KCNB1_HUMAN
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 03-AUG-2022, entry version 182.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVITY REGULATION, AND SUBCELLULAR 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, ACTIVITY 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 clonal
RT 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, Academic
RL 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., 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 LOCATION.
RX PubMed=10484328; DOI=10.1152/ajpcell.1999.277.3.c412;
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., Wheeler M.B.,
RA Cattral M.S., Lakey J.R., Salapatek A.M., Lotan I., Gaisano H.Y.;
RT "Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-
RT dependent K(+) channels in neuroendocrine islet beta-cells through an
RT 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 Kv
RT channel alpha-subunits identified in the human genome.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7986-7991(2002).
RN [10]
RP ACTIVITY 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 in
RT mammalian voltage-dependent potassium channels.";
RL Chem. Res. Toxicol. 16:1217-1225(2003).
RN [11]
RP FUNCTION, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP 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 Kv2.1
RT 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., Slaughter R.S.,
RA 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 vascular
RT 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., Van Bogaert P.P.,
RA Snyders D.J.;
RT "Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in
RT 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 Kv2.1
RT 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 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 is
RT determined by interactions between the N- and C-termini.";
RL PLoS ONE 9:E98960-E98960(2014).
RN [21]
RP VARIANTS DEE26 ARG-347; ILE-374 AND ARG-379, CHARACTERIZATION OF VARIANTS
RP DEE26 ARG-347; ILE-374 AND ARG-379, AND INVOLVEMENT IN DEE26.
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., George A.L. Jr.,
RA Kearney J.A.;
RT "De novo KCNB1 mutations in epileptic encephalopathy.";
RL Ann. Neurol. 76:529-540(2014).
RN [22]
RP VARIANT DEE26 ALA-378, CHARACTERIZATION OF VARIANT DEE26 ALA-378, AND
RP 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., Safina N.P.,
RA Grote L., Farrow E.G., Miller N., Soden S., Kingsmore S.F., Trimmer J.S.,
RA 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 DEE26 CYS-306 AND ARG-401, AND CHARACTERIZATION OF VARIANTS DEE26
RP CYS-306 AND ARG-401.
RX PubMed=26477325; DOI=10.1038/srep15199;
RA Saitsu H., Akita T., Tohyama J., Goldberg-Stern H., Kobayashi Y., Cohen R.,
RA Kato M., Ohba C., Miyatake S., Tsurusaki Y., Nakashima M., Miyake N.,
RA Fukuda A., Matsumoto N.;
RT "De novo KCNB1 mutations in infantile epilepsy inhibit repetitive neuronal
RT firing.";
RL Sci. Rep. 5:15199-15199(2015).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes, primarily in the brain, but
CC also in the pancreas and cardiovascular system. Contributes to the
CC regulation of the action potential (AP) repolarization, duration and
CC frequency of repetitive AP firing in neurons, muscle cells and
CC endocrine cells and plays a role in homeostatic attenuation of
CC electrical excitability throughout the brain (PubMed:23161216). Plays
CC also a 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 with
CC their electrochemical gradient. The channel alternates between opened
CC and closed conformations in response to the voltage difference across
CC the membrane. Homotetrameric channels mediate a delayed-rectifier
CC voltage-dependent outward potassium current that display rapid
CC activation and slow inactivation in response to membrane depolarization
CC (PubMed:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340,
CC PubMed:19074135, 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 alpha
CC subunits that are part of the channel (By similarity). Can also form
CC functional heterotetrameric channels with other alpha subunits that are
CC non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3,
CC KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a
CC functionally diverse range of channel complexes (PubMed:10484328,
CC PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558,
CC PubMed:24901643). Heterotetrameric channel activity formed with KCNS3
CC show increased current amplitude with the threshold for action
CC potential activation shifted towards more negative values in hypoxic-
CC treated pulmonary artery smooth muscle cells (By similarity). Channel
CC properties are also modulated by cytoplasmic ancillary beta subunits
CC such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and
CC inactivation rate of the delayed rectifier potassium channels (By
CC similarity). In vivo, membranes probably contain a mixture of
CC heteromeric potassium channel complexes, making it difficult to assign
CC currents observed in intact tissues to any particular potassium channel
CC family member. Major contributor to the slowly inactivating delayed-
CC rectifier voltage-gated potassium current in neurons of the central
CC nervous system, sympathetic ganglion neurons, neuroendocrine cells,
CC pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates
CC the major part of the somatodendritic delayed-rectifier potassium
CC current in hippocampal and cortical pyramidal neurons and sympathetic
CC superior cervical ganglion (CGC) neurons that acts to slow down periods
CC of firing, especially during high frequency stimulation. Plays a role
CC in the induction of long-term potentiation (LTP) of neuron excitability
CC in the CA3 layer of the hippocampus (By similarity). Contributes to the
CC regulation of glucose-induced action potential amplitude and duration
CC in pancreatic beta cells, hence limiting calcium influx and insulin
CC secretion (PubMed:23161216). Plays a role in the regulation of resting
CC membrane potential and contraction in hypoxia-treated pulmonary artery
CC smooth muscle cells. May contribute to the regulation of the duration
CC of both the action potential of cardiomyocytes and the heart
CC ventricular repolarization QT interval. Contributes to the pronounced
CC pro-apoptotic potassium current surge during neuronal apoptotic cell
CC death in response to oxidative injury. May confer neuroprotection in
CC response to hypoxia/ischemic insults by suppressing pyramidal neurons
CC hyperexcitability in hippocampal and cortical regions (By similarity).
