Family Search for PF11879 (DUF3399)

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PF11879 hits 24 sequences in PaperBLAST's database above the trusted cutoff. Showing all hits. Or show only hits to curated sequences or try another family.

KCND2_RABIT / P59995 Potassium voltage-gated channel subfamily D member 2; Voltage-gated potassium channel subunit Kv4.2 from Oryctolagus cuniculus (Rabbit) (see paper)
Aligns to 470:546 / 630 (12.2%), covers 97.4% of PF11879, 126.7 bits

• 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 (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. 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. Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).
  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).

KCND2_HUMAN / Q9NZV8 Potassium voltage-gated channel subfamily D member 2; Voltage-gated potassium channel subunit Kv4.2 from Homo sapiens (Human) (see 21 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 potassium voltage-gated channel subfamily D member 2 precursor from Homo sapiens
Aligns to 470:546 / 630 (12.2%), covers 97.4% of PF11879, 126.7 bits

• 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:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). 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:15454437, PubMed:14623880, PubMed:14980201, 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).
  subunit: Homotetramer or heterotetramer with KCND1 or KCND3 (PubMed:14980201, PubMed:16934482, PubMed:24811166). Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (PubMed:10676964, PubMed:11287421, PubMed:11847232, PubMed:12451113, PubMed:15358149, PubMed:14623880, PubMed:14980201, PubMed:14980207, PubMed:24811166). 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, DPP6 and DPP10 (PubMed:11102480, PubMed:15454437, PubMed:24811166).
• 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)
• 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;...”
• 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...”

NP_113918 potassium voltage-gated channel subfamily D member 2 precursor from Rattus norvegicus
Aligns to 470:546 / 630 (12.2%), covers 97.4% of PF11879, 126.7 bits

• 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_RAT / Q63881 Potassium voltage-gated channel subfamily D member 2; RK5; Shal1; Voltage-gated potassium channel subunit Kv4.2 from Rattus norvegicus (Rat) (see 45 papers)
Aligns to 470:546 / 630 (12.2%), covers 97.4% of PF11879, 126.7 bits

• function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart (PubMed:1840649, PubMed:1722463, PubMed:9093524, PubMed:9058605, PubMed:10676964, PubMed:12592409, PubMed:12754210, PubMed:16207878, PubMed:16123112, PubMed:19279261, PubMed:25352783, PubMed:14980206). 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:9093524, PubMed:9058605). 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:1840649, PubMed:1722463, PubMed:9093524, PubMed:10676964, PubMed:12451113, PubMed:12592409, PubMed:12754210, PubMed:15452711, PubMed:16207878, PubMed:16820361, PubMed:25352783, PubMed:14980206). 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:15452711, PubMed:16123112, PubMed:16820361, PubMed:20045463, PubMed:14980206). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (PubMed:15671030, PubMed:16123112, PubMed:19441798, PubMed:19901547, PubMed:19279261).
  subunit: Homotetramer or heterotetramer with KCND1 or KCND3 (PubMed:12754210, PubMed:15485870, PubMed:20224290, PubMed:25352783). Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (PubMed:10676964, PubMed:12451113, PubMed:11847232, PubMed:11805342, PubMed:15485870, PubMed:15356203, PubMed:15452711, PubMed:16820361, PubMed:20045463, PubMed:24811166, PubMed:14980206). Interacts with DPP6, DPP10, DLG4 and DLG1 (PubMed:11923279, PubMed:12575952, 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).
• 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...”

KCND2_MOUSE / Q9Z0V2 Potassium voltage-gated channel subfamily D member 2; Voltage-gated potassium channel subunit Kv4.2 from Mus musculus (Mouse) (see 21 papers)
NP_062671 potassium voltage-gated channel subfamily D member 2 precursor from Mus musculus
Aligns to 470:546 / 630 (12.2%), covers 97.4% of PF11879, 126.6 bits

• 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:9734479, PubMed:10601491, PubMed:11909823, PubMed:23713033). 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:9734479, PubMed:22311982). 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).
  subunit: Homotetramer or heterotetramer with KCND3 or KCND1 (PubMed:9734479, PubMed:11909823, PubMed:19713751, PubMed:20943905). Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (PubMed:11909823, PubMed:19713751, PubMed:20943905). 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 DPP6 and DPP10 (PubMed:19713751, PubMed:22311982). Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity).
  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).
• 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
• 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:...”

XP_015132111 potassium voltage-gated channel subfamily D member 2 isoform X1 from Gallus gallus
Aligns to 472:548 / 632 (12.2%), covers 96.1% of PF11879, 123.4 bits

• 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.

KCND3_RAT / Q62897 Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Rattus norvegicus (Rat) (see 7 papers)
Aligns to 468:563 / 655 (14.7%), covers 97.4% of PF11879, 122.2 bits

• function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
  subunit: Homotetramer or heterotetramer with KCND1 and/or KCND2. Interacts with DLG1. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 (By similarity).

Q9Z0V1 Potassium voltage-gated channel subfamily D member 3 from Mus musculus
Aligns to 468:563 / 655 (14.7%), covers 97.4% of PF11879, 122.2 bits

• 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...”

