 encephalopathy.
  Bar, Epilepsy & behavior : E&B 2022 (PubMed)
  • GeneRIF: Adaptive behavior and psychiatric comorbidities in KCNB1 encephalopathy.
• Cleavage of Kv2.1 by BACE1 decreases potassium current and reduces neuronal apoptosis.
  Sun, Neurochemistry international 2022 (PubMed)
  • GeneRIF: Cleavage of Kv2.1 by BACE1 decreases potassium current and reduces neuronal apoptosis.
• The role of the voltage-gated potassium channel, Kv2.1 in prostate cancer cell migration.
  Park, BMB reports 2021
  • GeneRIF: The role of the voltage-gated potassium channel, Kv2.1 in prostate cancer cell migration.
• Establishment of an induced pluripotent stem cell line (ZJSHi001-A) from a patient with epileptic encephalopathy carrying KCNB1 Glu330Asp mutation.
  Guo, Stem cell research 2021 (PubMed)
  • GeneRIF: Establishment of an induced pluripotent stem cell line (ZJSHi001-A) from a patient with epileptic encephalopathy carrying KCNB1 Glu330Asp mutation.
• Kv2 channel-AMIGO β-subunit assembly modulates both channel function and cell adhesion molecule surface trafficking.
  Maverick, Journal of cell science 2021
  • GeneRIF: Kv2 channel-AMIGO beta-subunit assembly modulates both channel function and cell adhesion molecule surface trafficking.
• Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature.
  Bar, Human mutation 2020 (PubMed)
  • GeneRIF: Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature.
• More
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 3.2 K v 3.3 K v 3.4 HGNC, UniProt KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1, K v 6.1-6.4,...”
• [Fuxinfang improves hypoxia-induced injury of human aortic endothelial cells by regulating c-Fos-NR4A1-p38 pathway].
  Xu, Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2021
• Modulation of Stem Cells as Therapeutics for Severe Mental Disorders and Cognitive Impairments.
  Zhang, Frontiers in psychiatry 2020
  • “...KCNB1 Potassium voltage-gated channel subfamily B member 1 (Q14721) Potassium channel family, B subfamily, Kv2.1/KCNB1 sub-subfamily CALM1,SNAP25,STX1A CYFIP1,KCND2,KCNH2,SCN2A AMIGO1,AKAP5,FAU,HSPA1B,KCHIP2,KCNAB1,KCNAB2,KCNAB3,KCNA2,KCNB2,KCNE1,KCNE2,KCNE5,KCNG1,KCNG2,KCNG3,KCNG4,KCNH1,KCNIP2,KCNS3,KCNV1,KCNV2,NEDD4L,PRKACB,PRKACG,PRKAR1A,PRKAR1B,PRKAR2A,PRKAR2B,PTPRE,RAB40B,SRC,SUMO1,SUMO2,SUMO3,UBE2I,ZNF579 KCNIP3 Calsenilin (Q9Y2W7) Recoverin family CALM2,CLN3 CACNA1C,GRIN1,KCND2...”
• Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.
  Schulien, Science advances 2020
  • “...Kv2.1 and Kv2.2 channels in mouse (UniProt Q03717 and UniProt A6H8H5, respectively) and human (UniProt Q14721 and UniProt Q92953, respectively). With this information, we hypothesized that the region encompassing amino acids 602 to 608 within Kv2.2 CT was most likely to be responsible for disrupting Kv2.1...”
• Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways.
  Santos, Cells 2020
  • “...protein GFAP P14136-2, P14136-3 49,881.40 35.40% GO:0031102 Potassium voltage-gated channel subfamily B member 1 KCNB1 Q14721 95,881.40 14.40% GO:1900454 Potassium voltage-gated channel subfamily G member 4 KCNG4 Q8TDN1 58,981.00 11.80% GO:0005251 Fibroblast growth factor receptor 3 FGFR3 P22607-2 877,100.00 6.20% GO:0043410...”
• A Proteomic-Based Approach to Study the Mechanism of Cytotoxicity Induced by Interleukin-1α and Cycloheximide.
  Macur, Chromatographia 2018
  • “...P11940 Poly(rC) binding protein 2 PCBP2 Q15366 Potassium voltage-gated channel subfamily B member 1 KCNB1 Q14721 Protein disulphide-isomerase P4HB P07237 RNA-binding protein 10 isoform 2 RBM10 P98175-2 TATA-binding protein-associated factor 172 BTAF1 O14981 Transcriptional activator Myb MYB P10242 Transient receptor potential cation channel, subfamily C, member...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 3.1 K v 3.2 K v 3.3 K v 3.4 HGNC, UniProt KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3...”
• Traumatic Brain Injury Induces Alterations in Cortical Glutamate Uptake without a Reduction in Glutamate Transporter-1 Protein Expression.
  Dorsett, Journal of neurotrauma 2017
• More

NP_001261345 shaker cognate b, isoform N from Drosophila melanogaster
34% identity, 28% coverage

• K⁺-dependent selectivity and external Ca²⁺ block of Shab K⁺ channels.
  Carrillo, PloS one 2015
  • GeneRIF: Shab is a typical K channel that excludes Na
• Light-dependent modulation of Shab channels via phosphoinositide depletion in Drosophila photoreceptors.
  Krause, Neuron 2008 (PubMed)
  • GeneRIF: Upon illumination, the delayed rectifier current mediated by Shab channels Drosophila photoreceptors was specifically increased.
• Distinct frequency-dependent regulation of nerve terminal excitability and synaptic transmission by IA and IK potassium channels revealed by Drosophila Shaker and Shab mutations.
  Ueda, The Journal of neuroscience : the official journal of the Society for Neuroscience 2006
  • GeneRIF: observations highlight crucial control of nerve terminal excitability by Shaker & Shab channels to confer temporal patterns of synaptic transmission & suggest participation of these channels in activity-dependent synaptic plasticity

KCNA2_ONCMY / Q9I830 Potassium voltage-gated channel subfamily A member 2; Shaker-related potassium channel tsha1; Trout shaker 1; Voltage-gated potassium channel subunit Kv1.2 from Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri) (see paper)
36% identity, 66% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and central nervous system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (By similarity). Can form functional homotetrameric channels and heterotetrameric channels with other family members; the channels characteristics depend critically on the types of channel-forming alpha subunits that are present (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (By similarity). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other family members.

LOC123728301 potassium voltage-gated channel subfamily A member 1-like from Salmo salar
38% identity, 59% coverage

• Epigenetic changes in pyloric caeca of Atlantic salmon fed diets containing increasing levels of lipids and choline
  Dhanasiri, Epigenetics 2024
  • “...2(2) TTS LOC106580941 major facilitator superfamily domain-containing protein 1-like ( mfsd1 ) 0 3(0) Exon LOC123728301 potassium voltage-gated channel subfamily A member 1-like ( kcna1 ) 2(0) 3(3) Intron ssa-mir-212a-2 ssa-mir-212a-2 1(1) 0 irf4a interferon regulatory factor 4a 0 3(0) LOC106594380 arf-GAP with coiled-coil, ANK repeat...”

NP_001075556 potassium voltage-gated channel subfamily B member 1 from Oryctolagus cuniculus
36% identity, 46% coverage

• Contribution of Kv2.1 channels to the delayed rectifier current in freshly dispersed smooth muscle cells from rabbit urethra.
  Kyle, American journal of physiology. Cell physiology 2011
  • GeneRIF: Analysis of the data suggested that Kv2.1 channels contribute significantly to the voltage-gated potassium current in smooth muscle cells from rabbit urethra.

KCNB1_MOUSE / Q03717 Potassium voltage-gated channel subfamily B member 1; Voltage-gated potassium channel subunit Kv2.1; mShab from Mus musculus (Mouse) (see 12 papers)
XP_017171221 potassium voltage-gated channel subfamily B member 1 isoform X1 from Mus musculus
35% identity, 46% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:14684365, PubMed:19383458, PubMed:24494598). Also plays a role in the regulation of exocytosis independently of its electrical function (By similarity). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:22056818). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (By similarity). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits, such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (PubMed:22056818). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle (PubMed:10506487, PubMed:12270920, PubMed:17767909, PubMed:23161216, PubMed:24494598). Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation (By similarity). Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (PubMed:24494598). Contributes to the regulation of the glucose-induced amplitude and duration of action potentials in pancreatic beta-cells, hence limiting calcium influx and insulin secretion (PubMed:12270920, PubMed:17767909, PubMed:19383458, PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells (By similarity). May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (PubMed:10506487, PubMed:14684365). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury (By similarity). May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (By similarity). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCNB2. Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (By similarity). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (PubMed:22056818). Interacts with KCNV2 (By similarity). Self- associates (via N-terminus and C-terminus); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel. Interacts (via C- terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons. Interacts (via N- terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner. Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate. Interacts with CREB1; this promotes channel acetylation in response to stimulation by incretin hormones. Interacts (via N-terminus and C-terminus) with MYL12B. Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface. Interacts with SUMO1 (By similarity). Interacts (via phosphorylated form) with PTPRE isoform 2; this reduces phosphorylation and channel activity in heterologous cells (PubMed:10921884). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).
  disruption phenotype: Mice show normal motor coordination and visual acuity, but are hyperactive, exhibit defects in spatial learning ability and show reduced anxiety-like behavior (PubMed:24494598). Show a higher incidence and a shorter latency to seizure progression compared to wild-type mice (PubMed:24494598). Display reduced fasting blood glucose levels and elevated serum insulin levels (PubMed:17767909, PubMed:19383458). Glucose tolerance and insulin secretion is enhanced compared to control animals (PubMed:17767909, PubMed:19383458). Show impaired long-term potentiation in hippocampal neurons (PubMed:24494598). Display a reduction in the slowly deactivating delayed rectifier potassium current in hippocampal pyramidal neurons (PubMed:24494598). Glucose-induced action potential (AP) duration and amplitude is increased while the firing frequency is reduced in pancreatic beta cells (PubMed:17767909, PubMed:19383458).
• Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling.
  Vierra, Nature communications 2023
  • “...proteins specifically copurifying with Kv2.1 Rank (abundance) Protein ID UniProt accession Mean s.e.m. 1 Kv2.1 Q03717 100.0 NA 2 SPHKAP E9PUC4 32.2 1.0 3 Kv2.2 A6H8H5 31.6 0.5 5 VAPA Q9WV55 25.3 1.7 8 PKA RI Q9DBC7 15.3 1.5 9 PKA RI P12849 12.9 0.6 15...”
• A comprehensive mouse brain acetylome-the cellular-specific distribution of acetylated brain proteins
  Ji, Frontiers in cellular neuroscience 2022
  • “...K861] C9K0Y7 Glutamate receptor Gria4 Acetyl [K783] A2AI21 Glutamate receptor Grin1 Acetyl [K207; K564; K565] Q03717 Potassium voltage-gated channel subfamily B member 1 Kcnb1 Acetyl [K822] Q91V14 Solute carrier family 12 member 5 Slc12a5 Acetyl [K691; K1085] P31650 Sodium- and chloride-dependent GABA transporter 3 Slc6a11 Acetyl...”
• Comparative Proteomic Analysis Reveals the Effect of Selenoprotein W Deficiency on Oligodendrogenesis in Fear Memory.
  Situ, Antioxidants (Basel, Switzerland) 2022
  • “...C region (A0A075B6A0), choline transporter-like protein 2 (A0A1L1SU40), potassium voltage-gated channel subfamily B member 1 (Q03717), 5-AMP-activated protein kinase subunit beta-2 (Q6PAM0), and THUMP domain-containing protein 1 (Q99J36). Their fold changes showed the same trend in both WT and KO after fear conditioning. 3.5. DEPs Common...”
  • “...mu chain C region (IgM) 0.66 0.69 A0A1L1SU40 Choline transporter-like protein 2 (CTL2) 0.41 0.49 Q03717 Potassium voltage-gated channel subfamily B member 1 (KCNB1) 1.31 1.25 Q6PAM0 5-AMP-activated protein kinase subunit beta-2 (PRKAB2) 0.49 0.45 Q99J36 THUMP domain-containing protein 1 (THUMPD1) 1.55 1.60...”
• Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.
  Schulien, Science advances 2020
  • “...Notably, these sequences are also conserved for both Kv2.1 and Kv2.2 channels in mouse (UniProt Q03717 and UniProt A6H8H5, respectively) and human (UniProt Q14721 and UniProt Q92953, respectively). With this information, we hypothesized that the region encompassing amino acids 602 to 608 within Kv2.2 CT was...”
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...S535 Kv1.6/KCNA6 W: Q61923 M: Q61923 N-term S6 N-term T8 T8 Kv2.1/KCNB1 W: Q8K0D1 TR: Q03717 M: Q8K0D1 T: Q8K0D1 N-term S12 N-term S15 C-term S444 C-term S484 C-term S517 C-term S518 C-term S519 C-term S520 C-term S567 C-term S655 S655 S655 S655 C-term S782 C-term...”
• Integrin-KCNB1 potassium channel complexes regulate neocortical neuronal development and are implicated in epilepsy.
  Bortolami, Cell death and differentiation 2023
  • GeneRIF: Integrin-KCNB1 potassium channel complexes regulate neocortical neuronal development and are implicated in epilepsy.
• Cdyl Deficiency Brakes Neuronal Excitability and Nociception through Promoting Kcnb1 Transcription in Peripheral Sensory Neurons.
  Sun, Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2022
  • GeneRIF: Cdyl Deficiency Brakes Neuronal Excitability and Nociception through Promoting Kcnb1 Transcription in Peripheral Sensory Neurons.
• Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K+ Channel Subunits Kv8.2 and K2.1.
  Jiang, International journal of molecular sciences 2021
  • GeneRIF: Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K(+) Channel Subunits Kv8.2 and K2.1.
• Kv2.1 expression in giant reticular neurons of the postnatal mouse brain.
  Ding, Journal of chemical neuroanatomy 2021
  • GeneRIF: Kv2.1 expression in giant reticular neurons of the postnatal mouse brain.
• Kv2.1 channels play opposing roles in regulating membrane potential, Ca2+ channel function, and myogenic tone in arterial smooth muscle.
  O'Dwyer, Proceedings of the National Academy of Sciences of the United States of America 2020
  • GeneRIF: Kv2.1 plays a canonical conductive role but found it also has a structural role in arterial myocytes to enhance clustering of CaV1.2 channels.
• Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kvβ1 subunit.
  Wang, The Journal of biological chemistry 2020
  • GeneRIF: Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kvbeta1 subunit.
• Clustered Kv2.1 decreases dopamine transporter activity and internalization.
  Lebowitz, The Journal of biological chemistry 2019
  • GeneRIF: results suggest that Kv2.1 clusters exert a spatially discrete homeostatic braking mechanism on dopamine transporter by inducing a relative increase in inward-facing transporters
• Neuronal ER-plasma membrane junctions organized by Kv2-VAP pairing recruit Nir proteins and affect phosphoinositide homeostasis.
  Kirmiz, The Journal of biological chemistry 2019
  • GeneRIF: the VAP-interacting membrane-associated phosphatidylinositol (PtdIns) transfer proteins PYK2 N-terminal domain-interacting receptor 2 (Nir2) and Nir3 specifically associate with Kv2.1 complexes.
• More

TC 1.A.1.2.1 / P17970 Voltage-sensitive K+ channel (PNa+/PK+ ≈ 0.1) from Drosophila melanogaster (Fruit fly) (see 6 papers)
Shab / RF|NP_728783.1 potassium voltage-gated channel protein Shab from Drosophila melanogaster
34% identity, 44% coverage

• substrates: K+
  tcdb comment: Shaker and Shab K+channels are blocked by quinidine (Gomez-Lagunas, 2010)
• Human-induced evolution caught in action: SNP-array reveals rapid amphi-atlantic spread of pesticide resistance in the salmon ecotoparasite Lepeophtheirus salmonis
  Besnier, BMC genomics 2014
  • “...LG1, Q28FI8, a cytochrome b5 domain-containing protein predicted near marker c8125.67718 on LG 5, or P17970 and P08510, two Potassium voltage-gated channel proteins predicted on LG 5 near markers c10059.23896, and c15581.45069 respectively (Additional file 2 : Table S1, and Additional file 3 : Table S2)....”
• Satellite DNA-like elements associated with genes within euchromatin of the beetle Tribolium castaneum
  Brajković, G3 (Bethesda, Md.) 2012
  • “...43 Inside Q9W2M7 FBgn0034580 Satellite 1440 4.0 D6WPE6 100142073 voltage-gated potassium channel 7 44 Inside P17970 FBgn0003383 Transposon 814 D2A2C6 663849 Putative uncharacterized protein 4 45 5 9489 Q9V3S3 FBgn0013300 Satellite 549 1.5 D2A2D1 663875 Putative uncharacterized protein 4 45 3 10,920 Q9W191 FBgn0034994 Satellite 549...”
• Comparison of K+-channel genes within the genomes of Anopheles gambiae and Drosophila melanogaster
  McCormack, Genome biology 2003
  • “...and Shal (Kv1, Kv2, Kv3, and Kv4) K + -channel pore region (from SwissProt P08510, P17970, P17971, P17972) as the query sequence against the DNA of the Anopheles genome. In addition, a probabilistic ancestral sequence (the most recent ancestor of the four major K + -channel...”
  • “...AG), 191-227, 257-297, 297-348, 411-448, 450-513 observed in both species. The Drosophila Shab sequence (SwissProt P17970) was used as a query against the Anopheles genome. The Drosophila gene Shab is located at chromosome 3L:63A1. The Anopheles Shab (Kv2) ortholog lies at chromosome 2L:23C (see Table 2...”
• Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus
  Wallner, Proceedings of the National Academy of Sciences of the United States of America 1996
  • “...Kv1.3, P22001; Shaker, X06742; Kv2.1 (drk1), P15387; Shab, P17970; Kv3.1, P15388; Shaw, P17972; Kv4, A39372; Shal, P17971. In Vitro Translation. H-S0 and D-S0...”
• Trinucleotide repeats and long homopeptides in genes and proteins associated with nervous system disease and development
  Karlin, Proceedings of the National Academy of Sciences of the United States of America 1996
  • “...PSC (P35820) Runt (P22814) Fork head (P14734) CF2, III (Q01522) SHAB11 (P17970) TKR (P14083) SOL (P27398) 647 1603 509 510 514 924 753 1597 0,0, 1 0, 0, 0 0, 0,...”

KCNB1_RAT / P15387 Potassium voltage-gated channel subfamily B member 1; Delayed rectifier potassium channel 1; DRK1; Voltage-gated potassium channel subunit Kv2.1 from Rattus norvegicus (Rat) (see 72 papers)
NP_037318 potassium voltage-gated channel subfamily B member 1 from Rattus norvegicus
35% identity, 46% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:10024359, PubMed:10618149, PubMed:12451110, PubMed:17379638, PubMed:19276663, PubMed:23878373). Also plays a role in the regulation of exocytosis independently of its electrical function (PubMed:20484665). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:12560340, PubMed:1875913, PubMed:2206531, PubMed:2770868, PubMed:8083226, PubMed:8978827, PubMed:9351973, PubMed:9565597). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20202934). Can also form functional heterotetrameric channels with other alpha subunits that are non- conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:8670833, PubMed:8980147, PubMed:9079713, PubMed:9305895, PubMed:9362476, PubMed:9696692). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (PubMed:9362476). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (PubMed:12954870, PubMed:19219384). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the slowly inactivating delayed- rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells (PubMed:10024359, PubMed:10414968, PubMed:10618149, PubMed:11463864, PubMed:12127166, PubMed:12403834, PubMed:12451110, PubMed:12621036, PubMed:12807875, PubMed:12832499, PubMed:12954870, PubMed:15195093, PubMed:15322114, PubMed:16407566, PubMed:17301173, PubMed:17379638, PubMed:18167541, PubMed:18463252, PubMed:19276663, PubMed:20484665, PubMed:21518833, PubMed:22411134, PubMed:23878373, PubMed:9362476, PubMed:9616203). Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation (PubMed:10618149, PubMed:12451110, PubMed:16319318, PubMed:16917065, PubMed:17379638, PubMed:19276663, PubMed:23878373). Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose- induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:11463864). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells (PubMed:9616203). May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (By similarity). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury (PubMed:12832499, PubMed:16273079, PubMed:17360683, PubMed:19077057, PubMed:19622611, PubMed:24928958). May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (PubMed:16319318). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (By similarity). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore- independent manner (PubMed:11463864, PubMed:17301173, PubMed:18167541, PubMed:20484665, PubMed:22411134).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCNB2 (PubMed:20202934). Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (PubMed:8670833, PubMed:8980147, PubMed:9079713, PubMed:9305895, PubMed:9362476, PubMed:9696692). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (PubMed:12954870, PubMed:19219384). Interacts with KCNV2 (By similarity). Self-associates (via N-terminus and C-terminus); self- association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (PubMed:12560340, PubMed:18463252, PubMed:19690160). Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons (PubMed:12621036, PubMed:12807875, PubMed:17301173, PubMed:18167541, PubMed:19077057, PubMed:20484665, PubMed:22411134, PubMed:24928958). Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner (PubMed:12403834, PubMed:12807875, PubMed:19077057). Interacts (via N- terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate (PubMed:18542995, PubMed:19077057, PubMed:19690160). Interacts with CREB1; this promotes channel acetylation in response to stimulation by incretin hormones (PubMed:21818121). Interacts (via N-terminus and C-terminus) with MYL12B (PubMed:24569993). Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface (PubMed:9565597). Interacts with SUMO1. Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells (By similarity). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).
• Kv2.1 Channels Prevent Vasomotion and Safeguard Myogenic Reactivity in Rat Small Superior Cerebellar Arteries.
  Här, Cells 2023
  • GeneRIF: Kv2.1 Channels Prevent Vasomotion and Safeguard Myogenic Reactivity in Rat Small Superior Cerebellar Arteries.
• Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1.
  Dallas, Scientific reports 2021
  • GeneRIF: Hydrogen sulfide regulates hippocampal neuron excitability via S-sulfhydration of Kv2.1.
• Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kvβ1 subunit.
  Wang, The Journal of biological chemistry 2020
  • GeneRIF: Site-specific contacts enable distinct modes of TRPV1 regulation by the potassium channel Kvbeta1 subunit.
• Tyrosine Phosphorylation of the Kv2.1 Channel Contributes to Injury in Brain Ischemia.
  Song, International journal of molecular sciences 2020
  • GeneRIF: Tyrosine Phosphorylation of the Kv2.1 Channel Contributes to Injury in Brain Ischemia.
• Clustered Kv2.1 decreases dopamine transporter activity and internalization.
  Lebowitz, The Journal of biological chemistry 2019
  • GeneRIF: results suggest that Kv2.1 clusters exert a spatially discrete homeostatic braking mechanism on dopamine transporter by inducing a relative increase in inward-facing transporters
• A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons.
  Romer, The Journal of physiology 2019 (PubMed)
  • GeneRIF: A molecular rheostat: Kv2.1 currents maintain or suppress repetitive firing in motoneurons.
• Defining the Kv2.1-syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant.
  Yeh, Proceedings of the National Academy of Sciences of the United States of America 2019
  • GeneRIF: Defining the Kv2.1-syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant.
• Kv2.1 clusters on β-cell plasma membrane act as reservoirs that replenish pools of newcomer insulin granule through their interaction with syntaxin-3.
  Greitzer-Antes, The Journal of biological chemistry 2018
  • GeneRIF: Kv2.1 forms reservoir clusters on the beta-cell plasma membrane and binds Syn-3 via its C-terminal C1b domain, which recruits newcomer insulin secretory granules into this large reservoir.
• More
• Electrically silent KvS subunits associate with native Kv2 channels in brain and impact diverse properties of channel function.
  Ferns, bioRxiv : the preprint server for biology 2024
  • “...the BBS inserted at amino acid 218 in the S1-S2 loop of rat Kv2.1 (Uniprot P15387). The DsRed-Kv2.1 S586A plasmid has been described previously ( Kirmiz et al., 2018a ). Plasmids encoding mouse KvS subunits with C-terminal myc-DDK tags were obtained from Origene (Kv6.1 (MR223857); Kv6.4...”
• Proteomic Analysis Unveils Expressional Changes in Cytoskeleton- and Synaptic Plasticity-Associated Proteins in Rat Brain Six Months after Withdrawal from Morphine
  Drastichova, Life (Basel, Switzerland) 2021
  • “...Cell division control protein 42 homolog (MW) P23385; G3V7U1 Grm1 Metabotropic glutamate receptor 1 (2.31) P15387; A0A0H2UI34 Kcnb1 Potassium voltage-gated channel subfamily B member1 (2.26) D4A7P2 Lrrtm2 Leucine-rich repeat transmembrane (2.43) Q99P74 Rab27b Ras-related protein Rab-27B (MW) P35280 Rab8a Ras-related protein Rab-8A (2.34) D3ZWS0 Scrib Scribble...”
• Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.
  Schulien, Science advances 2020
  • “...exist within the PRC domain of Kv2.1 (S587, S590, F591, and S593; rat sequence, UniProt P15387) that, when point-mutated, abolish the ability for Kv2.1 to form clusters in neurons ( 20 ). A sevenamino acid sequence that includes these four residues from Kv2.1 (amino acids 587...”
  • “...residues within the PRC domain of Kv2.1 (S587, S590, F591, and S593; rat sequence, UniProt P15387) correspond to S583, S586, F587, and S589 in ( 20 ). Plasmid constructs pCMV-DP-1 and pCMV-Sc-1 plasmids were generated by standard cloning into the multiple cloning sites of pCMV-IRES2-GFP (Clontech,...”
• Proteomics identification of radiation-induced changes of membrane proteins in the rat model of arteriovenous malformation in pursuit of targets for brain AVM molecular therapy
  Simonian, Clinical proteomics 2018
  • “...Lipid anchor Alpha 1 inhibitor 3 P04585 = Mylein P02688 Peripheral Potassium voltage gated channel P15387 Multi pass Serine protease inhibitor P27958 Single pass type 1 Endothelial cell specific molecule 1 P35918 = Chloride intracellular channel protein 2 O35433 Multi pass Vomeromodulin Q63751 Extracellular matrix Bone...”
• Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History
  Riedelsberger, PloS one 2015
  • “...Hsa -Kv9.1 AAC13165 Mmu -Kv3.1 Mus musculus CAA68814 Rno -Kv1.2 Rattus norvegicus P63142 Rno -Kv2.1 P15387 Rno -Kv8.1 CAA67174 Furthermore, the inclusion of available crystal structures and homology protein models in the comparison enabled the investigation of channel attributes that are not accessible by the primary...”
• Divining the design principles of voltage sensors.
  Toombes, The Journal of general physiology 2014
  • “...Kv1.2/2.1 paddle chimera (Protein Data Bank accession no. 2R9R_B ), rat Kv2.1 (UniProt accession no. P15387 ), rat Kv1.2 (UniProt accession no. P63142 ), human Kv11.1 (UniProt accession no. Q12809 ), KvAP (UniProt accession no. Q9YDF8 ), human Hv1 (UniProt accession no. Q96D96 ), Ciona VSP...”

KCNA5_RAT / P19024 Potassium voltage-gated channel subfamily A member 5; RCK7; RK4; Voltage-gated potassium channel subunit Kv1.5 from Rattus norvegicus (Rat) (see 5 papers)
NP_037104 potassium voltage-gated channel subfamily A member 5 from Rattus norvegicus
35% identity, 64% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:15618540, PubMed:2361015). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:15618540). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:15618540). Homotetrameric channels display rapid activation and slow inactivation. Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents (PubMed:11709425). Forms a ternary complex with DLG1 and CAV3 (PubMed:15277200). Interacts with KCNAB1 (By similarity). Interacts with UBE2I (By similarity). Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (By similarity).
• Increased Expression of MicroRNA-206 Inhibits Potassium Voltage-Gated Channel Subfamily A Member 5 in Pulmonary Arterial Smooth Muscle Cells and Is Related to Exaggerated Pulmonary Artery Hypertension Following Intrauterine Growth Retardation in Rats.
  Lv, Journal of the American Heart Association 2019
  • GeneRIF: expression of Kv1.5 and 4-aminopyridine (Kv channel special inhibitor)-sensitive Kv current were correlated with the inhibition of miR-206 in PA rings of IUGR - CH rats and cultured IUGR PASMC s exposed to hypoxia. Thus, miR-206 may be a trigger for induction of exaggerated CH-pulmonary artery hypertension of IUGR via Kv1.5.
• Imbalance of NFATc2 and KV1.5 Expression in Rat Pulmonary Vasculature of Nitrofen-Induced Congenital Diaphragmatic Hernia.
  Zimmer, European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie 2017 (PubMed)
  • GeneRIF: This study demonstrates for the first time an altered gene and protein expression of NFATc2 and KV1.5 in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia. Upregulation of NFATc2 with concomitant downregulation of KV1.5 channels may contribute to abnormal vascular remodeling.
• Angiotensin II reduces the surface abundance of KV 1.5 channels in arterial myocytes to stimulate vasoconstriction.
  Kidd, The Journal of physiology 2017
  • GeneRIF: Ang II selectively stimulates degradation of KV1.5 channels to reduce functional KV1.5 channel surface abundance in mesenteric artery myocytes
• H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation.
  Lu, Biochemical and biophysical research communications 2017 (PubMed)
  • GeneRIF: H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during atrial fibrillation
• AMP-activated protein kinase inhibits Kv 1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation.
  Moral-Sanz, The Journal of physiology 2016
  • GeneRIF: AMPK selectively inhibits Kv1.5 in pulmonary arterial myocytes
• Diphenyl phosphine oxide-1-sensitive K(+) channels contribute to the vascular tone and reactivity of resistance arteries from brain and skeletal muscle.
  Fancher, Microcirculation (New York, N.Y. : 1994) 2015
  • GeneRIF: KV1.5, a DPO-1-sensitive KDR channel, plays a major role in determining microvascular tone and the response to vasoconstrictors and vasodilators.
• Intravascular pressure enhances the abundance of functional Kv1.5 channels at the surface of arterial smooth muscle cells.
  Kidd, Science signaling 2015
  • GeneRIF: Data indicate that intravascular pressure-induced membrane depolarization selectively increased voltage-dependent potassium channels K(v)1.5 surface abundance to increase K(v) currents in arterial myocytes, which would limit vasoconstriction.
• Angiotensin II upregulates Kv1.5 expression through ROS-dependent transforming growth factor-beta1 and extracellular signal-regulated kinase 1/2 signalings in neonatal rat atrial myocytes.
  Lu, Biochemical and biophysical research communications 2014 (PubMed)
  • GeneRIF: Ang II upregulates the expression of Kv1.5, SAP97 and TGF-beta1 in neonatal rat atrial myocytes.
• More
• Striated muscle-specific serine/threonine-protein kinase beta segregates with high versus low responsiveness to endurance exercise training
  Kusić, Physiological genomics 2020 (secret)
• Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5.
  Zhao, Biomolecules 2019
  • “...a length of 602 amino acids in mice (Unitprot Entry: Q61762) and rat (Unitprot Entry: P19024) sequences and 613 amino acids in the human sequence (Unitprot Entry: P22460). According to the Basic Local Alignment Search Tool (BLAST) result, the sequence of Kv1.5 is similar to homology...”
• Proteomics identification of radiation-induced changes of membrane proteins in the rat model of arteriovenous malformation in pursuit of targets for brain AVM molecular therapy
  Simonian, Clinical proteomics 2018
  • “...P49002 53,416.56 7.9 4.95 0.01 790 0.001 Potassium voltage gated channel subfamily A member 5 P19024 67,237.32 3.4 2.42 0.01 340 0.005 Myelin protein P06907 27,741.78 7.4 6.48 0.01 737.5 0.017 Chloride intracellular channel protein 2 Q5M883 28,446.33 0.6 0.39 0.01 60 0.051 Vomeromodulin Q63751 10,890.35...”
• The N terminus and transmembrane segment S1 of Kv1.5 can coassemble with the rest of the channel independently of the S1-S2 linkage.
  Lamothe, The Journal of biological chemistry 2018

XP_021332960 potassium voltage-gated channel subfamily A member 2 from Danio rerio
37% identity, 62% coverage

• Transient knock-down of kcna2 reduces sleep in larval zebrafish.
  Srdanović, Behavioural brain research 2017 (PubMed)
  • GeneRIF: kcna2 knock-down reduces sleep in zebrafish larvae.

TC 1.A.1.2.22 / Q26094 K+ channel, jShak1 of 487 aas and 6 TMSs. Intramolecular interactions control voltage sensitivity from Polyorchis penicillatus
40% identity, 61% coverage

• substrates: K+

NP_001006646 potassium voltage-gated channel subfamily A member 5 from Canis lupus familiaris
35% identity, 63% coverage

• Localization of Kv1.5 channels in rat and canine myocyte sarcolemma.
  Eldstrom, FEBS letters 2006 (PubMed)
  • GeneRIF: Kv1.5 is not present in caveolae of rat and canine heart.

NP_989794 potassium voltage-gated channel subfamily A member 2 from Gallus gallus
37% identity, 60% coverage

• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...NP_005540); Gga: Gallus gallus (XP_425660; NP_989794; NP_001025549; XP_417226; NP_989793); Dre: D. rerio (XP_687507; XP_001334455; XP_699869; NP_001104640;...”

KCNB2_CANLF / Q95167 Potassium voltage-gated channel subfamily B member 2; Voltage-gated potassium channel subunit Kv2.2 from Canis lupus familiaris (Dog) (Canis familiaris) (see paper)
36% identity, 51% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells (PubMed:9612272). Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:9612272). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer or heterotetramer with KCNB1. Heterotetramer with KCNS1 and KCNS2 (By similarity). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).

