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 02-NOV-2016, entry version 150.
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;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND ENZYME REGULATION.
RC TISSUE=Brain;
RX PubMed=2002364;
RA Pak M.D., Covarrubias M., Ratcliffe A., Salkoff L.;
RT "A mouse brain homolog of the Drosophila Shab K+ channel with
RT conserved 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.,
RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of
RT the 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
RT project: 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
RT in 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-
RT cells 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
RT APD 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
RT vascular smooth muscle.";
RL Cell Biochem. Biophys. 42:167-195(2005).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-655, AND IDENTIFICATION
RP BY 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.,
RA 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,
RT enhancing 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.,
RA Gerrits B., Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in
RT naive 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
RT beta-cells.";
RL Biophys. J. 96:3126-3139(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-444; SER-457; SER-655
RP AND SER-804, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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
RT expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP FUNCTION, SUBUNIT, INTERACTION WITH AMIGO1, DOMAIN, SUBCELLULAR
RP LOCATION, 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
RT 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.,
RA Nerbonne J.M., Hell J.W., Trainor B.C., Sack J.T., Schwartzkroin P.A.,
RA 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.,
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).
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:14684365,
CC PubMed:19383458, PubMed:24494598). Plays also a role in the
CC regulation of exocytosis independently of its electrical function
CC (By similarity). Forms tetrameric potassium-selective channels
CC through which potassium ions pass in accordance with their
CC electrochemical gradient. The channel alternates between opened
CC and closed conformations in response to the voltage difference
CC across the membrane. Homotetrameric channels mediate a delayed-
CC rectifier voltage-dependent outward potassium current that display
CC rapid activation and slow inactivation in response to membrane
CC 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
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 (By similarity). Heterotetrameric channel activity formed with
CC KCNS3 show increased current amplitude with the threshold for
CC action potential activation shifted towards more negative values
CC in hypoxic-treated pulmonary artery smooth muscle cells (By
CC similarity). Channel properties are also modulated by cytoplasmic
CC ancillary beta subunits, such as AMIGO1, KCNE1, KCNE2 and KCNE3,
CC slowing activation and inactivation rate of the delayed rectifier
CC potassium channels (PubMed:22056818). 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 delayed-rectifier voltage-gated potassium
CC current in neurons of the central nervous system, sympathetic
CC ganglion neurons, neuroendocrine cells, pancreatic beta cells,
CC cardiomyocytes and smooth muscle (PubMed:10506487,
CC PubMed:12270920, PubMed:17767909, PubMed:23161216,
CC PubMed:24494598). Mediates the major part of the somatodendritic
CC delayed-rectifier potassium current in hippocampal and cortical
CC pyramidal neurons and sympathetic superior cervical ganglion (CGC)
CC neurons that acts to slow down periods of firing, especially
CC during high frequency stimulation (By similarity). Plays a role in
CC the induction of long-term potentiation (LTP) of neuron
CC excitability in the CA3 layer of the hippocampus
CC (PubMed:24494598). Contributes to the regulation of the glucose-
CC induced amplitude and duration of action potentials in pancreatic
CC beta-cells, hence limiting calcium influx and insulin secretion
CC (PubMed:12270920, PubMed:17767909, PubMed:19383458,
CC PubMed:23161216). Plays a role in the regulation of resting
CC membrane potential and contraction in hypoxia-treated pulmonary
CC artery smooth muscle cells (By similarity). 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 (PubMed:10506487, PubMed:14684365). Contributes to the
CC pronounced pro-apoptotic potassium current surge during neuronal
CC apoptotic cell death in response to oxidative injury (By
CC similarity). 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 (By similarity). Plays a role in the
CC 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:Q14721,
CC ECO:0000269|PubMed:10506487, ECO:0000269|PubMed:12270920,
CC ECO:0000269|PubMed:14684365, ECO:0000269|PubMed:17767909,
CC ECO:0000269|PubMed:19383458, ECO:0000269|PubMed:22056818,
CC ECO:0000269|PubMed:23161216, ECO:0000269|PubMed:24494598}.
