KCNB1_MOUSE
ID KCNB1_MOUSE Reviewed; 857 AA.
AC Q03717; Q8K0D1;
DT 25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Potassium voltage-gated channel subfamily B member 1 {ECO:0000250|UniProtKB:Q14721};
DE AltName: Full=Voltage-gated potassium channel subunit Kv2.1;
DE AltName: Full=mShab {ECO:0000303|PubMed:2002364};
GN Name=Kcnb1 {ECO:0000312|MGI:MGI:96666};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP ACTIVITY REGULATION.
RC TISSUE=Brain;
RX PubMed=2002364; DOI=10.1523/jneurosci.11-03-00869.1991;
RA Pak M.D., Covarrubias M., Ratcliffe A., Salkoff L.;
RT "A mouse brain homolog of the Drosophila Shab K+ channel with conserved
RT delayed-rectifier properties.";
RL J. Neurosci. 11:869-880(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10506487; DOI=10.1161/01.res.85.7.623;
RA Xu H., Barry D.M., Li H., Brunet S., Guo W., Nerbonne J.M.;
RT "Attenuation of the slow component of delayed rectification, action
RT potential prolongation, and triggered activity in mice expressing a
RT dominant-negative Kv2 alpha subunit.";
RL Circ. Res. 85:623-633(1999).
RN [7]
RP PHOSPHORYLATION, INTERACTION WITH PTPRE, AND TISSUE SPECIFICITY.
RX PubMed=10921884; DOI=10.1093/emboj/19.15.4036;
RA Peretz A., Gil-Henn H., Sobko A., Shinder V., Attali B., Elson A.;
RT "Hypomyelination and increased activity of voltage-gated K(+) channels in
RT mice lacking protein tyrosine phosphatase epsilon.";
RL EMBO J. 19:4036-4045(2000).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12270920; DOI=10.1074/jbc.m205532200;
RA MacDonald P.E., Sewing S., Wang J., Joseph J.W., Smukler S.R.,
RA Sakellaropoulos G., Wang J., Saleh M.C., Chan C.B., Tsushima R.G.,
RA Salapatek A.M., Wheeler M.B.;
RT "Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic beta-cells
RT enhances glucose-dependent insulin secretion.";
RL J. Biol. Chem. 277:44938-44945(2002).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14684365; DOI=10.1152/ajpheart.00303.2003;
RA Kodirov S.A., Brunner M., Nerbonne J.M., Buckett P., Mitchell G.F.,
RA Koren G.;
RT "Attenuation of I(K,slow1) and I(K,slow2) in Kv1/Kv2DN mice prolongs APD
RT and QT intervals but does not suppress spontaneous or inducible
RT arrhythmias.";
RL Am. J. Physiol. 286:H368-H374(2004).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-655, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=17767909; DOI=10.1016/j.cmet.2007.07.010;
RA Jacobson D.A., Kuznetsov A., Lopez J.P., Kash S., Ammala C.E.,
RA Philipson L.H.;
RT "Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing
RT insulin secretion.";
RL Cell Metab. 6:229-235(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19383458; DOI=10.1016/j.bpj.2009.01.029;
RA Fridlyand L.E., Jacobson D.A., Kuznetsov A., Philipson L.H.;
RT "A model of action potentials and fast Ca2+ dynamics in pancreatic beta-
RT cells.";
RL Biophys. J. 96:3126-3139(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-444; SER-457; SER-655 AND
RP SER-804, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP FUNCTION, SUBUNIT, INTERACTION WITH AMIGO1, DOMAIN, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=22056818; DOI=10.1038/embor.2011.204;
RA Peltola M.A., Kuja-Panula J., Lauri S.E., Taira T., Rauvala H.;
RT "AMIGO is an auxiliary subunit of the Kv2.1 potassium channel.";
RL EMBO Rep. 12:1293-1299(2011).
RN [17]
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 [18]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=24494598; DOI=10.1111/gbb.12120;
RA Speca D.J., Ogata G., Mandikian D., Bishop H.I., Wiler S.W., Eum K.,
RA Wenzel H.J., Doisy E.T., Matt L., Campi K.L., Golub M.S., Nerbonne J.M.,
RA Hell J.W., Trainor B.C., Sack J.T., Schwartzkroin P.A., Trimmer J.S.;
RT "Deletion of the Kv2.1 delayed rectifier potassium channel leads to
RT neuronal and behavioral hyperexcitability.";
RL Genes Brain Behav. 13:394-408(2014).
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 SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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).
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:14684365,
CC PubMed:19383458, PubMed:24494598). Also plays a role in the regulation
CC of exocytosis independently of its electrical function (By similarity).