NP_001104640 potassium voltage-gated channel subfamily A member 2b from Danio rerio
38% identity, 58% coverage

• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...NP_989793); Dre: D. rerio (XP_687507; XP_001334455; XP_699869; NP_001104640; XP_695984; XP_687427). RNA editing of the Kv1 K+ channel genes of D. melanogaster...”

XP_004938130 potassium voltage-gated channel subfamily A member 1 isoform X1 from Gallus gallus
36% identity, 58% coverage

• Redistribution of Kv1 and Kv7 enhances neuronal excitability during structural axon initial segment plasticity.
  Kuba, Nature communications 2015
  • GeneRIF: The activation kinetics of Kv7.2 is far slower than that of Kv1.1 during structural axon initial segment plasticity.

KCNAS_DROME / P08510 Potassium voltage-gated channel protein Shaker; Protein minisleep from Drosophila melanogaster (Fruit fly) (see 12 papers)
TC 1.A.1.2.6 / P08510 Voltage-gated K+ channel, Shaker. Shaker and Shab K+ channels are blocked by quinidine (Gomez-Lagunas, 2010). Also regulated by unsaturated fatty acids from Drosophila melanogaster (Fruit fly) (see 13 papers)
Sh / RF|NP_996497.1 potassium voltage-gated channel protein Shaker from Drosophila melanogaster
NP_728123 shaker, isoform E from Drosophila melanogaster
37% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Forms rapidly inactivating tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient and may contribute to A- type currents (PubMed:2448636). Plays a role in the regulation of sleep need or efficiency (PubMed:15858564). Plays a role in sexual behavior, where it is important for male sex discrimination (PubMed:22292044).
  subunit: Homotetramer or heterotetramer of potassium channel proteins (Probable). Interacts with qvr/quiver/sleepless (via loop 2 of the three-fingered Ly-6 domain); this interaction may stabilize both components of the complex and may be required for targeting to or retention of Sh/shaker in neural cell projections (PubMed:20010822, PubMed:24613312, PubMed:26828958).
  disruption phenotype: Hypersensitivity to reactive oxygen species generated by the redox-cycling agent paraquat (PubMed:10934243). Reduced sleep (PubMed:15858564). Flies sleep for one-third of the wild- type amount (PubMed:15858564). They perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation (PubMed:15858564). They also have a reduced lifespan (PubMed:15858564). Males are able to discriminate between males and females during courtship but their courtship of females is reduced, suggesting that their perception and/or response to wild-type female pheromones is decreased (PubMed:22292044). RNAi-mediated knockdown in all neurons or specifically in the mushroom bodies of adult males, impairs their ability to discriminate between males and females (PubMed:22292044). However, knockdown in various chemosensory peripheral neurons has no effect on male sex discrimination (PubMed:22292044).
• substrates: K+
  tcdb comment: TMSs 3 and 4 comprise the voltage sensor paddle (Xu et al. 2013). Partially responsible for action potential repolarization during synaptic transmission (Ford and Davis 2014). Shaker K+ channels can be mutated in S4 to create an analogous "omega" pore (Held et al. 2018). The NMR structure of the isolated Shaker voltage-sensing domain in LPPG micelles has been reported (Chen et al. 2019). Substituting the first S4 arginine with a smaller amino acid opens a high-conductance pathway for solution cations in the Shaker K+ channel at rest. The cationic current does not flow through the central K+ pore and is influenced by mutation of a conserved residue in S2, suggesting that it flows through a protein pathway within the voltage-sensing domain (Tombola et al. 2005). The current can be carried by guanidinium ions, suggesting that this is the pathway for transmembrane arginine permeation. Tombola et al. 2005 proposed that when S4 moves, it ratchets between conformations in which one arginine after another occupies and occludes to ions in the narrowest part of this pathway
• Targeted insertional mutagenesis libraries for deep domain insertion profiling
  Coyote-Maestas, Nucleic acids research 2020
  • “...the 2099 oligos for four target proteins (human Kir2.1 (Accession: NP_000882), Drosophila melanogaster Shaker (Accession: NP_728123), human 7 nAChR (Accession: NP_000735.1)and human ASIC1a (Accession: NP_001086.2)) was synthesized by Agilent and received as 10 pmol of lyophilized DNA. This DNA was resuspended in 500 l TE. OLS...”
  • “...purification kit (Zymo Research). The transposition targets, human Kir2.1 (Accession: NP_000882), Drosophila melanogaster Shaker (Accession: NP_728123), human 7 nAChR (Accession: NP_000735.1) and human ASIC1a (Accession: NP_001086.2) including a porcine teschovirus ribosomal skipping sequence (P2A) ( 61 ), were codon-optimized for mouse, synthesized (Gen9) and subcloned with...”
• Pore size matters for potassium channel conductance
  Naranjo, The Journal of general physiology 2016
  • “...no. Gene Protein Pore helix-S6 sequence pS Reference Pore helix Selectivity filter Pore-S6 Small conductance NP_728123 .1 SHAKER Shaker AFWWAVVTMT TVGYG D MTPVGVWGKIVGSLCAIA G VLTIALPV P VIVSNFNYFYHR 487 20 Carvacho et al., 2008 NP_000208 .2 KCNA1 Kv1.1 AFWWAVVSMT TVGYG D MYPVTIGGKIVGSLCAIA G VLTIALPV P VIVSNFNYFYHR 417...”
• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...K+ channel genes. Abbreviations: Dme: D. melanogaster (NP_728123); Lop: L. opalescens (AAB02884); Spu: S. purpuratus (XP_001178924); Aga: A. gambiae...”
• Structural Basis for Voltage Gating and Dalfampridine Binding in the Shaker Potassium Channel.
  Pinto-Anwandter, bioRxiv : the preprint server for biology 2024
  • “...the monomeric VSD we used residues 228382 of the Drosophila melanogaster Shaker channel (Uniprot ID: P08510). For calculating the R4 displacement we calculated the projection of F290 and R4 alpha carbon to a vector defined by the S2 helix (residues 279301) and then obtaining the distance...”
• Structure and electromechanical coupling of a voltage-gated Na⁺/H⁺ exchanger
  Yeo, Nature 2023
  • “...SLC9C1 (uniport: Q4G0N8 ), mouse SLC9C1 ( Q6UJY2 ), drosophila K + -shaker channel ( P08510 ), and VSD IV of human sodium channel Na V 1.7 ( Q15858 ). Conserved residues are highlighted in red and gating-charge residues in S4 are further highlighted with a...”
• Noncanonical electromechanical coupling paths in cardiac hERG potassium channel.
  Bassetto, Nature communications 2023
  • “...sequence alignment in Supplementary Fig. 3 between hERG (UniProt ID: Q12809) and Shaker (UniProt ID: P08510) using Clustal Omega 43 ). Finally, A614 was mutated into glycine because bulkier residues such as valine 20 or leucine (A614Lthis work) did not exhibit constructs able to generate currents....”
  • “...Accession codes used for the sequence alignment: hERG UniProt ID Q12809 and Shaker UniProt ID P08510. The data underling Figs. 2 5 are provided as Source Data File. Source data are provided with this paper. Competing interests The authors declare no competing interests. References 1. Hille,...”
• ResidueFinder: extracting individual residue mentions from protein literature.
  Becker, Journal of biomedical semantics 2021
  • “...our previous work [ 36 ], in what we discovered from the Shaker channel (UniProtKB P08510). There were 299 amino acid mentions in the literature while the UniProtKB page only contains 11. We conclude that, in at least some cases, our methods will uncover amino acid...”
• Conformational equilibrium shift underlies altered K⁺ channel gating as revealed by NMR
  Iwahashi, Nature communications 2020
  • “...P0A334), Homo sapiens Kv1.1 (Uniprot ID: Q09470), and Drosophila melanogaster Shaker Kv channel (Uniprot ID: P08510). The hot spot positions in the inner transmembrane helix are highlighted in magenta. The hot spot position of KcsA, Ala111, is indicated in the crystal structure of KcsA (PDB ID:...”
  • “...Shaker Kv channels are available in the UniProt Knowledgebase under accession codes P0A334, Q09470, and P08510. The PDB accession codes 1K4C, 3EFF 61 , and 5VK6 were used in this study. All other data are available from the corresponding author upon reasonable request. Source data are...”
• A Structural Model of the Inactivation Gate of Voltage-Activated Potassium Channels
  Vergara-Jaque, Biophysical journal 2019
  • “...Secondary structure predictions of the full-length Shaker sequence (UniProt: P08510 ) were performed using the software PSIPRED ( 24,29 ), SOPMA ( 30 ), SPIDER2...”
• Simulation of Gating Currents of the Shaker K Channel Using a Brownian Model of the Voltage Sensor.
  Catacuzzeno, Biophysical journal 2019
• A channelopathy mutation in the voltage-sensor discloses contributions of a conserved phenylalanine to gating properties of Kv1.1 channels and ataxia.
  Hasan, Scientific reports 2017
  • “...sequence alignments were performed with ClustalW using the following channel homologs: human Kv1.1 (3736), Shaker (P08510), and Kv1.2/2.1 Chimera (P62483). The final sequence alignment was further refined using Muscle 2.6 40 . EA1 mutations were performed in silico by substituting the wild type residue with the...”
• More

KCNA5_RABIT / P50638 Potassium voltage-gated channel subfamily A member 5; Voltage-gated potassium channel subunit Kv1.5 from Oryctolagus cuniculus (Rabbit) (see paper)
35% identity, 62% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:7556635). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:7556635). Homotetrameric channels display rapid activation and slow inactivation (PubMed:7556635). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1 (By similarity). Interacts with UBE2I (By similarity). Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (By similarity).

KCNA5_MOUSE / Q61762 Potassium voltage-gated channel subfamily A member 5; Voltage-gated potassium channel subunit Kv1.5; KV1-5 from Mus musculus (Mouse) (see 3 papers)
NP_666095 potassium voltage-gated channel subfamily A member 5 from Mus musculus
36% identity, 61% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11349004, PubMed:8226976). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (PubMed:11349004, PubMed:8226976). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (PubMed:29306897). May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity).
  function: [Isoform 2]: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane.
  function: [Isoform 3]: Inactive. Inhibits expression of isoform 1 and isoform 2.
  catalytic activity: [Isoform 1]: K(+)(in) = K(+)(out) (RHEA:29463)
  catalytic activity: [Isoform 2]: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1 (By similarity). Interacts with UBE2I (By similarity). Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (PubMed:29306897).
  disruption phenotype: No visible phenotype. The action potential in myocytes is not prolonged by low concentrations of 4-aminopyridine, contrary to the situation in wild-type.
• Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.
  Anton, International journal of molecular sciences 2021
  • GeneRIF: Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.
• Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes.
  Taufiq, Circulation journal : official journal of the Japanese Circulation Society 2019 (PubMed)
  • GeneRIF: Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70.
• Suppression of Kv1.5 protects against endothelial apoptosis induced by palmitate and in type 2 diabetes mice.
  Du, Life sciences 2017 (PubMed)
  • GeneRIF: Silencing of Kv1.5 improved endothelium-dependent vasodilatation in thoracic aorta from type 2 diabetes mice.
• Heteromeric complexes of aldo-keto reductase auxiliary KVβ subunits (AKR6A) regulate sarcolemmal localization of KV1.5 in coronary arterial myocytes.
  Nystoriak, Chemico-biological interactions 2017
  • GeneRIF: KV1.5 channels predominantly associate with KVbeta1 and KVbeta2 proteins and that KVbeta2 performs a chaperone function for KV1.5 channels in arterial myocytes, thereby facilitating Kv1alpha trafficking and membrane localization.
• Increased aldosterone-dependent Kv1.5 recycling predisposes to pacing-induced atrial fibrillation in Kcne3-/- mice.
  Lisewski, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2016 (PubMed)
  • GeneRIF: The findings uncover detailed molecular mechanisms underpinning a channelopathy-linked form of atrial fibrillation and emphasize the inevitability of considering extracardiac mechanisms in genetic arrhythmia syndromes.
• Diphenyl phosphine oxide-1-sensitive K(+) channels contribute to the vascular tone and reactivity of resistance arteries from brain and skeletal muscle.
  Fancher, Microcirculation (New York, N.Y. : 1994) 2015
  • GeneRIF: KV1.5, a DPO-1-sensitive KDR channel, plays a major role in determining microvascular tone and the response to vasoconstrictors and vasodilators.
• Regulation of Voltage-Gated K+ Channel Kv1.5 by the Janus Kinase JAK3.
  Warsi, The Journal of membrane biology 2015 (PubMed)
  • GeneRIF: JAK3 contributes to the regulation of membrane Kv1.5 protein abundance and activity, an effect sensitive to ouabain and thus possibly involving Na(+)/K(+) ATPase activity.
• Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation.
  Ohanyan, Circulation research 2015
  • GeneRIF: Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism.
• More
• Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5.
  Zhao, Biomolecules 2019
  • “...by the KCNA5 gene with a length of 602 amino acids in mice (Unitprot Entry: Q61762) and rat (Unitprot Entry: P19024) sequences and 613 amino acids in the human sequence (Unitprot Entry: P22460). According to the Basic Local Alignment Search Tool (BLAST) result, the sequence of...”
• The N terminus and transmembrane segment S1 of Kv1.5 can coassemble with the rest of the channel independently of the S1-S2 linkage.
  Lamothe, The Journal of biological chemistry 2018
• The proteome of mouse cerebral arteries
  Badhwar, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2014 (secret)
• Ion channel regulation by protein S-acylation.
  Shipston, The Journal of general physiology 2014
  • “...233 SFELVVRFFA C PSKTDFFKNI P16388 Gubitosi-Klug et al., 2005 Kv1.5 Kcna5 16 LRGGGEAGAS C VQSPRGECGC Q61762 Jindal et al., 2008 583 VDLRRSLYAL C LDTSRETDL -stop Q61762 Zhang et al., 2007 ; Jindal et al., 2008 Sodium NaV1.2 Scn2a1 ND Schmidt and Catterall, 1987 640 MNGKMHSAVD C...”
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...W: Q61423 Tr:Q8CBF8 M: Q61423 N-term S101 N-term S113 N-term S122 S122 S122 Kv1.5/KCNA5 W: Q61762 C-term S535 Kv1.6/KCNA6 W: Q61923 M: Q61923 N-term S6 N-term T8 T8 Kv2.1/KCNB1 W: Q8K0D1 TR: Q03717 M: Q8K0D1 T: Q8K0D1 N-term S12 N-term S15 C-term S444 C-term S484 C-term...”

KCNA2_RABIT / Q09081 Potassium voltage-gated channel subfamily A member 2; KC22; Voltage-gated potassium channel subunit Kv1.2 from Oryctolagus cuniculus (Rabbit) (see 4 papers)
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11717161). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:11717161). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:11717161, PubMed:19389710). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2- containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2- containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7. Channel activity is regulated by interaction with the beta subunits, including KCNAB1 and KCNAB2. Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA4 and FYN (PubMed:11149959). Identified in a complex with KCNA5 and KCNAB1 (PubMed:11717160). Interacts with the beta subunit KCNAB1 (PubMed:11717160). Interacts with PTK2B (By similarity). Interacts (via C-terminus) with CTTN (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (By similarity). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with ADAM11 (By similarity). Intercts with LYNX1 (By similarity).

XP_008262207 potassium voltage-gated channel subfamily A member 2 isoform X1 from Oryctolagus cuniculus
36% identity, 58% coverage

• Identification and functional characterization of protein kinase A-catalyzed phosphorylation of potassium channel Kv1.2 at serine 449.
  Johnson, The Journal of biological chemistry 2009
  • GeneRIF: Ser-449 in Kv1.2 is a site of PKA phosphorylation and a potential molecular mechanism for Kv1-containing KDR channel modulation by agonists via PKA activation

KCNA2_HUMAN / P16389 Potassium voltage-gated channel subfamily A member 2; NGK1; Voltage-gated K(+) channel HuKIV; Voltage-gated potassium channel HBK5; Voltage-gated potassium channel subunit Kv1.2 from Homo sapiens (Human) (see 17 papers)
TC 1.A.1.2.10 / P16389 Voltage-gated K+ channel, chain A, Shaker-related, Kv1.2 (Crystal structure known, Long et al., 2007; Chen et al. 2010). Functions with the auxiliary subunit, Ivβ1.2; 8.A.5.1.1) from Homo sapiens (Human)
XP_011539700 potassium voltage-gated channel subfamily A member 2 isoform X1 from Homo sapiens
NP_004965 potassium voltage-gated channel subfamily A member 2 isoform a from Homo sapiens
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11211111, PubMed:19912772, PubMed:23769686, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20220134, PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2- containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2- containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7. Channel activity is regulated by interaction with the beta subunits, including KCNAB1 and KCNAB2. Identified in a complex with KCNA1 and KCNAB2 (PubMed:11086297). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts with the beta subunit KCNAB1 (PubMed:19713757). Interacts with PTK2B (By similarity). Interacts (via C-terminus) with CTTN (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (By similarity). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with ADAM22 (By similarity). Interacts (via C- terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with CNTNAP2 (PubMed:10624965). Interacts with ADAM11 (By similarity). Intercts with LYNX1 (PubMed:24613312).
• substrates: K+
  tcdb comment: Delemotte et al. (2010) described the effects of sensor domain mutations on molecular dynamics of Kv1.2. The Sigma 1 receptor (Q99720; Sigma non-opioid intracellular receptor 1) interacts with Kv1.2 to shape neuronal and behavioral responses to cocaine (Kourrich et al. 2013). Amino acid substitutions cause Shaker to become heat-sensing (opens with increasing temperature as for TrpV1) or cold-sensing (opens with decreasing temperature as for TrpM8) (Chowdhury et al. 2014). The Shaker Kv channel was truncated after the 4th transmembrane helix S4 (Shaker-iVSD) which showed altered gating kinetics and formed a cation-selective ion channel with a strong preference for protons (Zhao and Blunck 2016). Direct axon-to-myelin linkage by abundant KV1/Cx29 (TC# 1.A.24.1.12) channel interactions in rodent axons supports the idea of an electrically active role for myelin in increasing both the saltatory conduction velocity and the maximal propagation frequency in mammalian myelinated axons (Rash et al. 2016). A cryoEM structure (3 - 4 Å resolution; paddle chimeric channel; closed form) in nanodiscs has been determined (Matthies et al. 2018). Possible gating mechanisms have been discussed (Kariev and Green 2018; Infield et al. 2018)
• KCNA2 IgG autoimmunity in neuropsychiatric diseases.
  Arlt, Brain, behavior, and immunity 2024 (PubMed)
  • GeneRIF: KCNA2 IgG autoimmunity in neuropsychiatric diseases.
• Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.
  Xie, Molecular neurobiology 2024 (PubMed)
  • GeneRIF: Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.
• Two epilepsy-associated variants in KCNA2 (KV 1.2) at position H310 oppositely affect channel functional expression.
  Mínguez-Viñas, The Journal of physiology 2023 (PubMed)
  • GeneRIF: Two epilepsy-associated variants in KCNA2 (KV 1.2) at position H310 oppositely affect channel functional expression.
• An epilepsy-associated KV1.2 charge-transfer-center mutation impairs KV1.2 and KV1.4 trafficking.
  Nilsson, Proceedings of the National Academy of Sciences of the United States of America 2022
  • GeneRIF: An epilepsy-associated KV1.2 charge-transfer-center mutation impairs KV1.2 and KV1.4 trafficking.
• Deep phenotyping unstructured data mining in an extensive pediatric database to unravel a common KCNA2 variant in neurodevelopmental syndromes.
  Hully, Genetics in medicine : official journal of the American College of Medical Genetics 2021
  • GeneRIF: Deep phenotyping unstructured data mining in an extensive pediatric database to unravel a common KCNA2 variant in neurodevelopmental syndromes.
• Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders.
  Döring, International journal of molecular sciences 2021
  • GeneRIF: Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders.
• Notch enhances Ca2+ entry by activating calcium-sensing receptors and inhibiting voltage-gated K+ channels.
  Song, American journal of physiology. Cell physiology 2020
  • GeneRIF: these results suggest that Notch activation enhances CaSR-mediated increases in [Ca(2+)]cyt by enhancing store-operated Ca(2+) entry and inhibits KCNA5/KV1.5 and KCNA2/KV1.2, ultimately leading to voltage-activated Ca(2+) entry.
• De novo KCNA1 variants in the PVP motif cause infantile epileptic encephalopathy and cognitive impairment similar to recurrent KCNA2 variants.
  Rogers, American journal of medical genetics. Part A 2018 (PubMed)
  • GeneRIF: recurrent de novo variants in the paralogous PVP motif of KCNA2 have previously been shown to abolish channel function and also cause early-onset epileptic encephalopathy. Importantly, this report extends the range of phenotypes associated with KCNA1 variants to include epileptic encephalopathy when the PVP motif is involved.
• More
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...used in this sequence alignment are as follows: K v 1.1 (NP_000208), K v 1.2 (NP_004965), K v 1.3 (NP_002223), K v 1.4 (NP_002224), K v 1.5 (NP_002225), K v 1.6 (NP_002226), K v 1.7 (NP_114092), K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v...”
• Proton currents constrain structural models of voltage sensor activation
  Randolph, eLife 2016
  • “...proteobacterium HIMB114 Nav (pdb: 4DXW; GI:388326718), Homo sapiens Kv1.2 (NP_004966; GI: 4826784), Homo sapiens Kv2.1 (NP_004965; GI:4826782), Drosophila melanogaster Shaker (CAA29917; GI:288442), Ciona intestinalis VSP (NP_001028998; GI:76253898) and Hv1 channels from Ciona intestinalis (NP_001071937; GI:118344228), Mus musculus (NP_001035954; GI:109809757) and Homo sapiens (NP_115745; GI:91992155) is shown....”
• Interactions of H562 in the S5 helix with T618 and S621 in the pore helix are important determinants of hERG1 potassium channel structure and function
  Lees-Miller, Biophysical journal 2009
  • “...aligned are Homo sapiens Kv1.2 NP_004965, Streptomyces coelicolor Kcsa NP_631700, Caenorhabditis elegans SLOwpoke-1 NP_001024260, Methanothermobacter...”
• Targeting heterozygous dominant negative variant of KCNA2 using Gapmer ASO for the treatment of drug-resistant epilepsy
  Huang, Molecular therapy. Nucleic acids 2024
  • “...amino acid change in P407R in the S6 segment closer to the intracellular face (uniprot: p16389, https://www.uniprot.org/uniprotkb/P16389/entry ) ( Figure1 A). The two proline residues in the PVP motif are highly conserved among vertebrates as revealed by sequence alignment data in the ENCODE database ( Figure1...”
• Pharmacological mechanism of Shaoyao Gancao Decoction in the treatment of depression based on bioinformatics and animal experiment.
  Li, Heliyon 2024
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 1.5 K v 1.6 K v 1.7 HGNC, UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2...”
• Kinome Analysis to Define Mechanisms of Adjuvant Action: PCEP Induces Unique Signaling at the Injection Site and Lymph Nodes.
  Awate, Vaccines 2022
  • “...Q09472 1.34 0.05 Keap1 S293 Q14145 1.28 0.02 EP300 S2366 Q09472 1.33 0.0001 MK2 Y132 P16389 1.27 0.05 CTNNB1 Y654 P35222 1.31 0.005 IKK-a S180 O15111 1.26 0.0002 TAK1 T178 O43318 1.3 0.02 p38-a Y322 Q16539 1.25 0.04 SEK1 T261 P45985 1.3 0.04 IRAK1 T100 P51617...”
  • “...P19878 1.46 0.0008 STAT1 S727 P42224 1.49 0.02 MSK2 S360 O75676 1.43 0.01 MK2 Y415 P16389 1.48 0.01 IKK-a S180 O15111 1.42 0.02 Rab5A S123 P20339 1.47 0.01 Lyn Y507 P07948 1.42 0.02 DVL1 S679 O14640 1.46 0.0002 PPARG S112 P37231 1.41 0.04 PI3K p85 b...”
• Signaling differences in peripheral blood mononuclear cells of high and low vaccine responders prior to, and following, vaccination in piglets.
  Lipsit, Vaccine: X 2022
  • “...1.70 0.0204 FGFR1 Y653 P11362 LR Day 2 vs. Day 6 1.61 0.0272 MK2 Y415 P16389 LR Day 2 vs. Day 6 1.77 0.0272 PLCG2 Y759 P16885 LR Day 2 vs. Day 6 1.60 0.0272 TBK1 S172 Q9UHD2 LR Day 2 vs. Day 6 2.30 0.0272...”
• Identification of Novel Substrates for cGMP Dependent Protein Kinase (PKG) through Kinase Activity Profiling to Understand Its Putative Role in Inherited Retinal Degeneration.
  Roy, International journal of molecular sciences 2021
  • “...9 7 KAP2_92_104 P13861 SRFNRRVSVCAET cAMP-dependent protein kinase type II-alpha regulatory subunit 6 5 KCNA2_442_454 P16389 PDLKKSRSASTIS Potassium voltage-gated channel subfamily A member 2 9 7 NCF1_296_308 P14598 RGAPPRRSSIRNA Neutrophil cytosol factor 1 9 7 MPIP1_172_184 P30304 FTQRQNSAPARML M-phase inducer phosphatase 1 9 4 ART_025_ CXGLRRWSLGGLRRWSL...”
• Comparative structural analysis of human Nav1.1 and Nav1.5 reveals mutational hotspots for sodium channelopathies.
  Pan, Proceedings of the National Academy of Sciences of the United States of America 2021
• Brain Proteomic Profiling in Intractable Epilepsy Caused by TSC1 Truncating Mutations: A Small Sample Study.
  Liu, Frontiers in neurology 2020
  • “...1.74 Mitochondrion/Cytoplasm/Early endosome O75077 Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23) 0.025278943 1.74 Cell membrane/Secreted P16389 Potassium voltage-gated channel subfamily A member 2 (KCNA2) 0.045913807 1.71 Cell membrane/Cell projection/Cell junction Q96D05 Uncharacterized protein FAM241B (FAM241B) 0.027804687 1.7 Membrane Q99707 Methionine synthase (MTR) 0.01578569 1.7 Cytoplasm O94817...”
• More

KCNA3_HUMAN / P22001 Potassium voltage-gated channel subfamily A member 3; HGK5; HLK3; HPCN3; Voltage-gated K(+) channel HuKIII; Voltage-gated potassium channel subunit Kv1.3 from Homo sapiens (Human) (see 4 papers)
TC 1.A.1.2.4 / P22001 Potassium voltage-gated channel subfamily A member 3, component of Margatoxin-sensitive voltage-gated K+ channel, Kv1.3 (in plasma and mitochondrial membranes of T lymphocytes) (Szabò et al., 2005). Kv1.3 associates with the sequence similar (>80%) Kv1.5 protein in macrophage forming heteromers that like Kv1.3 homomers are r-margatoxin sensitive (Vicente et al., 2006). However, the heteromers have different biophysical and pharmacological properties. The Kv1.3 mitochondrial potassium channel is involved in apoptotic signalling in lymphocytes (Gulbins et al., 2010). Interactions between the C-terminus from Homo sapiens (Human) (see 6 papers)
NP_002223 potassium voltage-gated channel subfamily A member 3 from Homo sapiens
35% identity, 66% coverage

• function: [Isoform 1]: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
  function: [Isoform 2]: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
  function: [Isoform 3]: Lacks voltage-gated potassium channel activity.
  catalytic activity: [Isoform 1]: K(+)(in) = K(+)(out) (RHEA:29463)
  catalytic activity: [Isoform 2]: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Forms heterooligomers with KCNE4 which inhibits KCNA3 activity by impairing localization to the cell membrane. The stoichiometry of KCNA3 and KCNE4 in the heterooligomers are 4:1, 4:2, 4:3 or 4:4 respectively. Increasing the number of KCNE4 subunits steadily slows the activation KCNA3 and decreases its abundance at the cell membrane. However, a single subunit of KCNE4 is sufficient for the cooperative enhancement of the inactivating function of the channel. Interacts with SEC24D; this interaction is reduced in the presence of KCNE4. Interacts with DLG1, DLG2 and DLG4 via their PDZ domains.
• substrates: K+
  tcdb comment: of Kv1.5 and Kvβ regulate pyridine nucleotide-dependent changes in channel gating (Tipparaju et al., 2012). Intracellular trafficking of the KV1.3 K+ channel is regulated by the pro-domain of a matrix metalloprotease (Nguyen et al. 2013). Direct binding of caveolin regulates Kv1 channels and allows association with lipid rafts (Pérez-Verdaguer et al. 2016). Addtionally, NavBeta1 interacts with the voltage sensing domain (VSD) of Kv1.3 through W172 in the transmembrane segment to modify the gating process (Kubota et al. 2017). During insertion of Kv1.3, the extended N-terminus of the secondα-helix, S2, inside the ribosomal tunnel is converted into a helix in a transition that depends on the nascent peptide sequence at specific tunnel locations (Tu and Deutsch 2017). The microRNA, mmumiR449a, reduced the mRNA expression levels of transient receptor potential cation channel subfamily A member 1 (TRPA1), and calcium activated potassium channel subunit alpha1 (KCNMA1) and increased the level of transmembrane phosphatase with tension homology (TPTE) in the DRG cells (Lu et al. 2017). This channel is regulation by sterols (Balajthy et al. 2017). Loss of function causes atrial fibrillation, a rhythm disorder characterized by chaotic electrical activity of cardiac atria (Olson et al. 2006). The N-terminus and S1 of Kv1.5 can attract and coassemble with the rest of the channel (i.e. Frag(304-613)) to form a functional channel independently of the S1-S2 linkage (Lamothe et al. 2018). This channel may be present in mitochondria (Parrasia et al. 2019)
• De novo variants in KCNA3 cause developmental and epileptic encephalopathy.
  Soldovieri, Annals of neurology 2024 (PubMed)
  • GeneRIF: De novo variants in KCNA3 cause developmental and epileptic encephalopathy.
• Effect of the rs2821557 Polymorphism of the Human Kv1.3 Gene on Olfactory Function and BMI in Different Age Groups.
  Melis, Nutrients 2024
  • GeneRIF: Effect of the rs2821557 Polymorphism of the Human Kv1.3 Gene on Olfactory Function and BMI in Different Age Groups.
• Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.
  Tyagi, Proceedings of the National Academy of Sciences of the United States of America 2022
  • GeneRIF: Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.
• Role of C-Terminal Domain and Membrane Potential in the Mobility of Kv1.3 Channels in Immune Synapse Forming T Cells.
  Sebestyén, International journal of molecular sciences 2022
  • GeneRIF: Role of C-Terminal Domain and Membrane Potential in the Mobility of Kv1.3 Channels in Immune Synapse Forming T Cells.
• Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.
  Selvakumar, Nature communications 2022
  • GeneRIF: Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.
• Olfactory Sensitivity Is Associated with Body Mass Index and Polymorphism in the Voltage-Gated Potassium Channels Kv1.3.
  Melis, Nutrients 2022
  • GeneRIF: Olfactory Sensitivity Is Associated with Body Mass Index and Polymorphism in the Voltage-Gated Potassium Channels Kv1.3.
• A common genetic variant rs2821557 in KCNA3 is linked to the severity of multiple sclerosis.
  Lioudyno, Journal of neuroscience research 2021 (PubMed)
  • GeneRIF: A common genetic variant rs2821557 in KCNA3 is linked to the severity of multiple sclerosis.
• The Kv1.3 ion channel acts as a host factor restricting viral entry.
  Lang, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2021 (PubMed)
  • GeneRIF: The Kv1.3 ion channel acts as a host factor restricting viral entry.
• More
• Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold.
  Nguyen, Channels (Austin, Tex.) 2024
  • “...protein sequence of KCNA3 gene encoded human K V 1.3 (hK V 1.3) (UniProt ID: P22001) was used as input into AlphaFold2, RoseTTAFold2, and ESMFold for structure prediction. We assessed the quality of predicted models using the pLDDT confidence score, compared how close they are to...”
• Computational engineering of water-soluble human potassium ion channels through QTY transformation.
  Smorodina, Scientific reports 2024
  • “...potassium ion channels are obtained from Uniprot ( https://www.uniprot.org ) 46 including KCNA1 (Q09470), KCNA3 (P22001), KCNA5 (P22460), KCNC4 (Q03721), KCND1 (Q9NSA2), KCNH2 (Q12809), KCNH5 (Q8NCM2), KCNJ3 (P48549), KCNJ8 (Q15842), KCNJ10 (P78508), KCNJ11 (Q14654), KCNJ12 (Q14500), KCNK2 (O95069), KCNK5 (O95279), KCNK9 (Q9NPC2), KCNMA1 (Q12791), KCNN3 (Q9UGI6),...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 1.6 K v 1.7 HGNC, UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 218 ]...”
• Purification and Characterization of Bot33: A Non-Toxic Peptide from the Venom of Buthus occitanus tunetanus Scorpion
  ElFessi, Molecules (Basel, Switzerland) 2022
  • “...of the voltage-gated potassium channel subunit Kv1.3 was extracted from UniProt under the accession number P22001 ( https://www.uniprot.org/uniprot/P22001 (25 November 2008)). Its amino acid sequence was compared with other sequences retrieved from the NCBI database using FASTA and BLAST. Using only the pore domain of the...”
• Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.
  Tyagi, Proceedings of the National Academy of Sciences of the United States of America 2022
  • “...Materials and Methods Cloning, Protein Expression, and Purification. DNA encoding human Kv1.3 (UniProtKB accession no. P22001), lacking the first 52 residues, and human Kv2.1(UniProtKB accession no. Q13303) were cloned for coexpression into a pFastBac dual vector (Invitrogen) with a FLAG tag (DYKDDDDK) at the amino terminus...”
• Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration.
  Roy, Cell death discovery 2022
  • “...[ 86 ] 19 . TY3H_65_77 P07101 Tyrosine 3-monooxygenase 0.054 9 3 20 . KCNA3_461_473 P22001 Potassium voltage-gated channel subfamily A member 3 0.055 8 7 ONL, IPL [ 42 ] 21 . F263_454_466 Q16875 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 0.059 10 3 INL, GCL 22 . VASP_150_162 P50552...”
• Brevilin A Isolated from Centipeda minima Induces Apoptosis in Human Gastric Cancer Cells via an Extrinsic Apoptotic Signaling Pathway.
  Lee, Plants (Basel, Switzerland) 2022
  • “...cyclin-dependent kinase 5 regulatory subunit 1 Enzyme modulator 58 P25774 CTSS cathepsin S Enzyme 59 P22001 KCNA3 potassium voltage-gated channel subfamily A member 3 Ion channel plants-11-01658-t002_Table 2 Table 2 A list of key targets based on proteinprotein interaction network topological analysis. No. UniProt ID Gene...”
• Seawater fungi-derived compound screening to identify novel small molecules against dengue virus NS5 methyltransferase and NS2B/NS3 protease.
  Hasan, Informatics in medicine unlocked 2022
  • “...2 F2RL1 P55085 Family A G protein-coupled receptor 0.1106122 Voltage-gated potassium channel subunit Kv1.3 KCNA3 P22001 Voltage-gated ion channel 0.1106122 Transient receptor potential cation channel subfamily V member 4 (by homology) TRPV4 Q9HBA0 Voltage-gated ion channel 0.1106122 Integrin alpha-4/beta-1 ITGB1 ITGA4 P05556 P13612 Membrane receptor 0.1106122...”
  • “...Cytochrome P450 0.106165761 Phosphodiesterase 10A PDE10A Q9Y233 Phosphodiesterase 0.106165761 Voltage-gated potassium channel subunit Kv1.3 KCNA3 P22001 Voltage-gated ion channel 0.106165761 Estrogen receptor beta ESR2 Q92731 Nuclear receptor 0.106165761 Peroxisome proliferator-activated receptor gamma PPARG P37231 Nuclear receptor 0.106165761 Tyrosine-protein kinase FYN FYN P06241 Kinase 0.106165761 Ligand-based virtual...”
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2i2rB / Q62897 Crystal structure of the kchip1/kv4.3 t1 complex (see paper)
90% identity, 21% coverage

