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DescriptionRecName: Full=Potassium voltage-gated channel subfamily B member 1 {ECO:0000312|HGNC:HGNC:6231}; AltName: Full=Delayed rectifier potassium channel 1 {ECO:0000303|PubMed:8081723}; Short=DRK1 {ECO:0000303|PubMed:8081723}; Short=h-DRK1 {ECO:0000303|PubMed:8081723}; AltName: Full=Voltage-gated potassium channel subunit Kv2.1 {ECO:0000303|PubMed:8081723};
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MyHits synonymsKCNB1_HUMAN , Q14721 , Q14193 , C4B426174ED0DEE4
match map segment
ipfam:Kv2channel ipfam:Kv2channel ismart:BTB ipfam:BTB_2 ipfam:Ion_trans  
Legends: 1, Phosphoserine. {ECO:0000250|UniProtKB:P15387}; 2, Phosphotyrosine; by Src. {ECO:0000250|UniProtKB:P15387}; 3, Phosphoserine. {ECO:0000250|UniProtKB:Q03717}; 4, Phosphoserine; by CDK5; in vitro. {ECO:0000250|UniProtKB:P15387}; 5, Phosphoserine; by CDK5. {ECO:0000250|UniProtKB:P15387}; 6, Phosphoserine; by CDK5, MAPK14; in vitro. {ECO:0000250|UniProtKB:P15387}; 7, CROSSLNK Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO). {ECO:0000250|UniProtKB:P15387}; 8, VARIANT R -> C (in EIEE26; reduces sensitivity and cooperativity of the voltage sensor for channel opening and greatly suppresses repetitive firing in cultured cortical neurons). {ECO:0000269|PubMed:26477325}; 9, VARIANT S -> R (in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface; dbSNP:rs587777848). {ECO:0000269|PubMed:25164438}; 10, VARIANT T -> I (in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface; dbSNP:rs587777849). {ECO:0000269|PubMed:25164438}; 11, VARIANT V -> A (in EIEE26; change in the ion selectivity from potassium-selective to nonselective cation channels and significant decrease in cell membrane localization). {ECO:0000269|PubMed:26503721}; 12, VARIANT G -> R (in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface; dbSNP:rs587777850). {ECO:0000269|PubMed:25164438}; 13, VARIANT G -> R (in EIEE26; dominant-negative mutation resulting in loss of endogenous channel currents and greatly suppresses repetitive firing in cultured cortical neurons). {ECO:0000269|PubMed:26477325}; 14, VARIANT T -> N (in dbSNP:rs2229006); 15, VARIANT T -> S (in dbSNP:rs2229006); 16, VARIANT P -> S (in dbSNP:rs34467662); 17, VARIANT S -> N (in dbSNP:rs34280195); 18, MUTAGEN E->Q: No effect on channel activity. {ECO:0000269|PubMed:12560340}; 19, MUTAGEN D->R: Reduces interaction with KCNG1 and self-interaction and impairs plasma membrane subcellular localization, homotetramerization and hetetrotetramerization with KCNG4; when associated with R-75. {ECO:0000269|PubMed:19717558, ECO:0000269|PubMed:24901643}; 20, MUTAGEN D->R: Reduces interaction with KCNG1 and self-interaction and impairs plasma membrane subcellular localization, homotetramerization and hetetrotetramerization with KCNG4; when associated with R-74. {ECO:0000269|PubMed:19717558, ECO:0000269|PubMed:24901643}; 21, MUTAGEN D->E: Increases channel activity. {ECO:0000269|PubMed:12560340}; 22, MUTAGEN H->V,R: Reduces channel activity. Inhibits interaction with KCNG4. Impairs hetetrotetramerization with KCNG1, KCNG3 or KCNG4. Does not impair homotetramerization. {ECO:0000269|PubMed:19074135}; 23, TOPO_DOM Cytoplasmic. {ECO:0000250|UniProtKB:P63142}; 24, TRANSMEM Helical; Name=Segment S1. {ECO:0000250|UniProtKB:P63142}; 25, TOPO_DOM Extracellular. {ECO:0000250|UniProtKB:P63142}; 26, TRANSMEM Helical; Name=Segment S2. {ECO:0000250|UniProtKB:P63142}; 27, TRANSMEM Helical; Name=Segment S3. {ECO:0000250|UniProtKB:P63142}; 28, TRANSMEM Helical; Voltage-sensor; Name=Segment S4. {ECO:0000250|UniProtKB:P63142}; 29, TRANSMEM Helical; Name=Segment S5. {ECO:0000250|UniProtKB:P63142}; 30, INTRAMEM Helical; Name=Pore helix. {ECO:0000250|UniProtKB:P63142}; 31, INTRAMEM {ECO:0000250|UniProtKB:P63142}; 32, TRANSMEM Helical; Name=Segment S6. {ECO:0000250|UniProtKB:P63142}; 33, REGION Self-association. {ECO:0000250|UniProtKB:P15387}; 34, MOTIF Selectivity filter. {ECO:0000250|UniProtKB:P63142}; 35, COMPBIAS Poly-Ser; 36, COMPBIAS Poly-Ala; 37, ipfam:Kv2channel [T]; 38, ipfam:BTB_2 [T].
ID   KCNB1_HUMAN             Reviewed;         858 AA.
AC   Q14721; Q14193;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2002, sequence version 2.
DT   30-NOV-2016, entry version 147.
DE   RecName: Full=Potassium voltage-gated channel subfamily B member 1 {ECO:0000312|HGNC:HGNC:6231};
DE   AltName: Full=Delayed rectifier potassium channel 1 {ECO:0000303|PubMed:8081723};
DE            Short=DRK1 {ECO:0000303|PubMed:8081723};
DE            Short=h-DRK1 {ECO:0000303|PubMed:8081723};
DE   AltName: Full=Voltage-gated potassium channel subunit Kv2.1 {ECO:0000303|PubMed:8081723};
GN   Name=KCNB1 {ECO:0000312|HGNC:HGNC:6231};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBUNIT,
RP   BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=8081723;
RA   Albrecht B., Lorra C., Stocker K., Pongs O.;
RT   "Cloning and characterization of a human delayed rectifier potassium
RT   channel gene.";
RL   Recept. Channels 1:99-110(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL
RP   PROPERTIES, ENZYME REGULATION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Brain cortex;
RX   PubMed=1283219; DOI=10.1007/BF00370422;
RA   Ikeda S.R., Soler F., Zuhlke R.D., Joho R.H., Lewis D.L.;
RT   "Heterologous expression of the human potassium channel Kv2.1 in
RT   clonal mammalian cells by direct cytoplasmic microinjection of cRNA.";
RL   Pflugers Arch. 422:201-203(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Lens epithelium;
RA   Rae J.L., Shepard A.R.;
RT   "Identification of potassium channels in human lens epithelium.";
RL   (In) Civan M.M. (eds.);
RL   The eye's aqueous humor-from secretion to glaucoma, pp.69-104,
RL   Academic Press, San Diego (1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [5]
RP   FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=10484328;
RA   Shepard A.R., Rae J.L.;
RT   "Electrically silent potassium channel subunits from human lens
RT   epithelium.";
RL   Am. J. Physiol. 277:C412-C424(1999).