CC Forms tetrameric potassium-selective channels through which potassium
CC ions pass in accordance with their electrochemical gradient. The
CC channel alternates between opened and closed conformations in response
CC to the voltage difference across the membrane. Homotetrameric channels
CC mediate a delayed-rectifier voltage-dependent outward potassium current
CC that display rapid activation and slow inactivation in response to
CC membrane depolarization (PubMed:22056818). 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 (By similarity).
CC Heterotetrameric channel activity formed with KCNS3 show increased
CC current amplitude with the threshold for action potential activation
CC shifted towards more negative values in hypoxic-treated pulmonary
CC artery smooth muscle cells (By similarity). Channel properties are also
CC modulated by cytoplasmic ancillary beta subunits, such as AMIGO1,
CC KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the
CC delayed rectifier potassium channels (PubMed:22056818). In vivo,
CC membranes probably contain a mixture of heteromeric potassium channel
CC complexes, making it difficult to assign currents observed in intact
CC tissues to any particular potassium channel family member. Major
CC contributor to the delayed-rectifier voltage-gated potassium current in
CC neurons of the central nervous system, sympathetic ganglion neurons,
CC neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth
CC muscle (PubMed:10506487, PubMed:12270920, PubMed:17767909,
CC PubMed:23161216, PubMed:24494598). Mediates the major part of the
CC somatodendritic delayed-rectifier potassium current in hippocampal and
CC cortical pyramidal neurons and sympathetic superior cervical ganglion
CC (CGC) neurons that acts to slow down periods of firing, especially
CC during high frequency stimulation (By similarity). Plays a role in the
CC induction of long-term potentiation (LTP) of neuron excitability in the
CC CA3 layer of the hippocampus (PubMed:24494598). Contributes to the
CC regulation of the glucose-induced amplitude and duration of action
CC potentials in pancreatic beta-cells, hence limiting calcium influx and
CC insulin secretion (PubMed:12270920, PubMed:17767909, PubMed:19383458,
CC PubMed:23161216). Plays a role in the regulation of resting membrane
CC potential and contraction in hypoxia-treated pulmonary artery smooth
CC muscle cells (By similarity). May contribute to the regulation of the
CC duration of both the action potential of cardiomyocytes and the heart
CC ventricular repolarization QT interval (PubMed:10506487,
CC PubMed:14684365). Contributes to the pronounced pro-apoptotic potassium
CC current surge during neuronal apoptotic cell death in response to
CC oxidative injury (By similarity). 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 (By similarity). 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:Q14721, ECO:0000269|PubMed:10506487,
CC ECO:0000269|PubMed:12270920, ECO:0000269|PubMed:14684365,
CC ECO:0000269|PubMed:17767909, ECO:0000269|PubMed:19383458,
CC ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:23161216,
CC ECO:0000269|PubMed:24494598}.
CC -!- ACTIVITY REGULATION: Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider
CC venom toxin of the tarantula G.spatulata. Inhibited by 100 nM
CC stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata
CC (By similarity). Modestly sensitive to millimolar levels of
CC tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:2002364,
CC PubMed:10414301, PubMed:15858231). Completely insensitive to toxins
CC such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).
CC {ECO:0000250|UniProtKB:P15387, ECO:0000269|PubMed:2002364,
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 more than 20 msec
CC (PubMed:2002364). After that, inactivate very slowly, i.e within more
CC than 5 sec (PubMed:2002364). Their activation requires low threshold
CC potentials at about -20 to -30 mV with a midpoint activation at about
CC 10 mV. For inactivation, the voltage at half-maximal amplitude is
CC about -20 mV. The time constant for recovery after inactivation is
CC about 1.6 sec. Channels have an unitary conductance of about 8 pS.
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:2002364, ECO:0000305|PubMed:10414301,
CC ECO:0000305|PubMed:15858231};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCNB2. Heterotetramer with
CC non-conducting channel-forming alpha subunits such as KCNF1, KCNG1,
CC KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (By
CC similarity). Channel activity is regulated by association with
CC ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3
CC (PubMed:22056818). Self-associates (via N-terminus and C-terminus);
CC self-association is required to regulate trafficking, gating and C-
CC terminal phosphorylation-dependent modulation of the channel. Interacts
CC (via C-terminus) with STX1A (via C-terminus); this decreases the rate
CC of channel activation and increases the rate of channel inactivation in
CC pancreatic beta cells, induces also neuronal apoptosis in response to
CC oxidative injury as well as pore-independent enhancement of exocytosis
CC in neuroendocrine cells, chromaffin cells, pancreatic beta cells and
CC from 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 by 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. Interacts with SUMO1 (By
CC similarity). Interacts (via phosphorylated form) with PTPRE isoform 2;
CC this reduces phosphorylation and channel activity in heterologous cells
CC (PubMed:10921884). {ECO:0000250|UniProtKB:P15387,
CC ECO:0000250|UniProtKB:Q14721, ECO:0000269|PubMed:10921884,
CC ECO:0000269|PubMed:22056818}.
