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 27-MAR-2024, entry version 193. 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 CC voltage-dependent potassium currents which are activated during CC membrane 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). Interacts with KCNV2 (By similarity). Self- CC associates (via N-terminus and C-terminus); self-association is CC required to regulate trafficking, gating and C-terminal CC phosphorylation-dependent modulation of the channel. Interacts (via C- CC terminus) with STX1A (via C-terminus); this decreases the rate of CC 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). Interacts (via phosphorylated FFAT motif) with VAPA CC and VAPB (By similarity). {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 a voltage-sensor and CC is 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 -!- DOMAIN: The FFAT motif is involved in the interaction with VAPA and CC VAPB and its phosphorylation regulates these interactions. CC {ECO:0000250|UniProtKB:Q14721}. 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). Phosphorylation at Ser-593 of the FFAT CC motif activates interaction with MOSPD2, VAPA and VAPB (By similarity). CC {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q14721, 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) CC (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 22. DR IntAct; Q03717; 3. DR MINT; Q03717; -. DR STRING; 10090.ENSMUSP00000147093; -. DR GuidetoPHARMACOLOGY; 546; -. DR GlyGen; Q03717; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q03717; -. DR PhosphoSitePlus; Q03717; -. DR SwissPalm; Q03717; -. DR jPOST; Q03717; -. DR MaxQB; Q03717; -. DR PaxDb; 10090-ENSMUSP00000057981; -. DR PeptideAtlas; Q03717; -. DR ProteomicsDB; 269451; -. DR ABCD; Q03717; 2 sequenced antibodies. DR Antibodypedia; 28477; 489 antibodies from 37 providers. DR DNASU; 16500; -. DR Ensembl; ENSMUST00000059826.10; ENSMUSP00000057981.8; ENSMUSG00000050556.10. DR Ensembl; ENSMUST00000207917.2; ENSMUSP00000147093.2; ENSMUSG00000050556.10. DR GeneID; 16500; -. DR KEGG; mmu:16500; -. DR UCSC; uc008nzh.2; mouse. DR AGR; MGI:96666; -. 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; PCKGGVN; -. DR OrthoDB; 1478695at2759; -. 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; 2 hits in 76 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 153 other cell types or tissues. 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:0098981; C:cholinergic synapse; ISO:MGI. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0032590; C:dendrite membrane; ISO:MGI. DR GO; GO:0016328; C:lateral plasma 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:0099634; C:postsynaptic specialization 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: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: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 CDD; cd18412; BTB_POZ_KCNB2; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 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; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR11537:SF63; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY B MEMBER 1; 1. DR PANTHER; PTHR11537; VOLTAGE-GATED POTASSIUM CHANNEL; 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; POZ domain; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; Q03717; MM. 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 MOTIF 590..596 FT /note="FFAT" FT /evidence="ECO:0000250|UniProtKB:Q14721" 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 593 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14721" 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 //