CC -!- ENZYME REGULATION: Inhibited by 42 nM hanatoxin 1 (HaTx1), a
CC spider venom toxin of the tarantula G.spatulata. Inhibited by 100
CC nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula
CC S.calceata (By similarity). Modestly sensitive to millimolar
CC levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP)
CC (PubMed:2002364, PubMed:10414301, PubMed:15858231). Completely
CC insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin
CC (CTX) (By similarity). {ECO:0000250|UniProtKB:P15387,
CC ECO:0000269|PubMed:2002364, ECO:0000305|PubMed:10414301,
CC 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
CC more than 5 sec (PubMed:2002364). Their activation requires low
CC threshold potentials at about -20 to -30 mV with a midpoint
CC activation at about 10 mV. For inactivation, the voltage at
CC half-maximal amplitude is about -20 mV. The time constant for
CC recovery after inactivation is about 1.6 sec. Channels have an
CC unitary conductance of about 8 pS. The voltage-dependence of
CC activation and inactivation and other channel characteristics
CC vary depending on the experimental conditions, the expression
CC system, the presence or absence of ancillary subunits and post-
CC translational modifications. {ECO:0000250|UniProtKB:P15387,
CC ECO:0000269|PubMed:2002364, ECO:0000305|PubMed:10414301,
CC ECO:0000305|PubMed:15858231};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCNB2. Heterotetramer
CC with non-conducting channel-forming alpha subunits such as KCNF1,
CC KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1
CC (By 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-
CC terminus); self-association is required to regulate trafficking,
CC gating and C-terminal phosphorylation-dependent modulation of the
CC channel. Interacts (via C-terminus) with STX1A (via C-terminus);
CC this decreases the rate of channel activation and increases the
CC rate of channel inactivation in pancreatic beta cells, induces
CC also neuronal apoptosis in response to oxidative injury as well as
CC pore-independent enhancement of exocytosis in neuroendocrine
CC cells, chromaffin cells, pancreatic beta cells and from the soma
CC of dorsal root ganglia (DRG) neurons. Interacts (via N-terminus)
CC with SNAP25; this decreases the rate of channel inactivation in
CC pancreatic beta cells and also increases interaction during
CC neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-
CC dependent manner. Interacts (via N-terminus and C-terminus) with
CC VAMP2 (via N-terminus); stimulates channel inactivation rate.
CC Interacts with CREB1; this promotes channel acetylation in
CC response to stimulation by incretin hormones. Interacts (via N-
CC terminus and C-terminus) with MYL12B. Interacts (via N-terminus)
CC with PIAS3; this increases the number of functional channels at
CC the cell surface. Interacts with SUMO1 (By similarity). Interacts
CC (via phosphorylated form) with PTPRE isoform 2; this reduces
CC 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 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}.
CC Perikaryon {ECO:0000269|PubMed:22056818,
CC ECO:0000269|PubMed:24477962}. Cell projection, axon
CC {ECO:0000269|PubMed:24477962}. Cell projection, dendrite
CC {ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}.
CC Membrane; Multi-pass membrane protein. Cell junction, synapse,
CC postsynaptic cell membrane {ECO:0000250|UniProtKB:P15387}. Cell
CC junction, synapse {ECO:0000250|UniProtKB:P15387}. Cell junction,
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
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 (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).
CC Expressed in pyramidal neurons and interneurons of the hippocampus
CC (PubMed:22056818, PubMed:24494598). Expressed in neocortical
CC pyramidal neurons (PubMed:22056818, PubMed:24477962). Expressed in
CC dorsal root ganglia (DRG) neurons (PubMed:19357235). Expressed in
CC pancreatic beta cells (PubMed:12270920, PubMed:17767909).
CC Expressed in Schwann cells (PubMed:10921884). Expressed in
CC ventricular myocytes (at protein level) (PubMed:14684365,
CC 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
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 (By similarity). The N-terminal
CC cytoplasmic region is important for interaction with other
CC channel-forming alpha subunits and with ancillary beta subunits
CC (PubMed:22056818). 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: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
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-804 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-655, Ser-607 and Ser-804 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-655 and Ser-719 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 activities
CC promote calcium/calcineurin-dependent dephosphorylation resulting
CC 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
CC levels on Ser-567 and Ser-607 are greatly reduced (By similarity).
CC Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein
CC kinases and tyrosine phosphatase PTPRE in primary Schwann cells
CC and sciatic nerve tissue (PubMed:10921884).
CC {ECO:0000250|UniProtKB:P15387, 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
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. Sumoylation increases the frequency
CC of repetitive action potential firing at the cell surface of
CC hippocampal neurons and decreases its frequency in pancreatic beta
CC cells. Desumoylated by SENP1. {ECO:0000250|UniProtKB:P15387,
CC ECO:0000250|UniProtKB:Q14721}.