RN   [6]
RP   REVIEW.
RX   PubMed=10414301; DOI=10.1111/j.1749-6632.1999.tb11293.x;
RA   Coetzee W.A., Amarillo Y., Chiu J., Chow A., Lau D., McCormack T.,
RA   Moreno H., Nadal M.S., Ozaita A., Pountney D., Saganich M.,
RA   Vega-Saenz de Miera E., Rudy B.;
RT   "Molecular diversity of K+ channels.";
RL   Ann. N. Y. Acad. Sci. 868:233-285(1999).
RN   [7]
RP   FUNCTION, SUBUNIT, INTERACTION WITH KCNG3, SELF-ASSOCIATION, DOMAIN,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX   PubMed=11852086; DOI=10.1016/S0014-5793(02)02267-6;
RA   Sano Y., Mochizuki S., Miyake A., Kitada C., Inamura K., Yokoi H.,
RA   Nozawa K., Matsushime H., Furuichi K.;
RT   "Molecular cloning and characterization of Kv6.3, a novel modulatory
RT   subunit for voltage-gated K(+) channel Kv2.1.";
RL   FEBS Lett. 512:230-234(2002).
RN   [8]
RP   TISSUE SPECIFICITY.
RX   PubMed=12403834; DOI=10.1210/me.2002-0058;
RA   MacDonald P.E., Wang G., Tsuk S., Dodo C., Kang Y., Tang L.,
RA   Wheeler M.B., Cattral M.S., Lakey J.R., Salapatek A.M., Lotan I.,
RA   Gaisano H.Y.;
RT   "Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1
RT   voltage-dependent K(+) channels in neuroendocrine islet beta-cells
RT   through an interaction with the channel N terminus.";
RL   Mol. Endocrinol. 16:2452-2461(2002).
RN   [9]
RP   FUNCTION, SUBUNIT, INTERACTION WITH KCNG3; KCNH1 AND KCNH2,
RP   SELF-ASSOCIATION, DOMAIN, AND SUBCELLULAR LOCATION.
RX   PubMed=12060745; DOI=10.1073/pnas.122617999;
RA   Ottschytsch N., Raes A., Van Hoorick D., Snyders D.J.;
RT   "Obligatory heterotetramerization of three previously uncharacterized
RT   Kv channel alpha-subunits identified in the human genome.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:7986-7991(2002).
RN   [10]
RP   ENZYME REGULATION.
RX   PubMed=14565763; DOI=10.1021/tx0341097;
RA   Shiau Y.S., Huang P.T., Liou H.H., Liaw Y.C., Shiau Y.Y., Lou K.L.;
RT   "Structural basis of binding and inhibition of novel tarantula toxins
RT   in mammalian voltage-dependent potassium channels.";
RL   Chem. Res. Toxicol. 16:1217-1225(2003).
RN   [11]
RP   FUNCTION, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION, AND
RP   MUTAGENESIS OF GLU-71 AND ASP-79.
RX   PubMed=12560340; DOI=10.1074/jbc.M212973200;
RA   Ju M., Stevens L., Leadbitter E., Wray D.;
RT   "The Roles of N- and C-terminal determinants in the activation of the
RT   Kv2.1 potassium channel.";
RL   J. Biol. Chem. 278:12769-12778(2003).
RN   [12]
RP   TISSUE SPECIFICITY.
RX   PubMed=14988243; DOI=10.2337/diabetes.53.3.597;
RA   Yan L., Figueroa D.J., Austin C.P., Liu Y., Bugianesi R.M.,
RA   Slaughter R.S., Kaczorowski G.J., Kohler M.G.;
RT   "Expression of voltage-gated potassium channels in human and rhesus
RT   pancreatic islets.";
RL   Diabetes 53:597-607(2004).
RN   [13]
RP   REVIEW.
RX   PubMed=15858231; DOI=10.1385/CBB:42:2:167;
RA   Cox R.H.;
RT   "Molecular determinants of voltage-gated potassium currents in
RT   vascular smooth muscle.";
RL   Cell Biochem. Biophys. 42:167-195(2005).
RN   [14]
RP   SUBUNIT.
RX   PubMed=19357235; DOI=10.1152/ajpcell.00088.2009;
RA   Bocksteins E., Raes A.L., Van de Vijver G., Bruyns T.,
RA   Van Bogaert P.P., Snyders D.J.;
RT   "Kv2.1 and silent Kv subunits underlie the delayed rectifier K+
RT   current in cultured small mouse DRG neurons.";
RL   Am. J. Physiol. 296:C1271-C1278(2009).
RN   [15]
RP   FUNCTION, SUBUNIT, INTERACTION WITH KCNG4, SELF-ASSOCIATION, DOMAIN,
RP   SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-105, AND TISSUE SPECIFICITY.
RX   PubMed=19074135; DOI=10.1074/jbc.M808786200;
RA   Mederos y Schnitzler M., Rinne S., Skrobek L., Renigunta V.,
RA   Schlichthorl G., Derst C., Gudermann T., Daut J., Preisig-Muller R.;
RT   "Mutation of histidine 105 in the T1 domain of the potassium channel
RT   Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.";
RL   J. Biol. Chem. 284:4695-4704(2009).
RN   [16]
RP   FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-74 AND
RP   ASP-75.
RX   PubMed=19717558; DOI=10.1074/jbc.M109.039479;
RA   Bocksteins E., Labro A.J., Mayeur E., Bruyns T., Timmermans J.P.,
RA   Adriaensen D., Snyders D.J.;
RT   "Conserved negative charges in the N-terminal tetramerization domain
RT   mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels.";
RL   J. Biol. Chem. 284:31625-31634(2009).