NP_001257891 potassium voltage-gated channel subfamily D member 3 isoform 1 precursor from Rattus norvegicus
Aligns to 468:563 / 655 (14.7%), covers 97.4% of PF11879, 122.2 bits

• 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_RABIT / Q9TTT5 Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Oryctolagus cuniculus (Rabbit) (see paper)
Aligns to 468:563 / 655 (14.7%), covers 97.4% of PF11879, 122.0 bits

• function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
  subunit: Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DLG1, KCNE1, KCNE2, SCN1B and KCNAB1 (By similarity).

KCND3_HUMAN / Q9UK17 Potassium voltage-gated channel subfamily D member 3; Voltage-gated potassium channel subunit Kv4.3 from Homo sapiens (Human) (see 12 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 potassium voltage-gated channel subfamily D member 3 isoform 1 precursor from Homo sapiens
Aligns to 468:563 / 655 (14.7%), covers 97.4% of PF11879, 121.9 bits

• function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
  subunit: Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (By similarity). Interacts with KCNE1, KCNE2, SCN1B and KCNAB1 and DLG1.
• 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)
• 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;...”
• 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...”

XP_005630924 potassium voltage-gated channel subfamily D member 3 isoform X1 from Canis lupus familiaris
Aligns to 468:563 / 679 (14.1%), covers 97.4% of PF11879, 121.9 bits

• 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
Aligns to 468:563 / 653 (14.7%), covers 97.4% of PF11879, 117.1 bits

• 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

KCND1_RABIT / P59994 Potassium voltage-gated channel subfamily D member 1; Voltage-gated potassium channel subunit Kv4.1 from Oryctolagus cuniculus (Rabbit) (see paper)
Aligns to 33:113 / 178 (45.5%), covers 97.4% of PF11879, 111.3 bits

• function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
  subunit: Homotetramer or heterotetramer with KCND2 and/or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DPP10 (By similarity).

XP_002719951 potassium voltage-gated channel subfamily D member 1 from Oryctolagus cuniculus
Aligns to 470:550 / 647 (12.5%), covers 97.4% of PF11879, 109.1 bits

• Comparative Bioinformatic Analysis of the Proteomes of Rabbit and Human Sex Chromosomes
  Pinto-Pinho, Animals : an open access journal from MDPI 2024
  • “...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 XP_016884927...”

KCND1_HUMAN / Q9NSA2 Potassium voltage-gated channel subfamily D member 1; Voltage-gated potassium channel subunit Kv4.1 from Homo sapiens (Human) (see paper)
NP_004970 potassium voltage-gated channel subfamily D member 1 precursor from Homo sapiens
Aligns to 470:550 / 647 (12.5%), covers 97.4% of PF11879, 107.3 bits

• function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits
  subunit: Homotetramer or heterotetramer with KCND2 and/or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (By similarity). Interacts with DPP10 (Probable).
• 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...”
• 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...”
• 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...”

KCND1_MOUSE / Q03719 Potassium voltage-gated channel subfamily D member 1; Voltage-gated potassium channel subunit Kv4.1; mShal from Mus musculus (Mouse) (see paper)
NP_032449 potassium voltage-gated channel subfamily D member 1 precursor from Mus musculus
Aligns to 470:550 / 651 (12.4%), covers 97.4% of PF11879, 105.4 bits

• function: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in the heart and I(Sa) current in neurons. Channel properties are modulated by subunit assembly.
  subunit: Homotetramer or heterotetramer with KCND2 and/or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DPP10 (By similarity).
• 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...”

NP_001099218 potassium voltage-gated channel subfamily D member 1 precursor from Rattus norvegicus
Aligns to 470:550 / 650 (12.5%), covers 97.4% of PF11879, 104.5 bits

• 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.

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
Aligns to 470:546 / 571 (13.5%), covers 86.8% of PF11879, 65.5 bits

• 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...”

7ukhA / Q9NZV8 Human kv4.2-kchip2-dpp6 channel complex in an open state, intracellular region (see paper)
Aligns to 176:203 / 203 (13.8%), covers 35.5% of PF11879, 52.6 bits

• Ligand: zinc ion (7ukhA)

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
Aligns to 471:543 / 578 (12.6%), covers 86.8% of PF11879, 48.1 bits

• substrates: K+

7e8eD / Q9NZV8 Cryoem structure of human kv4.2-dpp6s-kchip1 complex, transmembrane and intracellular region (see paper)
Aligns to 434:459 / 459 (5.7%), covers 32.9% of PF11879, 47.4 bits

• Ligand: peptide (7e8eD)

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)
Aligns to 470:490 / 490 (4.3%), covers 25.0% of PF11879, 31.1 bits

• substrates: K+

XP_026693459 potassium voltage-gated channel protein Shal from Ciona intestinalis
Aligns to 475:569 / 800 (11.9%), covers 69.7% of PF11879, 26.7 bits

• 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

Or search for genetic data about PF11879 in the Fitness Browser