CC -!- DISRUPTION PHENOTYPE: Mice show normal motor coordination and
CC visual acuity, but are hyperactive, exhibit defects in spatial
CC learning ability and show reduced anxiety-like behavior
CC (PubMed:24494598). Show a higher incidence and a shorter latency
CC to seizure progression compared to wild-type mice
CC (PubMed:24494598). Display reduced fasting blood glucose levels
CC and elevated serum insulin levels (PubMed:17767909,
CC PubMed:19383458). Glucose tolerance and insulin secretion is
CC enhanced compared to control animals (PubMed:17767909,
CC PubMed:19383458). Show impaired long-term potentiation in
CC hippocampal neurons (PubMed:24494598). Display a reduction in the
CC slowly deactivating delayed rectifier potassium current in
CC hippocampal pyramidal neurons (PubMed:24494598). Glucose-induced
CC action potential (AP) duration and amplitude is increased while
CC the firing frequency is reduced in pancreatic beta cells
CC (PubMed:17767909, PubMed:19383458). {ECO:0000269|PubMed:17767909,
CC ECO:0000269|PubMed:19383458, ECO:0000269|PubMed:24494598}.
CC -!- SIMILARITY: Belongs to the potassium channel family. B (Shab)
CC (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily. {ECO:0000305}.
DR EMBL; M64228; AAA40112.1; -; mRNA.
DR EMBL; AL591854; CAM13429.1; -; Genomic_DNA.
DR EMBL; AL591711; CAM13429.1; JOINED; Genomic_DNA.
DR EMBL; AL591711; CAM17304.1; -; Genomic_DNA.
DR EMBL; AL591854; CAM17304.1; JOINED; 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 UniGene; Mm.205341; -.
DR UniGene; Mm.490804; -.
DR ProteinModelPortal; Q03717; -.
DR SMR; Q03717; -.
DR BioGrid; 200886; 3.
DR IntAct; Q03717; 2.
DR MINT; MINT-8298631; -.
DR STRING; 10090.ENSMUSP00000057981; -.
DR GuidetoPHARMACOLOGY; 546; -.
DR iPTMnet; Q03717; -.
DR PhosphoSitePlus; Q03717; -.
DR MaxQB; Q03717; -.
DR PaxDb; Q03717; -.
DR PeptideAtlas; Q03717; -.
DR PRIDE; Q03717; -.
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 eggNOG; KOG3713; Eukaryota.
DR eggNOG; COG1226; LUCA.
DR GeneTree; ENSGT00760000118981; -.
DR HOGENOM; HOG000113206; -.
DR HOVERGEN; HBG052225; -.
DR InParanoid; Q03717; -.
DR KO; K04885; -.
DR OMA; TEGVIDM; -.
DR OrthoDB; EOG091G0FP3; -.
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 ChiTaRS; Kcnb1; mouse.
DR PRO; PR:Q03717; -.
DR Proteomes; UP000000589; Chromosome 2.
DR Bgee; ENSMUSG00000050556; -.
DR Genevisible; Q03717; MM.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IDA: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; IDA: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; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0032182; F:ubiquitin-like protein 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:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
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: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:0072661; P:protein targeting to plasma membrane; ISS:UniProtKB.
DR GO; GO:0098900; P:regulation of action potential; IMP:UniProtKB.
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; 1.
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 Exocytosis; Ion channel; Ion transport; Isopeptide bond; Membrane;
KW Phosphoprotein; Postsynaptic cell membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Synapse;
KW Synaptosome; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation; Voltage-gated channel.
FT CHAIN 1 857 Potassium voltage-gated channel subfamily
FT B member 1.
FT /FTId=PRO_0000054043.
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 421 857 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 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:0000244|PubMed:21183079}.
FT MOD_RES 457 457 Phosphoserine.
FT {ECO:0000244|PubMed:21183079}.
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 655 655 Phosphoserine.
FT {ECO:0000244|PubMed:16452087,
FT ECO:0000244|PubMed:21183079}.
FT MOD_RES 719 719 Phosphoserine.
FT {ECO:0000250|UniProtKB:P15387}.
FT MOD_RES 771 771 Phosphoserine.
FT {ECO:0000250|UniProtKB:P15387}.
FT MOD_RES 799 799 Phosphoserine.
FT {ECO:0000250|UniProtKB:P15387}.
FT MOD_RES 804 804 Phosphoserine.
FT {ECO:0000244|PubMed:21183079}.
FT MOD_RES 836 836 Phosphothreonine.
FT {ECO:0000250|UniProtKB:P15387}.
FT CROSSLNK 475 475 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO).
FT {ECO:0000250|UniProtKB:P15387}.
FT CONFLICT 701 701 A -> R (in Ref. 1; AAA40112).
FT {ECO:0000305}.
FT CONFLICT 773 773 P -> L (in Ref. 1; AAA40112).
FT {ECO:0000305}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 467 613 ipfam:Kv2channel [T]
FT MYHIT 189 423 ipfam:Ion_trans [T]
FT MYHIT 31 140 ismart:BTB [T]
FT MYHIT 33 132 ipfam:BTB_2 [T]
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
//
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