CC Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface
CC membrane, presumably by forming heterotetrameric channels with these
CC subunits (PubMed:12060745). Plays a role in the calcium-dependent
CC recruitment and release of fusion-competent vesicles from the soma of
CC neurons, neuroendocrine and glucose-induced pancreatic beta cells by
CC binding key components of the fusion machinery in a pore-independent
CC manner (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:19717558,
CC ECO:0000269|PubMed:23161216, ECO:0000269|PubMed:24901643,
CC ECO:0000269|PubMed:8081723}.
CC -!- ACTIVITY 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 the
CC 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 slowly,
CC i.e within more than 5 sec (PubMed:8081723, PubMed:1283219). Their
CC activation requires low threshold potentials of about -20 to -30 mV,
CC with a midpoint activation at about 10 mV. For inactivation, the
CC voltage at half-maximal amplitude is about -20 mV (PubMed:11852086).
CC The time constant for recovery after inactivation is about 1.6 sec.
CC Channels have an unitary conductance of about 8 pS (PubMed:10484328).
CC The 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:0000269|PubMed:10484328, ECO:0000269|PubMed:11852086,
CC ECO:0000269|PubMed:1283219, ECO:0000269|PubMed:8081723,
CC ECO:0000305|PubMed:10414301, ECO:0000305|PubMed:15858231};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCNB2 (PubMed:8081723,
CC PubMed:1283219). Heterotetramer with non-conducting channel-forming
CC alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1,
CC KCNS2, KCNS3 and KCNV1 (PubMed:10484328, PubMed:11852086,
CC PubMed:12060745, PubMed:19357235, PubMed:19074135, PubMed:19717558,
CC PubMed:24901643). Channel activity is regulated by association with
CC ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (By
CC similarity). Self-associates (via N-terminus and C-terminus)
CC (PubMed:12560340, PubMed:24901643); self-association is required to
CC regulate trafficking, gating and C-terminal phosphorylation-dependent
CC modulation of the channel (By similarity). Interacts (via C-terminus)
CC with STX1A (via C-terminus); this decreases the rate of channel
CC activation and increases the rate of channel inactivation in pancreatic
CC beta 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 from
CC the soma of dorsal root ganglia (DRG) neurons. Interacts (via N-
CC terminus) with SNAP25; this decreases the rate of channel inactivation
CC in pancreatic beta cells and also increases interaction during neuronal
CC apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner.
CC Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus);
CC stimulates channel inactivation rate. Interacts with CREB1; this
CC promotes channel acetylation in response to stimulation of incretin
CC hormones. Interacts (via N-terminus and C-terminus) with MYL12B.
CC Interacts (via N-terminus) with PIAS3; this increases the number of
CC functional channels at the cell surface (By similarity). Interacts with
CC SUMO1 (PubMed:19223394). Interacts (via phosphorylated form) with
CC 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 {ECO:0000269|PubMed:24477962}.
CC Cell projection, axon {ECO:0000269|PubMed:24477962}. Cell projection,
CC dendrite {ECO:0000269|PubMed:24477962}. Membrane; Multi-pass membrane
CC protein. Postsynaptic cell membrane {ECO:0000250|UniProtKB:P15387}.
