PaperBLAST

Full List of Papers Linked to NP_004761.2

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

• 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)
• Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study.
  Vasan, BMC medical genetics 2007
  • GeneRIF: Genome-wide association study of gene-disease association. (HuGE Navigator)
• 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)
• 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;...”

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How It Works

PaperBLAST builds a database of protein sequences that are linked to scientific articles. These links come from automated text searches against the articles in EuropePMC and from manually-curated information from GeneRIF, UniProtKB/Swiss-Prot, BRENDA, CAZy (as made available by dbCAN), BioLiP, CharProtDB, MetaCyc, EcoCyc, TCDB, REBASE, the Fitness Browser, and a subset of the European Nucleotide Archive with the /experiment tag. Given this database and a protein sequence query, PaperBLAST uses protein-protein BLAST to find similar sequences with E < 0.001.

To build the database, we query EuropePMC with locus tags, with RefSeq protein identifiers, and with UniProt accessions. We obtain the locus tags from RefSeq or from MicrobesOnline. We use queries of the form "locus_tag AND genus_name" to try to ensure that the paper is actually discussing that gene. Because EuropePMC indexes most recent biomedical papers, even if they are not open access, some of the links may be to papers that you cannot read or that our computers cannot read. We query each of these identifiers that appears in the open access part of EuropePMC, as well as every locus tag that appears in the 500 most-referenced genomes, so that a gene may appear in the PaperBLAST results even though none of the papers that mention it are open access. We also incorporate text-mined links from EuropePMC that link open access articles to UniProt or RefSeq identifiers. (This yields some additional links because EuropePMC uses different heuristics for their text mining than we do.)

For every article that mentions a locus tag, a RefSeq protein identifier, or a UniProt accession, we try to select one or two snippets of text that refer to the protein. If we cannot get access to the full text, we try to select a snippet from the abstract, but unfortunately, unique identifiers such as locus tags are rarely provided in abstracts.

PaperBLAST also incorporates manually-curated protein functions:

• Proteins from NCBI's RefSeq are included if a GeneRIF entry links the gene to an article in PubMed^®. GeneRIF also provides a short summary of the article's claim about the protein, which is shown instead of a snippet.
• Proteins from Swiss-Prot (the curated part of UniProt) are included if the curators identified experimental evidence for the protein's function (evidence code ECO:0000269). For these proteins, the fields of the Swiss-Prot entry that describe the protein's function are shown (with bold headings).
• Proteins from BRENDA, a curated database of enzymes, are included if they are linked to a paper in PubMed and their full sequence is known.
• Every protein from the non-redundant subset of BioLiP, a database of ligand-binding sites and catalytic residues in protein structures, is included. Since BioLiP itself does not include descriptions of the proteins, those are taken from the Protein Data Bank. Descriptions from PDB rely on the original submitter of the structure and cannot be updated by others, so they may be less reliable. (For SitesBLAST and Sites on a Tree, we use a larger subset of BioLiP so that every ligand is represented among a group of structures with similar sequences, but for PaperBLAST, we use the non-redundant set provided by BioLiP.)
• Every protein from EcoCyc, a curated database of the proteins in Escherichia coli K-12, is included, regardless of whether they are characterized or not.
• Proteins from the MetaCyc metabolic pathway database are included if they are linked to a paper in PubMed and their full sequence is known.
• Proteins from the Transport Classification Database (TCDB) are included if they have known substrate(s), have reference(s), and are not described as uncharacterized or putative. (Some of the references are not visible on the PaperBLAST web site.)
• Every protein from CharProtDB, a database of experimentally characterized protein annotations, is included.
• Proteins from the CAZy database of carbohydrate-active enzymes are included if they are associated with an Enzyme Classification number. Even though CAZy does not provide links from individual protein sequences to papers, these should all be experimentally-characterized proteins.
• Proteins from the REBASE database of restriction enzymes are included if they have known specificity.
• Every protein with an evidence-based reannotation (based on mutant phenotypes) in the Fitness Browser is included.
• Sequence-specific transcription factors (including sigma factors and DNA-binding response regulators) with experimentally-determined DNA binding sites from the PRODORIC database of gene regulation in prokaryotes.
• Putative transcription factors from RegPrecise that have manually-curated predictions for their binding sites. These predictions are based on conserved putative regulatory sites across genomes that contain similar transcription factors, so PaperBLAST clusters the TFs at 70% identity and retains just one member of each cluster.
• Coding sequence (CDS) features from the European Nucleotide Archive (ENA) are included if the /experiment tag is set (implying that there is experimental evidence for the annotation), the nucleotide entry links to paper(s) in PubMed, and the nucleotide entry is from the STD data class (implying that these are targeted annotated sequences, not from shotgun sequencing). Also, to filter out genes whose transcription or translation was detected, but whose function was not studied, nucleotide entries or papers with more than 25 such proteins are excluded. Descriptions from ENA rely on the original submitter of the sequence and cannot be updated by others, so they may be less reliable.