• Ligand: zinc ion (2i2rB)

KCNA1_HUMAN / Q09470 Potassium voltage-gated channel subfamily A member 1; Voltage-gated K(+) channel HuKI; Voltage-gated potassium channel HBK1; Voltage-gated potassium channel subunit Kv1.1 from Homo sapiens (Human) (see 23 papers)
TC 1.A.1.2.12 / TC 8.B.31.1.1 / Q09470 The shaker-like K+ channel inhibitor, Κ-actitoxin-Ate1a. See family description and Madio et al. 2018. This protein is also listed under TC# 1.A.1.2.12 (see 15 papers)
NP_000208 potassium voltage-gated channel subfamily A member 1 from Homo sapiens
37% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:19903818, PubMed:8845167). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12077175, PubMed:17156368). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:12077175, PubMed:17156368). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19307729, PubMed:19903818, PubMed:19912772, PubMed:19968958). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:19307729, PubMed:23903368).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:12077175, PubMed:17156368). Channel activity is regulated by interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:12077175, PubMed:17156368). Identified in a complex with KCNA2 and KCNAB2 (PubMed:11086297). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with LGI1 within a complex containing LGI1, KCNA4 and KCNAB1 (By similarity). Interacts (via N-terminus) with STX1A; this promotes channel inactivation (By similarity). Interacts (via N-terminus) with the heterodimer formed by GNB1 and GNG2; this promotes channel inactivation (By similarity). Can interact simultaneously with STX1A and the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG; this inhibits channel activity (PubMed:19968958). Interacts with ANK3; this inhibits channel activity (PubMed:23903368). Interacts with ADAM11 (By similarity).
• substrates: K+
  tcdb comment: Defects cause episodic ataxia type 1 (EA1), an autosomal dominant K+ channelopathy accompanied by short attacks of cerebellar ataxia and dysarthria (D'Adamo et al. 2014). Direct axon-to-myelin linkage by abundant KV1/Cx29 channel interactions in rodent axons supports the idea of an electrically active role for myelin in increasing both the saltatory conduction velocity and the maximal propagation frequency in mammalian myelinated axons (Rash et al. 2016). Kv1.1 is present in bull sperm where it is necessary for normal sperm progressive motility, per cent capacitated spermatozoa (B-pattern) and the acrosome reaction (Gupta et al. 2018). Gating induces large aqueous volumetric remodeling (Díaz-Franulic et al. 2018)
• Computational engineering of water-soluble human potassium ion channels through QTY transformation.
  Smorodina, Scientific reports 2024
  • “...sequences for potassium ion channels are obtained from Uniprot ( https://www.uniprot.org ) 46 including KCNA1 (Q09470), KCNA3 (P22001), KCNA5 (P22460), KCNC4 (Q03721), KCND1 (Q9NSA2), KCNH2 (Q12809), KCNH5 (Q8NCM2), KCNJ3 (P48549), KCNJ8 (Q15842), KCNJ10 (P78508), KCNJ11 (Q14654), KCNJ12 (Q14500), KCNK2 (O95069), KCNK5 (O95279), KCNK9 (Q9NPC2), KCNMA1 (Q12791),...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 1.4 K v 1.5 K v 1.6 K v 1.7 HGNC, UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and...”
• Intracellular IL-32 regulates mitochondrial metabolism, proliferation, and differentiation of malignant plasma cells
  Aass, iScience 2022
  • “...Q02127 1723 Homo sapiens Dihydroorotate dehydrogenase (quinone) (DHODH) Q08188 7053 Homo sapiens Transglutaminase 3 (TGM3) Q09470 3736 Homo sapiens Potassium voltage-gated channel subfamily A member 1 (KCNA1) Q15904 537 Homo sapiens ATPase H+ transporting accessory protein 1 (ATP6AP1) Q5VTU8 432369 Homo sapiens ATP synthase, H+ transporting,...”
• Conformational equilibrium shift underlies altered K⁺ channel gating as revealed by NMR
  Iwahashi, Nature communications 2020
  • “...a Sequence alignment of Streptomyces lividans KcsA (Uniprot ID: P0A334), Homo sapiens Kv1.1 (Uniprot ID: Q09470), and Drosophila melanogaster Shaker Kv channel (Uniprot ID: P08510). The hot spot positions in the inner transmembrane helix are highlighted in magenta. The hot spot position of KcsA, Ala111, is...”
  • “...Drosophila melanogaster Shaker Kv channels are available in the UniProt Knowledgebase under accession codes P0A334, Q09470, and P08510. The PDB accession codes 1K4C, 3EFF 61 , and 5VK6 were used in this study. All other data are available from the corresponding author upon reasonable request. Source...”
• Autophagic Network Analysis of the Dual Effect of Sevoflurane on Neurons Associated with GABARAPL1 and 2
  Lu, BioMed research international 2020
  • “...DB01236 Sevoflurane GLRA1 P23415 Agonist 3 DB01236 Sevoflurane GRIA1 P42261 Antagonist 4 DB01236 Sevoflurane KCNA1 Q09470 Inducer 5 DB01236 Sevoflurane ATP2C1 P98194 Inhibitor 6 DB01236 Sevoflurane ATP5D P30049 Other/unknown 7 DB01236 Sevoflurane MT-ND1 P03886 Unknown 8 DB01236 Sevoflurane GABRA1/2/3/4/5/6 P14867/P47869/P34903/P48169/P31644/Q16445 PAM 8 DB01236 Sevoflurane GABRB1/2/3, GABRD,...”
• Challenges Faced with Small Molecular Modulators of Potassium Current Channel Isoform Kv1.5.
  Zhao, Biomolecules 2019
  • “...of KCNA5_HUMAN (P22460), obtained from the NCBI BLAST+ database. ( D ) Sequence alignment ofKCNA1_HUMAN (Q09470), KCNA3_HUMAN (P22001), KCNA2_HUMAN (P16389), and KCNA5_HUMAN (P22460), acquired from the ESPript database. Figure 2 ( A ) Pharmacophore model of vernakalant (cyan ball: hydrophobic center; yellow ball: aromatic center; green...”
• Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0).
  Mi, Nature protocols 2019
  • “...Committee, https://www.genenames.org/ ) with ID HGNC:6218, and the protein sequence is from UniProt with id Q09470. Mapped IDs IDs from the uploaded gene list that are mapped to the gene ids in the first column. Gene Name/Gene Symbol The Entrez gene definition and gene symbol. PANTHER...”
• Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies
  Jiang, Chemical reviews 2018
  • “...NTSR-1 P30989 C381, C383 Cytoplasmic C terminus Required for receptor-mediated mitogenic-signaling 598 Kv1.1 ion channel Q09470 C243 Internal domain Modulate voltage sensing 599 P2X7R Q99572 C371, 373, 374, 477, 479, 482, 498, 499, 506, 572, 573 Cytoplasmic C terminus Required for lipid rafts localization 600 PAR2...”
• More
• Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia.
  Sun, Journal of genetics and genomics = Yi chuan xue bao 2024 (PubMed)
  • GeneRIF: Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia.
• Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia.
  Verdura, Journal of medical genetics 2020
  • GeneRIF: Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia.
• Isoform-Selective KCNA1 Potassium Channel Openers Built from Glycine.
  Manville, The Journal of pharmacology and experimental therapeutics 2020
  • GeneRIF: Isoform-Selective KCNA1 Potassium Channel Openers Built from Glycine.
• Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity.
  Paulhus, International journal of molecular sciences 2020
  • GeneRIF: Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity.
• Two novel KCNA1 variants identified in two unrelated Chinese families affected by episodic ataxia type 1 and neurodevelopmental disorders.
  Yuan, Molecular genetics & genomic medicine 2020
  • GeneRIF: Two novel KCNA1 variants identified in two unrelated Chinese families affected by episodic ataxia type 1 and neurodevelopmental disorders.
• The mono-ADP-ribosyltransferase ARTD10 regulates the voltage-gated K+ channel Kv1.1 through protein kinase C delta.
  Tian, BMC biology 2020
  • GeneRIF: The mono-ADP-ribosyltransferase ARTD10 regulates the voltage-gated K(+) channel Kv1.1 through protein kinase C delta.
• A Common Kinetic Property of Mutations Linked to Episodic Ataxia Type 1 Studied in the Shaker Kv Channel.
  Zhao, International journal of molecular sciences 2020
  • GeneRIF: A Common Kinetic Property of Mutations Linked to Episodic Ataxia Type 1 Studied in the Shaker Kv Channel.
• Hypermethylated promoters of genes UNC5D and KCNA1 as potential novel diagnostic biomarkers in colorectal cancer.
  Uhan, Epigenomics 2020 (PubMed)
  • GeneRIF: Hypermethylated promoters of genes UNC5D and KCNA1 as potential novel diagnostic biomarkers in colorectal cancer.
• More

KCNA1_RAT / P10499 Potassium voltage-gated channel subfamily A member 1; RBKI; RCK1; Voltage-gated potassium channel subunit Kv1.1 from Rattus norvegicus (Rat) (see 20 papers)
NP_775118 potassium voltage-gated channel subfamily A member 1 from Rattus norvegicus
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney. Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:12177193, PubMed:17855588, PubMed:22206926). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:23725331). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:2539643). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:10896669, PubMed:12177193, PubMed:2348860, PubMed:23725331). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:10896669, PubMed:12114518). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:12681381, PubMed:22206926, PubMed:2348860, PubMed:23725331, PubMed:8038169). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:2348860). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (PubMed:12177193, PubMed:23318870). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (PubMed:16306173). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (PubMed:17869444). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:22206926). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:10884227, PubMed:10896669). Channel activity is regulated by interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:12114518, PubMed:9334400). Identified in a complex with KCNA2 and KCNAB2 (PubMed:10884227, PubMed:10896669, PubMed:11086297, PubMed:23318870). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4. Interacts with LGI1 within a complex containing LGI1, KCNA4 and KCNAB1. Interacts (via cytoplasmic N-terminal domain) with KCNRG; this inhibits channel activity (By similarity). Interacts with ANK3; this inhibits channel activity (By similarity). Interacts (via N-terminus) with STX1A; this promotes channel inactivation (PubMed:12114518). Interacts (via N-terminus) with the heterodimer formed by GNB1 and GNG2; this promotes channel inactivation (PubMed:12114518). Can interact simultaneously with STX1A and the heterodimer formed by GNB1 and GNG2 (PubMed:12114518). Interacts with ADAM11 (By similarity).
• MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1.
  Zhou, Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2024
  • GeneRIF: MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1.
• Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility.
  Barrese, Physiological reports 2023
  • GeneRIF: Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility.
• Ion Channel Modeling beyond State of the Art: A Comparison with a System Theory-Based Model of the Shaker-Related Voltage-Gated Potassium Channel Kv1.1.
  Langthaler, Cells 2022
  • GeneRIF: Ion Channel Modeling beyond State of the Art: A Comparison with a System Theory-Based Model of the Shaker-Related Voltage-Gated Potassium Channel Kv1.1.
• Rapamycin reveals an mTOR-independent repression of Kv1.1 expression during epileptogenesis.
  Sosanya, Neurobiology of disease 2015 (PubMed)
  • GeneRIF: This stuidy demonstrated that kainic-acid induced status epilepticus there are two phases of Kv1.1 repression: (1) an initial mTOR-dependent repression of Kv1.1 that is followed by (2) a miR-129-5p persistent reduction of Kv1.1.
• Complex N-Glycans Influence the Spatial Arrangement of Voltage Gated Potassium Channels in Membranes of Neuronal-Derived Cells.
  Hall, PloS one 2015
  • GeneRIF: Our findings provide direct evidence that N-glycans of Kv3.1 splice variants contribute to the placement of these glycoproteins in the plasma membrane of neuronal-derived cells while those of Kv1.1 were absent.
• Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.
  Feng, Molecular pain 2013
  • GeneRIF: Endogenous H2S generating enzyme cystathionine-beta-synthetase was co-localized well with Kv1.1 and Kv1.4 in trigeminal ganglion neurons.
• Pharmacological characteristics of Kv1.1- and Kv1.2-containing channels are influenced by the stoichiometry and positioning of their α subunits.
  Al-Sabi, The Biochemical journal 2013 (PubMed)
  • GeneRIF: This study supports the possibility of alpha subunits being precisely arranged in Kv1 channels, rather than being randomly assembled.
• Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1.
  Sosanya, The Journal of cell biology 2013
  • GeneRIF: Overexpression of miR-129 represses Kv1.1 mRNA translation when mTORC1 kinase is inhibited.
• More
• Intracellular hemin is a potent inhibitor of the voltage-gated potassium channel Kv10.1.
  Sahoo, Scientific reports 2022
  • “...49 ( KCNH 2-S620T, here referred to as Kv11.1-ni), Kcna 1 (rat Kv1.1, acc. no. P10499), and KCNA 5 (human Kv1.5, acc. no. P22460). Kv10.1 channel mutant constructs C541A, H543A, H552V, and 2190 were prepared by using overlap-extension mutagenesis as described previously 26 . We also...”
• Investigating the Neurotoxic Impacts of Arsenic and the Neuroprotective Effects of Dictyophora Polysaccharide Using SWATH-MS-Based Proteomics.
  Zhang, Molecules (Basel, Switzerland) 2022
  • “...D3ZBP3 2.11 a 0.44 a 0.94 40 Potassium voltage-gated channel subfamily A member 1 Kcna1 P10499 2.30 a 0.53 a 1.21 41 Hydroxymethylbilane hydrolyase [cyclizing] Uros Q5XIF2 2.41 a 0.62 a 1.51 42 Long-chain-fatty-acid--CoA ligase 3 Acsl3 Q63151 2.50 a 0.63 a 1.57 43 Uridine-cytidine kinase...”
• Impact of intracellular hemin on N-type inactivation of voltage-gated K⁺ channels
  Coburger, Pflugers Archiv : European journal of physiology 2020
  • “...Kv1.2, Kv1.3 (KCNAB1, Q14722), Kv3.1 (KCNAB3, O43448), and DPP6a from Homo sapiens and Kv1.1 (Kcna1, P10499) and Kv4.2 (Kcnd2, Q63881) from Rattus norvegicus were subcloned into pcDNA3.1. Accession numbers refer to the UniProt database. Mutations were generated using the QuikChange Site-Directed Mutagenesis Kit (Agilent, Waldbronn, Germany)...”
• Membrane Protein Identification in Rodent Brain Tissue Samples and Acute Brain Slices
  Joost, Cells 2019
  • “...7 7 6 Ion Channels Q9Z2L0 Voltage-dependent anion-selective channel protein 1 0 9 12 11 P10499 Potassium voltage-gated channel subfamily A member 1 6 4 1 1 P25122 Potassium voltage-gated channel subfamily C member 1 7 4 3 3 P04775 Sodium channel protein type 2 subunit...”
• Identification and characterization of the BRI2 interactome in the brain
  Martins, Scientific reports 2018
  • “...Atp2b2 Plasma membrane calcium-transporting ATPase 2 CC Q64568 Atp2b3 Plasma membrane calcium-transporting ATPase 3 HP P10499 Kcna1 Potassium voltage-gated channel subfamily A member 1 CC Q6MG82 Prrt1 Proline-rich transmembrane protein 1 HP O88778 Bsn Protein bassoon CC, CB P63319 Prkcg Protein kinase C gamma type CC,...”
• Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons.
  Gazula, The Journal of comparative neurology 2010
  • “...440-4HK-42 Synthetic peptide amino acids 458476 C terminus of rat Kv 1.1 (EEDMNNSIAHYRQANIRTG; accession number P10499) NeuroMab 1: 100 Kv 1.2 Ms 75-008 clone K14/16 413-7RR-30 Antibody produced against bacterially-expressed GST-fusion protein corresponding to amino acids 428499 of rat heart Kv 1.2 Epitope mapped to within...”

KCNA1_MOUSE / P16388 Potassium voltage-gated channel subfamily A member 1; MBK1; MKI; Voltage-gated potassium channel subunit Kv1.1 from Mus musculus (Mouse) (see 28 papers)
NP_034725 potassium voltage-gated channel subfamily A member 1 from Mus musculus
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney. Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:10191303, PubMed:12611922, PubMed:21966978, PubMed:22158511, PubMed:23473320, PubMed:9581771, PubMed:9736643). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:15361858). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:15361858). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA1 forms a delayed- rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:15361858, PubMed:7517498). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability (PubMed:23466697). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (PubMed:20392939, PubMed:22641786, PubMed:25377007). Required for normal neuromuscular responses (PubMed:9736643). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (PubMed:23473320). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (PubMed:21966978, PubMed:22396426). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21233214). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (PubMed:17250763, PubMed:17315199, PubMed:22411008, PubMed:8995755). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8361541). Channel activity is regulated by interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:15361858). Identified in a complex with KCNA2 and KCNAB2. Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with LGI1 within a complex containing LGI1, KCNA4 and KCNAB1 (By similarity). Interacts (via N-terminus) with STX1A; this promotes channel inactivation (By similarity). Interacts (via N-terminus) with the heterodimer formed by GNB1 and GNG2; this promotes channel inactivation (By similarity). Can interact simultaneously with STX1A and the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG; this inhibits channel activity (By similarity). Interacts with ANK3; this inhibits channel activity (PubMed:23903368). Interacts with ADAM11 (PubMed:26269648).
  disruption phenotype: Mice are born at the expected Mendelian rate. After three weeks, mice begin to display episodic eye blinking, twitching of whiskers, forlimb padding, arrested motion and a hyperstartle response. About 50% of the homozygotes die between the third and the fifth week after birth. Surviving mice continue to display spontaneous seizures occurring once or twice every hour throughout adult life (PubMed:9581771). The fecundity of homozygotes is extremely low (PubMed:9581771). Mutant mice display interictal cardiac abnormalities, including a fivefold increase in atrioventricular conduction blocks, brachycardia and premature ventricular contractions; this may lead to sudden unexplained death in epilepsy (PubMed:20392939). Mutant mice have slightly elevated heart rates; they all have a reduced livespan and are subject to sudden death after presumed seizure activity and sinus bradycardia (PubMed:25377007). About 70% of the mutant mice have an enlarged hippocampus and ventral brain cortex (PubMed:17250763). Mutant mice show a temperature- sensitive alteration in neuromuscular transmission, causing nerve hyperexcitability when exposed to cold and delayed repetitive discharge after a single nerve stimulation (PubMed:9736643). After 2 minutes of swimming in cold water, mutant mice have impaired motor control; they fall over when placed on dry ground and exhibit severe neuromyotonia with violent tremors that decrease with time, leading to full recovery after twenty minutes (PubMed:9736643). Mutant mice have an increased frequency of spontaneous postsynaptic currents in Purkinje cells, impaired ability to maintain their balance on a thin stationary rod, but perform as well as wild-type on a rotarod (PubMed:10191303). Mutant mice have a normal hearing threshold, but altered brainstem responses to auditory stimuli and reduced sensitivity to small changes in sound location (PubMed:22396426). Mutant mice display no alteration of the islet of Langerhans, but have reduced blood glucose levels and increased insulin secretion in response to a glucose stimulus (PubMed:21483673).
• Adult-onset hypothyroidism causes mechanical hypersensitivity due to peripheral nerve hyperexcitability based on voltage-gated potassium channel downregulation in male mice.
  Suda, Journal of neuroscience research 2022 (PubMed)
  • GeneRIF: Adult-onset hypothyroidism causes mechanical hypersensitivity due to peripheral nerve hyperexcitability based on voltage-gated potassium channel downregulation in male mice.
• Genetic interaction between Scn8a and potassium channel genes Kcna1 and Kcnq2.
  Hill, Epilepsia 2022
  • GeneRIF: Genetic interaction between Scn8a and potassium channel genes Kcna1 and Kcnq2.
• Loss of functional System x-c uncouples aberrant postnatal neurogenesis from epileptogenesis in the hippocampus of Kcna1-KO mice.
  Aloi, Cell reports 2022
  • GeneRIF: Loss of functional System x-c uncouples aberrant postnatal neurogenesis from epileptogenesis in the hippocampus of Kcna1-KO mice.
• Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization.
  Trosclair, Physiological reports 2021
  • GeneRIF: Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization.
• Kv1.1 deficiency alters repetitive and social behaviors in mice and rescues autistic-like behaviors due to Scn2a haploinsufficiency.
  Indumathy, Brain and behavior 2021
  • GeneRIF: Kv1.1 deficiency alters repetitive and social behaviors in mice and rescues autistic-like behaviors due to Scn2a haploinsufficiency.
• Kv1.1 subunits localize to cardiorespiratory brain networks in mice where their absence induces astrogliosis and microgliosis.
  Dhaibar, Molecular and cellular neurosciences 2021
  • GeneRIF: Kv1.1 subunits localize to cardiorespiratory brain networks in mice where their absence induces astrogliosis and microgliosis.
• Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway.
  Chou, eLife 2021
  • GeneRIF: Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway.
• Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits.
  Thouta, Scientific reports 2021
  • GeneRIF: Kv1.1 channels mediate network excitability and feed-forward inhibition in local amygdala circuits.
• More
• Ion channel regulation by protein S-acylation.
  Shipston, The Journal of general physiology 2014
  • “...C GRSERDCSCM Q08460 Tian et al., 2008 ; 2010 Kv1.1 Kcna1 233 SFELVVRFFA C PSKTDFFKNI P16388 Gubitosi-Klug et al., 2005 Kv1.5 Kcna5 16 LRGGGEAGAS C VQSPRGECGC Q61762 Jindal et al., 2008 583 VDLRRSLYAL C LDTSRETDL -stop Q61762 Zhang et al., 2007 ; Jindal et al., 2008...”
• Heterogeneous calretinin expression in the avian cochlear nucleus angularis.
  Bloom, Journal of the Association for Research in Otolaryngology : JARO 2014
• Myelin proteomics: molecular anatomy of an insulating sheath.
  Jahn, Molecular neurobiology 2009
  • “...kDa P46660 Ina W,B,V,R,T,E Junctional adhesion molecule C Q9D8B7 Jam3 S,E K + channel A1 P16388 Kcna1 E K + channel A2 P63141 Kcna2 E K + channel A3 P16390 Kcna3 E K + channel B2 P62482 Kcnab2 E Lactate dehydrogenase A P06151 Ldha T,E Lactate...”
• Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.
  Fernández, Molecular systems biology 2009
  • “...2 O88602 2 2 2 3 b Kcna1 K+ voltage-gated channel, shaker-related subfamily, member 1 P16388 6 5 5 6 c Kcna2 K+ voltage-gated channel, shaker-related subfamily, member 2 P63141 4 5 7 6 c Kcna3 K+ voltage-gated channel, shaker-related subfamily, member 3 P16390 3 4...”
• Participation of Kv1 channels in control of membrane excitability and burst generation in mesencephalic V neurons.
  Hsiao, Journal of neurophysiology 2009
• K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom.
  Mouhat, The Biochemical journal 2005

KCNA2_MOUSE / P63141 Potassium voltage-gated channel subfamily A member 2; MK2; Voltage-gated potassium channel subunit Kv1.2 from Mus musculus (Mouse) (see 17 papers)
KCNA2_RAT / P63142 Potassium voltage-gated channel subfamily A member 2; RAK; RBK2; RCK5; Voltage-gated potassium channel subunit Kv1.2 from Rattus norvegicus (Rat) (see 40 papers)
XP_006501118 potassium voltage-gated channel subfamily A member 2 isoform X1 from Mus musculus
XP_006233195 potassium voltage-gated channel subfamily A member 2 isoform X1 from Rattus norvegicus
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:12527813, PubMed:21233214). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20696761). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:23864368). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:23864368). Contributes to the regulation of action potentials in neurons (PubMed:12527813, PubMed:17925011). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:17634333, PubMed:17925011). Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). KCNA2-containing channels play a role in GABAergic transmission from basket cells to Purkinje cells in the cerebellum, and thereby play an import role in motor coordination (PubMed:20696761). Plays a role in the induction of long- term potentiation of neuron excitability in the CA3 layer of the hippocampus (PubMed:23981714). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21233214). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (PubMed:17925011).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:23864368, PubMed:8361541, PubMed:9852577). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (By similarity). Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts with PTK2B (By similarity). Interacts (via C- terminus) with CTTN (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C- terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (PubMed:9635436). Interacts with DRD2 (PubMed:21233214). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (PubMed:23332758). Interacts with ADAM11 (PubMed:26269648). Intercts with LYNX1 (By similarity).
  disruption phenotype: Pups are born at the expected Mendelian rate and appear normal during the first 14 days after birth. Starting at 14 to 17 days after birth, mice exhibit susceptibility to generalized seizures, followed by full tonic extension, which in mice often results in fatal apne. The average lifespan is 17 days; none survive more than 28 days (PubMed:17634333, PubMed:17925011). At P17 seizures are very rare and abnormal electroencephalograph activity is only present during the seizure. P17 pups have significantly less non-rapid eye movement (NREM) sleep (-23%) and significantly more waking (+21%) than wild-type siblings with no change in rapid eye movement (REM) sleep time. The decrease in NREM sleep is due to an increase in the number of waking episodes, with no change in number or duration of sleep episodes (PubMed:17925011). Auditory neurons from the medial nucleus of the trapezoid body in brain stem are hypoexcitable and fire fewer action potentials than wild-type neurons with significantly smaller threshold current amplitudes (PubMed:17634333). In the inner ear, spiral ganglion neurons display a hyperpolarized resting membrane potential, increased excitability and increased outward potassium currents; this might be because normally channels there are heterotetramers formed by KCNA2 and KCNA4, so the loss of KCNA2 changes channel characteristics (PubMed:23864368).
• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:12151401, PubMed:21602278, PubMed:24472174). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:15618540, PubMed:20805574, PubMed:23725331, PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (PubMed:18003609, PubMed:19713757). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to a particular potassium channel family member. Homotetrameric KCNA2 forms a delayed- rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:16770729, PubMed:1715584, PubMed:17766348, PubMed:18003609, PubMed:18638484, PubMed:19713757, PubMed:20089912). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons (PubMed:23318870). KCNA2- containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:12777451). Response to toxins that are selective for KCNA2- containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (PubMed:16210348). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein- coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (PubMed:16306173). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (PubMed:17869444). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21647367). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (PubMed:24472174). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:10896669, PubMed:11007484, PubMed:12632190, PubMed:12777451, PubMed:15618540, PubMed:16002581, PubMed:18004376, PubMed:20534430, PubMed:8361540, PubMed:8495559). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (PubMed:16002581, PubMed:18003609, PubMed:18004376, PubMed:19713757, PubMed:20360102, PubMed:20534430, PubMed:23705070). Identified in a complex with KCNA1 and KCNAB2 (PubMed:11086297, PubMed:23318870). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1 and DLG2 (PubMed:7477295). Interacts with DLG4 (via PDZ domain) (PubMed:20089912, PubMed:7477295). Interacts with PTK2B (PubMed:11739373). Interacts (via C-terminus) with CTTN (PubMed:12151401). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (PubMed:9635436). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with CNTNAP2 (PubMed:10624965). Interacts with ADAM22 (PubMed:20089912). Interacts with ADAM11 (By similarity). Intercts with LYNX1 (By similarity).
• Transcription factor EBF1 mitigates neuropathic pain by rescuing Kv1.2 expression in primary sensory neurons.
  Liang, Translational research : the journal of laboratory and clinical medicine 2024
  • GeneRIF: Transcription factor EBF1 mitigates neuropathic pain by rescuing Kv1.2 expression in primary sensory neurons.
• Contribution of DNMT1 to Neuropathic Pain Genesis Partially through Epigenetically Repressing Kcna2 in Primary Afferent Neurons.
  Sun, The Journal of neuroscience : the official journal of the Society for Neuroscience 2019
  • GeneRIF: Dorsal root ganglion (DRG) DNMT1 contributes to neuropathic pain genesis partially through repression of DRG Kcna2 gene expression
• Sound Localization in Preweanling Mice Was More Severely Affected by Deleting the Kcna1 Gene Compared to Deleting Kcna2, and a Curious Inverted-U Course of Development That Appeared to Exceed Adult Performance Was Observed in All Groups.
  Ison, Journal of the Association for Research in Otolaryngology : JARO 2019
  • GeneRIF: Sound Localization in Preweanling Mice Was More Severely Affected by Deleting the Kcna1 Gene Compared to Deleting Kcna2, and a Curious Inverted-U Course of Development That Appeared to Exceed Adult Performance Was Observed in All Groups.
• Slc7a5 regulates Kv1.2 channels and modifies functional outcomes of epilepsy-linked channel mutations.
  Baronas, Nature communications 2018
  • GeneRIF: Slc7a5 regulates Kv1.2 channels and modifies functional outcomes of epilepsy-linked channel mutations
• Stress-dependent phosphorylation of myocardin-related transcription factor A (MRTF-A) by the p38(MAPK)/MK2 axis.
  Ronkina, Scientific reports 2016
  • GeneRIF: Results show that MK2 activation induces MRTF-A phosphorylation at S351 and S371 upon stress.
• G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons.
  Liang, Scientific reports 2016
  • GeneRIF: G9a contributes to neuropathic pain development through epigenetic silencing of Kcna2 in the axotomized dorsal root ganglion.
• Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells.
  Hyun, The Journal of physiology 2015
  • GeneRIF: Kv1.2 mediates heterosynaptic modulation of direct cortical synaptic inputs in CA3 pyramidal cells
• MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation.
  Bobo, Infection and immunity 2013
  • GeneRIF: This study showed that MK2 kinase is activated by TcdA and TcdB and regulates the expression of proinflammatory cytokines.
• More
• A Non-Invasive and DNA-free Approach to Upregulate Mammalian Voltage-Gated Calcium Channels and Neuronal Calcium Signaling via Terahertz Stimulation.
  Sun, Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2024
  • “...Q99250, P35499 and Q14524. UniProt IDs of the K V 1.2, KCNQ1, and KcsA channels: P63141, Q9Z0N7, and P0A334. UniProt IDs of the TRPV1 and TRPC5 channels: Q8NER1 and Q9UL62. The structural information for Ca V 1.1, Ca V 1.2, Ca V 1.3, Ca V 1.4,...”
• The central nervous system can directly regulate breast cancer progression and blockage by quercetin.
  Luo, Annals of translational medicine 2021
  • “...Thbs1 1.2617 0.0285 O55026 Entpd2 1.2583 0.0004 Q80YR2 Fam160b2 1.2482 0.0159 P56382 Atp5f1e 1.2359 0.0448 P63141 Kcna2 1.2320 0.0130 P51830 Adcy9 1.2311 0.0291 Q62234 Myom1 1.2224 0.0266 Q91WR3 Ascc2 1.2196 0.0225 Q80Z38 Shank2 1.2179 0.0143 Q9D6J4 Necab3 1.2039 0.0381 P62878 Rbx1 1.2028 0.0296 P03975 Iap 1.2002...”
• Pyridazine-derivatives Enhance Structural and Functional Plasticity of Tripartite Synapse Via Activation of Local Translation in Astrocytic Processes.
  Foster, Neuroscience 2018
  • “...type II, alpha 1.73 3.09 3.546 Q9Z1L5 Voltage-dependent calcium channel subunit alpha-2/delta-3 1.84 1.98 2.580 P63141 Potassium voltage-gated channel subfamily A2 3.35 1.87 2.529 J3QMG3 Voltage-dependent anion-selective channel protein 3 4.77 9.45 3.629 Ion Channel Regulator E9QN98 Inactive dipeptidyl peptidase 10 1.79 4.27 3.301 E9PWX1 Dipeptidyl...”
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...W: O70507 M: O70507 N-term S139 C-term S921 Kv1.1/KCNA1 W: IPI00133719 N-term S23 Kv1.2/KCNA2 W: P63141 M: P63141 T: P63141 C-term T421 C-term T433 C-term S434 S434 C-term S440 C-term S441 S441 C-term S447 Kv1.4/KCNA4 W: Q61423 Tr:Q8CBF8 M: Q61423 N-term S101 N-term S113 N-term S122...”
• Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.
  Fernández, Molecular systems biology 2009
  • “...1 P16388 6 5 5 6 c Kcna2 K+ voltage-gated channel, shaker-related subfamily, member 2 P63141 4 5 7 6 c Kcna3 K+ voltage-gated channel, shaker-related subfamily, member 3 P16390 3 4 6 5 c Kcna4 K+ voltage-gated channel, shaker-related subfamily, member 4 Q8CBF8 2 3...”
• Myelin proteomics: molecular anatomy of an insulating sheath.
  Jahn, Molecular neurobiology 2009
  • “...C Q9D8B7 Jam3 S,E K + channel A1 P16388 Kcna1 E K + channel A2 P63141 Kcna2 E K + channel A3 P16390 Kcna3 E K + channel B2 P62482 Kcnab2 E Lactate dehydrogenase A P06151 Ldha T,E Lactate dehydrogenase B P16125 Ldhb W,T,E Lactate dehydrogenase...”
• A Spectrum of Neural Autoantigens, Newly Identified by Histo-Immunoprecipitation, Mass Spectrometry, and Recombinant Cell-Based Indirect Immunofluorescence.
  Scharf, Frontiers in immunology 2018
  • “...61 357 34 316.4 10 Potassium voltage-gated channel subfamily A member 2 ( KCNA2_RAT ) P63142 61 105 27 57.1 11 Electrogenic sodium bicarbonate cotransporter 1 ( S4A4_RAT ) Q9JI66 61 69 15 122.1 12 Carnitine O-palmitoyltransferase 1, brain isoform ( CPT1C_RAT ) F1LN46 61 211...”
• Outward Rectification of Voltage-Gated K+ Channels Evolved at Least Twice in Life History
  Riedelsberger, PloS one 2015
  • “...Hsa -Kv6.1 AAC05635 Hsa -Kv9.1 AAC13165 Mmu -Kv3.1 Mus musculus CAA68814 Rno -Kv1.2 Rattus norvegicus P63142 Rno -Kv2.1 P15387 Rno -Kv8.1 CAA67174 Furthermore, the inclusion of available crystal structures and homology protein models in the comparison enabled the investigation of channel attributes that are not accessible...”
• Modeling Suggests TRPC3 Hydrogen Bonding and Not Phosphorylation Contributes to the Ataxia Phenotype of the Moonwalker Mouse.
  Hanson, Biochemistry 2015
  • “...is thought that the threonine corresponding to the mTRPC3 T635 (T320 according to UniprotKB entry P63142) fits inside a groove in the S6 helix along with a conserved isoleucine. 37 The same threonine to alanine mutation that induces the Mwk phenotype in TRPC3 produces faster desensitizing...”
• Divining the design principles of voltage sensors.
  Toombes, The Journal of general physiology 2014
  • “...no. 2R9R_B ), rat Kv2.1 (UniProt accession no. P15387 ), rat Kv1.2 (UniProt accession no. P63142 ), human Kv11.1 (UniProt accession no. Q12809 ), KvAP (UniProt accession no. Q9YDF8 ), human Hv1 (UniProt accession no. Q96D96 ), Ciona VSP (UniProt accession no. Q4W8A1 ), and NavAb...”
• Building KCNQ1/KCNE1 channel models and probing their interactions by molecular-dynamics simulations.
  Xu, Biophysical journal 2013
• Structural determinants of skeletal muscle ryanodine receptor gating.
  Ramachandran, The Journal of biological chemistry 2013
• Role of transverse bands in maintaining paranodal structure and axolemmal domain organization in myelinated nerve fibers: effect on longevity in dysmyelinated mutant mice.
  Mierzwa, The Journal of comparative neurology 2010
  • “...polyclonal APC-010 1:200 Kv1.2 Fusion protein amino acids 428499(cytoplasmic C-terminus) of rat Kv1.2 (accession number P63142), Epitope mapped to within amino acids 463480 Neuromab Balb/C mouse monoclonal 75-008 1:200 Table 2 Myelin thickness and ion channel domains are altered in the shaking mouse. G-ratio shows thinner...”
• Molecular template for a voltage sensor in a novel K+ channel. III. Functional reconstitution of a sensorless pore module from a prokaryotic Kv channel.
  Santos, The Journal of general physiology 2008
  • “...Cuello et al., 1998 ), and of KCNA2, a Kv channel from rat (Kv1.2, sp P63142), were aligned by ClustalX with the 87-PM sequences from Kv bacterial origin. The aligned sequences of KvLm (gi 16411529), KvAP (gi 14601099), Kv 1.2, and KcsA were extracted from this...”
• Epigenetic restoration of voltage-gated potassium channel Kv1.2 alleviates nerve injury-induced neuropathic pain.
  Zhang, Journal of neurochemistry 2021 (PubMed)
  • GeneRIF: Epigenetic restoration of voltage-gated potassium channel Kv1.2 alleviates nerve injury-induced neuropathic pain.
• Upregulation of ubiquitin conjugating enzyme E2B (Ube2b) ameliorates neuropathic pain by regulating Kcna2 (potassium voltage-gated channel subfamily A member 2) in primary afferent neurons.
  Peng, Bioengineered 2021
  • GeneRIF: Upregulation of ubiquitin conjugating enzyme E2B (Ube2b) ameliorates neuropathic pain by regulating Kcna2 (potassium voltage-gated channel subfamily A member 2) in primary afferent neurons.
• Structural and molecular insight into the pH-induced low-permeability of the voltage-gated potassium channel Kv1.2 through dewetting of the water cavity.
  Lee, PLoS computational biology 2020
  • GeneRIF: two residues E327 and H418 in the proximity of the water cavity of Kv1.2 play crucial roles as a pH switch
• [Expression of KCNA2 in the dorsal root ganglia of rats with osteoarthritis pain induced by monoiodoacetate].
  Zhao, Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2019
  • GeneRIF: The expression of KCNA2 is decreased in the DRG neurons of rats with OA pain likely as a result of enhanced methylation of Kcna2 promoter region
• Long Noncoding RNA Kcna2 Antisense RNA Contributes to Ventricular Arrhythmias via Silencing Kcna2 in Rats With Congestive Heart Failure.
  Long, Journal of the American Heart Association 2017
  • GeneRIF: Ventricular Kcna2 AS expression increases in rats with CHF and contributes to reduced IKs, prolonged APs, and the occurrence of ventricular arrhythmias by silencing Kcna2.
• Statistical modeling and removal of lipid membrane projections for cryo-EM structure determination of reconstituted membrane proteins.
  Jensen, Journal of structural biology 2016
  • GeneRIF: Data indicate that in cryo-electron microscopy (cryo-EM) images of the relatively small Kv1.2 channel complex, the protein particle's contribution is quite weak compared to the membrane density.
• Ion Concentration- and Voltage-Dependent Push and Pull Mechanisms of Potassium Channel Ion Conduction.
  Kasahara, PloS one 2016
  • GeneRIF: the dynamics of the ion conduction processes in the Kv1.2 pore domain
• Caution is required in interpretation of mutations in the voltage sensing domain of voltage gated channels as evidence for gating mechanisms.
  Kariev, International journal of molecular sciences 2015
  • GeneRIF: An R300C mutation creates a large cavity in the voltage sensing domain.
• More