CC Synapse {ECO:0000250|UniProtKB:P15387}. Synapse, synaptosome
CC {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 ankyrin-G-
CC deficient sites, on the surface of neocortical and hippocampal
CC pyramidal neurons (PubMed:24477962). KCNB1-containing AIS clusters
CC localize either in close apposition to smooth endoplasmic reticulum
CC cisternal organelles or with GABA-A receptor-containing synapses of
CC hippocampal and cortical pyramidal neurons, respectively
CC (PubMed:24477962). Localizes to high-density clusters on the cell
CC surface of atrial and ventricular myocytes and at the lateral plasma
CC membrane in epithelial cells. Localizes both to the axial and
CC transverse tubules (T tubule) and sarcolemma in ventricular myocytes.
CC Associated with lipid raft domains. In cortical neurons, apoptotic
CC injuries induce de novo plasma membrane insertion in a SNARE-dependent
CC manner causing an apoptotic potassium current surge.
CC {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q03717,
CC ECO:0000269|PubMed:12060745, ECO:0000269|PubMed:19074135,
CC ECO:0000269|PubMed:24477962, 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, heart,
CC lung, liver, colon, kidney and adrenal gland (PubMed:19074135).
CC Expressed in the cortex, amygdala, cerebellum, pons, thalamus,
CC hypothalamus, hippocampus and substantia nigra (PubMed:19074135).
CC {ECO:0000269|PubMed:12403834, ECO:0000269|PubMed:14988243,
CC ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:24477962}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {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 modulation
CC of the channel (PubMed:11852086, PubMed:12060745, PubMed:12560340,
CC PubMed:19074135, PubMed:24901643). The N-terminal cytoplasmic region is
CC important for interaction with other channel-forming alpha subunits and
CC with ancillary beta subunits (PubMed:24901643). The C-terminus is
CC necessary and sufficient for the restricted localization to, and
CC clustering within, both in soma and proximal portions of dendrite of
CC neurons and in lateral membrane of non-neuronal polarized cells. The C-
CC terminus is both necessary and sufficient as a mediator of cholinergic
CC and calcium-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 the
CC phosphatase PTPRE. CDK5-induced Ser-607 phosphorylation increases in
CC response to acute blockade of neuronal activity. Phosphorylated on Tyr-
CC 128 by Src and on Ser-805 by MAPK14/P38MAPK; phosphorylations are
CC necessary and sufficient for an increase in plasma membrane insertion,
CC apoptotic potassium current surge and completion of the neuronal cell
CC death program. Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805
CC by CDK5; phosphorylation is necessary for KCNB1 channel clustering
CC formation. The Ser-607 phosphorylation state differs between KCNB1-
CC containing clusters on the proximal and distal portions of the axon
CC initial segment (AIS). Highly phosphorylated on serine residues in the
CC C-terminal cytoplasmic tail in resting neurons. Phosphorylated in
CC pancreatic beta cells in response to incretin hormones stimulation in a
CC PKA- 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 reach
CC adult levels by P14. Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-
CC 607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive
CC to calcineurin-mediated dephosphorylation contributing to the
CC modulation of the voltage-dependent gating properties.
CC Dephosphorylation by phosphatase PTPRE confers neuroprotection by its
CC inhibitory influence on the neuronal apoptotic potassium current surge
CC in a Zn(2+)-dependent manner. Dephosphorylated at Ser-607 by protein
CC phosphatase PPP1CA. Hypoxia-, seizure- or glutamate-induced neuronal
CC activity promote calcium/calcineurin-dependent dephosphorylation
CC resulting in a loss of KCNB1-containing clustering and enhanced channel
CC activity. In response to brain ischemia, Ser-567 and Ser-607 are
CC strongly dephosphorylated while Ser-457 and Ser-720 are less
CC dephosphorylated. In response to brain seizures, phosphorylation levels
CC on Ser-567 and Ser-607 are greatly reduced.
CC Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases
CC and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic
CC nerve tissue (By similarity). {ECO:0000250|UniProtKB:P15387,
CC 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 signaling
CC pathway, promoting beta cell survival. {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 and
CC inhibits channel activity (PubMed:19223394). Sumoylation increases the
CC frequency of repetitive action potential firing at the cell surface of
CC hippocampal neurons and decreases its frequency in pancreatic beta
CC cells (PubMed:19223394). Desumoylated by SENP1 (PubMed:19223394).