RN   [17]
RP   FUNCTION, SUMOYLATION, DESUMOYLATION, INTERACTION WITH SUMO1, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=19223394; DOI=10.1242/jcs.036632;
RA   Dai X.Q., Kolic J., Marchi P., Sipione S., Macdonald P.E.;
RT   "SUMOylation regulates Kv2.1 and modulates pancreatic beta-cell
RT   excitability.";
RL   J. Cell Sci. 122:775-779(2009).
RN   [18]
RP   FUNCTION.
RX   PubMed=23161216; DOI=10.1124/jpet.112.199083;
RA   Li X.N., Herrington J., Petrov A., Ge L., Eiermann G., Xiong Y.,
RA   Jensen M.V., Hohmeier H.E., Newgard C.B., Garcia M.L., Wagner M.,
RA   Zhang B.B., Thornberry N.A., Howard A.D., Kaczorowski G.J., Zhou Y.P.;
RT   "The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the
RT   regulation of insulin and somatostatin release from pancreatic
RT   islets.";
RL   J. Pharmacol. Exp. Ther. 344:407-416(2013).
RN   [19]
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=24477962; DOI=10.1002/cne.23551;
RA   King A.N., Manning C.F., Trimmer J.S.;
RT   "A unique ion channel clustering domain on the axon initial segment of
RT   mammalian neurons.";
RL   J. Comp. Neurol. 522:2594-2608(2014).
RN   [20]
RP   FUNCTION, SUBUNIT, INTERACTION WITH KCNG4, SELF-ASSOCIATION, DOMAIN,
RP   SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-74 AND ASP-75.
RX   PubMed=24901643; DOI=10.1371/journal.pone.0098960;
RA   Bocksteins E., Mayeur E., Van Tilborg A., Regnier G., Timmermans J.P.,
RA   Snyders D.J.;
RT   "The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits
RT   is determined by interactions between the N- and C-termini.";
RL   PLoS ONE 9:E98960-E98960(2014).
RN   [21]
RP   VARIANTS EIEE26 ARG-347; ILE-374 AND ARG-379, CHARACTERIZATION OF
RP   VARIANTS EIEE26 ARG-347; ILE-374 AND ARG-379, AND INVOLVEMENT IN
RP   EIEE26.
RX   PubMed=25164438; DOI=10.1002/ana.24263;
RA   Torkamani A., Bersell K., Jorge B.S., Bjork R.L. Jr., Friedman J.R.,
RA   Bloss C.S., Cohen J., Gupta S., Naidu S., Vanoye C.G.,
RA   George A.L. Jr., Kearney J.A.;
RT   "De novo KCNB1 mutations in epileptic encephalopathy.";
RL   Ann. Neurol. 76:529-540(2014).
RN   [22]
RP   VARIANT EIEE26 ALA-378, CHARACTERIZATION OF VARIANT EIEE26 ALA-378,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=26503721; DOI=10.1085/jgp.201511444;
RA   Thiffault I., Speca D.J., Austin D.C., Cobb M.M., Eum K.S.,
RA   Safina N.P., Grote L., Farrow E.G., Miller N., Soden S.,
RA   Kingsmore S.F., Trimmer J.S., Saunders C.J., Sack J.T.;
RT   "A novel epileptic encephalopathy mutation in KCNB1 disrupts Kv2.1 ion
RT   selectivity, expression, and localization.";
RL   J. Gen. Physiol. 146:399-410(2015).
RN   [23]
RP   VARIANTS EIEE26 CYS-306 AND ARG-401, AND CHARACTERIZATION OF VARIANTS
RP   EIEE26 CYS-306 AND ARG-401.
RX   PubMed=26477325; DOI=10.1038/srep15199;
RA   Saitsu H., Akita T., Tohyama J., Goldberg-Stern H., Kobayashi Y.,
RA   Cohen R., Kato M., Ohba C., Miyatake S., Tsurusaki Y., Nakashima M.,
RA   Miyake N., Fukuda A., Matsumoto N.;
RT   "De novo KCNB1 mutations in infantile epilepsy inhibit repetitive
RT   neuronal firing.";
RL   Sci. Rep. 5:15199-15199(2015).
CC   -!- FUNCTION: Voltage-gated potassium channel that mediates
CC       transmembrane potassium transport in excitable membranes,
CC       primarily in the brain, but also in the pancreas and
CC       cardiovascular system. Contributes to the regulation of the action
CC       potential (AP) repolarization, duration and frequency of
CC       repetitive AP firing in neurons, muscle cells and endocrine cells
CC       and plays a role in homeostatic attenuation of electrical
CC       excitability throughout the brain (PubMed:23161216). Plays also a
CC       role in the regulation of exocytosis independently of its
CC       electrical function (By similarity). Forms tetrameric potassium-
CC       selective channels through which potassium ions pass in accordance
CC       with their electrochemical gradient. The channel alternates
CC       between opened and closed conformations in response to the voltage
CC       difference across the membrane. Homotetrameric channels mediate a
CC       delayed-rectifier voltage-dependent outward potassium current that
CC       display rapid activation and slow inactivation in response to
CC       membrane depolarization (PubMed:8081723, PubMed:1283219,
CC       PubMed:10484328, PubMed:12560340, PubMed:19074135,
CC       PubMed:19717558, PubMed:24901643). Can form functional
CC       homotetrameric and heterotetrameric channels that contain variable
CC       proportions of KCNB2; channel properties depend on the type of
CC       alpha subunits that are part of the channel (By similarity). Can
CC       also form functional heterotetrameric channels with other alpha
CC       subunits that are non-conducting when expressed alone, such as
CC       KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and
CC       KCNV1, creating a functionally diverse range of channel complexes
CC       (PubMed:10484328, PubMed:11852086, PubMed:12060745,
CC       PubMed:19074135, PubMed:19717558, PubMed:24901643).