XP_018100229 potassium voltage-gated channel subfamily A member 2 isoform X1 from Xenopus laevis
37% identity, 58% coverage

• Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.
  Soler-Llavina, Neuron 2006 (PubMed)
  • GeneRIF: When mapped onto the X-ray structure of the K(v)1.2 channel the large number of permissive mutations support the notion of relatively independent domains, consistent with crystallographic studies

AAA27756.1 potassium channel from Aplysia californica (see paper)
37% identity, 59% coverage

LOC106566321 potassium voltage-gated channel subfamily A member 2-like from Salmo salar
37% identity, 58% coverage

• Micronutrient supplementation affects DNA methylation in male gonads with potential intergenerational epigenetic inheritance involving the embryonic development through glutamate receptor-associated genes
  Saito, BMC genomics 2022
  • “...P1K for gonads Region Gene symbol Gene name Ortholog a #DMCs b Hypo Hyper Exon150 LOC106566321 potassium voltage-gated channel subfamily A member 2-like KCNA2 0 3 LOC106568430 putative uncharacterized protein DDB_G0286901 DDB_G0286901 0 2 LOC106591755 nuclear pore complex protein Nup50-like NUP50 0 1 P250 LOC106572512 glutamate...”

XP_015002446 potassium voltage-gated channel subfamily A member 3 isoform X1 from Macaca mulatta
34% identity, 66% coverage

• Pharmacokinetics, toxicity, and functional studies of the selective Kv1.3 channel blocker 5-(4-phenoxybutoxy)psoralen in rhesus macaques.
  Pereira, Experimental biology and medicine (Maywood, N.J.) 2007
  • GeneRIF: 5-(4-phenoxybutoxy)psoralen (PAP-1) is a selective blocker of the voltage-gated potassium channel Kv1.3 that is highly expressed in cell membranes of activated effector memory T cells.

NP_523393 shaker, isoform B from Drosophila melanogaster
36% identity, 61% coverage

• The voltage-gated potassium channel Shaker promotes sleep via thermosensitive GABA transmission.
  Kim, Communications biology 2020
  • GeneRIF: The voltage-gated potassium channel Shaker promotes sleep via thermosensitive GABA transmission.
• Molecular and cellular correlates in Kv channel clustering: entropy-based regulation of cluster ion channel density.
  Lewin, Scientific reports 2020
  • GeneRIF: Molecular and cellular correlates in Kv channel clustering: entropy-based regulation of cluster ion channel density.
• S4-S5 linker movement during activation and inactivation in voltage-gated K+ channels.
  Kalstrup, Proceedings of the National Academy of Sciences of the United States of America 2018
  • GeneRIF: S4-S5 linker movement during activation and inactivation in voltage-gated K(+) channels.
• Why the Drosophila Shaker K+ channel is not a good model for ligand binding to voltage-gated Kv1 channels.
  Mahdavi, Biochemistry 2013 (PubMed)
  • GeneRIF: This study demonstrates that Shaker is not always a good model for Kv1 channels for ligand binding.
• Energetic role of the paddle motif in voltage gating of Shaker K(+) channels.
  Xu, Nature structural & molecular biology 2013
  • GeneRIF: Authors provide evidence that in the Drosophila Shaker voltage-gated K(+) channels the S3 domain acts as an extracellular hydrophobic 'stabilizer' for the S4 domain biasing the gating chemical equilibrium toward the open state.
• Tracking a complete voltage-sensor cycle with metal-ion bridges.
  Henrion, Proceedings of the National Academy of Sciences of the United States of America 2012
  • GeneRIF: Data show several strong Cysteine-Cadmium-Cysteine bridges in Shaker potassium channel.
• The shaker potassium channel is no target for xenon anesthesia in short-sleeping Drosophila melanogaster mutants.
  Schaper, TheScientificWorldJournal 2012
  • GeneRIF: The xenon requirement in Drosophila melanogaster is not influenced by a single gene mutation at the shaker locus, whereas a reduced expression of a nonselective cation channel leads to an increased xenon requirement.
• Modulation of the frequency response of Shaker potassium channels by the quiver peptide suggesting a novel extracellular interaction mechanism.
  Wang, Journal of neurogenetics 2010
  • GeneRIF: Synaptic transmission at the larval neuromuscular junction and the transient Shaker potassium current IA in larval muscles have been characterized.
• More

XP_005163101 potassium voltage-gated channel subfamily A member 1 from Danio rerio
36% identity, 61% coverage

• A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
  Meserve, PLoS genetics 2021
  • GeneRIF: A forward genetic screen identifies Dolk as a regulator of startle magnitude through the potassium channel subunit Kv1.1.
• Expression of the voltage-gated potassium channel subunit Kv1.1 in embryonic zebrafish Mauthner cells.
  Brewster, Neuroscience letters 2013 (PubMed)
  • GeneRIF: Mauthner cells express potassium channels that contain Kv1.1 subunits, which might contribute to cell firing.

KCNA3_MOUSE / P16390 Potassium voltage-gated channel subfamily A member 3; MK3; Voltage-gated potassium channel subunit Kv1.3 from Mus musculus (Mouse) (see 3 papers)
NP_032444 potassium voltage-gated channel subfamily A member 3 from Mus musculus
35% identity, 66% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (By similarity). Forms heterooligomers with KCNE4 which inhibits KCNA3 activity by impairing localization to the cell membrane (PubMed:27802162). The stoichiometry of KCNA3 and KCNE4 in the heterooligomers are 4:1, 4:2, 4:3 or 4:4 respectively. Increasing the number of KCNE4 subunits steadily slows the activation KCNA3 and decreases its abundance at the cell membrane. However, a single subunit of KCNE4 is sufficient for the cooperative enhancement of the inactivating function of the channel. Interacts with SEC24D; this interaction is reduced in the presence of KCNE4. Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (By similarity).
• Quantitative proteomic analysis of the brain reveals the potential antidepressant mechanism of Jiawei Danzhi Xiaoyao San in a chronic unpredictable mild stress mouse model of depression.
  Yajing, Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan 2025
• The proteome of mouse cerebral arteries
  Badhwar, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2014 (secret)
• Myelin proteomics: molecular anatomy of an insulating sheath.
  Jahn, Molecular neurobiology 2009
  • “...A1 P16388 Kcna1 E K + channel A2 P63141 Kcna2 E K + channel A3 P16390 Kcna3 E K + channel B2 P62482 Kcnab2 E Lactate dehydrogenase A P06151 Ldha T,E Lactate dehydrogenase B P16125 Ldhb W,T,E Lactate dehydrogenase C P00342 Ldhc E Leucine rich repeat...”
• Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins.
  Fernández, Molecular systems biology 2009
  • “...2 P63141 4 5 7 6 c Kcna3 K+ voltage-gated channel, shaker-related subfamily, member 3 P16390 3 4 6 5 c Kcna4 K+ voltage-gated channel, shaker-related subfamily, member 4 Q8CBF8 2 3 5 5 c Kcnab1 K+ voltage-gated channel, shaker-related subfamily, beta member 1 P63143 3...”
• K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom.
  Mouhat, The Biochemical journal 2005
• Kv1.3 mediates ox-LDL-induced vascular smooth muscle cell proliferation through JAK2/STAT3 signaling pathway.
  Liu, Archives of biochemistry and biophysics 2023 (PubMed)
  • GeneRIF: Kv1.3 mediates ox-LDL-induced vascular smooth muscle cell proliferation through JAK2/STAT3 signaling pathway.
• The voltage-gated potassium channel KV1.3 regulates neutrophil recruitment during inflammation.
  Immler, Cardiovascular research 2022
  • GeneRIF: The voltage-gated potassium channel KV1.3 regulates neutrophil recruitment during inflammation.
• Kv1.3 Channel Is Involved In Ox-LDL-induced Macrophage Inflammation Via ERK/NF-κB signaling pathway.
  Zhang, Archives of biochemistry and biophysics 2022 (PubMed)
  • GeneRIF: Kv1.3 Channel Is Involved In Ox-LDL-induced Macrophage Inflammation Via ERK/NF-kappaB signaling pathway.
• The Kv1.3 ion channel acts as a host factor restricting viral entry.
  Lang, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2021 (PubMed)
  • GeneRIF: The Kv1.3 ion channel acts as a host factor restricting viral entry.
• Unique molecular characteristics and microglial origin of Kv1.3 channel-positive brain myeloid cells in Alzheimer's disease.
  Ramesha, Proceedings of the National Academy of Sciences of the United States of America 2021
  • GeneRIF: Unique molecular characteristics and microglial origin of Kv1.3 channel-positive brain myeloid cells in Alzheimer's disease.
• Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.
  Anton, International journal of molecular sciences 2021
  • GeneRIF: Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.
• β1-Integrin- and KV1.3 channel-dependent signaling stimulates glutamate release from Th17 cells.
  Birkner, The Journal of clinical investigation 2020
  • GeneRIF: beta1-Integrin- and KV1.3 channel-dependent signaling stimulates glutamate release from Th17 cells.
• Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease.
  Sarkar, The Journal of clinical investigation 2020
  • GeneRIF: Kv1.3 modulates neuroinflammation and neurodegeneration in Parkinson's disease.
• More

5wieB / P63142 Crystal structure of a kv1.2-2.1 chimera k+ channel v406w mutant in an inactivated state (see paper)
36% identity, 58% coverage

• Ligand: (1r)-2-{[(s)-{[(2s)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl(9z)-octadec-9-enoate (5wieB)

KCNA2_XENLA / P22739 Potassium voltage-gated channel subfamily A member 2; Voltage-gated potassium channel subunit Kv1.2; xSHA2 from Xenopus laevis (African clawed frog) (see paper)
37% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and central nervous system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:2223094). Can form functional homotetrameric channels and heterotetrameric channels with other family members; the channels characteristics depend critically on the types of channel-forming alpha subunits that are present (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:2223094). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other family members.

KCNA3_RAT / P15384 Potassium voltage-gated channel subfamily A member 3; RCK3; RGK5; Voltage-gated potassium channel subunit Kv1.3; Voltage-gated potassium channel subunit Kv3 from Rattus norvegicus (Rat) (see 9 papers)
NP_062143 potassium voltage-gated channel subfamily A member 3 from Rattus norvegicus
35% identity, 66% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Forms heterooligomers with KCNE4 which inhibits KCNA3 activity by impairing localization to the cell membrane. The stoichiometry of KCNA3 and KCNE4 in the heterooligomers are 4:1, 4:2, 4:3 or 4:4 respectively. Increasing the number of KCNE4 subunits steadily slows the activation KCNA3 and decreases its abundance at the cell membrane. However, a single subunit of KCNE4 is sufficient for the cooperative enhancement of the inactivating function of the channel (PubMed:19773357, PubMed:27802162, PubMed:32370164). Interacts with SEC24D; this interaction is reduced in the presence of KCNE4 (PubMed:27802162). Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (PubMed:7477295).
• Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via the promotion of microglial M1 polarization and activation of the NLRP3 inflammasome.
  Yuan, European journal of pain (London, England) 2023 (PubMed)
  • GeneRIF: Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via the promotion of microglial M1 polarization and activation of the NLRP3 inflammasome.
• Functional Consequences of the Variable Stoichiometry of the Kv1.3-KCNE4 Complex.
  Solé, Cells 2020
  • GeneRIF: Functional Consequences of the Variable Stoichiometry of the Kv1.3-KCNE4 Complex.
• KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis.
  Tanner, Arthritis research & therapy 2019
  • GeneRIF: Interactions of fibroblast-like synoviocytes in collagen-induced arthritis are regulated by Kv1.3 and KCa1.1
• Voltage Gated Potassium Channel Kv1.3 Is Upregulated on Activated Astrocytes in Experimental Autoimmune Encephalomyelitis.
  Bozic, Neurochemical research 2018 (PubMed)
  • GeneRIF: Kv1.3 may be a therapeutic target of interest for multiple sclerosis and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions
• Ubiquitination mediates Kv1.3 endocytosis as a mechanism for protein kinase C-dependent modulation.
  Martínez-Mármol, Scientific reports 2017
  • GeneRIF: PKC activation triggers down-regulation of Kv1.3 by inducing a clathrin-mediated endocytic event that targets the channel to lysosomal-degradative compartments.
• Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions.
  Chiang, Nature communications 2017
  • GeneRIF: T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure.
• Distribution and kinetics of the Kv1.3-blocking peptide HsTX1[R14A] in experimental rats.
  Bergmann, Scientific reports 2017
  • GeneRIF: The high stability and bioavailability, low normal-tissue uptake of [(64)Cu]Cu-NOTA-HsTX1[R14A], and accumulation in regions of up-regulated Kv channels both in vitro and in vivo demonstrate that HsTX1[R14A] represents a valuable lead for conditions treatable by blockade of the voltage-gated potassium channel Kv1.3.
• Effect of methamphetamine on the microglial damage: role of potassium channel Kv1.3.
  Wang, PloS one 2014
  • GeneRIF: Kv1.3 is involved in methamphetamine-mediated microglial damage
• More
• iTRAQ-based proteomic profiling reveals protein alterations after traumatic brain injury and supports thyroxine as a potential treatment
  Zhang, Molecular brain 2021
  • “...87.0 0.0014 0.77 P08050 Gap junction alpha-1 protein (Gja1) 17 43 113.0 87.0 0.00010 0.77 P15384 Potassium voltage-gated channel subfamily A member 3 (Kcna3) 8 58.4 111.3 88.7 0.042 0.80 P49655 ATP-sensitive inward rectifier potassium channel 10 (Kcnj10) 4 42.5 111.1 88.9 0.012 0.80 Q6P7A9 Lysosomal...”
• Regulation of Proliferation by a Mitochondrial Potassium Channel in Pancreatic Ductal Adenocarcinoma Cells.
  Peruzzo, Frontiers in oncology 2017
  • “...which is similar to the predicted size of Kv1.3 subunits deposited in the database (Kv1.3 P15384). Next, we tested sensitivity of PANC-1 cells to treatment with membrane permeant Kv1.3 inhibitors. In particular, we incubated these cells for 24h with clofazimine or with the newly synthetized PAP-1...”
• Targeting the ion channel Kv1.3 with scorpion venom peptides engineered for potency, selectivity, and half-life.
  Edwards, The Journal of biological chemistry 2014
• Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons.
  Gazula, The Journal of comparative neurology 2010
  • “...Kv 1.3 Ms 75-009 cloneL23/27 413-5RR-07 C-terminus) of rat Kv 1.3 (GGMNHSAFPQTPFKTGNSY ATC, accession number P15384) NeuroMab 1: 100 Kv1.6 Ms 75-012 cloneK19/36 413-5RR-51A Synthetic peptide 507525 (RERRSSYLPTPHRAYAEKR; cytoplasmic C-terminus ) of rat Kv 1.6 (accession number P17659) NeuroMab 1: 100 PSD 95 Rb 2507 1...”

7ssyA / P22001,P42212 Structure of human kv1.3 (alternate conformation) (see paper)
39% identity, 57% coverage

• Ligand: potassium ion (7ssyA)

KCNA4_BOVIN / Q05037 Potassium voltage-gated channel subfamily A member 4; BAK4; Voltage-gated potassium channel subunit Kv1.4 from Bos taurus (Bovine) (see 2 papers)
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:1505668). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:1505668). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (PubMed:8110763). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (By similarity).

KCNA2_CANLF / Q28293 Potassium voltage-gated channel subfamily A member 2; CSMK1; Voltage-gated potassium channel subunit Kv1.2 from Canis lupus familiaris (Dog) (Canis familiaris) (see paper)
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:8415758). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:8415758). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long- term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (By similarity). Channel activity is regulated by interaction with the beta subunits, including KCNAB1 and KCNAB2 (By similarity). Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Interacts with the beta subunit KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts with PTK2B (By similarity). Interacts (via C- terminus) with CTTN (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (By similarity). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with ADAM11 (By similarity). Intercts with LYNX1 (By similarity).

KCNA4_HUMAN / P22459 Potassium voltage-gated channel subfamily A member 4; HPCN2; Voltage-gated K(+) channel HuKII; Voltage-gated potassium channel HBK4; Voltage-gated potassium channel HK1; Voltage-gated potassium channel subunit Kv1.4 from Homo sapiens (Human) (see 6 papers)
NP_002224 potassium voltage-gated channel subfamily A member 4 from Homo sapiens
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (PubMed:19968958).
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 1.7 HGNC, UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 218 ] K v 1.1,...”
• Mechanical stretch increases Kv1.5 current through an interaction between the S1-S2 linker and N-terminus of the channel.
  Milton, The Journal of biological chemistry 2020
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 1.4 HGNC, UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 73 ] K v 1.1, K v 1.4, K v 1 and K v...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 1.5 HGNC, UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 68 ] K v 1.1, K v 1.4, K v 1...”
• Characterization of Kbot21 Reveals Novel Side Chain Interactions of Scorpion Toxins Inhibiting Voltage-Gated Potassium Channels.
  ElFessi-Magouri, PloS one 2015
  • “...human Kv2.1 and Kv1.4 were retrieved from Uniprot database ( http://www.uniprot.org/ ) under Q14721 and P22459 codes, respectively. Twenty structures were generated for each subtype and their respective DOPE [ 31 ] scores were calculated. The models of Kv1.4 and Kv2.1 with the lowest DOPE values...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCa4.2, KCa5.1 KCa2.1, KCa2.2, KCa2.3, KCa3.1 HGNC, UniProt KCNA1, Q09470; KCNA2, P16389; KCNA3, P22001; KCNA4, P22459; KCNA5, P22460; KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526;...”
• Mechanisms underlying modulation of neuronal KCNQ2/KCNQ3 potassium channels by extracellular protons.
  Prole, The Journal of general physiology 2003
  • “...residues H260 of KCNQ2 and K260 of KCNQ3. EMBL/GenBank/DDBJ accession nos. used were: Kv1.4 ( P22459 ), Kv1.5 ( P22460 ), and Kv2.1 (NP_004966). F igure 14. Pore determinants of KCNQ2/3 channel sensitivity to H + ions. (A) Whole-cell KCNQ2/3 ( n = 9), KCNQ2/KCNQ3(K260Q) (...”
• miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure.
  Kang, Heart rhythm 2023
  • GeneRIF: miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure.
• An epilepsy-associated KV1.2 charge-transfer-center mutation impairs KV1.2 and KV1.4 trafficking.
  Nilsson, Proceedings of the National Academy of Sciences of the United States of America 2022
  • GeneRIF: An epilepsy-associated KV1.2 charge-transfer-center mutation impairs KV1.2 and KV1.4 trafficking.
• Human adrenal glomerulosa cells express K2P and GIRK potassium channels that are inhibited by ANG II and ACTH.
  Enyeart, American journal of physiology. Cell physiology 2021
  • GeneRIF: Human adrenal glomerulosa cells express K2P and GIRK potassium channels that are inhibited by ANG II and ACTH.
• KCNA4 Gene Variant is Auxiliary in Endurance Running Performance Level.
  Flecha-Velazquez, International journal of sports medicine 2019 (PubMed)
  • GeneRIF: statistically significant association between the KCNA4 rs1323860 C/T transition and endurance running performance level
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 1.1 (NP_000208), K v 1.2 (NP_004965), K v 1.3 (NP_002223), K v 1.4 (NP_002224), K v 1.5 (NP_002225), K v 1.6 (NP_002226), K v 1.7 (NP_114092), K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v...”
• K+ channel alterations in the progression of experimental autoimmune encephalomyelitis.
  Jukkola, Neurobiology of disease 2012
  • GeneRIF: Expression of Kv1.4 appears to increase in the spinal cord of mice modelling remitting-relapsing experimental allergic encephalomyelitis (rrEAE) in peak and remitting phases.
• Episodic ataxia type 1 mutations affect fast inactivation of K+ channels by a reduction in either subunit surface expression or affinity for inactivation domain.
  Imbrici, American journal of physiology. Cell physiology 2011 (PubMed)
  • GeneRIF: Data suggest that episodic ataxia type 1 mutations affect fast inactivation of Kv1.1/1.4 channels by a reduction in either subunit surface expression or altered affinity for the inactivation domain.
• Hypermethylated DNA as potential biomarkers for gastric cancer diagnosis.
  Zheng, Clinical biochemistry 2011 (PubMed)
  • GeneRIF: Detection of the methylation prevalence of KCNA4 and CYP26B1 together in serum demonstrated the good sensitivity and specificityin gastric cancer
• More

KCA10_CHICK / Q7T199 Potassium voltage-gated channel subfamily A member 10 from Gallus gallus (Chicken) (see paper)
NP_989793 potassium voltage-gated channel subfamily A member 10 from Gallus gallus
37% identity, 63% coverage

• function: Voltage-gated potassium ion channel that mediates K(+) permeability of excitable membranes. When opened in response to the voltage difference across the membrane, KCNA10 channel selectively allows the flow of potassium ions across the membrane down their electrochemical gradient (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer.
• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...gallus (XP_425660; NP_989794; NP_001025549; XP_417226; NP_989793); Dre: D. rerio (XP_687507; XP_001334455; XP_699869; NP_001104640; XP_695984; XP_687427). RNA...”
• Cloning and developmental expression of Shaker potassium channels in the cochlea of the chicken.
  Duzhyy, Brain research. Molecular brain research 2004 (PubMed)
  • GeneRIF: During development of chicken inner ear, RT-PCR studies show expression of cKv1.2, cKv1.3 and cKv1.5 as early as Embryonic Day (ED) 3, while cKCNA10 was detected at low levels beginning on ED6 and was highly expressed by ED9.

