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 31 140 ismart:BTB [T]
FT MYHIT 33 132 ipfam:BTB_2 [T]
FT MYHIT 467 614 ipfam:Kv2channel [T]
FT MYHIT 189 423 ipfam:Ion_trans [T]
FT MYHIT 649 680 ipfam:Kv2channel [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
//
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