CC       Heterotetrameric channel activity formed with KCNS3 show increased
CC       current amplitude with the threshold for action potential
CC       activation shifted towards more negative values in hypoxic-treated
CC       pulmonary artery smooth muscle cells (By similarity). Channel
CC       properties are also modulated by cytoplasmic ancillary beta
CC       subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing
CC       activation and inactivation rate of the delayed rectifier
CC       potassium channels (By similarity). In vivo, membranes probably
CC       contain a mixture of heteromeric potassium channel complexes,
CC       making it difficult to assign currents observed in intact tissues
CC       to any particular potassium channel family member. Major
CC       contributor to the slowly inactivating delayed-rectifier voltage-
CC       gated potassium current in neurons of the central nervous system,
CC       sympathetic ganglion neurons, neuroendocrine cells, pancreatic
CC       beta cells, cardiomyocytes and smooth muscle cells. Mediates the
CC       major part of the somatodendritic delayed-rectifier potassium
CC       current in hippocampal and cortical pyramidal neurons and
CC       sympathetic superior cervical ganglion (CGC) neurons that acts to
CC       slow down periods of firing, especially during high frequency
CC       stimulation. Plays a role in the induction of long-term
CC       potentiation (LTP) of neuron excitability in the CA3 layer of the
CC       hippocampus (By similarity). Contributes to the regulation of
CC       glucose-induced action potential amplitude and duration in
CC       pancreatic beta cells, hence limiting calcium influx and insulin
CC       secretion (PubMed:23161216). Plays a role in the regulation of
CC       resting membrane potential and contraction in hypoxia-treated
CC       pulmonary artery smooth muscle cells. May contribute to the
CC       regulation of the duration of both the action potential of
CC       cardiomyocytes and the heart ventricular repolarization QT
CC       interval. Contributes to the pronounced pro-apoptotic potassium
CC       current surge during neuronal apoptotic cell death in response to
CC       oxidative injury. May confer neuroprotection in response to
CC       hypoxia/ischemic insults by suppressing pyramidal neurons
CC       hyperexcitability in hippocampal and cortical regions (By
CC       similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the
CC       cell surface membrane, presumably by forming heterotetrameric
CC       channels with these subunits (PubMed:12060745). Plays a role in
CC       the calcium-dependent recruitment and release of fusion-competent
CC       vesicles from the soma of neurons, neuroendocrine and glucose-
CC       induced pancreatic beta cells by binding key components of the
CC       fusion machinery in a pore-independent manner (By similarity).
CC       {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q03717,
CC       ECO:0000269|PubMed:10484328, ECO:0000269|PubMed:11852086,
CC       ECO:0000269|PubMed:12060745, ECO:0000269|PubMed:12560340,
CC       ECO:0000269|PubMed:1283219, ECO:0000269|PubMed:19074135,
CC       ECO:0000269|PubMed:19717558, ECO:0000269|PubMed:23161216,
CC       ECO:0000269|PubMed:24901643, ECO:0000269|PubMed:8081723}.
CC   -!- ENZYME REGULATION: Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a
CC       spider venom toxin of the tarantula S.calceata (PubMed:14565763).
CC       Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of
CC       the tarantula G.spatulata (PubMed:14565763). Modestly sensitive to
CC       millimolar levels of tetraethylammonium (TEA) (PubMed:8081723,
CC       PubMed:1283219). Modestly sensitive to millimolar levels of 4-
CC       aminopyridine (4-AP). Completely insensitive to toxins such as
CC       dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).
CC       {ECO:0000250|UniProtKB:P15387, ECO:0000269|PubMed:1283219,
CC       ECO:0000269|PubMed:14565763, ECO:0000269|PubMed:8081723,
CC       ECO:0000305|PubMed:10414301, ECO:0000305|PubMed:15858231}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         Note=Homotetrameric channels expressed in xenopus oocytes or in
CC         mammalian non-neuronal cells display delayed-rectifier voltage-
CC         dependent potassium currents which are activated during membrane
CC         depolarization, i.e within a risetime of about 20 msec
CC         (PubMed:8081723, PubMed:1283219). After that, inactivate very
CC         slowly, i.e within more than 5 sec (PubMed:8081723,
CC         PubMed:1283219). Their activation requires low threshold
CC         potentials of about -20 to -30 mV, with a midpoint activation at
CC         about 10 mV. For inactivation, the voltage at half-maximal
CC         amplitude is about -20 mV (PubMed:11852086). The time constant
CC         for recovery after inactivation is about 1.6 sec. Channels have
CC         an unitary conductance of about 8 pS (PubMed:10484328). The
CC         voltage-dependence of activation and inactivation and other
CC         channel characteristics vary depending on the experimental
CC         conditions, the expression system, the presence or absence of
CC         ancillary subunits and post-translational modifications.
CC         {ECO:0000250|UniProtKB:P15387, ECO:0000269|PubMed:10484328,
CC         ECO:0000269|PubMed:11852086, ECO:0000269|PubMed:1283219,
CC         ECO:0000269|PubMed:8081723, ECO:0000305|PubMed:10414301,
CC         ECO:0000305|PubMed:15858231};
CC   -!- SUBUNIT: Homotetramer or heterotetramer with KCNB2
CC       (PubMed:8081723, PubMed:1283219). Heterotetramer with non-
CC       conducting channel-forming alpha subunits such as KCNF1, KCNG1,
CC       KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1
CC       (PubMed:10484328, PubMed:11852086, PubMed:12060745,
CC       PubMed:19357235, PubMed:19074135, PubMed:19717558,
CC       PubMed:24901643). Channel activity is regulated by association
CC       with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and
CC       KCNE3 (By similarity). Self-associates (via N-terminus and C-
CC       terminus) (PubMed:12560340, PubMed:24901643); self-association is
CC       required to regulate trafficking, gating and C-terminal
CC       phosphorylation-dependent modulation of the channel (By
CC       similarity). Interacts (via C-terminus) with STX1A (via C-
CC       terminus); this decreases the rate of channel activation and
CC       increases the rate of channel inactivation in pancreatic beta
CC       cells, induces also neuronal apoptosis in response to oxidative
CC       injury as well as pore-independent enhancement of exocytosis in
CC       neuroendocrine cells, chromaffin cells, pancreatic beta cells and
CC       from the soma of dorsal root ganglia (DRG) neurons. Interacts (via
CC       N-terminus) with SNAP25; this decreases the rate of channel
CC       inactivation in pancreatic beta cells and also increases
CC       interaction during neuronal apoptosis in a N-methyl-D-aspartate
CC       receptor (NMDAR)-dependent manner. Interacts (via N-terminus and
CC       C-terminus) with VAMP2 (via N-terminus); stimulates channel
CC       inactivation rate. Interacts with CREB1; this promotes channel
CC       acetylation in response to stimulation of incretin hormones.