KCNA5_HUMAN / P22460 Potassium voltage-gated channel subfamily A member 5; HPCN1; Voltage-gated potassium channel HK2; Voltage-gated potassium channel subunit Kv1.5 from Homo sapiens (Human) (see 9 papers)
TC 1.A.1.2.4 / P22460 Potassium voltage-gated channel subfamily A member 5, component of Margatoxin-sensitive voltage-gated K+ channel, Kv1.3 (in plasma and mitochondrial membranes of T lymphocytes) (Szabò et al., 2005). Kv1.3 associates with the sequence similar (>80%) Kv1.5 protein in macrophage forming heteromers that like Kv1.3 homomers are r-margatoxin sensitive (Vicente et al., 2006). However, the heteromers have different biophysical and pharmacological properties. The Kv1.3 mitochondrial potassium channel is involved in apoptotic signalling in lymphocytes (Gulbins et al., 2010). Interactions between the C-terminus from Homo sapiens (Human) (see 11 papers)
KCNA5 / RF|NP_002225.2 potassium voltage-gated channel subfamily A member 5 from Homo sapiens (see paper)
NP_002225 potassium voltage-gated channel subfamily A member 5 from Homo sapiens
34% identity, 62% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:12130714, PubMed:8505626). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity). May play a role in regulating the secretion of insulin in normal pancreatic islets.
  function: [Isoform 2]: Exhibits a faster depolarization rate, reduced voltage-dependent recovery from inactivation and an excessive cumulative inactivation.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  catalytic activity: [Isoform 2]: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (PubMed:20018952). Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1 (PubMed:12130714). Interacts with UBE2I (PubMed:17261810). Interacts with XIRP2; the interaction is required for normal action potential configuration in the heart (By similarity).
• substrates: K+
  tcdb comment: of Kv1.5 and Kvβ regulate pyridine nucleotide-dependent changes in channel gating (Tipparaju et al., 2012). Intracellular trafficking of the KV1.3 K+ channel is regulated by the pro-domain of a matrix metalloprotease (Nguyen et al. 2013). Direct binding of caveolin regulates Kv1 channels and allows association with lipid rafts (Pérez-Verdaguer et al. 2016). Addtionally, NavBeta1 interacts with the voltage sensing domain (VSD) of Kv1.3 through W172 in the transmembrane segment to modify the gating process (Kubota et al. 2017). During insertion of Kv1.3, the extended N-terminus of the secondα-helix, S2, inside the ribosomal tunnel is converted into a helix in a transition that depends on the nascent peptide sequence at specific tunnel locations (Tu and Deutsch 2017). The microRNA, mmumiR449a, reduced the mRNA expression levels of transient receptor potential cation channel subfamily A member 1 (TRPA1), and calcium activated potassium channel subunit alpha1 (KCNMA1) and increased the level of transmembrane phosphatase with tension homology (TPTE) in the DRG cells (Lu et al. 2017). This channel is regulation by sterols (Balajthy et al. 2017). Loss of function causes atrial fibrillation, a rhythm disorder characterized by chaotic electrical activity of cardiac atria (Olson et al. 2006). The N-terminus and S1 of Kv1.5 can attract and coassemble with the rest of the channel (i.e. Frag(304-613)) to form a functional channel independently of the S1-S2 linkage (Lamothe et al. 2018). This channel may be present in mitochondria (Parrasia et al. 2019)
• Computational Studies Show How the H463R Mutation Turns hKv1.5 into an Inactivation State.
  Rahman, The journal of physical chemistry. B 2024 (PubMed)
  • GeneRIF: Computational Studies Show How the H463R Mutation Turns hKv1.5 into an Inactivation State.
• Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension.
  Vera-Zambrano, American journal of respiratory cell and molecular biology 2023 (PubMed)
  • GeneRIF: Novel Loss-of-Function KCNA5 Variants in Pulmonary Arterial Hypertension.
• KV1.5-KVβ1.3 Recycling Is PKC-Dependent.
  Macias, International journal of molecular sciences 2021
  • GeneRIF: KV1.5-KVbeta1.3 Recycling Is PKC-Dependent.
• MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome.
  Gao, Biochemical and biophysical research communications 2020 (PubMed)
  • GeneRIF: MiR-3940-5p promotes granulosa cell proliferation through targeting KCNA5 in polycystic ovarian syndrome.
• Mechanical stretch increases Kv1.5 current through an interaction between the S1-S2 linker and N-terminus of the channel.
  Milton, The Journal of biological chemistry 2020
  • GeneRIF: Mechanical stretch increases Kv1.5 current through an interaction between the S1-S2 linker and N-terminus of the channel.
• Notch enhances Ca2+ entry by activating calcium-sensing receptors and inhibiting voltage-gated K+ channels.
  Song, American journal of physiology. Cell physiology 2020
  • GeneRIF: these results suggest that Notch activation enhances CaSR-mediated increases in [Ca(2+)]cyt by enhancing store-operated Ca(2+) entry and inhibits KCNA5/KV1.5 and KCNA2/KV1.2, ultimately leading to voltage-activated Ca(2+) entry.
• Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma.
  Farah, BMC cancer 2020
  • GeneRIF: Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma.
• Identification of Verapamil Binding Sites Within Human Kv1.5 Channel Using Mutagenesis and Docking Simulation.
  Ding, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2019 (PubMed)
  • GeneRIF: Verapamil acts as an open-channel blocker of hKv1.5 channel, presumably due to direct binding to specific amino acids within pore region of hKv1.5 channel, such as Thr479, Thr480, Val505, Ile508, Val512 and Val516.
• More
• Computational engineering of water-soluble human potassium ion channels through QTY transformation.
  Smorodina, Scientific reports 2024
  • “...channels are obtained from Uniprot ( https://www.uniprot.org ) 46 including KCNA1 (Q09470), KCNA3 (P22001), KCNA5 (P22460), KCNC4 (Q03721), KCND1 (Q9NSA2), KCNH2 (Q12809), KCNH5 (Q8NCM2), KCNJ3 (P48549), KCNJ8 (Q15842), KCNJ10 (P78508), KCNJ11 (Q14654), KCNJ12 (Q14500), KCNK2 (O95069), KCNK5 (O95279), KCNK9 (Q9NPC2), KCNMA1 (Q12791), KCNN3 (Q9UGI6), and KCNN4...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...UniProt KCNA1 , Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 218 ] K v 1.1, K v 1.4,...”
• Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial.
  Kangasniemi, Human reproduction (Oxford, England) 2023
  • “...1.0 1.0 S S NS LOW P06396 GSN Gelsolin 0.7* 0.9 1.1 S S NS P22460 KCNA5 Voltage-gated potassium channel HK2 Q8N1V2 CFAP52 Cilia- and flagella-associated protein 52 Q99607 ELF4 ETS-related transcription factor Elf-4 Q9UH62 ARMCX3 Armadillo repeat-containing X-linked protein 3 Q9Y2M5 KLHL20 Kelch-like protein 20...”
• Impact of rs1805127 and rs55742440 Variants on Atrial Remodeling in Hypertrophic Cardiomyopathy Patients with Atrial Fibrillation: A Romanian Cohort Study.
  Popa-Fotea, International journal of molecular sciences 2023
  • “...potassium channel 4 (Q9Y3Q4) [ 16 ] KCNA5 Potassium voltage-gated channel subfamily A member 5 (P22460) [ 17 ] KCND3 Potassium voltage-gated channel subfamily D member 3 (Q9UK17) [ 18 ] KCNE1 Potassium voltage-gated channel subfamily E member 1 (P15382) [ 19 ] KCNE2 Potassium voltage-gated...”
• Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants
  Shan, Scientific reports 2022
  • “...P25774 Cathepsin S CXCR1 P25024 C-X-C chemokine receptor type 1 TBXAS1 P24557 Thromboxane-A synthase KCNA5 P22460 Potassium voltage-gated channel subfamily A member 5 ERBB3 P21860 Receptor tyrosine-protein kinase erbB-3 CXCL2 P19875 C-X-C motif chemokine 2 ALOX12 P18054 Polyunsaturated fatty acid lipoxygenase ALOX12 IGFBP3 P17936 Insulin-like growth...”
• Seawater fungi-derived compound screening to identify novel small molecules against dengue virus NS5 methyltransferase and NS2B/NS3 protease.
  Hasan, Informatics in medicine unlocked 2022
  • “...protein GLI1 GLI1 P08151 Transcription factor 0.1106122 Brevione K Voltage-gated potassium channel subunit Kv1.5 KCNA5 P22460 Voltage-gated ion channel 0.106542926 Protein farnesyltransferase FNTA FNTB P49354 P49356 Enzyme 0.106542926 11-beta-hydroxysteroid dehydrogenase 1 HSD11B1 P28845 Enzyme 0.106542926 CC chemokine receptor type 5 CCR5 P51681 Family A G protein-coupled...”
• Identification of Molecular Targets and Potential Mechanisms of Yinchen Wuling San Against Head and Neck Squamous Cell Carcinoma by Network Pharmacology and Molecular Docking.
  Zhang, Frontiers in genetics 2022
  • “...CHEMBL2095189 Kinase PDGFRB P09619 CHEMBL2095189 Kinase STS P08842 CHEMBL3559 Enzyme MAPK1 P28482 CHEMBL4040 Kinase KCNA5 P22460 CHEMBL4306 Voltage-gated ion channel F2 P00734 CHEMBL204 Protease IKBKB O14920 CHEMBL1991 Kinase SMO Q99835 CHEMBL5971 Frizzled family G protein-coupled receptor MC1R Q01726 CHEMBL3795 Family A G protein-coupled receptor JAK1 P23458...”
• Intracellular hemin is a potent inhibitor of the voltage-gated potassium channel Kv10.1.
  Sahoo, Scientific reports 2022
  • “...Kv11.1-ni), Kcna 1 (rat Kv1.1, acc. no. P10499), and KCNA 5 (human Kv1.5, acc. no. P22460). Kv10.1 channel mutant constructs C541A, H543A, H552V, and 2190 were prepared by using overlap-extension mutagenesis as described previously 26 . We also utilized the human cyclic-nucleotide gated channel CNGA 2...”
• More

KCNA4_RAT / P15385 Potassium voltage-gated channel subfamily A member 4; RCK4; RHK1; RK3; Voltage-gated potassium channel subunit Kv1.4 from Rattus norvegicus (Rat) (see 12 papers)
37% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:10896669, PubMed:2348860, PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:2384173). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:2348860).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (PubMed:10896669). Interacts with KCNAB1 and KCNAB2 (PubMed:9334400). Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (PubMed:7477295). Interacts with SIGMAR1 (PubMed:11988171). Part of a complex containing KCNA1, KCNAB1 and LGI1 (PubMed:16504945). Detected in a complex with KCNA1 (PubMed:10896669, PubMed:2348860). Interacts with KCNA2 (PubMed:10896669, PubMed:12632190, PubMed:8361540). Interacts (via cytoplasmic N-terminal domain) with KCNRG (By similarity).
• Impact of intracellular hemin on N-type inactivation of voltage-gated K⁺ channels
  Coburger, Pflugers Archiv : European journal of physiology 2020
  • “...solution immediately before use. Channel constructs and mutagenesis The expression plasmids coding for Kv1.4 (Kcna4, P15385) and Kv3.4 from Rattus norvegicus (Kcnc4, Q63734) and mutants were cloned as described before [ 34 , 39 ]. The expression plasmids encoding Kv1.5 (KCNA5, P22460), Kv1.1, Kv1.2, Kv1.3 (KCNAB1,...”
• Identification of an evolutionarily conserved extracellular threonine residue critical for surface expression and its potential coupling of adjacent voltage-sensing and gating domains in voltage-gated potassium channels.
  Mckeown, The Journal of biological chemistry 2008
• Innate differences in protein expression in the nucleus accumbens and hippocampus of inbred alcohol-preferring and -nonpreferring rats.
  Witzmann, Proteomics 2003
• A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors.
  Nitabach, Proceedings of the National Academy of Sciences of the United States of America 2001

KCNA4_MOUSE / Q61423 Potassium voltage-gated channel subfamily A member 4; Voltage-gated potassium channel subunit Kv1.4 from Mus musculus (Mouse) (see 2 papers)
NP_067250 potassium voltage-gated channel subfamily A member 4 from Mus musculus
37% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:8020965). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:8020965). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (By similarity).
• Amyloid-β Protein Precursor Regulates Electrophysiological Properties in the Hippocampus via Altered Kv1.4 Expression and Function in Mice.
  Li, Journal of Alzheimer's disease : JAD 2023 (PubMed)
  • GeneRIF: Amyloid-beta Protein Precursor Regulates Electrophysiological Properties in the Hippocampus via Altered Kv1.4 Expression and Function in Mice.
• Functional role of endogenous Kv1.4 in experimental demyelination.
  González-Alvarado, Journal of neuroimmunology 2020 (PubMed)
  • GeneRIF: Functional role of endogenous Kv1.4 in experimental demyelination.
• IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus.
  Granados-Fuentes, Journal of biological rhythms 2015
  • GeneRIF: Data show that suprachiasmatic nucleus (SCN) explants from potassium channel Kv1.4(-/-)period2 protein Per2(Luc) and potassium channel Kv4.2(-/-) period2 protein Per2(Luc) mice have significantly shorter circadian periods in PER2 rhythms.
• Reduced excitability of gp130-deficient nociceptors is associated with increased voltage-gated potassium currents and Kcna4 channel upregulation.
  Langeslag, Pflugers Archiv : European journal of physiology 2014 (PubMed)
  • GeneRIF: Increased A-type K(+) currents and expression of voltage-gated potassium channel Kcna4 (Kv1.4) in SNS-gp130(-/-) nociceptors.
• Patterned expression of ion channel genes in mouse dorsal raphe nucleus determined with the Allen Mouse Brain Atlas.
  Templin, Brain research 2012
  • GeneRIF: This study demonistrated that Kcna4 gene expression in mouse dorsal raphe nucleus
• A-type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate intrinsic excitability of cortical pyramidal neurons.
  Carrasquillo, The Journal of physiology 2012
  • GeneRIF: The experiments here demonstrate that Kv4.2, Kv4.3 and Kv1.4 all contribute to the generation of potassium channels in mature cortical pyramidal (CP) neurons; these channels play distinct roles in regulating the intrinsic properties of mature CP neurons.
• I(A) channels encoded by Kv1.4 and Kv4.2 regulate neuronal firing in the suprachiasmatic nucleus and circadian rhythms in locomotor activity.
  Granados-Fuentes, The Journal of neuroscience : the official journal of the Society for Neuroscience 2012
  • GeneRIF: Kv1.4- and Kv4.2-encoded I(A) channels regulate the intrinsic excitability of SCN neurons during the day and night and determine the period and amplitude of circadian rhythms in SCN neuron firing and locomotor behavior.
• Molecular dissection of I(A) in cortical pyramidal neurons reveals three distinct components encoded by Kv4.2, Kv4.3, and Kv1.4 alpha-subunits.
  Norris, The Journal of neuroscience : the official journal of the Society for Neuroscience 2010
  • GeneRIF: Targeted deletion of Kv1.4 alpha-subunit (along with Kv4.2 and Kv4.3) demonstrates that individual alpha-subunits encode for the I(A) current in cortical pyramidal neurons.
• More
• iTRAQ-Based Proteomic Analysis of APP Transgenic Mouse Urine Exosomes.
  Zhou, International journal of molecular sciences 2022
  • “...zinc finger protein 2A Kif21b Q9QXL1 Kinesin-like protein KIF21B Kdm2b Q6P1G2 Lysine-specific demethylase 2B Kcna4 Q61423 Potassium voltage-gated channel subfamily A member 4 Igkc P01837 Ig kappa chain C region Epc2 Q8C0I4 Enhancer of polycomb homolog 2 Cacna1b O55017 Voltage-dependent N-type calcium channel subunit alpha-1B Atp1b1...”
• Alterations in the cerebellar (Phospho)proteome of a cyclic guanosine monophosphate (cGMP)-dependent protein kinase knockout mouse
  Corradini, Molecular & cellular proteomics : MCP 2014
  • “...Q91XV3 P11276 P01027 Q921I1 Q9DB26 Q91WP6 Q8BHH2 Q8CHT1 Q61423 Q03517 O35526 Q9CZS1 D3YVF0 Q60673 Q9WTR5 Q9WUC3 Q01097 Q9QXV0 Q68ED2 P06728 Q3TW96 P16460 P31324...”
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...T421 C-term T433 C-term S434 S434 C-term S440 C-term S441 S441 C-term S447 Kv1.4/KCNA4 W: Q61423 Tr:Q8CBF8 M: Q61423 N-term S101 N-term S113 N-term S122 S122 S122 Kv1.5/KCNA5 W: Q61762 C-term S535 Kv1.6/KCNA6 W: Q61923 M: Q61923 N-term S6 N-term T8 T8 Kv2.1/KCNB1 W: Q8K0D1 TR:...”

KCNA4_MUSPF / Q28527 Potassium voltage-gated channel subfamily A member 4; FK1; Voltage-gated potassium channel subunit Kv1.4 from Mustela putorius furo (European domestic ferret) (Mustela furo) (see paper)
37% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:7943383). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:7943383). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Interacts with DLG1, DLG2 and DLG4 via their PDZ domains (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (By similarity).

XP_006234735 potassium voltage-gated channel subfamily A member 4 isoform X1 from Rattus norvegicus
37% identity, 58% coverage

• Altered gating of Kv1.4 in the nucleus accumbens suppresses motivation for reward.
  O'Donovan, eLife 2019
  • GeneRIF: Neuronal and behavioral outputs associated with low motivation were linked to faster inactivation of a voltage-gated potassium channel, Kv1.4.
• Amino Acid Properties of Trafficking Determinants in the Outer Pore-Forming Region of Kv1 Potassium Channels in Cell Lines.
  Gomez, Cell biochemistry and biophysics 2017 (PubMed)
  • GeneRIF: Four prolines and four lysines in a Kv1.4 homotetramer might provide a binding site for a putative endoplasmic reticulum-export molecule to ensure high cell surface protein expression of the channel.
• Synaptotagmin I delays the fast inactivation of Kv1.4 channel through interaction with its N-terminus.
  Xie, Molecular brain 2014
  • GeneRIF: synaptotagmin I is an interacting protein of Kv1.4 channel.
• Hydrogen sulfide increases excitability through suppression of sustained potassium channel currents of rat trigeminal ganglion neurons.
  Feng, Molecular pain 2013
  • GeneRIF: Endogenous H2S generating enzyme cystathionine-beta-synthetase was co-localized well with Kv1.1 and Kv1.4 in trigeminal ganglion neurons.
• Heme impairs the ball-and-chain inactivation of potassium channels.
  Sahoo, Proceedings of the National Academy of Sciences of the United States of America 2013
  • GeneRIF: Kv1.4 K(+) channels are potently regulated by intracellular free heme; heme binds to the N-terminal inactivation domain and thereby impairs the inactivation process
• Position-dependent attenuation by Kv1.6 of N-type inactivation of Kv1.4-containing channels.
  Al-Sabi, The Biochemical journal 2011 (PubMed)
  • GeneRIF: N-type inactivation prevention (NIP) domain function was shown to require positioning of Kv1.6 adjacent to the Kv1.4 subunit.
• Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.
  Guan, Journal of neurophysiology 2011
  • GeneRIF: Immunocytochemistry indicated that protein expression for Kv1.4 increased between 1 wk and 4-5 wk of age.
• Bladder hyperactivity and increased excitability of bladder afferent neurons associated with reduced expression of Kv1.4 alpha-subunit in rats with cystitis.
  Hayashi, American journal of physiology. Regulatory, integrative and comparative physiology 2009
  • GeneRIF: Bladder inflammation increases bladder afferent neuron excitability by decreasing expression of Kv1.4 alpha-subunits.
• More

4jtaQ / P15387,P63142 Crystal structure of kv1.2-2.1 paddle chimera channel in complex with charybdotoxin (see paper)
38% identity, 57% coverage

• Ligand: (1r)-2-{[(s)-{[(2s)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl(9z)-octadec-9-enoate (4jtaQ)

7ukhA / Q9NZV8 Human kv4.2-kchip2-dpp6 channel complex in an open state, intracellular region (see paper)
75% identity, 23% coverage

• Ligand: zinc ion (7ukhA)

TC 1.A.1.2.14 / H2EZS9 Voltage-gated delayed rectifier K+ from Octopus vulgaris (see paper)
38% identity, 59% coverage

• substrates: K+
  tcdb comment: channel, Kv1 of the octopus. RNA editing underlies adaption (Garrett and Rosenthal, 2012). 94% identical to the squid giant axon delayed rectifier voltage-dependent potassium channel, SqKv1A (Q25376)

NP_001260001 shaker cognate w, isoform E from Drosophila melanogaster
36% identity, 60% coverage

• Function of the Shaw potassium channel within the Drosophila circadian clock.
  Hodge, PloS one 2008
  • GeneRIF: increasing Shaw levels in all clock neurons (LNv, LNd, DN(1), DN(2) and DN(3)), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night

LOC101745659 potassium voltage-gated channel protein Shaw from Bombyx mori
37% identity, 59% coverage

• Molecular Disruption of Ion Transport Peptide Receptor Results in Impaired Water Homeostasis and Developmental Defects in Bombyx mori
  Sun, Frontiers in physiology 2020
  • “...1.183 0.000355605 0.000111834 XP_004933911.1| 4.4e-82| heat shock 70 kDa protein, partial [ Bombyx mori ] LOC101745659 1.848 7.47E-11 1.32E-11 XP_012544306.1| 1.1e-246| potassium voltage-gated channel protein Shaw [ Bombyx mori ] LOC101745823 1.359 1.90E-14 2.83E-15 XP_004927809.1| 1.3e-252| proton-coupled amino acid transporter-like protein pathetic [ Bombyx mori ]...”

8qucA / P48547 Cryo-em structure of human kv3.1 in complex with modulator aut1 (see paper)
39% identity, 57% coverage

• Ligands: (5r)-5-ethyl-3-[6-(3-methoxy-4-methyl-phenoxy)pyridin-3-yl]imidazolidine-2,4-dione; cholesterol hemisuccinate (8qucA)

TC 1.A.1.2.2 / P17972 Voltage-sensitive K+ channel from Drosophila melanogaster (Fruit fly) (see 4 papers)
36% identity, 60% coverage

• substrates: K+
• Comparison of K+-channel genes within the genomes of Anopheles gambiae and Drosophila melanogaster
  McCormack, Genome biology 2003
  • “...(Kv1, Kv2, Kv3, and Kv4) K + -channel pore region (from SwissProt P08510, P17970, P17971, P17972) as the query sequence against the DNA of the Anopheles genome. In addition, a probabilistic ancestral sequence (the most recent ancestor of the four major K + -channel families) was...”
  • “...the same locus as Shab ( Anopheles chromosome 2L:23). I used the Drosophila Shaw (SwissProt P17972) sequence as a query for homologs in Anopheles . The Shaw gene in Drosophila is located at chromosome 2L:24A3-4. Not one but three genes encoding K + -channel subunits of...”
• Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus
  Wallner, Proceedings of the National Academy of Sciences of the United States of America 1996
  • “...Kv2.1 (drk1), P15387; Shab, P17970; Kv3.1, P15388; Shaw, P17972; Kv4, A39372; Shal, P17971. In Vitro Translation. H-S0 and D-S0 clones were made by introducing...”

KCNAG_CAEEL / G5EFC3 Potassium voltage-gated channel protein egl-36; Egg-laying defective protein 36 from Caenorhabditis elegans (see 2 papers)
36% identity, 61% coverage

• function: Voltage-dependent potassium channel involved in the excitation of muscles operating egg-laying and defecation.
  disruption phenotype: Egg-laying defects; retain many more eggs in utero, laid eggs appear later in development. Moderately defective in generating the expulsion step of defecation. Hyperpolarizing shifts in the voltage dependence of channel activation.

KCNA7_HUMAN / Q96RP8 Potassium voltage-gated channel subfamily A member 7; Voltage-gated potassium channel subunit Kv1.7 from Homo sapiens (Human) (see 2 papers)
NP_114092 potassium voltage-gated channel subfamily A member 7 from Homo sapiens
38% identity, 58% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Heterotetramer of potassium channel proteins.
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 218 ] K v 1.1, K v 1.4, K v 1 and K v...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 1.7 K v 1.8 HGNC, UniProt KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v 1 and K v 2 K v 1 and...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 1.8 K v 2.1 K v 2.2 HGNC, UniProt KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v 1 and K...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...HGNC, UniProt KCNA1, Q09470; KCNA2, P16389; KCNA3, P22001; KCNA4, P22459; KCNA5, P22460; KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82...”
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 1.4 (NP_002224), K v 1.5 (NP_002225), K v 1.6 (NP_002226), K v 1.7 (NP_114092), K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v...”
• Paternal age effects on sperm FOXK1 and KCNA7 methylation and transmission into the next generation.
  Atsem, Human molecular genetics 2016
  • GeneRIF: For FOXK1 and KCNA7, the age effect on the sperm epigenome was replicated in an independent cohort of 188 sperm samples.
• Block of Kv1.7 potassium currents increases glucose-stimulated insulin secretion.
  Finol-Urdaneta, EMBO molecular medicine 2012
  • GeneRIF: The authors conclude that K(v) 1.7 contributes to the membrane-repolarizing current of beta cells during glucose-stimulated insulin.
• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...(NP_000208; BAF82750; NP_002223; NP_002224; NP_002225; NP_114092; NP_005540); Gga: Gallus gallus (XP_425660; NP_989794; NP_001025549; XP_417226; NP_989793);...”
• [Distribution and significance of cSNP in KCNA7 gene as a novel NIDDM candidate gene in the population of northeast China].
  Ding, Yi chuan = Hereditas 2003 (PubMed)
  • GeneRIF: Observational study of genotype prevalence. (HuGE Navigator)
• Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI).
  Bardien-Kruger, European journal of human genetics : EJHG 2002 (PubMed)
  • GeneRIF: Expressed in heart, but not the cause of progressive familial heart block I.

KCNC1_RAT / P25122 Voltage-gated potassium channel KCNC1; NGK2; Potassium voltage-gated channel subfamily C member 1; RAW2; Voltage-gated potassium channel subunit Kv3.1; Voltage-gated potassium channel subunit Kv4 from Rattus norvegicus (Rat) (see 5 papers)
36% identity, 57% coverage

• function: Voltage-gated potassium channel that opens in response to the voltage difference across the membrane and through which potassium ions pass in accordance with their electrochemical gradient (Probable) (PubMed:10482766, PubMed:1378392, PubMed:14679187). The mechanism is time-dependent and inactivation is slow (PubMed:10482766, PubMed:1378392). Plays an important role in the rapid repolarization of fast-firing brain neurons (PubMed:10482766). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well (PubMed:10482766, PubMed:14679187). Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons (PubMed:10482766).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Homomultimer (By similarity). Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity). Heteromultimer with KCNC2 (PubMed:10482766, PubMed:14679187). Heterotetramer with KCNC3 (By similarity). Interacts with the ancillary subunits KCNE1 and KCNE2; the interaction modulates channel activity (PubMed:14679187).
• Membrane Protein Identification in Rodent Brain Tissue Samples and Acute Brain Slices
  Joost, Cells 2019
  • “...9 12 11 P10499 Potassium voltage-gated channel subfamily A member 1 6 4 1 1 P25122 Potassium voltage-gated channel subfamily C member 1 7 4 3 3 P04775 Sodium channel protein type 2 subunit alpha 24 8 3 3 Q00954 Sodium channel beta-1 subunit 2 1...”
• Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque
  Soares, The Journal of comparative neurology 2017
  • “...Kv3.1b protein, which is identical to the same sequence in the macaque monkey (Accession No P25122). Homology between rat ( Rattus norvegicus; NP 036988.1 ) and macaque monkey ( M. mulatta NP001180751.1 ) full length Kv3.1b amino acid sequence is 99.8%, with one single amino acid...”

XP_006540709 potassium voltage-gated channel subfamily C member 1 isoform X1 from Mus musculus
36% identity, 57% coverage

• Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels.
  Stevens, eLife 2021
  • GeneRIF: Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K(+) channels.
• The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state.
  Kopljar, The Journal of general physiology 2013
  • GeneRIF: The resting (closed) Kv3.1 channel conformation forms the high-affinity state for gambierol.
• Kv3.1 channels stimulate adult neural precursor cell proliferation and neuronal differentiation.
  Yasuda, The Journal of physiology 2013
  • GeneRIF: Kv3.1 channels stimulate adult neural precursor cell proliferation and neuronal differentiation.
• Activation of conventional kinesin motors in clusters by Shaw voltage-gated K+ channels.
  Barry, Journal of cell science 2013
  • GeneRIF: high-affinity multimeric binding between the Kv3.1 T1 domain and KIF5B requires three basic residues in the KIF5B tail. Kv3.1 T1 competes with the motor domain and microtubules, but not with kinesin light chain 1 (KLC1), for binding to the KIF5B tail.
• Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.
  Boda, Journal of molecular neuroscience : MN 2012 (PubMed)
  • GeneRIF: Although all Kv3 transcripts were significantly expressed at embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins were present, suggesting a novel role for Kv3 channels at this developmental stage.
• Fast delayed rectifier potassium current: critical for input and output of the circadian system.
  Kudo, The Journal of neuroscience : the official journal of the Society for Neuroscience 2011
  • GeneRIF: Mice lacking both Kcnc1 and Kcnc2 genes fail to express the Kv3.1 and Kv3.2 channels in in the suprachiasmatic nucleus.
• BK and Kv3.1 potassium channels control different aspects of deep cerebellar nuclear neurons action potentials and spiking activity.
  Pedroarena, Cerebellum (London, England) 2011 (PubMed)
  • GeneRIF: Block of Kv3.1 channels hinders spike repolarization and severely depresses evoked fast firing in deep cerebellar nuclear neurons.
• Sound stimulation modulates high-threshold K(+) currents in mouse auditory brainstem neurons.
  Leão, The European journal of neuroscience 2010
  • GeneRIF: These results provide evidence that acoustically driven auditory activity can selectively regulate high-threshold potassium currents in the MNTB of normal hearing mice, likely due to an increased membrane expression of Kv3.1b channels.
• More

KCNA7_MOUSE / Q17ST2 Potassium voltage-gated channel subfamily A member 7; Voltage-gated potassium channel subunit Kv1.7 from Mus musculus (Mouse) (see 3 papers)
NP_034726 potassium voltage-gated channel subfamily A member 7 from Mus musculus
38% identity, 58% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. Channels formed by isoform 1 inactivate faster than channels formed by isoform 2.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Heterotetramer of potassium channel proteins.
• Subproteomic profiling of sarcolemma from dystrophic mdx-4cv skeletal muscle.
  Murphy, Data in brief 2018
  • “...1 2.1 6.72E-04 3.6 P15532 Nme1 Nucleoside diphosphate kinase A 1 1 50.7 7.89E-03 3.6 Q17ST2 Kcna7 Potassium voltage-gated channel subfamily A member 7 1 1 1.7 2.01E-04 3.2 Q9CQR4 Acot13 Acyl-coenzyme A thioesterase 13 1 1 53.0 7.37E-04 3.0 P51174 Acadl Long-chain specific acyl-CoA dehydrogenase,...”
• The proteome of mouse cerebral arteries
  Badhwar, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2014 (secret)
• Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
  Finol-Urdaneta, The Journal of general physiology 2006
  • GeneRIF: Kv1.7 channels from mouse heart muscle have two putative translation initiation start sites that generate two channel isoforms with different functional characteristics, mKv1.7L (489 aa) and a shorter mKv1.7S (457 aa).

KCNC1_HUMAN / P48547 Voltage-gated potassium channel KCNC1; NGK2; Potassium voltage-gated channel subfamily C member 1; Voltage-gated potassium channel subunit Kv3.1; Voltage-gated potassium channel subunit Kv4 from Homo sapiens (Human) (see 3 papers)
NP_004967 voltage-gated potassium channel KCNC1 isoform 2 from Homo sapiens
36% identity, 57% coverage

• function: Voltage-gated potassium channel that opens in response to the voltage difference across the membrane and through which potassium ions pass in accordance with their electrochemical gradient (PubMed:25401298, PubMed:35840580). The mechanism is time-dependent and inactivation is slow (By similarity). Plays an important role in the rapid repolarization of fast-firing brain neurons (By similarity). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (PubMed:35840580). Homomultimer (PubMed:35840580). Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity). Heteromultimer with KCNC2 (By similarity). Heterotetramer with KCNC3 (PubMed:23734863). Interacts with the ancillary subunits KCNE1 and KCNE2; the interaction modulates channel activity (By similarity).
• Structure-Function Relationship of a Novel MTX-like Peptide (MTX1) Isolated and Characterized from the Venom of the Scorpion Maurus palmatus.
  ElFessi, International journal of molecular sciences 2024
  • “...subtype sequence, comprising 511 amino acids, was obtained from the Uniprot database under accession number P48547. The template chosen for modeling MTX1 was maurotoxin (MTX) sourced from Scorpio maurus (PDB code 1TXM). Models with the highest DOPE scores were selected after generating 1000 conformers [ 45...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 3.4 HGNC, UniProt KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1, K v 6.1-6.4, K v 8.1-8.2 and K v...”
• Apo and ligand-bound high resolution Cryo-EM structures of the human Kv3.1 channel reveal a novel binding site for positive modulators.
  Botte, PNAS nexus 2022
  • “...cDNA of the wild type full length human Kv3.1 isoform a (flWT-Kv3.1a with uniprot reference P48547) with a carboxy-terminal tag composed of prescission 3C cleavage site followed by GFP was cloned in the expression plasmid pLXBM7, which allows expression of the target protein in mammalian cells...”
• Cross Pharmacological, Biochemical and Computational Studies of a Human Kv3.1b Inhibitor from Androctonus australis Venom.
  Maatoug, International journal of molecular sciences 2021
  • “...Kv3.1 K + channel subtype was extracted from the Uniprot database under the accession number P48547 and contains 511 amino acids. We removed the segments S1, S2, S3 and S4 of Kv 3.1 channel prior to the docking. Indeed, AmmTX3 has the highest sequence identity (93%)...”
  • “...human Kv3.1 K + channel subtype was extracted from Uniprot database under the accession number P48547. The sequence of the human Kv3.1 K + channel subtype contains 511 amino acids. The chosen template for model building of alpha-KTx 15.1 and AaTXK-beta is, respectively AmmTx3 from Androctonus...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 3.3 K v 3.4 HGNC, UniProt KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3 K v 5.1, K v 6.16.4,...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 3.2 K v 3.3 K v 3.4 K v 4.1 HGNC, UniProt KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 KCND1 , Q9NSA2 Associated subunits MiRP2 is an associated subunit for K v 3.4 KChIP and KChAP Functional Characteristics K V...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNA4, P22459; KCNA5, P22460; KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809; KCNH6, Q9H252;...”
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v...”

KCNC1_MOUSE / P15388 Voltage-gated potassium channel KCNC1; NGK2; Potassium voltage-gated channel subfamily C member 1; Voltage-gated potassium channel subunit Kv3.1; Voltage-gated potassium channel subunit Kv4 from Mus musculus (Mouse) (see 6 papers)
36% identity, 57% coverage

• function: Voltage-gated potassium channel that opens in response to the voltage difference across the membrane and through which potassium ions pass in accordance with their electrochemical gradient (PubMed:1400413, PubMed:2599109). The mechanism is time-dependent and inactivation is slow (PubMed:2599109). Plays an important role in the rapid repolarization of fast-firing brain neurons. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well. Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Homomultimer (By similarity). Heteromultimer with KCNG3, KCNG4 and KCNV2 (By similarity). Heteromultimer with KCNC2 (By similarity). Heterotetramer with KCNC3 (By similarity). Interacts with the ancillary subunits KCNE1 and KCNE2; the interaction modulates channel activity (By similarity).
  disruption phenotype: Mutant mice are born at the expected Mendelian rate. They are viable and fertile, but have lower body weight than wild-type. They have normal spontaneous locomotor activity, but impaired motor skills (PubMed:9037088). Mice lacking both Kcnc3 and Kcnc1 are born at the expected Mendelian rate, but the pups do not thrive and all die about 26 days after birth when kept together with other littermates. Their failure to thrive may be due to motor problems; mutant pups survive when fed separately, but 45 days after birth their body weight is only 50 to 60 % of that of wild-type (PubMed:11517255). They appear uncoordinated and display severe ataxia, myoclonus and spontaneous whole-body muscle jerks, but display no obvious alterations in brain morphology (PubMed:11517255, PubMed:15217387, PubMed:16923152). Mutant mice are also much more sensitive to ethanol and fall sideways at ethanol concentrations that have no effect on wild-type mice (PubMed:11517255). They display increased locomotor and exploratory activity (PubMed:11517255, PubMed:15217387). Mice lacking Kcnc1 show reduced response to tremorogenic agent harmaline; mice lacking both Kcnc3 and Kcnc1 are resistant to the tremorogenic agent harmaline (PubMed:15217387).
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...T478 C-term S481 C-term S488 C-term S490 C-term S503 C-term S507 C-term S530 Kv3.1/KCNC1 W: P15388 Tr: Q3TR92 T: P15388 N-term S158 N-term S160 S160 C-term T421 C-term S468 C-term T483 Kv3.2/KCNC2 W: P70311 C-term S509 C-term S557 C-term S604 C-term S619 Kv3.3/KCNC3 W: Q63959 Tr:...”

NP_001182170 potassium voltage-gated channel subfamily C member 3b from Danio rerio
36% identity, 57% coverage

• A novel <i>KCNC3</i> gene variant in the voltage-dependent Kv3.3 channel in an atypical form of SCA13 with dominant central vertigo
  Bernhard, Frontiers in cellular neuroscience 2024
  • “...norvegicus (NM_053997.5), Bos taurus (XM_027515050.1), Pan troglodytes (XM_054672643.2), Canis lupus familiaris (XM_038656201.1) and Danio rerio (NP_001182170) Kv3.3 proteins was performed with Clustal Omega. 3 The pathogenicity of the Kv3.3 E675K , USH2A V2306L and LOXHD1 A553V variants was predicted using SIFT, PolyPhen-2 and MutationTaster. 2.3 Cloning...”