CC -!- INTERACTION:
CC Q03717; Q80ZD8: Amigo1; NbExp=4; IntAct=EBI-7511364, EBI-7511393;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10506487,
CC ECO:0000269|PubMed:12270920, ECO:0000269|PubMed:14684365,
CC ECO:0000269|PubMed:17767909, ECO:0000269|PubMed:19357235,
CC ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}. Perikaryon
CC {ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}. Cell
CC projection, axon {ECO:0000269|PubMed:24477962}. Cell projection,
CC dendrite {ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}.
CC Membrane; Multi-pass membrane protein. Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:P15387}. Synapse {ECO:0000250|UniProtKB:P15387}.
CC Synapse, synaptosome {ECO:0000250|UniProtKB:P15387}. Lateral cell
CC membrane {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 (By similarity).
CC {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q14721,
CC ECO:0000269|PubMed:19357235, ECO:0000269|PubMed:22056818,
CC ECO:0000269|PubMed:24477962}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain (PubMed:17767909,
CC PubMed:22056818). Expressed in the heart (PubMed:14684365). Expressed
CC in pyramidal neurons and interneurons of the hippocampus
CC (PubMed:22056818, PubMed:24494598). Expressed in neocortical pyramidal
CC neurons (PubMed:22056818, PubMed:24477962). Expressed in dorsal root
CC ganglia (DRG) neurons (PubMed:19357235). Expressed in pancreatic beta
CC cells (PubMed:12270920, PubMed:17767909). Expressed in Schwann cells
CC (PubMed:10921884). Expressed in ventricular myocytes (at protein level)
CC (PubMed:14684365, PubMed:10506487). {ECO:0000269|PubMed:10506487,
CC ECO:0000269|PubMed:10921884, ECO:0000269|PubMed:12270920,
CC ECO:0000269|PubMed:14684365, ECO:0000269|PubMed:17767909,
CC ECO:0000269|PubMed:19357235, ECO:0000269|PubMed:22056818,
CC ECO:0000269|PubMed:24477962, ECO:0000269|PubMed:24494598}.
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 (By similarity). The N-terminal cytoplasmic region is
CC important for interaction with other channel-forming alpha subunits and
CC with ancillary beta subunits (PubMed:22056818). 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:0000250|UniProtKB:Q14721,
CC ECO:0000269|PubMed:22056818}.
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-804 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-655, Ser-607 and Ser-804
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-655 and Ser-719 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 activities 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-719 are less
CC dephosphorylated. In response to brain seizures, phosphorylation levels
CC on Ser-567 and Ser-607 are greatly reduced (By similarity).
CC Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases
CC and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic
CC nerve tissue (PubMed:10921884). {ECO:0000250|UniProtKB:P15387,
CC ECO:0000269|PubMed:10921884}.
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. Sumoylation increases the frequency of
CC repetitive action potential firing at the cell surface of hippocampal
CC neurons and decreases its frequency in pancreatic beta cells.
CC Desumoylated by SENP1. {ECO:0000250|UniProtKB:P15387,
CC ECO:0000250|UniProtKB:Q14721}.
CC -!- DISRUPTION PHENOTYPE: Mice show normal motor coordination and visual
CC acuity, but are hyperactive, exhibit defects in spatial learning
CC ability and show reduced anxiety-like behavior (PubMed:24494598). Show
CC a higher incidence and a shorter latency to seizure progression
CC compared to wild-type mice (PubMed:24494598). Display reduced fasting
CC blood glucose levels and elevated serum insulin levels
CC (PubMed:17767909, PubMed:19383458). Glucose tolerance and insulin
CC secretion is enhanced compared to control animals (PubMed:17767909,
CC PubMed:19383458). Show impaired long-term potentiation in hippocampal
CC neurons (PubMed:24494598). Display a reduction in the slowly
CC deactivating delayed rectifier potassium current in hippocampal
CC pyramidal neurons (PubMed:24494598). Glucose-induced action potential
CC (AP) duration and amplitude is increased while the firing frequency is
CC reduced in pancreatic beta cells (PubMed:17767909, PubMed:19383458).
CC {ECO:0000269|PubMed:17767909, ECO:0000269|PubMed:19383458,
CC ECO:0000269|PubMed:24494598}.
CC -!- SIMILARITY: Belongs to the potassium channel family. B (Shab) (TC
CC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily. {ECO:0000305}.
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DR EMBL; M64228; AAA40112.1; -; mRNA.
DR EMBL; AL591711; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06500.1; -; Genomic_DNA.
DR EMBL; BC031776; AAH31776.1; -; mRNA.
DR EMBL; BC061501; AAH61501.1; -; mRNA.