CC       Interacts (via N-terminus and C-terminus) with MYL12B. Interacts
CC       (via N-terminus) with PIAS3; this increases the number of
CC       functional channels at the cell surface (By similarity). Interacts
CC       with SUMO1 (PubMed:19223394). Interacts (via phosphorylated form)
CC       with PTPRE; this reduces phosphorylation and channel activity in
CC       heterologous cells (By similarity). {ECO:0000250|UniProtKB:P15387,
CC       ECO:0000250|UniProtKB:Q03717, ECO:0000269|PubMed:10484328,
CC       ECO:0000269|PubMed:11852086, ECO:0000269|PubMed:12060745,
CC       ECO:0000269|PubMed:12560340, ECO:0000269|PubMed:1283219,
CC       ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:19223394,
CC       ECO:0000269|PubMed:19357235, ECO:0000269|PubMed:19717558,
CC       ECO:0000269|PubMed:24901643, ECO:0000269|PubMed:8081723}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10484328,
CC       ECO:0000269|PubMed:11852086, ECO:0000269|PubMed:12060745,
CC       ECO:0000269|PubMed:12560340, ECO:0000269|PubMed:1283219,
CC       ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:19223394,
CC       ECO:0000269|PubMed:19717558, ECO:0000269|PubMed:24477962,
CC       ECO:0000269|PubMed:24901643, ECO:0000269|PubMed:26503721,
CC       ECO:0000269|PubMed:8081723}. Perikaryon
CC       {ECO:0000269|PubMed:24477962}. Cell projection, axon
CC       {ECO:0000269|PubMed:24477962}. Cell projection, dendrite
CC       {ECO:0000269|PubMed:24477962}. Membrane; Multi-pass membrane
CC       protein. Cell junction, synapse, postsynaptic cell membrane
CC       {ECO:0000250|UniProtKB:P15387}. Cell junction, synapse
CC       {ECO:0000250|UniProtKB:P15387}. Cell junction, synapse,
CC       synaptosome {ECO:0000250|UniProtKB:P15387}. Lateral cell membrane
CC       {ECO:0000250|UniProtKB:P15387}. Cell membrane, sarcolemma
CC       {ECO:0000250|UniProtKB:P15387}. Note=Localizes to high-density
CC       somatodendritic clusters and non-clustered sites on the surface of
CC       neocortical and hippocampal pyramidal neurons in a cortical actin
CC       cytoskeleton-dependent manner (PubMed:24477962). Localizes also to
CC       high-density clusters in the axon initial segment (AIS), at
CC       ankyrin-G-deficient sites, on the surface of neocortical and
CC       hippocampal pyramidal neurons (PubMed:24477962). KCNB1-containing
CC       AIS clusters localize either in close apposition to smooth
CC       endoplasmic reticulum cisternal organelles or with GABA-A
CC       receptor-containing synapses of hippocampal and cortical pyramidal
CC       neurons, respectively (PubMed:24477962). Localizes to high-density
CC       clusters on the cell surface of atrial and ventricular myocytes
CC       and at the lateral plasma membrane in epithelial cells. Localizes
CC       both to the axial and transverse tubules (T tubule) and sarcolemma
CC       in ventricular myocytes. Associated with lipid raft domains. In
CC       cortical neurons, apoptotic injuries induce de novo plasma
CC       membrane insertion in a SNARE-dependent manner causing an
CC       apoptotic potassium current surge. {ECO:0000250|UniProtKB:P15387,
CC       ECO:0000250|UniProtKB:Q03717, ECO:0000269|PubMed:12060745,
CC       ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:24477962,
CC       ECO:0000269|PubMed:24901643}.
CC   -!- TISSUE SPECIFICITY: Expressed in neocortical pyramidal cells
CC       (PubMed:24477962). Expressed in pancreatic beta cells (at protein
CC       level) (PubMed:12403834, PubMed:14988243). Expressed in brain,
CC       heart, lung, liver, colon, kidney and adrenal gland
CC       (PubMed:19074135). Expressed in the cortex, amygdala, cerebellum,
CC       pons, thalamus, hypothalamus, hippocampus and substantia nigra
CC       (PubMed:19074135). {ECO:0000269|PubMed:12403834,
CC       ECO:0000269|PubMed:14988243, ECO:0000269|PubMed:19074135,
CC       ECO:0000269|PubMed:24477962}.
CC   -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor
CC       and is characterized by a series of positively charged amino acids
CC       at every third position. Channel opening and closing is effected
CC       by a conformation change that affects the position and orientation
CC       of the voltage-sensor paddle formed by S3 and S4 within the
CC       membrane. A transmembrane electric field that is positive inside
CC       would push the positively charged S4 segment outwards, thereby
CC       opening the pore, while a field that is negative inside would pull
CC       the S4 segment inwards and close the pore. Changes in the position
CC       and orientation of S4 are then transmitted to the activation gate
CC       formed by the inner helix bundle via the S4-S5 linker region.
CC       {ECO:0000250|UniProtKB:P63142}.
CC   -!- DOMAIN: The N-terminal and C-terminal cytoplasmic regions mediate
CC       homooligomerization; self-association is required to regulate
CC       trafficking, gating and C-terminal phosphorylation-dependent
CC       modulation of the channel (PubMed:11852086, PubMed:12060745,
CC       PubMed:12560340, PubMed:19074135, PubMed:24901643). The N-terminal
CC       cytoplasmic region is important for interaction with other
CC       channel-forming alpha subunits and with ancillary beta subunits
CC       (PubMed:24901643). The C-terminus is necessary and sufficient for
CC       the restricted localization to, and clustering within, both in
CC       soma and proximal portions of dendrite of neurons and in lateral
CC       membrane of non-neuronal polarized cells. The C-terminus is both
CC       necessary and sufficient as a mediator of cholinergic and calcium-
CC       stimulated modulation of channel cell membrane clustering
CC       localization and activity in hippocampal neurons (By similarity).
CC       {ECO:0000250|UniProtKB:P15387, ECO:0000269|PubMed:11852086,
CC       ECO:0000269|PubMed:12060745, ECO:0000269|PubMed:12560340,
CC       ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:24901643}.