NP_001397003 potassium voltage-gated channel subfamily A member 6 from Mus musculus
Q61923 Potassium voltage-gated channel subfamily A member 6 from Mus musculus
36% identity, 58% coverage

• Proteome landscape and interactome of voltage-gated potassium channel 1.6 (Kv1.6) of the murine ophthalmic artery and neuroretina.
  Perumal, International journal of biological macromolecules 2024 (PubMed)
  • GeneRIF: Proteome landscape and interactome of voltage-gated potassium channel 1.6 (Kv1.6) of the murine ophthalmic artery and neuroretina.
• Elevated potassium outward currents in hyperoxia treated atrial cardiomyocytes.
  Vysotskaya, Journal of cellular physiology 2018 (PubMed)
  • GeneRIF: we are investigating the effects of hyperoxia on atrial electrophysiology using whole-cell patch-clamp electrophysiology experiments along with assessment of Kv1.5, Kv4.2, and KChIP2 transcripts and protein profiles using real-time quantitative RT-PCR and Western blotting.
• The proteome of mouse cerebral arteries
  Badhwar, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2014 (secret)
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...N-term S101 N-term S113 N-term S122 S122 S122 Kv1.5/KCNA5 W: Q61762 C-term S535 Kv1.6/KCNA6 W: Q61923 M: Q61923 N-term S6 N-term T8 T8 Kv2.1/KCNB1 W: Q8K0D1 TR: Q03717 M: Q8K0D1 T: Q8K0D1 N-term S12 N-term S15 C-term S444 C-term S484 C-term S517 C-term S518 C-term S519...”

KCNC3_RAT / Q01956 Voltage-gated potassium channel KCNC3; KSHIIID; Potassium voltage-gated channel subfamily C member 3; Voltage-gated potassium channel subunit Kv3.3 from Rattus norvegicus (Rat) (see 2 papers)
35% identity, 42% coverage

• function: Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:1381835). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis. Required for normal motor function (By similarity). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Heterotetramer with KCNC1. Interacts (via C- terminus) with HAX1; this interaction modulates channel gating. Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1.

KCNA6_RAT / P17659 Potassium voltage-gated channel subfamily A member 6; RCK2; Voltage-gated potassium channel subunit Kv1.6; Voltage-gated potassium channel subunit Kv2 from Rattus norvegicus (Rat) (see 3 papers)
36% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KNCA5, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:15618540, PubMed:1993474). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (Probable). Homotetrameric channels display rapid activation and slow inactivation (PubMed:1993474).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (Probable). Interacts with KCNAB1 and KCNAB2 (PubMed:9334400).
• Artificial pore blocker acts specifically on voltage-gated potassium channel isoform KV1.6.
  Gigolaev, The Journal of biological chemistry 2022
  • “...rK V 1.6 channels. Residue numbering is above each sequence (UniProt accession numbers P22001 and P17659); identical residues are shaded gray . Functional segments of the channels are marked above the alignment. B E , orientation of peptides and intermolecular contacts in the complexes rK V...”
• Localization of Kv1.3 channels in presynaptic terminals of brainstem auditory neurons.
  Gazula, The Journal of comparative neurology 2010
  • “...cloneK19/36 413-5RR-51A Synthetic peptide 507525 (RERRSSYLPTPHRAYAEKR; cytoplasmic C-terminus ) of rat Kv 1.6 (accession number P17659) NeuroMab 1: 100 PSD 95 Rb 2507 1 Synthetic peptide (KLH-coupled) toaa310336 of the human PSD 95 protein. Cell Signaling 1:200 Ms: Mouse, Rb: Rabbit, na: not available Table 2...”

G3V8L6 Potassium voltage-gated channel subfamily A member 6 from Rattus norvegicus
NP_076444 potassium voltage-gated channel subfamily A member 6 from Rattus norvegicus
36% identity, 58% coverage

• iTRAQ-Based Proteomics Analysis Reveals the Effect of Rhubarb in Rats with Ischemic Stroke.
  Lin, BioMed research international 2018
  • “...heavy chain 213 1.76 54 A0A0G2K839 Clcn5 2 4.41 Chloride channel protein 3 0.02 55 G3V8L6 Kcna6 2.13 6.04 Potassium voltage-gated channel subfamily A member 6 2 0.65 56 D3ZV91 L3hypdh 4 7.34 Protein L3hypdh 2 0.48 57 F1LSV4 Sptlc2 4 5.18 Protein Sptlc2 3 0.52...”
• Proteome landscape and interactome of voltage-gated potassium channel 1.6 (Kv1.6) of the murine ophthalmic artery and neuroretina.
  Perumal, International journal of biological macromolecules 2024 (PubMed)
  • GeneRIF: Proteome landscape and interactome of voltage-gated potassium channel 1.6 (Kv1.6) of the murine ophthalmic artery and neuroretina.
• The Kv1.3 potassium channel is localized to the cis-Golgi and Kv1.6 is localized to the endoplasmic reticulum in rat astrocytes.
  Zhu, The FEBS journal 2014 (PubMed)
  • GeneRIF: Kv1.6 is localized to the endoplasmic reticulum in rat astrocytes.
• Developmental changes in the expression of Κv1 potassium channels in rat vestibular ganglion cells.
  Iwasaki, Brain research 2012 (PubMed)
  • GeneRIF: down-regulation of the Kv1.6 protein and mRNA may be associated with maturation of excitable properties of primary vestibular neurons
• Position-dependent attenuation by Kv1.6 of N-type inactivation of Kv1.4-containing channels.
  Al-Sabi, The Biochemical journal 2011 (PubMed)
  • GeneRIF: N-type inactivation prevention (NIP) domain function was shown to require positioning of Kv1.6 adjacent to the Kv1.4 subunit.
• Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of spikes in rat mesencephalic trigeminal neurons.
  Saito, Journal of neurophysiology 2006 (PubMed)
  • GeneRIF: Consistent with these findings, strong immunoreactivities for Kv1.1 and Kv1.6, among 4-AP-sensitive and low-voltage-activated Kv1 family examined, were detected in the soma but not in the stem axon of MTN neurons.

KCNC2_HUMAN / Q96PR1 Voltage-gated potassium channel KCNC2; Potassium voltage-gated channel subfamily C member 2; Shaw-like potassium channel; Voltage-gated potassium channel Kv3.2 from Homo sapiens (Human) (see 7 papers)
NP_631875 voltage-gated potassium channel KCNC2 isoform KV3.2b from Homo sapiens
32% identity, 75% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high- threshold voltages and inactivate slowly. Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (Probable) (PubMed:15709110, PubMed:35314505, PubMed:36090251). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 or KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons (PubMed:15709110). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation- dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike- evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1. Interacts with KCNC1. Homotetramer or heterotetramer channel activity is regulated by association with modulating ancillary subunits such as KCNE1, KCNE2 and KCNE3, creating a functionally diverse range of channel complexes. Interacts with KCNE1, KCNE2 and KCNE3.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v...”
• A structurally precise mechanism links an epilepsy-associated KCNC2 potassium channel mutation to interneuron dysfunction.
  Clatot, Proceedings of the National Academy of Sciences of the United States of America 2024
  • “...to 500) was taken from the AlphaFold2 EBI database based on the UniProt sequence ID: Q96PR1. The disordered regions between Pro43 and Ala92 and between Asp173 and Leu198 were removed as these residues are absent in the Kv3.1 structure. The residues lining the missing gap were...”
• Case Report: Targeted treatment by fluoxetine/norfluoxetine of a KCNC2 variant causing developmental and epileptic encephalopathy.
  Li, Frontiers in pharmacology 2024
  • “...in the Kv3.1 sequence is equivalent to residue V473 in Kv3.2 [P48547 KCNC1 compared to Q96PR1 KCNC2 - UniProt]. The images of human Kv3.1 structure were prepared in UCSF Chimera ( Pettersen et al., 2004 ). The V436A (V473A) variation in the Kv3.1 (Kv3.2) structure was...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...UniProt KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1, K v 6.1-6.4, K v 8.1-8.2 and K v 9.1-9.3 K v...”
• Germline mosaicism of a missense variant in KCNC2 in a multiplex family with autism and epilepsy characterized by long-read sequencing
  Mehinovic, American journal of medical genetics. Part A 2022
  • “...) tests were run on the data. The DNVs were plotted on the protein (UniProtKB Q96PR1 [KCNC2_HUMAN]) using PROTTER (Omasits et al., 2013 ). TABLE 1 Individuals with neurodevelopmental disorders with DNVs in the KCNC2 gene Sample Publication Sex Autism Epilepsy Developmental delay or intellectual disability...”
• Emerging evidence of genotype-phenotype associations of developmental and epileptic encephalopathy due to KCNC2 mutation: Identification of novel R405G.
  Wang, Frontiers in molecular neuroscience 2022
  • “...(b) Represents the mutated KCNC2 with Gly405. Based on the reviewed structure data (UniProtKB id: Q96PR1), KCNC2 contains cytosolic N- and C-termini and six membrane-spanning segments. KCNC2 R405 is located within the S5-S6 linker, an extracellular loop that forms one of the ion-selective macromolecular protein pores...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 3.4 HGNC, UniProt KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3 K v 5.1, K v 6.16.4, K v 8.18.2...”
• Mechanisms Underlying Adaptation to Life in Hydrogen Sulfide-Rich Environments.
  Kelley, Molecular biology and evolution 2016
  • “...inhibitor 2 ppp1r2 1 TCONS_00010396 Q7KZN9 Cytochrome c oxidase assembly protein COX15 cox15 1 TCONS_00011484 Q96PR1 Potassium voltage-gated channel subfamily C member 2 kcnc2 1 TCONS_00011526 P58743 Prestin slc26a5 1 TCONS_00011778 P21266 Glutathione S-transferase Mu 3 ENSXMAG00000009961 1 TCONS_00012045 Q12805 EGF-containing fibulin-like extracellular matrix protein 1...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 3.3 K v 3.4 K v 4.1 HGNC, UniProt KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 KCND1 , Q9NSA2 Associated subunits MiRP2 is an associated subunit for K v 3.4 KChIP and KChAP Functional Characteristics K V K V K...”
• More

KCNA6_HUMAN / P17658 Potassium voltage-gated channel subfamily A member 6; Voltage-gated potassium channel HBK2; Voltage-gated potassium channel subunit Kv1.6 from Homo sapiens (Human) (see 3 papers)
NP_002226 potassium voltage-gated channel subfamily A member 6 from Homo sapiens
XP_016874760 potassium voltage-gated channel subfamily A member 6 isoform X1 from Homo sapiens
35% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:14575698, PubMed:2347305). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:14575698, PubMed:2347305). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (PubMed:2347305).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity).
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...Q09470 KCNA2 , P16389 KCNA3 , P22001 KCNA4 , P22459 KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 Associated subunits K v 1.2, K v 1.4, K v 1 and K v 2 [ 218 ] K v 1.1, K v 1.4, K v 1...”
• Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration.
  Roy, Cell death discovery 2022
  • “...3 . PTN12_32_44 Q05209 Tyrosine-protein phosphatase non-receptor type 12 0.031 10 5 4 . KCNA6_504_516 P17658 Potassium voltage-gated channel subfamily A member 6 0.032 9 3 GCL [ 42 ] 5 . NCF1_296_308 P14598 Neutrophil cytosol factor 1 0.032 9 7 GCL [ 82 ] 6...”
• Identification of Novel Substrates for cGMP Dependent Protein Kinase (PKG) through Kinase Activity Profiling to Understand Its Putative Role in Inherited Retinal Degeneration.
  Roy, International journal of molecular sciences 2021
  • “...on kemptide sequence 8 4 CDN1A_139_151 P38936 GRKRRQTSMTDFY Cyclin-dependent kinase inhibitor 1 6 3 KCNA6_504_516 P17658 ANRERRPSYLPTP Potassium voltage-gated channel subfamily A member 6 9 3 ERBB2_679_691 P04626 QQKIRKYTMRRLL Receptor tyrosine-protein kinase erbB-2 precursor 7 8 A (PKGII) DESP_2842_2854 P15924 RSGSRRGSFDATG Desmoplakin 8 7 KCNA3_461_473 P22001...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 1.6 K v 1.7 K v 1.8 HGNC, UniProt KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v 1 and K v 2 K...”
• Traumatic Brain Injury Induces Alterations in Cortical Glutamate Uptake without a Reduction in Glutamate Transporter-1 Protein Expression.
  Dorsett, Journal of neurotrauma 2017
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 1.7 K v 1.8 K v 2.1 K v 2.2 HGNC, UniProt KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v...”
• Targeting the ion channel Kv1.3 with scorpion venom peptides engineered for potency, selectivity, and half-life.
  Edwards, The Journal of biological chemistry 2014
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCa2.3, KCa3.1 HGNC, UniProt KCNA1, Q09470; KCNA2, P16389; KCNA3, P22001; KCNA4, P22459; KCNA5, P22460; KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696;...”
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 1.3 (NP_002223), K v 1.4 (NP_002224), K v 1.5 (NP_002225), K v 1.6 (NP_002226), K v 1.7 (NP_114092), K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v...”
• De novo KCNA6 variants with attenuated KV 1.6 channel deactivation in patients with epilepsy.
  Salpietro, Epilepsia 2023
  • GeneRIF: De novo KCNA6 variants with attenuated KV 1.6 channel deactivation in patients with epilepsy.
• The RCK2 domain of the human BKCa channel is a calcium sensor.
  Yusifov, Proceedings of the National Academy of Sciences of the United States of America 2008
  • GeneRIF: analysis of how the RCK2 domain of the human BKCa channel is a calcium sensor
• Clinical spectrum of voltage-gated potassium channel autoimmunity.
  Tan, Neurology 2008 (PubMed)
  • GeneRIF: The spectrum of neurologic manifestations and neoplasms associated with voltage-gated potassium channel (VGKC) autoimmunity is broader than previously recognized
• Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  Rose, Molecular medicine (Cambridge, Mass.)
  • GeneRIF: Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)

Q811T3 Kv3.3c voltage gated potassium channel subunit splice variant C from Rattus norvegicus
35% identity, 48% coverage

• Proteomic analysis of spinal dorsal horn in prior exercise protection against neuropathic pain.
  Chen, Scientific reports 2025
  • “...diagram to further screen key proteins. The results showed that 5 overlapping DEPs (protein accession: Q811T3, D4ABP4, P61314, D4A7V6 and M0R439) were significantly downregulated after CCI, while they were significantly upregulated in the CCI_Ex group compared to the CCI group. A total of 13 overlapping DEPs...”
  • “...vs. Sham CCI_Ex vs. CCI NP-related FC P value FC P value NP inflammation Hyperalgesia Q811T3 Potassium voltage-gated channel subfamily C member 3variant C Kcnc3 0.50072 0.02365 2.7346 0.03660 D4ABP4 RAB3 GTPase activating non-catalytic protein subunit 2 Rab3gap2 0.00221 0.00747 205.85 0.00444 P61314 Large ribosomal subunit...”
• Transcriptomic and proteomic profiling of the anterior cingulate cortex in neuropathic pain model rats
  Qiu, Frontiers in molecular neuroscience 2023
  • “...260.9 214.6 0.01073 0.82 Q63327 Myelin-associated oligodendrocyte basic protein (Mobp) 6 928.1 733.7 0.01040 0.79 Q811T3 Kv3.3c voltage gated potassium channel subunit splice variant C (Kcnc3) 5 285.1 229.3 0.00033 0.80 Q5XIU4 B-cell receptor-associated protein (Bcap29) 5 465.9 369.8 0.00182 0.79 Q7TP52 Carboxymethylenebutenolidase homolog (Cmbl) 4...”

KCNC3_MOUSE / Q63959 Voltage-gated potassium channel KCNC3; KSHIIID; Potassium voltage-gated channel subfamily C member 3; Voltage-gated potassium channel subunit Kv3.3 from Mus musculus (Mouse) (see 8 papers)
35% identity, 48% coverage

• function: Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:15217387, PubMed:18539595, PubMed:24218544, PubMed:26997484). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells (PubMed:15217387, PubMed:18448641, PubMed:24218544). Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (PubMed:24218544). Required for normal motor function (PubMed:16923152, PubMed:18448641). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Heterotetramer with KCNC1 (By similarity). Interacts (via C-terminus) with HAX1; this interaction modulates channel gating (PubMed:26997484). Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1 (By similarity).
  disruption phenotype: Mice lacking both Kcnc3 and Kcnc1 are born at the expected Mendelian rate, but the pups do not thrive and all die about 26 days after birth when kept together with other littermates. Their failure to thrive may be due to motor problems; mutant pups survive when fed separately, but 45 days after birth their body weight is only 50 to 60 % of that of wild-type (PubMed:11517255). They appear uncoordinated and display severe ataxia, myoclonus and spontaneous whole-body muscle jerks, but display no obvious alterations in brain morphology (PubMed:11517255, PubMed:15217387, PubMed:16923152). Mice lacking only Kcnc3 still display ataxic gait and decreased motor skill, but to a lesser degree than mice lacking both Kcnc3 and Kcnc1 (PubMed:16923152, PubMed:18448641). Purkinje cell-specific expression of Kcnc3 restores normal motor skills (PubMed:18448641). Mutant mice are also much more sensitive to ethanol and fall sideways at ethanol concentrations that have no effect on wild-type mice (PubMed:11517255). They display increased locomotor and exploratory activity (PubMed:11517255, PubMed:15217387). Mice lacking Kcnc3 or both Kcnc3 and Kcnc1 are resistant to the tremorogenic agent harmaline (PubMed:15217387).
• The amyloid peptide β disrupts intercellular junctions and increases endothelial permeability in a NADPH oxidase 1-dependent manner.
  Tarafdar, Redox biology 2022
  • “...0.0035973 Q62442 Vesicle-associated membrane protein 1 Vamp1 0.0043429 Q8BLE7 Vesicular glutamate transporter 2 Slc17a6 0.0049574 Q63959 Potassium voltage-gated channel subfamily C member 3 Kcnc3 0.0168435 P12961 Neuroendocrine protein 7B2 Scg5 0.0087150 Q9JIS5 Synaptic vesicle glycoprotein 2A Sv2a 0.0192159 O35633 Vesicular inhibitory amino acid transporter Slc32a1 0.0365301...”
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...C-term T483 Kv3.2/KCNC2 W: P70311 C-term S509 C-term S557 C-term S604 C-term S619 Kv3.3/KCNC3 W: Q63959 Tr: Q63959 C-term S717 S717 C-term S732 C-term S740 C-term T751 C-term S755 Kv3.4/KCNC4 W: Q8R1C0 C-term S555 Kv4.1/KCND1 W: Q03719 C-term S460 C-term S555 Kv4.2/KCND2 W: Q9Z0V2 M: Q9Z0V2...”
• Protein kinase C modulates inactivation of Kv3.3 channels.
  Desai, The Journal of biological chemistry 2008
• A C-terminal domain directs Kv3.3 channels to dendrites.
  Deng, The Journal of neuroscience : the official journal of the Society for Neuroscience 2005
• Positive selection on protein-length in the evolution of a primate sperm ion channel
  Podlaha, Proceedings of the National Academy of Sciences of the United States of America 2003
  • “...KV1.4, NP067250.1; human KV3.3, NP004968.1; mouse KV3.3, Q63959; human KV4.3, NP004971.1; mouse KV4.3, NP064315.1; human CaV2.2, Q00975; mouse CaV2.2, O55017;...”
• The contribution of dendritic Kv3 K+ channels to burst threshold in a sensory neuron.
  Rashid, The Journal of neuroscience : the official journal of the Society for Neuroscience 2001

NP_001124098 potassium voltage-gated channel subfamily A member 6a from Danio rerio
39% identity, 58% coverage

• Deep RNA sequencing of the skeletal muscle transcriptome in swimming fish
  Palstra, PloS one 2013
  • “...1.70E99 Drerio R Ion channels potassium voltage-gated channel subfamily A member 6 [D. rerio] 1103 NP_001124098 5.48E81 Drerio W sodium- and chloride-dependent creatine transporter 1 isoform 3 [M. musculus] 1370 NP_001136282 1.15E155 RefSeq W sodium channel protein type 4 subunit alpha A [D. rerio] 753 NP_001034914...”

KCNC2_RAT / P22462 Voltage-gated potassium channel KCNC2; Potassium channel voltage-gated Shaw-related subfamily C member 2; Potassium voltage-gated channel subfamily C member 2; Shaw-like potassium channel; Voltage-gated potassium channel subunit Kv3.2 from Rattus norvegicus (Rat) (see 15 papers)
32% identity, 75% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system (PubMed:10414968, PubMed:10482766, PubMed:11506885, PubMed:22831914). Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly (PubMed:10414303, PubMed:10482766, PubMed:11281123, PubMed:14679187, PubMed:1879548, PubMed:2367536, PubMed:7643197, PubMed:8120636). Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:1879548, PubMed:2367536, PubMed:7643197, PubMed:8120636). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:10482766, PubMed:14679187). Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 and KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG- mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (PubMed:11281123, PubMed:14679187). Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons (PubMed:10414968, PubMed:10482766, PubMed:11506885, PubMed:22831914). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation- dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike- evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (By similarity).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1. Interacts with KCNC1 (PubMed:10482766, PubMed:14679187). Homotetramer or heterotetramer channel activity is regulated by association with modulating ancillary subunits such as KCNE1, KCNE2 and KCNE3, creating a functionally diverse range of channel complexes. Interacts with KCNE1, KCNE2 and KCNE3 (PubMed:14679187).

KCNC4_HUMAN / Q03721 Voltage-gated potassium channel KCNC4; KSHIIIC; Potassium voltage-gated channel subfamily C member 4; Voltage-gated potassium channel subunit Kv3.4 from Homo sapiens (Human) (see 2 papers)
NP_004969 voltage-gated potassium channel KCNC4 isoform a from Homo sapiens
35% identity, 57% coverage

• function: Voltage-gated potassium channel that opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient (PubMed:7993631). The channel displays rapid activation and inactivation kinetics (PubMed:7993631).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (Probable). Heterotetramer of potassium channel proteins (By similarity).
• Computational engineering of water-soluble human potassium ion channels through QTY transformation.
  Smorodina, Scientific reports 2024
  • “...obtained from Uniprot ( https://www.uniprot.org ) 46 including KCNA1 (Q09470), KCNA3 (P22001), KCNA5 (P22460), KCNC4 (Q03721), KCND1 (Q9NSA2), KCNH2 (Q12809), KCNH5 (Q8NCM2), KCNJ3 (P48549), KCNJ8 (Q15842), KCNJ10 (P78508), KCNJ11 (Q14654), KCNJ12 (Q14500), KCNK2 (O95069), KCNK5 (O95279), KCNK9 (Q9NPC2), KCNMA1 (Q12791), KCNN3 (Q9UGI6), and KCNN4 (O15554).Native and...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1, K v 6.1-6.4, K v 8.1-8.2 and K v 9.1-9.3 K v 5.1, K v 6.1-6.4, K v...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3 K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3 MiRP2 is...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 4.1 HGNC, UniProt KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 KCND1 , Q9NSA2 Associated subunits MiRP2 is an associated subunit for K v 3.4 KChIP and KChAP Functional Characteristics K V K V K A K A K A Channel...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809; KCNH6, Q9H252; KCNH7, Q9NS40; KCNH8, Q96L42; KCNH3, Q9ULD8;...”
• A novel high throughput invasion screen identifies host actin regulators required for efficient cell entry by Toxoplasma gondii.
  Gaji, PloS one 2013
  • “...activity Ion transport 3749 KCNC4 K + voltage gated channel, shaw related subfamily, member 4 Q03721 Membrane, multi-pass membrane protein Voltage gated potassium channel Ion transport 55799 CACNA2D3 Ca 2+ channel, voltage dependent, 2/ subunit 3 Q8IZS8 Membrane, type 1 single pass membrane prorein Voltage gated...”
• Tunable Action Potential Repolarization Governed by Kv3.4 Channels in Dorsal Root Ganglion Neurons.
  Alexander, The Journal of neuroscience : the official journal of the Society for Neuroscience 2022
  • GeneRIF: Tunable Action Potential Repolarization Governed by Kv3.4 Channels in Dorsal Root Ganglion Neurons.
• PKCε associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
  Zemel, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2021 (PubMed)
  • GeneRIF: PKCepsilon associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
• HIF-1α Regulates Proliferation and Invasion of Oral Cancer Cells through Kv3.4 Channel.
  Qian, Annals of clinical and laboratory science 2019 (PubMed)
  • GeneRIF: HIF-1alpha regulates the invasion, migration and proliferation of oral cancer cells by regulating Kv3.4 expression.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v...”
• Expression of the voltage-gated potassium channel Kv3.4 in oral leucoplakias and oral squamous cell carcinomas.
  Fernández-Valle, Histopathology 2016 (PubMed)
  • GeneRIF: This study provides original evidence to demonstrate the early occurrence and high prevalence of abnormal Kv3.4 expression in oral leucoplakias. Our results support a role for Kv3.4 potassium channel in OSCC tumorigenesis rather than tumour progression and disease outcome.
• Dysregulation of Kv3.4 channels in dorsal root ganglia following spinal cord injury.
  Ritter, The Journal of neuroscience : the official journal of the Society for Neuroscience 2015
  • GeneRIF: These results suggest a novel peripheral mechanism of post-spinal cord injury pain sensitization implicating Kv3.4 channel dysregulation and potential Kv3.4-based therapeutic interventions.
• Kv3.4 potassium channel-mediated electrosignaling controls cell cycle and survival of irradiated leukemia cells.
  Palme, Pflugers Archiv : European journal of physiology 2013 (PubMed)
  • GeneRIF: Ionizing radiation-induced G2/M arrest was preceded by activation of Kv3.4-like voltage-gated potassium channels.
• Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.
  Boda, Journal of molecular neuroscience : MN 2012 (PubMed)
  • GeneRIF: Although all KV3 subunit transcripts are significantly expressed at embryonic age in whole mouse brain extracts, only KV3.1, KV3.2 and KV3.4 subunit transgenic proteins are present.
• More

KCNA1_ONCMY / Q9I829 Shaker-related potassium channel tsha2; Trout shaker 2 from Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri) (see paper)
39% identity, 58% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient (By similarity).
  subunit: Heterotetramer of potassium channel proteins. Binds PDZ domains of dlg1, dlg2 and dlg4 (By similarity).

KCNC2_MOUSE / Q14B80 Voltage-gated potassium channel KCNC2; Potassium voltage-gated channel subfamily C member 2; Shaw-like potassium channel; Voltage-gated potassium channel Kv3.2 from Mus musculus (Mouse) (see 12 papers)
32% identity, 75% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system (PubMed:10414303, PubMed:10561420, PubMed:10903572, PubMed:11124984, PubMed:11506885, PubMed:15317859, PubMed:15917463, PubMed:17761775, PubMed:21414897). Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly (PubMed:10414303, PubMed:10561420, PubMed:10903572, PubMed:15317859). Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (By similarity). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:10531438, PubMed:12000114). Channel properties may be modulated by either the association with ancillary subunits, such as KCNE1, KCNE2 and KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in thalamocortical and suprachiasmatic nucleus (SCN) neurons, in hippocampal and neocortical interneurons and in retinal ganglion cells (PubMed:10561420, PubMed:10903572, PubMed:11506885, PubMed:17761775). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner (PubMed:10903572). Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release (PubMed:15917463). Required for long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (PubMed:21414897).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNC1 (PubMed:10531438). Interacts with KCNC1 (PubMed:10531438, PubMed:12000114). Homotetramer or heterotetramer channel activity is regulated by association with modulating ancillary subunits such as KCNE1, KCNE2 and KCNE3, creating a functionally diverse range of channel complexes. Interacts with KCNE1, KCNE2 and KCNE3 (By similarity).
  disruption phenotype: Mice are healthy, grow normally, are fertile and show no evidence of severe sensory or motor abnormalities (PubMed:11124984). Show increased seizure susceptibility and reduced long-range synchronization of gamma oscillations over distance in the neocortex (PubMed:22539821). Thalamocortical neurons show a strong attenuation in maximal peak firing rates, with larger spikes and slower action potential repolarization (PubMed:17761775). Neocortical GABAergic interneurons display broader spikes and sustain lower trains of high-frequency spikes without accommodation or spike doublets in rapid succession (PubMed:11124984, PubMed:22539821). Histamine H2 receptor- and PKA-induced hippocampal inhibitory interneurons display no maximal sustainable firing frequency modulation (PubMed:10903572). Double knockout of KCNC2 and KCNC1 exhibited disrupted daily rhythms in wheel-running behavior (PubMed:21414897). Display smaller outward currents and slower deactivation in starburst amacrine cells compared with KCNC2 knockout mice (PubMed:15317859). Neocortical GABAergic interneuron terminals display also a reduced rate of spike repolarization, broader spike, increased calcium influx and release of GABA neurotransmitter (PubMed:15917463). Suprachiasmatic nucleus (SCN) neurons display a reduction in the magnitude of fast delayed rectifier potassium currents, wider action potentials, reduced spontaneous firing activity during the day and reduced NMDA-evoked increase firing responses during the night (PubMed:21414897).
• The proteome of mouse cerebral arteries
  Badhwar, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2014 (secret)

KCNS3_RAT / O88759 Delayed-rectifier potassium channel regulatory subunit KCNS3; Delayed-rectifier K(+) channel alpha subunit 3; Delayed-rectifier potassium channel subunit Kv9.3; Kv9.3; Potassium voltage-gated channel subfamily S member 3 from Rattus norvegicus (Rat) (see 2 papers)
NP_113966 potassium voltage-gated channel subfamily S member 3 from Rattus norvegicus
36% identity, 58% coverage

• function: Potassium channel regulatory subunit that modulates the delayed rectifier potassium channel activity of KCNB1 by namely slowing down the deactivation and inactivation time constants (PubMed:9362476). While it does not form functional channel on its own, it can form functional heterotetrameric channels with KCNB1 (PubMed:9362476).
  subunit: Heterotetramer with KCNB1 (PubMed:9362476). Does not form homomultimers (By similarity).
• Different Kv2.1/Kv9.3 heteromer expression during brain and lung post-natal development in the rat.
  Coma, Journal of physiology and biochemistry 2002 (PubMed)
  • GeneRIF: different Kv9.3/Kv2.1 ratios could have physiological implications in lung and brain during post-natal development, and that diet composition and selective tissue-specific insulin regulation modulate the expression of Kv2.1 and Kv9.3.

Q8R1C0 Voltage-gated potassium channel KCNC4 from Mus musculus
32% identity, 65% coverage

• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...Tr: Q63959 C-term S717 S717 C-term S732 C-term S740 C-term T751 C-term S755 Kv3.4/KCNC4 W: Q8R1C0 C-term S555 Kv4.1/KCND1 W: Q03719 C-term S460 C-term S555 Kv4.2/KCND2 W: Q9Z0V2 M: Q9Z0V2 T: Q9Z0V2 N-term T154 C-term S548 S548 C-term S552 S552 Kv4.3/KCND3 W: Q9Z0V1 N-term S153 Kv5.1/KCNF1...”

KCNC4_RAT / Q63734 Voltage-gated potassium channel KCNC4; Potassium voltage-gated channel subfamily C member 4; Raw3; Voltage-gated potassium channel subunit Kv3.4 from Rattus norvegicus (Rat) (see 3 papers)
35% identity, 57% coverage

• function: Voltage-gated potassium channel that opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient (PubMed:12592408, PubMed:1378392, PubMed:1840526). The channel displays rapid activation and inactivation kinetics (PubMed:12592408, PubMed:1378392, PubMed:1840526).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer (Probable). Heterotetramer of potassium channel proteins.
• Impact of intracellular hemin on N-type inactivation of voltage-gated K⁺ channels
  Coburger, Pflugers Archiv : European journal of physiology 2020
  • “...mutagenesis The expression plasmids coding for Kv1.4 (Kcna4, P15385) and Kv3.4 from Rattus norvegicus (Kcnc4, Q63734) and mutants were cloned as described before [ 34 , 39 ]. The expression plasmids encoding Kv1.5 (KCNA5, P22460), Kv1.1, Kv1.2, Kv1.3 (KCNAB1, Q14722), Kv3.1 (KCNAB3, O43448), and DPP6a from...”

NP_001116248 potassium voltage-gated channel subfamily C member 4 isoform 2 from Rattus norvegicus
35% identity, 57% coverage

• PKCε associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
  Zemel, FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2021 (PubMed)
  • GeneRIF: PKCepsilon associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
• Kv3.4 channel function and dysfunction in nociceptors.
  Ritter, Channels (Austin, Tex.) 2015
  • GeneRIF: Data indicate ubiquitous expression of Kv3.4 potassium channel protein in nociceptors.
• Voltage-gated potassium currents within the dorsal vagal nucleus: inhibition by BDS toxin.
  Dallas, Brain research 2008 (PubMed)
  • GeneRIF: Given the role of the Kv3 proteins in shaping neuronal excitability, these data highlight a role for homomeric Kv3.4 channels in spike timing and neurotransmitter release in low frequency firing neurons of the DVN.
• Subacute hypoxia suppresses Kv3.4 channel expression and whole-cell K+ currents through endogenous 15-hydroxyeicosatetraenoic acid in pulmonary arterial smooth muscle cells.
  Guo, European journal of pharmacology 2008 (PubMed)
  • GeneRIF: the 15-lipoxygenase pathway via its metabolite, 15-hydroxyeicosatetraenoic acid , seems to play a role in the down-regulation of Kv3.4
• Up-regulation and increased activity of KV3.4 channels and their accessory subunit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death.
  Pannaccione, Molecular pharmacology 2007 (PubMed)
  • GeneRIF: Up-regulation and increased activity of KV3.4 channels and their accessory sububnit MinK-related peptide 2 induced by amyloid peptide are involved in apoptotic neuronal death.
• Reduced expression of A-type potassium channels in primary sensory neurons induces mechanical hypersensitivity.
  Chien, The Journal of neuroscience : the official journal of the Society for Neuroscience 2007
  • GeneRIF: Kv3.4 is expressed in nociceptive dorsal root ganglion neurons and is greatly reduced following neuropathic pain.