CC {ECO:0000269|PubMed:19223394}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 26 (DEE26)
CC [MIM:616056]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE26 patients manifest multiple types of seizures,
CC delayed psychomotor development, poor or absent speech, hypotonia,
CC hypsarrhythmia. {ECO:0000269|PubMed:25164438,
CC ECO:0000269|PubMed:26477325, ECO:0000269|PubMed:26503721}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the potassium channel family. B (Shab) (TC
CC 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};
CC ---------------------------------------------------------------------------
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DR EMBL; X68302; CAA48374.1; -; Genomic_DNA.
DR EMBL; L02840; AAA36156.1; ALT_INIT; mRNA.
DR EMBL; AF026005; AAB88808.1; -; mRNA.
DR EMBL; AL035685; -; NOT_ANNOTATED_CDS; 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 AlphaFoldDB; Q14721; -.
DR SMR; Q14721; -.
DR BioGRID; 109947; 27.
DR CORUM; Q14721; -.
DR IntAct; Q14721; 2.
DR STRING; 9606.ENSP00000360806; -.
DR BindingDB; Q14721; -.
DR ChEMBL; CHEMBL2363000; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q14721; -.
DR GuidetoPHARMACOLOGY; 546; -.
DR TCDB; 1.A.1.2.11; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q14721; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14721; -.
DR PhosphoSitePlus; Q14721; -.
DR BioMuta; KCNB1; -.
DR DMDM; 24418854; -.
DR OGP; Q14721; -.
DR MassIVE; Q14721; -.
DR MaxQB; Q14721; -.
DR PaxDb; Q14721; -.
DR PeptideAtlas; Q14721; -.
DR PRIDE; Q14721; -.
DR ProteomicsDB; 60144; -.
DR ABCD; Q14721; 4 sequenced antibodies.
DR Antibodypedia; 28477; 419 antibodies from 37 providers.
DR DNASU; 3745; -.
DR Ensembl; ENST00000371741.6; ENSP00000360806.3; ENSG00000158445.10.
DR Ensembl; ENST00000635465.1; ENSP00000489193.1; ENSG00000158445.10.
DR GeneID; 3745; -.
DR KEGG; hsa:3745; -.
DR MANE-Select; ENST00000371741.6; ENSP00000360806.3; NM_004975.4; NP_004966.1.
DR UCSC; uc002xur.2; human.
DR CTD; 3745; -.
DR DisGeNET; 3745; -.
DR GeneCards; KCNB1; -.
DR HGNC; HGNC:6231; KCNB1.
DR HPA; ENSG00000158445; Tissue enriched (retina).
DR MalaCards; KCNB1; -.
DR MIM; 600397; gene.
DR MIM; 616056; phenotype.
DR neXtProt; NX_Q14721; -.
DR OpenTargets; ENSG00000158445; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA209; -.
DR VEuPathDB; HostDB:ENSG00000158445; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000154899; -.
DR HOGENOM; CLU_011722_2_1_1; -.
DR InParanoid; Q14721; -.
DR OMA; EMETIPG; -.
DR OrthoDB; 203440at2759; -.
DR PhylomeDB; Q14721; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q14721; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR SignaLink; Q14721; -.
DR SIGNOR; Q14721; -.
DR BioGRID-ORCS; 3745; 12 hits in 1071 CRISPR screens.
DR ChiTaRS; KCNB1; human.
DR GeneWiki; KCNB1; -.
DR GenomeRNAi; 3745; -.
DR Pharos; Q14721; Tclin.
DR PRO; PR:Q14721; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q14721; protein.
DR Bgee; ENSG00000158445; Expressed in Brodmann (1909) area 23 and 173 other tissues.
DR ExpressionAtlas; Q14721; baseline and differential.
DR Genevisible; Q14721; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
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:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:1990635; C:proximal dendrite; IEA:Ensembl.
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:0015271; F:outward rectifier potassium channel activity; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0000149; F:SNARE binding; IEA:Ensembl.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0001508; P:action potential; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl.
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:0045163; P:clustering of voltage-gated potassium channels; IEA:Ensembl.
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:0097623; P:potassium ion export across plasma membrane; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0098900; P:regulation of action potential; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:2000671; P:regulation of motor neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; ISS:UniProtKB.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_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_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03521; Kv2channel; 2.