CC   -!- PTM: Phosphorylated. Differential C-terminal phosphorylation on a
CC       subset of serines allows graded activity-dependent regulation of
CC       channel gating in hippocampal neurons. Ser-607 and Tyr-128 are
CC       significant sites of voltage-gated regulation through
CC       phosphorylation/dephosphorylation activities. Tyr-128 can be
CC       phosphorylated by Src and dephosphorylated by cytoplasmic form of
CC       the phosphatase PTPRE. CDK5-induced Ser-607 phosphorylation
CC       increases in response to acute blockade of neuronal activity.
CC       Phosphorylated on Tyr-128 by Src and on Ser-805 by MAPK14/P38MAPK;
CC       phosphorylations are necessary and sufficient for an increase in
CC       plasma membrane insertion, apoptotic potassium current surge and
CC       completion of the neuronal cell death program. Phosphorylated on
CC       Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is
CC       necessary for KCNB1 channel clustering formation. The Ser-607
CC       phosphorylation state differs between KCNB1-containing clusters on
CC       the proximal and distal portions of the axon initial segment
CC       (AIS). Highly phosphorylated on serine residues in the C-terminal
CC       cytoplasmic tail in resting neurons. Phosphorylated in pancreatic
CC       beta cells in response to incretin hormones stimulation in a PKA-
CC       and RPS6KA5/MSK1-dependent signaling pathway, promoting beta cell
CC       survival. Phosphorylation on Ser-567 is reduced during postnatal
CC       development with low levels at P2 and P5; levels then increase to
CC       reach adult levels by P14. Phosphorylation on Ser-457, Ser-541,
CC       Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal
CC       Ser-15 are sensitive to calcineurin-mediated dephosphorylation
CC       contributing to the modulation of the voltage-dependent gating
CC       properties. Dephosphorylation by phosphatase PTPRE confers
CC       neuroprotection by its inhibitory influence on the neuronal
CC       apoptotic potassium current surge in a Zn(2+)-dependent manner.
CC       Dephosphorylated at Ser-607 by protein phosphatase PPP1CA.
CC       Hypoxia-, seizure- or glutamate-induced neuronal activity promote
CC       calcium/calcineurin-dependent dephosphorylation resulting in a
CC       loss of KCNB1-containing clustering and enhanced channel activity.
CC       In response to brain ischemia, Ser-567 and Ser-607 are strongly
CC       dephosphorylated while Ser-457 and Ser-720 are less
CC       dephosphorylated. In response to brain seizures, phosphorylation
CC       levels on Ser-567 and Ser-607 are greatly reduced.
CC       Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein
CC       kinases and tyrosine phosphatase PTPRE in primary Schwann cells
CC       and sciatic nerve tissue (By similarity).
CC       {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q03717}.
CC   -!- PTM: Acetylated. Acetylation occurs in pancreatic beta cells in
CC       response to stimulation by incretin hormones in a histone
CC       acetyltransferase (HAT)/histone deacetylase (HDAC)-dependent
CC       signaling pathway, promoting beta cell survival.
CC       {ECO:0000250|UniProtKB:P15387}.
CC   -!- PTM: Sumoylated on Lys-474, preferentially with SUMO1; sumoylation
CC       induces a positive shift in the voltage-dependence of activation
CC       and inhibits channel activity (PubMed:19223394). Sumoylation
CC       increases the frequency of repetitive action potential firing at
CC       the cell surface of hippocampal neurons and decreases its
CC       frequency in pancreatic beta cells (PubMed:19223394). Desumoylated
CC       by SENP1 (PubMed:19223394). {ECO:0000269|PubMed:19223394}.
CC   -!- DISEASE: Epileptic encephalopathy, early infantile, 26 (EIEE26)
CC       [MIM:616056]: A form of epileptic encephalopathy, a heterogeneous
CC       group of severe childhood onset epilepsies characterized by
CC       refractory seizures, neurodevelopmental impairment, and poor
CC       prognosis. Development is normal prior to seizure onset, after
CC       which cognitive and motor delays become apparent. EIEE26 patients
CC       manifest multiple types of seizures, delayed psychomotor
CC       development, poor or absent speech, hypotonia, hypsarrhythmia.
CC       {ECO:0000269|PubMed:25164438, ECO:0000269|PubMed:26477325,
CC       ECO:0000269|PubMed:26503721}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the potassium channel family. B (Shab)
CC       (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA36156.1; Type=Erroneous initiation; Evidence={ECO:0000305};
DR   EMBL; X68302; CAA48374.1; -; Genomic_DNA.
DR   EMBL; L02840; AAA36156.1; ALT_INIT; mRNA.
DR   EMBL; AF026005; AAB88808.1; -; mRNA.
DR   EMBL; AL035685; CAB89417.1; -; Genomic_DNA.
DR   CCDS; CCDS13418.1; -.
DR   PIR; S31761; S31761.
DR   RefSeq; NP_004966.1; NM_004975.3.
DR   RefSeq; XP_006723847.1; XM_006723784.3.
DR   RefSeq; XP_011527101.1; XM_011528799.2.
DR   UniGene; Hs.633143; -.
DR   UniGene; Hs.84244; -.
DR   ProteinModelPortal; Q14721; -.
DR   SMR; Q14721; -.
DR   BioGrid; 109947; 15.
DR   IntAct; Q14721; 1.
DR   STRING; 9606.ENSP00000360806; -.
DR   ChEMBL; CHEMBL2363000; -.
DR   DrugBank; DB06637; Dalfampridine.
DR   GuidetoPHARMACOLOGY; 546; -.
DR   TCDB; 1.A.1.2.11; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; Q14721; -.
DR   PhosphoSitePlus; Q14721; -.
DR   BioMuta; KCNB1; -.
DR   DMDM; 24418854; -.
DR   OGP; Q14721; -.
DR   MaxQB; Q14721; -.
DR   PaxDb; Q14721; -.
DR   PeptideAtlas; Q14721; -.
DR   PRIDE; Q14721; -.
DR   DNASU; 3745; -.
DR   Ensembl; ENST00000371741; ENSP00000360806; ENSG00000158445.
DR   Ensembl; ENST00000635465; ENSP00000489193; ENSG00000158445.
DR   GeneID; 3745; -.
DR   KEGG; hsa:3745; -.
DR   UCSC; uc002xur.2; human.
DR   CTD; 3745; -.
DR   DisGeNET; 3745; -.
DR   GeneCards; KCNB1; -.
DR   HGNC; HGNC:6231; KCNB1.
DR   HPA; CAB001979; -.
DR   HPA; HPA042434; -.