NP_715624 voltage-gated potassium channel KCNC2 isoform KV3.2c from Homo sapiens
34% identity, 62% coverage

• Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With KCNC2 Pathogenic Variants.
  Schwarz, Neurology 2022
  • GeneRIF: Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With KCNC2 Pathogenic Variants.
• Investigation of novel de novo KCNC2 variants causing severe developmental and early-onset epileptic encephalopathy.
  Li, Seizure 2022 (PubMed)
  • GeneRIF: Investigation of novel de novo KCNC2 variants causing severe developmental and early-onset epileptic encephalopathy.
• A recurrent de novo variant supports KCNC2 involvement in the pathogenesis of developmental and epileptic encephalopathy.
  Rydzanicz, American journal of medical genetics. Part A 2021 (PubMed)
  • GeneRIF: A recurrent de novo variant supports KCNC2 involvement in the pathogenesis of developmental and epileptic encephalopathy.
• Mechanisms Underlying the Hyperexcitability of CA3 and Dentate Gyrus Hippocampal Neurons Derived From Patients With Bipolar Disorder.
  Stern, Biological psychiatry 2020
  • GeneRIF: Mechanisms Underlying the Hyperexcitability of CA3 and Dentate Gyrus Hippocampal Neurons Derived From Patients With Bipolar Disorder.
• An integrative study identifies KCNC2 as a novel predisposing factor for childhood obesity and the risk of diabetes in the Korean population.
  Hwang, Scientific reports 2016
  • GeneRIF: these data suggest that reduction of KCNC2 is associated with modified hepatic gluconeogenesis and increased ER stress on obesity-mediated diabetic risk.
• Kv3.1-containing K(+) channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs.
  Yanagi, Molecular psychiatry 2014 (PubMed)
  • GeneRIF: Kv3.2 is not different in distribution or in level between normal and schizophrenia cases, nor influenced by antipsychotic drugs, in any brain region tested
• Deletion of chromosome 12q21 affecting KCNC2 and ATXN7L3B in a family with neurodevelopmental delay and ataxia.
  Rajakulendran, Journal of neurology, neurosurgery, and psychiatry 2013 (PubMed)
  • GeneRIF: This family's complex phenotype is associated with a new chromosomal deletion, which suggests potential roles for the two genes, KCNC2 and ATXN7L3B, in human neurological disease.
• Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.
  Boda, Journal of molecular neuroscience : MN 2012 (PubMed)
  • GeneRIF: Although all KV3 subunit transcripts are significantly expressed at embryonic age in whole brain extracts, only KV3.1, KV3.2 and KV3.4 subunit transgenic proteins are present.
• More

XP_021326531 potassium voltage-gated channel subfamily C member 3a isoform X3 from Danio rerio
35% identity, 57% coverage

• Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo.
  Hsieh, eLife 2020
  • GeneRIF: Infant and adult SCA13 mutations differentially affect Purkinje cell excitability, maturation, and viability in vivo.

KCNS3_HUMAN / Q9BQ31 Delayed-rectifier potassium channel regulatory subunit KCNS3; Delayed-rectifier K(+) channel alpha subunit 3; Delayed-rectifier potassium channel subunit Kv9.3; Kv9.3; Potassium voltage-gated channel subfamily S member 3 from Homo sapiens (Human) (see 2 papers)
TC 1.A.1.2.15 / Q9BQ31 Potassium voltage-gated channel subfamily S member 3 (Delayed-rectifier K(+) channel alpha subunit 3) (Voltage-gated potassium channel subunit Kv9.3) from Homo sapiens (see 3 papers)
NP_001269357 potassium voltage-gated channel subfamily S member 3 from Homo sapiens
NP_002243 delayed-rectifier potassium channel regulatory subunit KCNS3 from Homo sapiens
35% identity, 59% coverage

• function: Potassium channel regulatory subunit that modulates the delayed rectifier potassium channel activity of KCNB1 by namely slowing down the deactivation and inactivation time constants (PubMed:10484328). While it does not form functional channel on its own, it can form functional heterotetrameric channels with KCNB1 (PubMed:10484328).
  subunit: Heterotetramer with KCNB1 (Probable). Does not form homomultimers (Probable).
• substrates: K+
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v 12.3 HGNC, UniProt KCNH2 , Q12809...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v 12.3 HGNC, UniProt KCNH2 , Q12809...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v 12.3 HGNC, UniProt KCNH2 , Q12809...”
• Association analysis and polygenic risk score evaluation of 38 GWAS-identified Loci in a Chinese population with Parkinson's disease.
  Zheng, Neuroscience letters 2021 (PubMed)
  • GeneRIF: Association analysis and polygenic risk score evaluation of 38 GWAS-identified Loci in a Chinese population with Parkinson's disease.
• Lower gene expression for KCNS3 potassium channel subunit in parvalbumin-containing neurons in the prefrontal cortex in schizophrenia.
  Georgiev, The American journal of psychiatry 2014
  • GeneRIF: By in situ hybridization, KCNS3 mRNA levels were 23% lower in schizophrenia subjects than in controls. At the cellular level, both KCNS3 mRNA-expressing neuron density and KCNS3 mRNA level per neuron were significantly lower.
• Expression and function of K(V)2-containing channels in human urinary bladder smooth muscle.
  Hristov, American journal of physiology. Cell physiology 2012
  • GeneRIF: stromatoxin-1 -sensitive KV2-containing channels are expressed in detrusor smooth muscle (DSM); they control DSM excitability, intracellular Ca2+ levels, and myogenic and nerve-evoked contractions
• Expression of an electrically silent voltage-gated potassium channel in the human placenta.
  Fyfe, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology 2012 (PubMed)
  • GeneRIF: study concluded that potassium voltage-gated channel K(V)9.3 is localised to human placental vascular tissues and syncytiotrophoblast
• Stromatoxin-sensitive, heteromultimeric Kv2.1/Kv9.3 channels contribute to myogenic control of cerebral arterial diameter.
  Zhong, The Journal of physiology 2010
  • GeneRIF: There is evidence of heteromultimeric Kv2.1/Kv9.3 channel expression in control of middle cerebral arterial diameter.
• A high-density association screen of 155 ion transport genes for involvement with common migraine.
  Nyholt, Human molecular genetics 2008
  • GeneRIF: Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
• Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness.
  Hao, Human genetics 2005 (PubMed)
  • GeneRIF: Our findings suggest that SNPs located at the 3' downstream region of KCNS3 have a significant role in the etiology of AHR.
  • GeneRIF: Observational study of gene-disease association. (HuGE Navigator)
• Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits.
  Kerschensteiner, Proceedings of the National Academy of Sciences of the United States of America 2005
  • GeneRIF: formation of heteromeric Kv2.1/Kv9.3 channels of fixed stoichiometry consisting of three Kv2.1 subunits and one Kv9.3 subunit
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 8.2 (NP_598004); K v 9.1 (NP_002242), K v 9.2 (NP_065748), K v 9.3 (NP_002243); K v 10.1 (NP_758872) K v 10.2 (NP_647479); K v 11.1 (NP_000229), K v 11.2 (NP_110416), K v 11.3 (NP_150375); K v 12.1 (NP_653234), K v 12.2 (NP_036416), and K...”

XP_017450151 potassium voltage-gated channel subfamily C member 2 isoform X3 from Rattus norvegicus
33% identity, 67% coverage

• Visual experience regulates Kv3.1b and Kv3.2 expression in developing rat visual cortex.
  Grabert, Neuroscience 2009 (PubMed)
  • GeneRIF: The results suggest that an altered expression of Kv3 channels affects the functional properties of FS neurons, and may contribute to the deficits in inhibition observed in the sensory-deprived cortex.
• Control of voltage-gated K+ channel permeability to NMDG+ by a residue at the outer pore.
  Wang, The Journal of general physiology 2009
  • GeneRIF: In the absence of potassium ion, significant N-methyl-D-glucamine (NMDG)-positive currents could be recorded from human embryonic kidney cells expressing Kv3.1 or Kv3.2b channels and Kv1.5 Arg487Tyr/Val, but not wild-type channels.
• Gating currents from a Kv3 subfamily potassium channel: charge movement and modification by BDS-II toxin.
  Wang, The Journal of physiology 2007
  • GeneRIF: data provide the first description of Kv3 gating currents and give further insight into the interaction of BDS toxins and Kv3 channels
• Differential expression of Kv3.1b and Kv3.2 potassium channel subunits in interneurons of the basolateral amygdala.
  McDonald, Neuroscience 2006 (PubMed)
  • GeneRIF: The significance of Kv3.2 expression in some parvalbumin+ and somatostatin+ interneurons in the amygdala is not determined
• High-threshold, Kv3-like potassium currents in magnocellular neurosecretory neurons and their role in spike repolarization.
  Shevchenko, Journal of neurophysiology 2004 (PubMed)
  • GeneRIF: Kv3-like currents may be important for maintaining spike width and calcium influx within acceptable limits during repetitive firing.
• Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau.
  Bobik, Brain research 2004 (PubMed)
  • GeneRIF: strong, selective localization of Kv3.2 to basket cell axons of cerebellum.

XP_006513757 potassium voltage-gated channel subfamily C member 2 isoform X4 from Mus musculus
34% identity, 60% coverage

• Brain expression of Kv3 subunits during development, adulthood and aging and in a murine model of Alzheimer's disease.
  Boda, Journal of molecular neuroscience : MN 2012 (PubMed)
  • GeneRIF: Although all Kv3 transcripts were significantly expressed in embryonic age in whole brain extracts, only Kv3.1, Kv3.2 and Kv3.4 subunit proteins aree present, suggesting a novel role for Kv3 channels at this developmental stage.
• Fast delayed rectifier potassium current: critical for input and output of the circadian system.
  Kudo, The Journal of neuroscience : the official journal of the Society for Neuroscience 2011
  • GeneRIF: Mice lacking both Kcnc1 and Kcnc2 genes fail to express the Kv3.1 and Kv3.2 channels in in the suprachiasmatic nucleus.
• Differential regulation of action potential firing in adult murine thalamocortical neurons by Kv3.2, Kv1, and SK potassium and N-type calcium channels.
  Kasten, The Journal of physiology 2007
  • GeneRIF: Kv3.2, Kv1, SK potassium and N-type calcium channels strongly regulate thalamic relay neuron sensory transmission and that each channel subtype controls a different stimulus-response curve property.
• Developmental changes in the expression of calbindin and potassium-channel subunits Kv3.1b and Kv3.2 in mouse Renshaw cells.
  Song, Neuroscience 2006 (PubMed)
  • GeneRIF: Kv3.2 expression became detectable in the lumbar cord from postnatal day 12, and increased steadily until reaching an adult level at postnatal day 28. In contrast to the Kv3.1b results, Kv3.2 was not expressed in Renshaw cells.
• A unique role for Kv3 voltage-gated potassium channels in starburst amacrine cell signaling in mouse retina.
  Ozaita, The Journal of neuroscience : the official journal of the Society for Neuroscience 2004
  • GeneRIF: Starburst amacrine cells have large outward currents which are mediated in part by the Kv3.2 channel.
• Developmental expression of potassium-channel subunit Kv3.2 within subpopulations of mouse hippocampal inhibitory interneurons.
  Tansey, Hippocampus 2002 (PubMed)
  • GeneRIF: Developmental expression of potassium-channel subunit Kv3.2 within subpopulations of mouse hippocampal inhibitory interneurons.

XP_540095 potassium voltage-gated channel subfamily S member 3 from Canis lupus familiaris
35% identity, 58% coverage

• CNS Schwann cells display oligodendrocyte precursor-like potassium channel activation and antigenic expression in vitro.
  Kegler, Journal of neural transmission (Vienna, Austria : 1996) 2014 (PubMed)
  • GeneRIF: This study demonistrated that Kcns3 expression in schwamnn cell in CNS and scitae nerve of dog.

KCA10_MOUSE / B2RQA1 Potassium voltage-gated channel subfamily A member 10; Voltage-gated potassium channel subunit Kv1.8 from Mus musculus (Mouse) (see 2 papers)
NP_001074609 potassium voltage-gated channel subfamily A member 10 from Mus musculus
36% identity, 60% coverage

• function: Voltage-gated potassium ion channel that mediates K(+) permeability of excitable membranes. When opened in response to the voltage difference across the membrane, KCNA10 channel selectively allows the flow of potassium ions across the membrane down their electrochemical gradient.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Interacts with KCN4B/POMP. Interaction with KCN4B/POMP is necessary for the modulation of channel activity by cAMP.
  disruption phenotype: Viable with no gross defects. Vestibular evoked potentials (VsEPs) are highly abnormal suggesting impaired function of the balance organ, although mice do not display any obvious imbalance behaviors.
• A null mutation of mouse Kcna10 causes significant vestibular and mild hearing dysfunction.
  Lee, Hearing research 2013
  • GeneRIF: Kcna10 is expressed primarily in hair cells of the inner ear and null mutations cause significant vestibular/mild hearing dysfunction.
• Specific expression of Kcna10, Pxn and Odf2 in the organ of Corti.
  Carlisle, Gene expression patterns : GEP
  • GeneRIF: Kcna10 is most strikingly expressed in the hair cells in late embryonic stage however, at adult stages, however, Kcna10 expression is no longer specific to hair cells.

KCNSK_CAEEL / Q8I4B0 Potassium voltage-gated channel protein shk-1 from Caenorhabditis elegans (see 3 papers)
TC 1.A.1.2.20 / Q8I4B0 Shaker K+ channel, Shk-1, Shk1, Kv1 of 536 aas and 6 TMSs from Caenorhabditis elegans
37% identity, 58% coverage

• function: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Has an important role in repolarization and in regulating the pattern of action potential firing. Isoform a expresses currents in a more depolarized voltage range than isoform d.
  disruption phenotype: Delayed spike repolarization.
• substrates: K+
  tcdb comment: Mediates the voltage-dependent potassium ion permeability of excitable membranes. Has an important role in repolarization and in regulating the pattern of action potential firing. Isoform a expresses currents in a more depolarized voltage range than isoform d (Liu et al. 2011)

NP_001178642 potassium voltage-gated channel subfamily A member 10 from Rattus norvegicus
36% identity, 60% coverage

• Expression of KCNA10, a voltage-gated K channel, in glomerular endothelium and at the apical membrane of the renal proximal tubule.
  Yao, Journal of the American Society of Nephrology : JASN 2002 (PubMed)
  • GeneRIF: KCNA10 protein was easily detectable at the apical membrane of rat proximal tubular cells, and a weaker signal was also evident in the glomerulus.

Q7TSH7 Voltage-gated potassium channel regulatory subunit KCNF1 from Mus musculus
34% identity, 61% coverage

• Tandem mass tag-based quantitative proteomic analysis of effects of multiple sevoflurane exposures on the cerebral cortex of neonatal and adult mice.
  Feng, Frontiers in neurology 2022
• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...N-term T154 C-term S548 S548 C-term S552 S552 Kv4.3/KCND3 W: Q9Z0V1 N-term S153 Kv5.1/KCNF1 W: Q7TSH7 C-term S444 C-term S470 C-term S472 Kv7.2/KCNQ2 W: NP_034741 Tr: NP_034741 M: NP_034741 T: NP_034741 N-term S52 C-term S352 S352 C-term S457 C-term T462 C-term S466 S466 C-term S468 S468...”

TC 1.A.1.2.18 / Q9H3M0 Potassium voltage-gated channel subfamily F member 1 (Voltage-gated potassium channel subunit Kv5.1) (kH1) from Homo sapiens (see 4 papers)
NP_002227 voltage-gated potassium channel regulatory subunit KCNF1 from Homo sapiens
34% identity, 61% coverage

• substrates: K+
• Electrically silent KvS subunits associate with native Kv2 channels in brain and impact diverse properties of channel function.
  Ferns, bioRxiv : the preprint server for biology 2024
  • “...recombinant fragment corresponding to the C-terminal 76 amino acids (a.a. 419-494) of human Kv5.1 (Uniprot Q9H3M0) produced in E. coli (Genscript, Piscataway, NJ). This C-terminal sequence is unrelated to the C-termini of Kv2.1 and Kv2.2 and is also highly divergent between KvS family members. Rabbit antisera...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 6.1 K v 6.2 K v 6.3 K v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt...”
• Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1.
  Ryaboshapkina, Molecular & cellular proteomics : MCP 2022
  • “...P01859 IGHG2 127 O43598 DNPH1 28 P10599 TXN 78 P01034 CST3 128 Q00688 FKBP3 29 Q9H3M0 KCNF1 79 P63261 ACTG1 129 Q99729 HNRNPAB 30 P20674 COX5A 80 P23526 AHCY 130 P16401 H1-5 31 P07737 PFN1 81 P35030 PRSS3 131 P31946 YWHAB 32 P62318 SNRPD3 82 Q9H299...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 6.1 K v 6.2 K v 6.3 K v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 6.3 K v 6.4 HGNC, UniProt KCND2 , Q9NZV8 KCND3 , Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A K A Nomenclature K v 7.1...”
• KCNF1 promotes lung cancer by modulating ITGB4 expression.
  Chen, Cancer gene therapy 2023
  • GeneRIF: KCNF1 promotes lung cancer by modulating ITGB4 expression.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v 7.2 (NP_742105), K v 7.3 (NP_004510), K v...”

KCNF1_RAT / D4ADX7 Voltage-gated potassium channel regulatory subunit KCNF1; Potassium voltage-gated channel subfamily F member 1; Voltage-gated potassium channel subunit Kv5.1 from Rattus norvegicus (Rat) (see 3 papers)
34% identity, 61% coverage

• function: Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1 or KCNB2, can modulate their expression and their gating kinetics by acting on deactivation upon repolarization and inactivation during maintained depolarization (PubMed:9305895, PubMed:9696692). Accelerates inactivation but has relatively little effect on deactivation (PubMed:9696692). Coexpression with KCNB1 or KCNB2 markedly slows inactivation (PubMed:9305895). Each modulatory subunit has its own specific properties of regulation, and can lead to extensive inhibitions, to large changes in kinetics, and/or to large shifts in the voltage dependencies of the inactivation process (PubMed:9305895). The gating kinetics depends on the nature and stoichiometry of the associated regulatory sunbunit (PubMed:9305895, PubMed:9696692). Fails to produce a potassium current when expressed alone (PubMed:9305895).
  subunit: Heterotetramer with KCNB1 or KCNB2.

KCA10_HUMAN / Q16322 Potassium voltage-gated channel subfamily A member 10; Voltage-gated potassium channel subunit Kv1.8 from Homo sapiens (Human) (see 3 papers)
NP_005540 potassium voltage-gated channel subfamily A member 10 from Homo sapiens
35% identity, 65% coverage

• function: Voltage-gated potassium ion channel that mediates K(+) permeability of excitable membranes. When opened in response to the voltage difference across the membrane, KCNA10 channel selectively allows the flow of potassium ions across the membrane down their electrochemical gradient.
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Interacts with KCN4B/POMP. Interaction with KCN4B/POMP is necessary for the modulation of channel activity by cAMP.
• Proteome-Wide Genetic Investigation of Large Artery Stiffness.
  Dib, JACC. Basic to translational science 2024
  • “...brain cell damage following ischemic stroke; increased expression of TREM2 is associated with Parkinsons disease. Q16322 KCNA10 Potassium voltage-gated channel subfamily A member-10 A potassium gated channel that potentially mediates proximal tubule sodium reabsorption and vascular tone in the kidneys and the cardiac action potential; SNPs...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 3.1 K v 3.2 K v 3.3 K v 3.4 HGNC, UniProt KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1,...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 1.8 HGNC, UniProt KCNA5 , P22460 KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v 1 and K v 2 K v 1 and K v 2...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 2.1 K v 2.2 HGNC, UniProt KCNA6 , P17658 KCNA7 , Q96RP8 KCNA10 , Q16322 KCNB1 , Q14721 KCNB2 , Q92953 Associated subunits K v 1 and K v 2 K v 1 and K v 2 K v 1 and K v 2 K...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNA1, Q09470; KCNA2, P16389; KCNA3, P22001; KCNA4, P22459; KCNA5, P22460; KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259;...”
• Association of Single Nucleotide Polymorphisms in KCNA10 and SLC13A3 Genes with the Susceptibility to Chronic Kidney Disease of Unknown Etiology in Central Indian Patients.
  Kumari, Biochemical genetics 2023 (PubMed)
  • GeneRIF: Association of Single Nucleotide Polymorphisms in KCNA10 and SLC13A3 Genes with the Susceptibility to Chronic Kidney Disease of Unknown Etiology in Central Indian Patients.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 1.5 (NP_002225), K v 1.6 (NP_002226), K v 1.7 (NP_114092), K v 1.8 (NP_005540); K v 2.1 (NP_004966), K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v...”
• Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
  Bailey, Diabetes care 2010
  • GeneRIF: Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
• Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
  Talmud, American journal of human genetics 2009
  • GeneRIF: Observational study of gene-disease association. (HuGE Navigator)
• A-to-I RNA editing alters less-conserved residues of highly conserved coding regions: implications for dual functions in evolution
  Yang, RNA (New York, N.Y.) 2008
  • “...BAF82750; NP_002223; NP_002224; NP_002225; NP_114092; NP_005540); Gga: Gallus gallus (XP_425660; NP_989794; NP_001025549; XP_417226; NP_989793); Dre: D....”
• Expression of KCNA10, a voltage-gated K channel, in glomerular endothelium and at the apical membrane of the renal proximal tubule.
  Yao, Journal of the American Society of Nephrology : JASN 2002 (PubMed)
  • GeneRIF: KCNA10 in human proximal tubular cells, glomerular and vascular endothelial cells, and also in vascular smooth muscle cells.

5wieH / P63142 Crystal structure of a kv1.2-2.1 chimera k+ channel v406w mutant in an inactivated state (see paper)
36% identity, 58% coverage

• Ligand: (1r)-2-{[(s)-{[(2s)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl(9z)-octadec-9-enoate (5wieH)

KCNG1_HUMAN / Q9UIX4 Voltage-gated potassium channel regulatory subunit KCNG1; Potassium voltage-gated channel subfamily G member 1; Voltage-gated potassium channel subunit Kv6.1; kH2 from Homo sapiens (Human) (see 2 papers)
NP_002228 potassium voltage-gated channel subfamily G member 1 from Homo sapiens
34% identity, 60% coverage

• function: Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1 or KCNB2, can modulate their expression and their gating kinetics by acting on deactivation upon repolarization and inactivation during maintained depolarization (PubMed:19074135). Potassium channel subunit that does not form functional channels by itself (PubMed:19074135).
  subunit: Heterotetramer with KCNB1 (Probable). Heterotetramer with KCNB2 (By similarity).
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 6.2 K v 6.3 K v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787...”
• KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf
  Jacinto, Genes 2021
  • “...KCNG1 the Uniprot database ( https://www.uniprot.org/ ; accessed on 17 July 2021) with accession number Q9UIX4 was used. 3. Results 3.1. Clinical Phenotype On clinical examination at the time of admission, the calf was bright and alert but with generalized muscle stiffness that prevented it from...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 6.2 K v 6.3 K v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 6.4 HGNC, UniProt KCND2 , Q9NZV8 KCND3 , Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A K A Nomenclature K v 7.1 K v 7.2...”
• Integrated protein array screening and high throughput validation of 70 novel neural calmodulin-binding proteins.
  O'Connell, Molecular & cellular proteomics : MCP 2010
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v 7.2 (NP_742105), K v 7.3 (NP_004510), K v 7.4 (NP_004691), K v...”

Q86Y85 Potassium voltage-gated channel, subfamily G, member 1 from Homo sapiens
34% identity, 60% coverage

• Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum
  Gao, Cancer biology & medicine 2015
  • “...(Fragment) OS=Homo sapiens GN=CAD PE=2 SV=2 - [Q96CK3_HUMAN] 0.82 3 1 1 851 93.4 7.66 Q86Y85 Potassium voltage-gated channel, subfamily G, member 1 OS=Homo sapiens GN=KCNG1 PE=2 SV=1 - [Q86Y85_HUMAN] 4.09 2 1 1 513 57.8 6.46 Q9UFB4 Putative uncharacterized protein DKFZp434B1917 (Fragment) OS=Homo sapiens GN=DKFZp434B1917...”

KCNG1_RAT / D4AD53 Voltage-gated potassium channel regulatory subunit KCNG1; Potassium voltage-gated channel subfamily G member 1; Voltage-gated potassium channel subunit Kv6.1 from Rattus norvegicus (Rat) (see 3 papers)
33% identity, 63% coverage

• function: Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1 or KCNB2, can modulate their expression and their gating kinetics by acting on deactivation upon repolarization and inactivation during maintained depolarization (PubMed:8980147, PubMed:9305895, PubMed:9696692). Potassium channel subunit that does not form functional channels by itself (PubMed:8980147, PubMed:9305895).
  subunit: Heterotetramer with KCNB1 or KCNB2.

KCNS2_RAT / Q9ER26 Delayed-rectifier potassium channel regulatory subunit KCNS2; Delayed-rectifier K(+) channel alpha subunit 2; Delayed-rectifier potassium channel subunit Kv9.2; Potassium voltage-gated channel subfamily S member 2 from Rattus norvegicus (Rat) (see paper)
34% identity, 58% coverage

• function: Potassium channel regulatory subunit that modulate the delayed rectifier voltage-gated potassium channel activity of KCNB1 and KCNB2 by altering their kinetics, expression levels, and shifting the half-inactivation potential to more polarized values. While it does not form functional channels on its own, it can form functional heterotetrameric channels with KCNB1 and KCNB2. Each regulatory subunit has unique regulatory properties that can lead to extensive inhibition, significant changes in kinetics, and/or substantial shifts in the voltage dependencies of the inactivation process.
  subunit: Heterotetramer with KCNB1 and KCNB2. Does not form homomultimers.

KCNS2_MOUSE / O35174 Delayed-rectifier potassium channel regulatory subunit KCNS2; Delayed-rectifier K(+) channel alpha subunit 2; Delayed-rectifier potassium channel subunit Kv9.2; Potassium voltage-gated channel subfamily S member 2 from Mus musculus (Mouse) (see paper)
34% identity, 58% coverage

• function: Potassium channel regulatory subunit that modulate the delayed rectifier voltage-gated potassium channel activity of KCNB1 and KCNB2 by altering their kinetics, expression levels, and shifting the half-inactivation potential to more polarized values (PubMed:9305895). While it does not form functional channels on its own, it can form functional heterotetrameric channels with KCNB1 and KCNB2 (PubMed:9305895). Each regulatory subunit has unique regulatory properties that can lead to extensive inhibition, significant changes in kinetics, and/or substantial shifts in the voltage dependencies of the inactivation process (PubMed:9305895).
  subunit: Heterotetramer with KCNB1 and KCNB2 (Probable). Does not form homomultimers (Probable).

TC 1.A.1.2.16 / Q9ULS6 Potassium voltage-gated channel subfamily S member 2 (Delayed-rectifier K(+) channel alpha subunit 2) (Voltage-gated potassium channel subunit Kv9.2) from Homo sapiens (see 3 papers)
NP_065748 potassium voltage-gated channel subfamily S member 2 from Homo sapiens
34% identity, 58% coverage

• substrates: K+
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 8.1 (NP_055194), K v 8.2 (NP_598004); K v 9.1 (NP_002242), K v 9.2 (NP_065748), K v 9.3 (NP_002243); K v 10.1 (NP_758872) K v 10.2 (NP_647479); K v 11.1 (NP_000229), K v 11.2 (NP_110416), K v 11.3 (NP_150375); K v 12.1 (NP_653234), K v...”
• A Drosophila Model of Essential Tremor.
  Smith, Scientific reports 2018
  • GeneRIF: KCNS2 mutation is associated with Essential Tremor.
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v 12.3 HGNC, UniProt...”
• Proteomic Analysis of Aqueous Humor Proteins in Association with Cataract Risks: Diabetes and Smoking.
  Chang, Journal of clinical medicine 2021
  • “...D Q15149 Plectin P02649 Apolipoprotein E P0CG47 Polyubiquitin-B P54253 Ataxin-1 P0CG48 Polyubiquitin-C P02749 Beta-2-glycoprotein 1 Q9ULS6 Potassium voltage-gated channel subfamily S member 2 P61769 Beta-2-microglobulin O94913 Pre-mRNA cleavage complex 2 protein Pcf11 P05813 Beta-crystallin A3 Q13395 Probable methyltransferase TARBP1 P53674 Beta-crystallin B1 A0A075B6H7 Probable non-functional immunoglobulin...”
  • “...7.11 P0CG47 Polyubiquitin-B 1.54 1.41 0.10 0.33 0.06 P0CG48 Polyubiquitin-C 1.54 1.41 0.10 0.33 0.06 Q9ULS6 Potassium voltage-gated channel subfamily S member 2 0.11 0.32 0.65 0.75 5.91 P62979 Ubiquitin-40S ribosomal protein S27a 1.54 1.41 0.10 0.33 0.06 P62987 Ubiquitin-60S ribosomal protein L40 1.54 1.41 0.10...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v 12.3 HGNC, UniProt...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v 12.3 HGNC, UniProt...”
• Molecular signatures of sanguinarine in human pancreatic cancer cells: A large scale label-free comparative proteomics approach.
  Singh, Oncotarget 2015
  • “...splicing regulatory protein 1 66,390 2 2 7 3 10 4.19% 5.74% 1.80E-02 0.529 36 Q9ULS6 KCNS2 Potassium voltage_gated channel subfamily S member 2 54,237 2 2 14 3 21 6.65% 8.31% 1.51E-02 0.477 37 O95760 IL33 Interleukin_33 30,759 2 1 2 2 3 6.64% 7.18%...”

A2BDX4 Voltage-gated potassium channel regulatory subunit KCNG1 from Mus musculus
34% identity, 58% coverage

• ITRAQ-based quantitative proteomic analysis of processed Euphorbia lathyris L. for reducing the intestinal toxicity.
  Zhang, Proteome science 2018
  • “...SE EFL 1 SEP Up-regulated Q62010 Oviduct-specific glycoprotein Ovgp1 Chit5 Ogp 1 0.4252 0.451 0.5825 A2BDX4 Potassium voltage-gated channel subfamily G member 1 Kcng1 1 0.4347 0.856 0.6645 P97816 Protein S100-G S100g Calb3 S100d 1 0.4485 0.599 0.653 Q8BV14 Ankyrin repeat domain-containing protein 55 Ankrd55 1...”

KCNV1_MESAU / Q60565 Potassium voltage-gated channel subfamily V member 1; Voltage-gated potassium channel subunit Kv8.1 from Mesocricetus auratus (Golden hamster) (see paper)
32% identity, 63% coverage

• function: Potassium channel subunit that does not form functional channels by itself. Modulates KCNB1 and KCNB2 channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. Can down-regulate the channel activity of KCNB1, KCNB2, KCNC4 and KCND1, possibly by trapping them in intracellular membranes (By similarity).
  subunit: Heteromultimer with KCNB1 and KCNB2. Interacts with KCNC4 and KCND1 (By similarity).

KCNV1_HUMAN / Q6PIU1 Potassium voltage-gated channel subfamily V member 1; Neuronal potassium channel alpha subunit HNKA; Voltage-gated potassium channel subunit Kv8.1 from Homo sapiens (Human) (see 3 papers)
NP_055194 potassium voltage-gated channel subfamily V member 1 from Homo sapiens
32% identity, 63% coverage

• function: Potassium channel subunit that does not form functional channels by itself. Modulates KCNB1 and KCNB2 channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. Can down-regulate the channel activity of KCNB1, KCNB2, KCNC4 and KCND1, possibly by trapping them in intracellular membranes.
  subunit: Heteromultimer with KCNB1 and KCNB2. Interacts with KCNC4 and KCND1.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 7.3 (NP_004510), K v 7.4 (NP_004691), K v 7.5 (NP_062816), K v 8.1 (NP_055194), K v 8.2 (NP_598004); K v 9.1 (NP_002242), K v 9.2 (NP_065748), K v 9.3 (NP_002243); K v 10.1 (NP_758872) K v 10.2 (NP_647479); K v 11.1 (NP_000229), K v...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 9.2 K v 9.3 K v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v...”
• Abstracts from the 52nd European Society of Human Genetics (ESHG) Conference: Posters
  , European journal of human genetics : EJHG 2019
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 9.2 K v 9.3 K v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v...”
• Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.
  Garrido-Urbani, FEBS letters 2016
  • “...underlined when applicable Peptide Motif Total count Gene Uniprot Comment/Reference GGDDFWF 2 30 205 KCNV1 Q6PIU1 SKKEWYV 2 15 632 PVRL1 Q15223 AALNGPV 4 765 PPP6R2 O75170 33 SRREWYV 2 300 PVRL3 Q9NQS3 IRDFLRW 2 252 GAL3ST1 Q99999 L YAA DKH cryptic 213 OTUB2 Q96DC9 EEEPMNL...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 9.2 K v 9.3 K v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v...”