DR CCDS; CCDS17096.1; -.
DR PIR; I56529; I56529.
DR RefSeq; NP_032446.2; NM_008420.4.
DR RefSeq; XP_017171221.1; XM_017315732.1.
DR RefSeq; XP_017171222.1; XM_017315733.1.
DR AlphaFoldDB; Q03717; -.
DR SMR; Q03717; -.
DR BioGRID; 200886; 15.
DR IntAct; Q03717; 3.
DR MINT; Q03717; -.
DR STRING; 10090.ENSMUSP00000057981; -.
DR GuidetoPHARMACOLOGY; 546; -.
DR iPTMnet; Q03717; -.
DR PhosphoSitePlus; Q03717; -.
DR SwissPalm; Q03717; -.
DR jPOST; Q03717; -.
DR MaxQB; Q03717; -.
DR PaxDb; Q03717; -.
DR PeptideAtlas; Q03717; -.
DR PRIDE; Q03717; -.
DR ProteomicsDB; 269451; -.
DR ABCD; Q03717; 2 sequenced antibodies.
DR Antibodypedia; 28477; 419 antibodies from 37 providers.
DR DNASU; 16500; -.
DR Ensembl; ENSMUST00000059826; ENSMUSP00000057981; ENSMUSG00000050556.
DR Ensembl; ENSMUST00000207917; ENSMUSP00000147093; ENSMUSG00000050556.
DR GeneID; 16500; -.
DR KEGG; mmu:16500; -.
DR UCSC; uc008nzh.2; mouse.
DR CTD; 3745; -.
DR MGI; MGI:96666; Kcnb1.
DR VEuPathDB; HostDB:ENSMUSG00000050556; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000154899; -.
DR HOGENOM; CLU_011722_2_1_1; -.
DR InParanoid; Q03717; -.
DR OMA; EMETIPG; -.
DR OrthoDB; 203440at2759; -.
DR PhylomeDB; Q03717; -.
DR TreeFam; TF313103; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR Reactome; R-MMU-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR BioGRID-ORCS; 16500; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Kcnb1; mouse.
DR PRO; PR:Q03717; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q03717; protein.
DR Bgee; ENSMUSG00000050556; Expressed in retinal neural layer and 151 other tissues.
DR Genevisible; Q03717; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0032809; C:neuronal cell body membrane; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
DR GO; GO:1990635; C:proximal dendrite; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0000149; F:SNARE binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISO:MGI.
DR GO; GO:0001508; P:action potential; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISO:MGI.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR GO; GO:0045163; P:clustering of voltage-gated potassium channels; ISO:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0007215; P:glutamate receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP: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; IMP: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; ISS:UniProtKB.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; ISO:MGI.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; ISO:MGI.
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; IMP: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; Exocytosis; Ion channel; Ion transport;
KW Isopeptide bond; Membrane; Phosphoprotein; Postsynaptic cell membrane;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Synapse; Synaptosome; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..857
FT /note="Potassium voltage-gated channel subfamily B member
FT 1"
FT /id="PRO_0000054043"
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..857
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 475..569
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..627
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 768..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 816..857
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 491..506
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..561
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:0007744|PubMed:21183079"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 719
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 771
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 799
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT MOD_RES 804
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 836
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT CROSSLNK 475
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P15387"
FT CONFLICT 701
FT /note="A -> R (in Ref. 1; AAA40112)"
FT /evidence="ECO:0000305"
FT CONFLICT 773
FT /note="P -> L (in Ref. 1; AAA40112)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 857 AA; 95591 MW; 5FE2D80E58E60710 CRC64;
MPAGMTKHGS RSTSSLPPEP MEIVRSKACS RRVRLNVGGL AHEVLWRTLD RLPRTRLGKL
RDCNTHDSLL QVCDDYSLED 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 GVAKKDKVQD
NHLSPNKWKW TKRALSETSS SKSFETKEQG SPEKARSSSS PQHLNVQQLQ DMYSKMAKTQ
SQPILNTKEM APQSQPQEEL EMGSMPSPVA PLPTRTEGVI DMRSMSSIDS FISCATDFPE
ATRFSHSPLA SLSGKSGGST APEVGWRGAL GASGGRLMET NPIPEASRSG FFVESPRSSM
KTHNPMKLRA LKVNFLEGDP TPLLPALGLY HDPLRNRGGA AAAVAGLECA SLLDKPVLSP
ESSIYTTASA RTPPRSPEKH TAIAFNFEAG VHQYIDTDTD DEGQLLYSVD SSPPKSLHGS
TSPKFSLGAR TEKNHFESSP LPTSPKFLRP NCVYASEGLP GKGPGAQEKC KLENHTSPDV
HMLPGGGAHG STRDQSI