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 membrane; Cell projection; Disease variant; Epilepsy; Exocytosis;
KW Ion channel; Ion transport; Isopeptide bond; Membrane; Phosphoprotein;
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
FT /note="Potassium voltage-gated channel subfamily B member
FT 1"
FT /id="PRO_0000054042"
FT TOPO_DOM 1..186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 187..208
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 209..228
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 229..250
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 251..259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 260..280
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 281..294
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 295..316
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 317..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 331..351
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 352..364
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 365..376
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 377..384
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 385..391
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 392..420
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 421..858
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 59..75
FT /note="Self-association"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT REGION 448..481
FT /note="Self-association"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT REGION 471..524
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 538..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 770..807
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 836..858
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 377..382
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT COMPBIAS 471..487
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..506
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 128
FT /note="Phosphotyrosine; by Src"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03717"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q03717"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 520
FT /note="Phosphoserine; by CDK5; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 541
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 607
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 656
FT /note="Phosphoserine; by CDK5; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 772
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 800
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 805
FT /note="Phosphoserine; by CDK5, MAPK14; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT CROSSLNK 474
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT VARIANT 306
FT /note="R -> C (in DEE26; reduces sensitivity and
FT cooperativity of the voltage sensor for channel opening and
FT greatly suppresses repetitive firing in cultured cortical
FT neurons; dbSNP:rs1555889130)"
FT /evidence="ECO:0000269|PubMed:26477325"
FT /id="VAR_075573"
FT VARIANT 347
FT /note="S -> R (in DEE26; inhibits ion selectivity and gain
FT of a depolarizing inward cation conductance; trafficks
FT normally to the cell surface; dbSNP:rs587777848)"
FT /evidence="ECO:0000269|PubMed:25164438"
FT /id="VAR_071991"
FT VARIANT 374
FT /note="T -> I (in DEE26; inhibits ion selectivity and gain
FT of a depolarizing inward cation conductance; trafficks
FT normally to the cell surface; dbSNP:rs587777849)"
FT /evidence="ECO:0000269|PubMed:25164438"
FT /id="VAR_071992"
FT VARIANT 378
FT /note="V -> A (in DEE26; change in the ion selectivity from
FT potassium-selective to nonselective cation channels and
FT significant decrease in cell membrane localization)"
FT /evidence="ECO:0000269|PubMed:26503721"
FT /id="VAR_075574"
FT VARIANT 379
FT /note="G -> R (in DEE26; inhibits ion selectivity and gain
FT of a depolarizing inward cation conductance; trafficks
FT normally to the cell surface; dbSNP:rs587777850)"
FT /evidence="ECO:0000269|PubMed:25164438"
FT /id="VAR_071993"
FT VARIANT 401
FT /note="G -> R (in DEE26; dominant-negative mutation
FT resulting in loss of endogenous channel currents and
FT greatly suppresses repetitive firing in cultured cortical
FT neurons)"
FT /evidence="ECO:0000269|PubMed:26477325"
FT /id="VAR_075575"
FT VARIANT 616
FT /note="T -> N (in dbSNP:rs2229006)"
FT /id="VAR_062182"
FT VARIANT 616
FT /note="T -> S (in dbSNP:rs2229006)"
FT /id="VAR_062183"
FT VARIANT 825
FT /note="P -> S (in dbSNP:rs34467662)"
FT /id="VAR_034049"
FT VARIANT 857
FT /note="S -> N (in dbSNP:rs34280195)"
FT /id="VAR_062184"
FT MUTAGEN 71
FT /note="E->Q: No effect on channel activity."
FT /evidence="ECO:0000269|PubMed:12560340"
FT MUTAGEN 74
FT /note="D->R: Reduces interaction with KCNG1 and self-
FT interaction and impairs plasma membrane subcellular
FT localization, homotetramerization and
FT hetetrotetramerization with KCNG4; when associated with R-
FT 75."
FT /evidence="ECO:0000269|PubMed:19717558,
FT ECO:0000269|PubMed:24901643"
FT MUTAGEN 75
FT /note="D->R: Reduces interaction with KCNG1 and self-
FT interaction and impairs plasma membrane subcellular
FT localization, homotetramerization and
FT hetetrotetramerization with KCNG4; when associated with R-
FT 74."
FT /evidence="ECO:0000269|PubMed:19717558,
FT ECO:0000269|PubMed:24901643"
FT MUTAGEN 79
FT /note="D->E: Increases channel activity."
FT /evidence="ECO:0000269|PubMed:12560340"
FT MUTAGEN 105
FT /note="H->V,R: Reduces channel activity. Inhibits
FT interaction with KCNG4. Impairs hetetrotetramerization with
FT KCNG1, KCNG3 or KCNG4. Does not impair
FT homotetramerization."
FT /evidence="ECO:0000269|PubMed:19074135"
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