DR   MalaCards; KCNB1; -.
DR   MIM; 600397; gene.
DR   MIM; 616056; phenotype.
DR   neXtProt; NX_Q14721; -.
DR   OpenTargets; ENSG00000158445; -.
DR   Orphanet; 1934; Early infantile epileptic encephalopathy.
DR   PharmGKB; PA209; -.
DR   eggNOG; KOG3713; Eukaryota.
DR   eggNOG; COG1226; LUCA.
DR   GeneTree; ENSGT00760000118981; -.
DR   HOGENOM; HOG000113206; -.
DR   HOVERGEN; HBG052225; -.
DR   InParanoid; Q14721; -.
DR   KO; K04885; -.
DR   OMA; TEGVIDM; -.
DR   OrthoDB; EOG091G0FP3; -.
DR   PhylomeDB; Q14721; -.
DR   TreeFam; TF313103; -.
DR   BioCyc; ZFISH:ENSG00000158445-MONOMER; -.
DR   Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR   Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR   SIGNOR; Q14721; -.
DR   GeneWiki; KCNB1; -.
DR   GenomeRNAi; 3745; -.
DR   PRO; PR:Q14721; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   Bgee; ENSG00000158445; -.
DR   CleanEx; HS_KCNB1; -.
DR   Genevisible; Q14721; HS.
DR   GO; GO:0030424; C:axon; ISS:UniProtKB.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR   GO; GO:0005622; C:intracellular; IEA:GOC.
DR   GO; GO:0016328; C:lateral plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR   GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR   GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0044325; F:ion channel binding; IPI:UniProtKB.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR   GO; GO:0032182; F:ubiquitin-like protein binding; IPI:UniProtKB.
DR   GO; GO:0001508; P:action potential; IDA:UniProtKB.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB.
DR   GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR   GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR   GO; GO:0007215; P:glutamate receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0046676; P:negative regulation of insulin secretion; ISS:UniProtKB.
DR   GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; ISS:UniProtKB.
DR   GO; GO:0033605; P:positive regulation of catecholamine secretion; ISS:UniProtKB.
DR   GO; GO:1900454; P:positive regulation of long term synaptic depression; ISS:UniProtKB.
DR   GO; GO:0010701; P:positive regulation of norepinephrine secretion; ISS:UniProtKB.
DR   GO; GO:0090314; P:positive regulation of protein targeting to membrane; IDA:UniProtKB.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR   GO; GO:0072661; P:protein targeting to plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098900; P:regulation of action potential; ISS:UniProtKB.
DR   GO; GO:0050796; P:regulation of insulin secretion; TAS:Reactome.
DR   GO; GO:2000671; P:regulation of motor neuron apoptotic process; ISS:UniProtKB.
DR   GO; GO:0006904; P:vesicle docking involved in exocytosis; ISS:UniProtKB.
DR   Gene3D; 1.20.120.350; -; 1.
DR   InterPro; IPR000210; BTB/POZ_dom.
DR   InterPro; IPR027359; Channel_four-helix_dom.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR   InterPro; IPR003973; K_chnl_volt-dep_Kv2.
DR   InterPro; IPR004350; K_chnl_volt-dep_Kv2.1.
DR   InterPro; IPR011333; SKP1/BTB/POZ.
DR   InterPro; IPR003131; T1-type_BTB.
DR   InterPro; IPR028325; VG_K_chnl.
DR   PANTHER; PTHR11537; PTHR11537; 1.
DR   Pfam; PF02214; BTB_2; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF03521; Kv2channel; 2.
DR   PRINTS; PR00169; KCHANNEL.
DR   PRINTS; PR01514; KV21CHANNEL.
DR   PRINTS; PR01491; KVCHANNEL.
DR   PRINTS; PR01495; SHABCHANNEL.
DR   SMART; SM00225; BTB; 1.
DR   SUPFAM; SSF54695; SSF54695; 1.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Cell projection; Complete proteome;
KW   Disease mutation; Epilepsy; Exocytosis; Ion channel; Ion transport;
KW   Isopeptide bond; Membrane; Phosphoprotein; Polymorphism;
KW   Postsynaptic cell membrane; Potassium; Potassium channel;
KW   Potassium transport; Reference proteome; Synapse; Synaptosome;
KW   Transmembrane; Transmembrane helix; Transport; Ubl conjugation;
KW   Voltage-gated channel.
FT   CHAIN         1    858       Potassium voltage-gated channel subfamily
FT                                B member 1.
FT                                /FTId=PRO_0000054042.
FT   TOPO_DOM      1    186       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    187    208       Helical; Name=Segment S1.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    209    228       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    229    250       Helical; Name=Segment S2.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    251    259       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    260    280       Helical; Name=Segment S3.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    281    294       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    295    316       Helical; Voltage-sensor; Name=Segment S4.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    317    330       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    331    351       Helical; Name=Segment S5.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    352    364       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   INTRAMEM    365    376       Helical; Name=Pore helix.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   INTRAMEM    377    384       {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    385    391       Extracellular.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TRANSMEM    392    420       Helical; Name=Segment S6.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   TOPO_DOM    421    858       Cytoplasmic.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   REGION       59     75       Self-association.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   REGION      448    481       Self-association.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOTIF       377    382       Selectivity filter.
FT                                {ECO:0000250|UniProtKB:P63142}.
FT   COMPBIAS    517    520       Poly-Ser.
FT   COMPBIAS    701    706       Poly-Ala.
FT   MOD_RES      15     15       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     128    128       Phosphotyrosine; by Src.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     444    444       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03717}.
FT   MOD_RES     457    457       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q03717}.
FT   MOD_RES     484    484       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     496    496       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     503    503       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     519    519       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     520    520       Phosphoserine; by CDK5; in vitro.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     541    541       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     567    567       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     590    590       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     607    607       Phosphoserine; by CDK5.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     656    656       Phosphoserine; by CDK5; in vitro.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     720    720       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     772    772       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     800    800       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   MOD_RES     805    805       Phosphoserine; by CDK5, MAPK14; in vitro.
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   CROSSLNK    474    474       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000250|UniProtKB:P15387}.
FT   VARIANT     306    306       R -> C (in EIEE26; reduces sensitivity
FT                                and cooperativity of the voltage sensor
FT                                for channel opening and greatly
FT                                suppresses repetitive firing in cultured
FT                                cortical neurons).