KCNV1_RAT / P97557 Potassium voltage-gated channel subfamily V member 1; Voltage-gated potassium channel subunit Kv2.3r; Voltage-gated potassium channel subunit Kv8.1 from Rattus norvegicus (Rat) (see paper)
TC 1.A.1.2.9 / P97557 Brain-specific regulatory α-chain homologue that coassembles with other α-subunits to form active heteromultimeric K+ channels of unique kinetic properties, Kv2.3r. The functional expression of this regulatory α-subunit represents a novel mechanism without precedents in voltage-gated channels, which contributes to the functional diversity of K+ channels (Castellano et al., 1997). Beta subunits regulate the response of human Kv4.3 to protein kinae C phosphorylation and provide a potential mechanism for modifying the response of ion conductance to alpha-adrenergic regulation in vivo from Rattus norvegicus (Rat) (see paper)
32% identity, 63% coverage

• function: Potassium channel subunit that does not form functional channels by itself. Modulates KCNB1 and KCNB2 channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. Can down-regulate the channel activity of KCNB1, KCNB2, KCNC4 and KCND1, possibly by trapping them in intracellular membranes (By similarity).
  subunit: Heteromultimer with KCNB1 and KCNB2. Interacts with KCNC4 and KCND1 (By similarity).
• substrates: K+

XP_009301775 potassium voltage-gated channel subfamily G member 4 from Danio rerio
33% identity, 60% coverage

• Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development.
  Jędrychowska, Developmental biology 2024 (PubMed)
  • GeneRIF: Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development.
• Functional antagonism of voltage-gated K+ channel α-subunits in the developing brain ventricular system.
  Shen, Development (Cambridge, England) 2016 (PubMed)
  • GeneRIF: Mutation of kcnb1 reduces the size of the ventricular system and its gain of function causes hydrocephalus, which is opposite to the function of Kcng4b. This demonstrates the dynamic interplay between potassium channel subunits in the neuroepithelium as a novel and crucial regulator of ventricular development in the vertebrate brain.

KCNG4_HUMAN / Q8TDN1 Voltage-gated potassium channel regulatory subunit KCNG4; Potassium voltage-gated channel subfamily G member 4; Voltage-gated potassium channel subunit Kv6.3; Voltage-gated potassium channel subunit Kv6.4 from Homo sapiens (Human) (see 2 papers)
NP_758857 potassium voltage-gated channel subfamily G member 4 from Homo sapiens
30% identity, 61% coverage

• function: Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the time course of activation, deactivation and inactivation and on the voltage-dependence of activation (PubMed:12060745, PubMed:19074135). Potassium channel subunit that does not form functional channels by itself (Probable) (PubMed:12060745). Reduces the deactivation rate (PubMed:12060745, PubMed:19074135). Modulates the threshold for activation by shifting by approximately 20 mV in hyperpolarizing direction (PubMed:12060745). Markedly changes the inactivation by shifting the voltage dependence of inactivation by approximately 40 mV in hyperpolarizing direction (PubMed:12060745). Acceleratee activation and enhances the time course of activation (PubMed:12060745).
  subunit: Heterotetramer with KCNB1 (PubMed:12060745, PubMed:19074135). Does not form homomultimer (PubMed:12060745).
• KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.
  Lacroix, International journal of molecular sciences 2024
  • GeneRIF: KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.
• Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit.
  Lee, Cell reports 2020
  • GeneRIF: Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v 7.2 (NP_742105), K v 7.3 (NP_004510), K v 7.4 (NP_004691), K v 7.5 (NP_062816), K v 8.1 (NP_055194), K v 8.2 (NP_598004); K v...”
• Auxiliary KCNE subunits modulate both homotetrameric Kv2.1 and heterotetrameric Kv2.1/Kv6.4 channels.
  David, Scientific reports 2015
  • GeneRIF: KCNE5 subunits may affect Kv2.1 homotetramers and Kv2.1/Kv6.4 heterotetramers in vivo, resulting in more tissue-specific fine-tuning mechanisms.
• Modulation of Closed-State Inactivation in Kv2.1/Kv6.4 Heterotetramers as Mechanism for 4-AP Induced Potentiation.
  Stas, PloS one 2015
  • GeneRIF: KvS subunits modify the pharmacological response of Kv2 subunits when assembled in heterotetramers and illustrate the potential of KvS subunits to provide unique properties to the heterotetramers, as is the case for 4-AP on Kv2.1/Kv6.4 channels.
• Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
  Mederos, The Journal of biological chemistry 2009 (PubMed)
  • GeneRIF: Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
• Domain analysis of Kv6.3, an electrically silent channel.
  Ottschytsch, The Journal of physiology 2005
  • GeneRIF: This study suggests that the silent behaviour of Kv6.3 is largely caused by the C-terminal part of its sixth transmembrane domain that causes ER retention of the subunit.
• Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.
  Ottschytsch, Proceedings of the National Academy of Sciences of the United States of America 2002
  • GeneRIF: Obligatory heterotetramerization of three previously uncharacterized Kv channel subunits identified in human genome (Kv6.3)(Kv10.1) (Kv11.1)
• More
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787 KCNQ2 , O43526 KCNQ3 , O43525 KCNQ4 , P56696...”
• Valproic Acid Promotes Early Neural Differentiation in Adult Mesenchymal Stem Cells Through Protein Signalling Pathways.
  Santos, Cells 2020
  • “...member 1 KCNB1 Q14721 95,881.40 14.40% GO:1900454 Potassium voltage-gated channel subfamily G member 4 KCNG4 Q8TDN1 58,981.00 11.80% GO:0005251 Fibroblast growth factor receptor 3 FGFR3 P22607-2 877,100.00 6.20% GO:0043410...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787 KCNQ2 , O43526 KCNQ3 , O43525 KCNQ4 , P56696...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A K A Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5...”
• Proteomics approaches for identification of tumor relevant protein targets in pulmonary squamous cell carcinoma by 2D-DIGE-MS.
  Lihong, PloS one 2014
  • “...0.067 5.46 P05787.7 Keratin, type II cytoskeletal 8 56 KRT8 60/4.8 53671/5.52 45 0.018 16.32 Q8TDN1 Potassium voltage-gated channel subfamily G member 4 58 KCNG4 60/5.1 59797/6.23 46 0.021 14.23 P05787 Keratin, type II cytoskeletal 8 134 KRT8 60/5.2 53671/5.52 Q6NVY7 Inositol monophosphatase 3 56 IMPAD1...”

KCNS1_HUMAN / Q96KK3 Delayed-rectifier potassium channel regulatory subunit KCNS1; Delayed-rectifier K(+) channel alpha subunit 1; Delayed-rectifier potassium channel subunit Kv9.1; hKv9.1; Potassium voltage-gated channel modifier subfamily S member 1 from Homo sapiens (Human) (see paper)
TC 1.A.1.2.7 / Q96KK3 Electrically silent lens epithelium K+ channel (Delayed rectifier K+ channel α-subunit, Kv9.1 (Shepard & Rae, 1999)) from Homo sapiens (Human) (see 3 papers)
KCNS1 / GI|13450882 potassium voltage-gated channel subfamily S member 1 from Homo sapiens
NP_001309728 potassium voltage-gated channel subfamily S member 1 from Homo sapiens
NP_002242 potassium voltage-gated channel subfamily S member 1 from Homo sapiens
30% identity, 58% coverage

• function: Potassium channel regulatory subunit that modulate the delayed rectifier voltage-gated potassium channel activity of KCNB1 and KCNB2 by altering their kinetics, expression levels, and shifting the half-inactivation potential to more polarized values (PubMed:10484328). While it does not form functional channels on its own, it can form functional heterotetrameric channels with KCNB1 and KCNB2 (PubMed:10484328). Each regulatory subunit has unique regulatory properties that can lead to extensive inhibition, significant changes in kinetics, and/or substantial shifts in the voltage dependencies of the inactivation process (By similarity).
  subunit: Heterotetramer with KCNB1 (Probable). Heterotetramer with KCNB2 (By similarity). Does not form homomultimers (Probable).
• substrates: K+
• Biopsychosocial influence on exercise-induced injury: genetic and psychological combinations are predictive of shoulder pain phenotypes.
  George, The journal of pain 2014
  • GeneRIF: There was moderate statistical evidence for interactions shoulder pain phenotypes between KCNS1 and depressive symptoms, pain catastrophizing, or kinesiophobia
• KCNS1, but not GCH1, is associated with pain intensity in a black southern African population with HIV-associated sensory neuropathy: a genetic association study.
  Hendry, Journal of acquired immune deficiency syndromes (1999) 2013 (PubMed)
  • GeneRIF: Several haplotypes of population-specific tagSNPs correlated with pain intensity in black southern African population with HIV-associated sensory neuropathy.
• Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1.
  Costigan, Brain : a journal of neurology 2010
  • GeneRIF: Thia study presented the KCNS1 allele rs734784 as one of the first prognostic indicators of chronic pain risk.
  • GeneRIF: Observational study of gene-disease association. (HuGE Navigator)
• Variations in potassium channel genes are associated with breast pain in women prior to breast cancer surgery.
  Langford, Journal of neurogenetics
  • GeneRIF: For KCNS1 rs4499491, individuals homozygous for the rare A allele (CC+ CA versus AA) had a 3.0-fold increase in the odds of reporting preoperative breast pain.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 7.5 (NP_062816), K v 8.1 (NP_055194), K v 8.2 (NP_598004); K v 9.1 (NP_002242), K v 9.2 (NP_065748), K v 9.3 (NP_002243); K v 10.1 (NP_758872) K v 10.2 (NP_647479); K v 11.1 (NP_000229), K v 11.2 (NP_110416), K v 11.3 (NP_150375); K v...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v...”
• Abstracts from the 52nd European Society of Human Genetics (ESHG) Conference: Posters
  , European journal of human genetics : EJHG 2019
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v...”
• Quantitative proteomic analysis for high-throughput screening of differential glycoproteins in hepatocellular carcinoma serum
  Gao, Cancer biology & medicine 2015
  • “...1 OS=Homo sapiens GN=NKIRAS1 PE=1 SV=1 - [KBRS1_HUMAN] 4.69 1 1 1 192 21.6 6.35 Q96KK3 Potassium voltage-gated channel subfamily S member 1 OS=Homo sapiens GN=KCNS1 PE=2 SV=2 - [KCNS1_HUMAN] 2.85 1 1 1 526 58.3 7.15 Q9BYZ2 L-lactate dehydrogenase A-like 6B OS=Homo sapiens GN=LDHAL6B PE=1...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v 12.2 K v...”
• Quantitative gingival crevicular fluid proteome in health and periodontal disease using stable isotope chemistries and mass spectrometry
  Carneiro, Journal of clinical periodontology 2014
  • “...receptor 11H1 1.08 0.26 SNS 3 2 S P13796 Plastin-2 1.37 0.34 SNS 4 2 Q96KK3 Potassium voltage-gated channel subfamily S member 0.73 0.22 SNS 3 2 S P07737 Profilin-1 0.92 0.24 SNS 7 3 Q658L4 Putative uncharacterized protein DKFZp666E157 1.13 0.17 SNS 3 2 Q5VUG0...”

NP_001023792 BTB domain-containing protein from Caenorhabditis elegans
35% identity, 50% coverage

• CCA-1, EGL-19 and EXP-2 currents shape action potentials in the Caenorhabditis elegans pharynx.
  Shtonda, The Journal of experimental biology 2005
  • GeneRIF: Our results suggest that EXP-2 is a potassium channel with unusual properties that uses a hyperpolarization threshold to activate a regenerative hyperpolarizing current.

L8IEN6 Potassium voltage-gated channel subfamily B member 1 (Fragment) from Bos mutus
44% identity, 31% coverage

• Comparative Analysis of Erythrocyte Proteomes of Water Buffalo, Dairy Cattle, and Beef Cattle by Shotgun LC-MS/MS
  Guo, Frontiers in veterinary science 2019
  • “...N-methyltransferase 5 1 1 72627.87 5.88 L8IC80 Stress-70 protein, mitochondrial (Fragment) 2 2 73930.94 5.97 L8IEN6 Potassium voltage-gated channel subfamily B member 1 (Fragment) 1 1 74156.15 8.88 L8HYQ4 Coiled-coil domain-containing protein 162 (Fragment) 1 1 75200.66 8.69 L8ILT2 Erythrocyte membrane protein band 4.2 (Fragment) 14...”

Q8CFS6 Potassium voltage-gated channel subfamily V member 2 from Mus musculus
29% identity, 56% coverage

• The proteome of mouse cerebral arteries
  Badhwar, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2014 (secret)

KCNV2_HUMAN / Q8TDN2 Potassium voltage-gated channel subfamily V member 2; Voltage-gated potassium channel subunit Kv8.2 from Homo sapiens (Human) (see 3 papers)
NP_598004 potassium voltage-gated channel subfamily V member 2 from Homo sapiens
31% identity, 58% coverage

• function: Potassium channel subunit. Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values
  subunit: Heteromultimer with KCNB1, KCNC1 and KCNF1. Does not form homomultimers.
• KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.
  de, The British journal of ophthalmology 2024
  • GeneRIF: KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3.
• Initial diagnoses of patients found to be homozygous for a KCNV2 founder mutation on the Arabian Peninsula (c.427G>T; p.Glu143*).
  Khan, Ophthalmic genetics 2023 (PubMed)
  • GeneRIF: Initial diagnoses of patients found to be homozygous for a KCNV2 founder mutation on the Arabian Peninsula (c.427G>T; p.Glu143*).
• Cone dystrophy with supernormal rod responses: A rare KCNV2 gene variant.
  Esteves-Leandro, European journal of ophthalmology 2022 (PubMed)
  • GeneRIF: Cone dystrophy with supernormal rod responses: A rare KCNV2 gene variant.
• KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.
  Georgiou, American journal of ophthalmology 2021
  • GeneRIF: KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1.
• KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints-KCNV2 Study Group Report 2.
  Georgiou, American journal of ophthalmology 2021
  • GeneRIF: KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints-KCNV2 Study Group Report 2.
• A novel KCNV2 mutation in a patient taking hydroxychloroquine associated with cone dystrophy with supernormal rod response.
  Liu, Ophthalmic genetics 2021
  • GeneRIF: A novel KCNV2 mutation in a patient taking hydroxychloroquine associated with cone dystrophy with supernormal rod response.
• Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K+ Channel Subunits Kv8.2 and K2.1.
  Jiang, International journal of molecular sciences 2021
  • GeneRIF: Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K(+) Channel Subunits Kv8.2 and K2.1.
• Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family.
  Liu, Molecular genetics & genomic medicine 2021
  • GeneRIF: Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family.
• More
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 9.3 K v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 9.3 K v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 9.3 K v 10.1 K v 10.2 HGNC, UniProt KCNV1 , Q6PIU1 KCNV2 , Q8TDN2 KCNS1 , Q96KK3 KCNS2 , Q9ULS6 KCNS3 , Q9BQ31 KCNH1 , O95259 KCNH5 , Q8NCM2 Nomenclature K v 11.1 K v 11.2 K v 11.3 K v 12.1 K v...”

XP_011242169 potassium voltage-gated channel subfamily S member 3 isoform X2 from Mus musculus
35% identity, 48% coverage

• Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia.
  Miyamae, Neurobiology of disease 2021
  • GeneRIF: Kcns3 deficiency disrupts Parvalbumin neuron physiology in mouse prefrontal cortex: Implications for the pathophysiology of schizophrenia.

KCNS1_RAT / O88758 Delayed-rectifier potassium channel regulatory subunit KCNS1; Delayed-rectifier K(+) channel alpha subunit 1; Delayed-rectifier potassium channel subunit Kv9.1; Potassium voltage-gated channel modifier subfamily S member 1 from Rattus norvegicus (Rat) (see paper)
XP_017446922 potassium voltage-gated channel subfamily S member 1 isoform X1 from Rattus norvegicus
29% identity, 58% coverage

• function: Potassium channel regulatory subunit that modulate the delayed rectifier voltage-gated potassium channel activity of KCNB1 and KCNB2 by altering their kinetics, expression levels, and shifting the half-inactivation potential to more polarized values. While it does not form functional channels on its own, it can form functional heterotetrameric channels with KCNB1 and KCNB2 (By similarity). Each regulatory subunit has unique regulatory properties that can lead to extensive inhibition, significant changes in kinetics, and/or substantial shifts in the voltage dependencies of the inactivation process (By similarity).
  subunit: Heterotetramer with KCNB1 (By similarity). Heterotetramer with KCNB2 (By similarity). Does not form homomultimers (By similarity).
• Sensory neuron downregulation of the Kv9.1 potassium channel subunit mediates neuropathic pain following nerve injury.
  Tsantoulas, The Journal of neuroscience : the official journal of the Society for Neuroscience 2012
  • GeneRIF: our results demonstrate that Kv9.1 dysfunction leads to spontaneous and evoked neuronal hyperexcitability in myelinated fibers, coupled with development of neuropathic pain behaviors.

KVS4_CAEEL / Q9XXD1 Probable voltage-gated potassium channel subunit kvs-4 from Caenorhabditis elegans (see paper)
30% identity, 58% coverage

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
  subunit: Homotetramer or heterotetramer (Probable). Interacts with unc- 101 (via N-terminus); which targets kvs-4 to dendrites (PubMed:26762178).

NP_001029129 potassium voltage-gated channel subfamily G member 3 isoform 2 from Rattus norvegicus
33% identity, 57% coverage

• Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
  Mederos, The Journal of biological chemistry 2009 (PubMed)
  • GeneRIF: Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.

LOC109320566 potassium voltage-gated channel subfamily V member 2-like from Crocodylus porosus
26% identity, 66% coverage

• Dynamic Changes in Host Gene Expression following In Vitro Viral Mimic Stimulation in Crocodile Cells
  Sarker, Frontiers in immunology 2017
  • “...LOC109311611 Rho-related GTP-binding protein RhoB 2.36 3.81E06 1.01E05 TLL1 Tolloid like 1 2.14 2.06E12 8.84E12 LOC109320566 Potassium voltage-gated channel subfamily V member 2 2.02 4.90E12 2.04E11 LOC109320408 Heat shock protein 30D 1.99 8.49E95 2.44E93 WNT5B Wnt family member 5B 1.98 1.40E214 9.37E213 LMOD1 Leiomodin 1 1.97...”

KCNG3_RAT / Q8R523 Voltage-gated potassium channel regulatory subunit KCNG3; Potassium voltage-gated channel subfamily G member 3; Voltage-gated potassium channel subunit Kv10.1; Voltage-gated potassium channel subunit Kv6.3 from Rattus norvegicus (Rat) (see paper)
TC 1.A.1.2.17 / Q8R523 Potassium voltage-gated channel (KCNH) subfamily G member 3 (Voltage-gated potassium channel subunit Kv10.1) (Voltage-gated potassium channel subunit Kv6.3) from Rattus norvegicus (see paper)
33% identity, 57% coverage

• function: Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the inactivation and deactivation rate. Potassium channel subunit that does not form functional channels by itself. Reduces the deactivation rate. Moderately acceleratee activation.
  subunit: Heterotetramer with KCNB1. Does not form homomultimers.
• substrates: K+
  tcdb comment: Splice variants have different properties and can activate cyclin-dependent protein kinases (Ramos Gomes et al. 2015). Control of transport (pore) function by the voltage sensor may involve more than one mechanism (Tomczak et al. 2017). The silent (non transporting) behaviour of Kv6.3 in the ER is caused by the C-terminal part of its sixth transmembrane domain that causes ER retentio (Ottschytsch et al. 2005)

KCNS1_MOUSE / O35173 Delayed-rectifier potassium channel regulatory subunit KCNS1; Delayed-rectifier K(+) channel alpha subunit 1; Delayed-rectifier potassium channel subunit Kv9.1; Potassium voltage-gated channel modifier subfamily S member 1 from Mus musculus (Mouse) (see paper)
XP_036014685 potassium voltage-gated channel subfamily S member 1 isoform X1 from Mus musculus
28% identity, 63% coverage

• function: Potassium channel regulatory subunit that modulate the delayed rectifier voltage-gated potassium channel activity of KCNB1 and KCNB2 by altering their kinetics, expression levels, and shifting the half-inactivation potential to more polarized values (PubMed:9305895). While it does not form functional channels on its own, it can form functional heterotetrameric channels with KCNB1 and KCNB2 (PubMed:9305895). Each regulatory subunit has unique regulatory properties that can lead to extensive inhibition, significant changes in kinetics, and/or substantial shifts in the voltage dependencies of the inactivation process (PubMed:9305895).
  subunit: Heterotetramer with KCNB1 and KCNB2 (Probable). Does not form homomultimers (Probable).
• Mice lacking Kcns1 in peripheral neurons show increased basal and neuropathic pain sensitivity.
  Tsantoulas, Pain 2018
  • GeneRIF: After neuropathic injury, Kcns1 KO mice exhibited exaggerated mechanical pain responses and hypersensitivity to both noxious and innocuous cold, consistent with increased A-fiber activity. Interestingly, Kcns1 deletion also improved locomotor performance in the rotarod test, indicative of augmented proprioceptive signalling.

KCNG2_HUMAN / Q9UJ96 Voltage-gated potassium channel regulatory subunit KCNG2; Cardiac potassium channel subunit; Potassium voltage-gated channel subfamily G member 2; Voltage-gated potassium channel subunit Kv6.2 from Homo sapiens (Human) (see paper)
NP_036415 potassium voltage-gated channel subfamily G member 2 from Homo sapiens
30% identity, 61% coverage

• function: Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, can modulate the kinetics and conductance-voltage relationship (PubMed:10551266). Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values (Probable). Potassium channel subunit that does not form functional channels by itself (Probable).
  subunit: Heterodimer with KCNB1.
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 6.3 K v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787 KCNQ2 , O43526...”
• Molecular Network Analysis of the Urinary Proteome of Alzheimer's Disease Patients.
  Watanabe, Dementia and geriatric cognitive disorders extra 2019
  • “...0 0.045 0.206 O00622 42.0 Protein CYR61 (CYR61) 6.95 0.0124 0.0001 9 0 0.006 0.065 Q9UJ96 51.2 Potassium voltage-gated channel subfamily G member 2 (KCNG2) 7.00 0.0128 0.0001 9 0 0.005 0.060 P50897 34.2 Palmitoyl-protein thioesterase 1 (PPT1) 7.29 0.0157 0.0001 9 0 0.034 0.172 P55083-2...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 6.3 K v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787 KCNQ2 , O43526...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...UniProt KCND2 , Q9NZV8 KCND3 , Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A K A Nomenclature K v 7.1 K v 7.2 K v 7.3...”
• Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome.
  Sun, Physiological genomics 2022 (PubMed)
  • GeneRIF: Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome.
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v 7.2 (NP_742105), K v 7.3 (NP_004510), K v 7.4 (NP_004691), K v 7.5 (NP_062816), K v...”

NP_758847 potassium voltage-gated channel subfamily G member 3 isoform 2 from Homo sapiens
33% identity, 57% coverage

• Original association of ion transporters mediates the ECM-induced breast cancer cell survival: Kv10.1-Orai1-SPCA2 partnership.
  Peretti, Scientific reports 2019
  • GeneRIF: Original association of ion transporters mediates the ECM-induced breast cancer cell survival: Kv10.1-Orai1-SPCA2 partnership.
• Analysis of the expression of Kv10.1 potassium channel in patients with brain metastases and glioblastoma multiforme: impact on survival.
  Martínez, BMC cancer 2015
  • GeneRIF: the correlation between dismal prognosis and Kv10.1 expression to patients with brain metastases or glioblastoma multiforme and, moreover, they strongly suggest a role of tricyclic antidepressants for personalized therapy of brain malignancies.
• Approaches targeting K(V)10.1 open a novel window for cancer diagnosis and therapy.
  Pardo, Current medicinal chemistry 2012 (PubMed)
  • GeneRIF: [review] an overview of the current status of data linking K(V)10.1 to cancer, and techniques that could exploit K(V)10.1's properties for the management of cancer
• Molecular cloning and characterization of Kv6.3, a novel modulatory subunit for voltage-gated K(+) channel Kv2.1.
  Sano, FEBS letters 2002 (PubMed)
  • GeneRIF: These results indicate that Kv6.3 is a novel member of the voltage-gated K(+) channel which functions as a modulatory subunit of the Kv2.1 channel.
• Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.
  Ottschytsch, Proceedings of the National Academy of Sciences of the United States of America 2002
  • GeneRIF: Obligatory heterotetramerization of three previously uncharacterized Kv channel subunits identified in human genome (Kv6.3)(Kv10.1) (Kv11.1)

KCNG2_RAT / Q9QYU3 Voltage-gated potassium channel regulatory subunit KCNG2; Cardiac potassium channel subunit; Potassium voltage-gated channel subfamily G member 2; Voltage-gated potassium channel subunit Kv6.2 from Rattus norvegicus (Rat) (see paper)
31% identity, 58% coverage

• function: Regulatory alpha-subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, can modulate the kinetics and conductance-voltage relationship (PubMed:10551266). Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values (PubMed:10551266). Potassium channel subunit that does not form functional channels by itself (PubMed:10551266).
  subunit: Heterodimer with KCNB1.

KCNG3_HUMAN / Q8TAE7 Voltage-gated potassium channel regulatory subunit KCNG3; Potassium voltage-gated channel subfamily G member 3; Voltage-gated potassium channel subunit Kv10.1; Voltage-gated potassium channel subunit Kv6.3 from Homo sapiens (Human) (see 3 papers)
NP_579875 potassium voltage-gated channel subfamily G member 3 isoform 1 from Homo sapiens
33% identity, 57% coverage

• function: Regulatory subunit of the voltage-gated potassium (Kv) channel which, when coassembled with KCNB1, modulates the kinetics parameters of the heterotetrameric channel namely the inactivation and deactivation rate (PubMed:11852086, PubMed:12060745, PubMed:19074135). Potassium channel subunit that does not form functional channels by itself (PubMed:11852086, PubMed:12060745). Reduces the deactivation rate (PubMed:11852086). Moderately accelerates activation (PubMed:12060745).
  subunit: Heterotetramer with KCNB1 (PubMed:11852086, PubMed:12060745, PubMed:19074135). Does not form homomultimers (PubMed:12060745).
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787 KCNQ2 , O43526 KCNQ3 , O43525...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...v 6.4 HGNC, UniProt KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4 K v 7.5 HGNC, UniProt KCNQ1 , P51787 KCNQ2 , O43526 KCNQ3 , O43525...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...Q9NZV8 KCND3 , Q9UK17 KCNF1 , Q9H3M0 KCNG1 , Q9UIX4 KCNG2 , Q9UJ96 KCNG3 , Q8TAE7 KCNG4 , Q8TDN1 Associated subunits KChIP and KChAP KChIP and KChAP Functional Characteristics K A K A Nomenclature K v 7.1 K v 7.2 K v 7.3 K v 7.4...”
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v 6.3 (NP_579875), K v 6.4 (NP_758857), K v 7.1 (NP_000209), K v 7.2 (NP_742105), K v 7.3 (NP_004510), K v 7.4 (NP_004691), K v 7.5 (NP_062816), K v 8.1 (NP_055194), K v...”

TC 1.A.1.2.8 / Q86GI9 KVS-1, component of Voltage gated K+ channel/MiNK related peptide (MiRP) complex, KVS1(α)/MPS-1/MiRPβ (expressed in chemo- and mechano-sensory neurons. Involved in chemotaxis, mechanotransduction and locomotion (Bianchi et al., 2003)). KVS-1 and KVS-2 are homologous; MPS-1 is member of the MiNK family (8.A.10). KVS-1/MPS-1 association involves hydrophobic forces from Caenorhabditis elegans (see paper)
31% identity, 57% coverage

• substrates: K+

NP_001024489 BTB domain-containing protein from Caenorhabditis elegans
33% identity, 50% coverage

• Oxidation of a potassium channel causes progressive sensory function loss during aging.
  Cai, Nature neuroscience 2009
  • GeneRIF: Together, these findings establish a pivotal role for ROS-mediated oxidation of voltage-gated K(+) channels in sensorial decline during aging in invertebrates.
• A new mode of regulation of N-type inactivation in a Caenorhabditis elegans voltage-gated potassium channel.
  Cai, The Journal of biological chemistry 2007 (PubMed)
  • GeneRIF: KVS-1 is the first example of a novel type of Kv channel simultaneously possessing an N-inactivating ball preceded by an N inactivation regulatory domain (NIRD) that acts to slow down inactivation through steric mechanisms
• A family of K+ channel ancillary subunits regulate taste sensitivity in Caenorhabditis elegans.
  Park, The Journal of biological chemistry 2005 (PubMed)
  • GeneRIF: three different MPS subunits combine with KVS-1 to form both binary (MPS-1.KVS-1) and ternary (MPS-2.MPS-3.KVS-1) complexes in chemosensory neurons
• A potassium channel-MiRP complex controls neurosensory function in Caenorhabditis elegans.
  Bianchi, The Journal of biological chemistry 2003 (PubMed)
  • GeneRIF: the cloning and functional characterization of a MiRP beta-subunit, MPS-1, and of a voltage-gated pore-forming potassium subunit, KVS-1 [MPS-1] [KVS-1]

KCNC3_HUMAN / Q14003 Voltage-gated potassium channel KCNC3; KSHIIID; Potassium voltage-gated channel subfamily C member 3; Voltage-gated potassium channel subunit Kv3.3 from Homo sapiens (Human) (see 9 papers)
TC 1.A.1.2.13 / Q14003 Voltage-gated K+ channel subfamily C member 3,KCNC3 or Kv3.3. It is negatively modulated by protein kinase C from Homo sapiens (see 3 papers)
NP_004968 voltage-gated potassium channel KCNC3 isoform 1 from Homo sapiens
38% identity, 32% coverage

• function: Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons. The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. The channel displays rapid activation and inactivation kinetics (PubMed:10712820, PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:22289912, PubMed:23734863, PubMed:25756792, PubMed:26997484). It plays a role in the regulation of the frequency, shape and duration of action potentials in Purkinje cells. Required for normal survival of cerebellar neurons, probably via its role in regulating the duration and frequency of action potentials that in turn regulate the activity of voltage-gated Ca(2+) channels and cellular Ca(2+) homeostasis (By similarity). Required for normal motor function (PubMed:16501573, PubMed:19953606, PubMed:21479265, PubMed:23734863, PubMed:25756792). Plays a role in the reorganization of the cortical actin cytoskeleton and the formation of actin veil structures in neuronal growth cones via its interaction with HAX1 and the Arp2/3 complex (PubMed:26997484).
  catalytic activity: K(+)(in) = K(+)(out) (RHEA:29463)
  subunit: Homotetramer. Heterotetramer with KCNC1 (PubMed:23734863). Interacts (via C-terminus) with HAX1; this interaction modulates channel gating (PubMed:26997484). Identified in a complex with ACTR3, a subunit of the Arp2/3 complex; this interaction is indirect and depends on the presence of HAX1 (PubMed:26997484).
• substrates: K+
  tcdb comment: Phosphorylation of Kv3.3 by PKC may allow neurons to maintain action potential height during stimulation at high frequencies, and therefore contributes to stimulus-induced changes in the intrinsic excitability of neurons such as those of the auditory brainstem (Desai et al., 2008). N-glycosylation impacts the sub-plasma membrane localization and activity of Kv3.1b-containing channels, and N-glycosylation processing of Kv3.1b-containing channels contributes to neuronal excitability (Hall et al. 2017). Spinocerebellar ataxia (SCA), a genetically heterogeneous disease characterized by cerebellar ataxia, involves the abnormal expansion of repeat sequences as well as the mutation of K+ and Ca2+ channel genes (Tada et al. 2020)
• Regulatory Effect of General Anesthetics on Activity of Potassium Channels
  Li, Neuroscience bulletin 2018
  • “...K v 2.2 (NP_004761), K v 3.1 (NP_004967), K v 3.2 (NP_631875), K v 3.3 (NP_004968), K v 3.4 (NP_004969), K v 4.1 (NP_004970), K v 4.2 (NP_036413), K v 4.3 (NP_004971); K v 5.1 (NP_002227), K v 6.1 (NP_002228), K v 6.2 (NP_036415), K v...”
• The Concise Guide to PHARMACOLOGY 2023/24: Ion channels
  Alexander, British journal of pharmacology 2023
  • “...Q16322 KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 1 and K v 2 K v 5.1, K v 6.1-6.4, K v 8.1-8.2 and K v 9.1-9.3 K v 5.1, K v...”
• THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2017
  • “...UniProt KCNB1 , Q14721 KCNB2 , Q92953 KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 Associated subunits K v 5.1, K v 6.16.4, K v 8.18.2 and K v 9.19.3 K v 5.1, K v 6.16.4, K v 8.18.2 and K v...”
• The Concise Guide to PHARMACOLOGY 2015/16: Voltage-gated ion channels
  Alexander, British journal of pharmacology 2015
  • “...v 3.4 K v 4.1 HGNC, UniProt KCNC1 , P48547 KCNC2 , Q96PR1 KCNC3 , Q14003 KCNC4 , Q03721 KCND1 , Q9NSA2 Associated subunits MiRP2 is an associated subunit for K v 3.4 KChIP and KChAP Functional Characteristics K V K V K A K A...”
• The Concise Guide to PHARMACOLOGY 2013/14: ion channels
  Alexander, British journal of pharmacology 2013
  • “...KCNA6, P17658; KCNA7, Q96RP8; KCNA10, Q16322 KCNB1, Q14721; KCNB2, Q92953 KCNC1, P48547; KCNC2, Q96PR1; KCNC3, Q14003; KCNC4, Q03721 KCND1, Q9NSA2; KCND2, Q9NZV8; KCND3, Q9UK17 KCNQ1, P51787; KCNQ2, O43526; KCNQ3, O43525; KCNQ4, P56696; KCNQ5, Q9NR82 KCNH1, O95259; KCNH5, Q8NCM2; KCNH2, Q12809; KCNH6, Q9H252; KCNH7, Q9NS40; KCNH8, Q96L42;...”

Q3TR92 Ion transport domain-containing protein from Mus musculus
39% identity, 37% coverage

• Mining recent brain proteomic databases for ion channel phosphosite nuggets
  Cerda, The Journal of general physiology 2011
  • “...S481 C-term S488 C-term S490 C-term S503 C-term S507 C-term S530 Kv3.1/KCNC1 W: P15388 Tr: Q3TR92 T: P15388 N-term S158 N-term S160 S160 C-term T421 C-term S468 C-term T483 Kv3.2/KCNC2 W: P70311 C-term S509 C-term S557 C-term S604 C-term S619 Kv3.3/KCNC3 W: Q63959 Tr: Q63959 C-term...”