Except for GeneRIF and ENA, the curated entries include a short curated description of the protein's function. For entries from BioLiP, the protein's function may not be known beyond binding to the ligand. Many of these entries also link to articles in PubMed.

For more information see the PaperBLAST paper (mSystems 2017) or the code. You can download PaperBLAST's database here.

Changes to PaperBLAST since the paper was written:

• November 2023: incorporated PRODORIC and RegPrecise. Many PRODORIC entries were not linked to a protein sequence (no UniProt identifier), so we added this information.
• February 2023: BioLiP changed their download format. PaperBLAST now includes their non-redundant subset. SitesBLAST and Sites on a Tree use a larger non-redundant subset that ensures that every ligand is represented within each cluster. This should ensure that every binding site is represented.
• June 2022: incorporated some coding sequences from ENA with the /experiment tag.
• March 2022: incorporated BioLiP.
• April 2020: incorporated TCDB.
• April 2019: EuropePMC now returns table entries in their search results. This has expanded PaperBLAST's database, but most of the new entries are of low relevance, and the resulting snippets are often just lists of locus tags with annotations.
• February 2018: the alignment page reports the conservation of the hit's functional sites (if available from from Swiss-Prot or UniProt)
• January 2018: incorporated BRENDA.
• December 2017: incorporated MetaCyc, CharProtDB, CAZy, REBASE, and the reannotations from the Fitness Browser.
• September 2017: EuropePMC no longer returns some table entries in their search results. This has shrunk PaperBLAST's database, but has also reduced the number of low-relevance hits.

Many of these changes are described in Interactive tools for functional annotation of bacterial genomes.

Secrets

PaperBLAST cannot provide snippets for many of the papers that are published in non-open-access journals. This limitation applies even if the paper is marked as "free" on the publisher's web site and is available in PubmedCentral or EuropePMC. If a journal that you publish in is marked as "secret," please consider publishing elsewhere.

Omissions from the PaperBLAST Database

Many important articles are missing from PaperBLAST, either because the article's full text is not in EuropePMC (as for many older articles), or because the paper does not mention a protein identifier such as a locus tag, or because of PaperBLAST's heuristics. If you notice an article that characterizes a protein's function but is missing from PaperBLAST, please notify the curators at UniProt or add an entry to GeneRIF. Entries in either of these databases will eventually be incorporated into PaperBLAST. Note that to add an entry to UniProt, you will need to find the UniProt identifier for the protein. If the protein is not already in UniProt, you can ask them to create an entry. To add an entry to GeneRIF, you will need an NCBI Gene identifier, but unfortunately many prokaryotic proteins in RefSeq do not have corresponding Gene identifers.

References

PaperBLAST: Text-mining papers for information about homologs.
M. N. Price and A. P. Arkin (2017). mSystems, 10.1128/mSystems.00039-17.

Europe PMC in 2017.
M. Levchenko et al (2017). Nucleic Acids Research, 10.1093/nar/gkx1005.

Gene indexing: characterization and analysis of NLM's GeneRIFs.
J. A. Mitchell et al (2003). AMIA Annu Symp Proc 2003:460-464.

UniProt: the universal protein knowledgebase.
The UniProt Consortium (2016). Nucleic Acids Research, 10.1093/nar/gkw1099.

BRENDA in 2017: new perspectives and new tools in BRENDA.
S. Placzek et al (2017). Nucleic Acids Research, 10.1093/nar/gkw952.

The EcoCyc database: reflecting new knowledge about Escherichia coli K-12.
I. M. Keeseler et al (2016). Nucleic Acids Research, 10.1093/nar/gkw1003.

The MetaCyc database of metabolic pathways and enzymes.
R. Caspi et al (2018). Nucleic Acids Research, 10.1093/nar/gkx935.

CharProtDB: a database of experimentally characterized protein annotations.
R. Madupu et al (2012). Nucleic Acids Research, 10.1093/nar/gkr1133.

The carbohydrate-active enzymes database (CAZy) in 2013.
V. Lombard et al (2014). Nucleic Acids Research, 10.1093/nar/gkt1178.

The Transporter Classification Database (TCDB): recent advances
M. H. Saier, Jr. et al (2016). Nucleic Acids Research, 10.1093/nar/gkv1103.

REBASE - a database for DNA restriction and modification: enzymes, genes and genomes.
R. J. Roberts et al (2015). Nucleic Acids Research, 10.1093/nar/gku1046.

Deep annotation of protein function across diverse bacteria from mutant phenotypes.
M. N. Price et al (2016). bioRxiv, 10.1101/072470.