FT                                {ECO:0000269|PubMed:26477325}.
FT                                /FTId=VAR_075573.
FT   VARIANT     347    347       S -> R (in EIEE26; inhibits ion
FT                                selectivity and gain of a depolarizing
FT                                inward cation conductance; trafficks
FT                                normally to the cell surface;
FT                                dbSNP:rs587777848).
FT                                {ECO:0000269|PubMed:25164438}.
FT                                /FTId=VAR_071991.
FT   VARIANT     374    374       T -> I (in EIEE26; inhibits ion
FT                                selectivity and gain of a depolarizing
FT                                inward cation conductance; trafficks
FT                                normally to the cell surface;
FT                                dbSNP:rs587777849).
FT                                {ECO:0000269|PubMed:25164438}.
FT                                /FTId=VAR_071992.
FT   VARIANT     378    378       V -> A (in EIEE26; change in the ion
FT                                selectivity from potassium-selective to
FT                                nonselective cation channels and
FT                                significant decrease in cell membrane
FT                                localization).
FT                                {ECO:0000269|PubMed:26503721}.
FT                                /FTId=VAR_075574.
FT   VARIANT     379    379       G -> R (in EIEE26; inhibits ion
FT                                selectivity and gain of a depolarizing
FT                                inward cation conductance; trafficks
FT                                normally to the cell surface;
FT                                dbSNP:rs587777850).
FT                                {ECO:0000269|PubMed:25164438}.
FT                                /FTId=VAR_071993.
FT   VARIANT     401    401       G -> R (in EIEE26; dominant-negative
FT                                mutation resulting in loss of endogenous
FT                                channel currents and greatly suppresses
FT                                repetitive firing in cultured cortical
FT                                neurons). {ECO:0000269|PubMed:26477325}.
FT                                /FTId=VAR_075575.
FT   VARIANT     616    616       T -> N (in dbSNP:rs2229006).
FT                                /FTId=VAR_062182.
FT   VARIANT     616    616       T -> S (in dbSNP:rs2229006).
FT                                /FTId=VAR_062183.
FT   VARIANT     825    825       P -> S (in dbSNP:rs34467662).
FT                                /FTId=VAR_034049.
FT   VARIANT     857    857       S -> N (in dbSNP:rs34280195).
FT                                /FTId=VAR_062184.
FT   MUTAGEN      71     71       E->Q: No effect on channel activity.
FT                                {ECO:0000269|PubMed:12560340}.
FT   MUTAGEN      74     74       D->R: Reduces interaction with KCNG1 and
FT                                self-interaction and impairs plasma
FT                                membrane subcellular localization,
FT                                homotetramerization and
FT                                hetetrotetramerization with KCNG4; when
FT                                associated with R-75.
FT                                {ECO:0000269|PubMed:19717558,
FT                                ECO:0000269|PubMed:24901643}.
FT   MUTAGEN      75     75       D->R: Reduces interaction with KCNG1 and
FT                                self-interaction and impairs plasma
FT                                membrane subcellular localization,
FT                                homotetramerization and
FT                                hetetrotetramerization with KCNG4; when
FT                                associated with R-74.
FT                                {ECO:0000269|PubMed:19717558,
FT                                ECO:0000269|PubMed:24901643}.
FT   MUTAGEN      79     79       D->E: Increases channel activity.
FT                                {ECO:0000269|PubMed:12560340}.
FT   MUTAGEN     105    105       H->V,R: Reduces channel activity.
FT                                Inhibits interaction with KCNG4. Impairs
FT                                hetetrotetramerization with KCNG1, KCNG3
FT                                or KCNG4. Does not impair
FT                                homotetramerization.
FT                                {ECO:0000269|PubMed:19074135}.
CC   --------------------------------------------------------------------------
CC   The following FT lines are automated annotations from the MyHits database.
CC   --------------------------------------------------------------------------
FT   MYHIT       467    614       ipfam:Kv2channel [T]
FT   MYHIT       649    680       ipfam:Kv2channel [T]
FT   MYHIT        31    140       ismart:BTB [T]
FT   MYHIT        33    132       ipfam:BTB_2 [T]
FT   MYHIT       189    423       ipfam:Ion_trans [T]
SQ   SEQUENCE   858 AA;  95878 MW;  C4B426174ED0DEE4 CRC64;
     MPAGMTKHGS RSTSSLPPEP MEIVRSKACS RRVRLNVGGL AHEVLWRTLD RLPRTRLGKL
     RDCNTHDSLL EVCDDYSLDD NEYFFDRHPG AFTSILNFYR TGRLHMMEEM CALSFSQELD
     YWGIDEIYLE SCCQARYHQK KEQMNEELKR EAETLREREG EEFDNTCCAE KRKKLWDLLE
     KPNSSVAAKI LAIISIMFIV LSTIALSLNT LPELQSLDEF GQSTDNPQLA HVEAVCIAWF
     TMEYLLRFLS SPKKWKFFKG PLNAIDLLAI LPYYVTIFLT ESNKSVLQFQ NVRRVVQIFR
     IMRILRILKL ARHSTGLQSL GFTLRRSYNE LGLLILFLAM GIMIFSSLVF FAEKDEDDTK
     FKSIPASFWW ATITMTTVGY GDIYPKTLLG KIVGGLCCIA GVLVIALPIP IIVNNFSEFY
     KEQKRQEKAI KRREALERAK RNGSIVSMNM KDAFARSIEM MDIVVEKNGE NMGKKDKVQD
     NHLSPNKWKW TKRTLSETSS SKSFETKEQG SPEKARSSSS PQHLNVQQLE DMYNKMAKTQ
     SQPILNTKES AAQSKPKEEL EMESIPSPVA PLPTRTEGVI DMRSMSSIDS FISCATDFPE
     ATRFSHSPLT SLPSKTGGST APEVGWRGAL GASGGRFVEA NPSPDASQHS SFFIESPKSS
     MKTNNPLKLR ALKVNFMEGD PSPLLPVLGM YHDPLRNRGS AAAAVAGLEC ATLLDKAVLS
     PESSIYTTAS AKTPPRSPEK HTAIAFNFEA GVHQYIDADT DDEGQLLYSV DSSPPKSLPG
     STSPKFSTGT RSEKNHFESS PLPTSPKFLR QNCIYSTEAL TGKGPSGQEK CKLENHISPD
     VRVLPGGGAH GSTRDQSI
//