Kcnb1
entrez
16500
canonical
uniprot
Q03717
canonical
ensembl
ENSMUSG00000050556
resolver
ensp
ENSMUSP00000057981
resolver
ensp
ENSMUSP00000147093
resolver
enst
ENSMUST00000059826
resolver
enst
ENSMUST00000207917
resolver
genesymbol
Kcnb1
resolver
uniprot
Q8K0D1
resolver
uniprot_entry
KCNB1_MOUSE
resolver
uniprot_sec
Q8K0D1
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata. Inhibited by 100 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (By similarity). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:10414301, PubMed:15858231, PubMed:2002364). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity). {ECO:0000250|UniProtKB:P15387, ECO:0000269|PubMed:2002364, ECO:0000305|PubMed:10414301, ECO:0000305|PubMed:15858231}.
uniprot
proteins
amino_acid_sequence
MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKLRDCNTHDSLLQVCDDYSLEDNEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELDYWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREGEEFDNTCCAEKRKKLWDLLEKPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWFTMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFRIMRILRILKLARHSTGLQSLGFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIAGVLVIALPIPIIVNNFSEFYKEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGEGVAKKDKVQDNHLSPNKWKWTKRALSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLQDMYSKMAKTQSQPILNTKEMAPQSQPQEELEMGSMPSPVAPLPTRTEGVIDMRSMSSIDSFISCATDFPEATRFSHSPLASLSGKSGGSTAPEVGWRGALGASGGRLMETNPIPEASRSGFFVESPRSSMKTHNPMKLRALKVNFLEGDPTPLLPALGLYHDPLRNRGGAAAAVAGLECASLLDKPVLSPESSIYTTASARTPPRSPEKHTAIAFNFEAGVHQYIDTDTDDEGQLLYSVDSSPPKSLHGSTSPKFSLGARTEKNHFESSPLPTSPKFLRPNCVYASEGLPGKGPGAQEKCKLENHTSPDVHMLPGGGAHGSTRDQSI
uniprot
proteins
function
FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:14684365, PubMed:19383458, PubMed:24494598). Also plays a role in the regulation of exocytosis independently of its electrical function (By similarity). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:22056818). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (By similarity). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits, such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (PubMed:22056818). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle (PubMed:10506487, PubMed:12270920, PubMed:17767909, PubMed:23161216, PubMed:24494598). Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation (By similarity). Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (PubMed:24494598). Contributes to the regulation of the glucose-induced amplitude and duration of action potentials in pancreatic beta-cells, hence limiting calcium influx and insulin secretion (PubMed:12270920, PubMed:17767909, PubMed:19383458, PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells (By similarity). May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (PubMed:10506487, PubMed:14684365). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury (By similarity). May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (By similarity). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity). {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q14721, ECO:0000269|PubMed:10506487, ECO:0000269|PubMed:12270920, ECO:0000269|PubMed:14684365, ECO:0000269|PubMed:17767909, ECO:0000269|PubMed:19383458, ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:23161216, ECO:0000269|PubMed:24494598}.
uniprot
proteins
mass_dalton
95591
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Differential C-terminal phosphorylation on a subset of serines allows graded activity-dependent regulation of channel gating in hippocampal neurons. Ser-607 and Tyr-128 are significant sites of voltage-gated regulation through phosphorylation/dephosphorylation activities. Tyr-128 can be phosphorylated by Src and dephosphorylated by cytoplasmic form of the phosphatase PTPRE. CDK5-induced Ser-607 phosphorylation increases in response to acute blockade of neuronal activity. Phosphorylated on Tyr-128 by Src and on Ser-804 by MAPK14/P38MAPK; phosphorylations are necessary and sufficient for an increase in plasma membrane insertion, apoptotic potassium current surge and completion of the neuronal cell death program. Phosphorylated on Ser-520, Ser-655, Ser-607 and Ser-804 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation. The Ser-607 phosphorylation state differs between KCNB1-containing clusters on the proximal and distal portions of the axon initial segment (AIS). Highly phosphorylated on serine residues in the C-terminal cytoplasmic tail in resting neurons. Phosphorylated in pancreatic beta cells in response to incretin hormones stimulation in a PKA- and RPS6KA5/MSK1-dependent signaling pathway, promoting beta cell survival. Phosphorylation on Ser-567 is reduced during postnatal development with low levels at P2 and P5; levels then increase to reach adult levels by P14. Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-655 and Ser-719 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties. Dephosphorylation by phosphatase PTPRE confers neuroprotection by its inhibitory influence on the neuronal apoptotic potassium current surge in a Zn(2+)-dependent manner. Dephosphorylated at Ser-607 by protein phosphatase PPP1CA. Hypoxia-, seizure- or glutamate-induced neuronal activities promote calcium/calcineurin-dependent dephosphorylation resulting in a loss of KCNB1-containing clustering and enhanced channel activity. In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-719 are less dephosphorylated. In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced (By similarity). Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic nerve tissue (PubMed:10921884). Phosphorylation at Ser-593 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB (By similarity). {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q14721, ECO:0000269|PubMed:10921884}.; PTM: Acetylated. Acetylation occurs in pancreatic beta cells in response to stimulation by incretin hormones in a histone acetyltransferase (HAT)/histone deacetylase (HDAC)-dependent signaling pathway, promoting beta cell survival. {ECO:0000250|UniProtKB:P15387}.; PTM: Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity. Sumoylation increases the frequency of repetitive action potential firing at the cell surface of hippocampal neurons and decreases its frequency in pancreatic beta cells. Desumoylated by SENP1. {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q14721}.
uniprot
proteins
protein_family
B (Shab) (TC 1.A.1.2) subfamily
uniprot
proteins
protein_family
Kv2.1/KCNB1 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10414301
uniprot
proteins
pubmed
10506487
uniprot
proteins
pubmed
10921884
uniprot
proteins
pubmed
12270920
uniprot
proteins
pubmed
14684365
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15858231
uniprot
proteins
pubmed
16452087
uniprot
proteins
pubmed
17114649
uniprot
proteins
pubmed
17767909
uniprot
proteins
pubmed
19357235
uniprot
proteins
pubmed
19383458
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
2002364
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22056818
uniprot
proteins
pubmed
23161216
uniprot
proteins
pubmed
24477962
uniprot
proteins
pubmed
24494598
uniprot
proteins
sequence_length
857
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10506487, ECO:0000269|PubMed:12270920, ECO:0000269|PubMed:14684365, ECO:0000269|PubMed:17767909, ECO:0000269|PubMed:19357235, ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}. Perikaryon {ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}. Cell projection, axon {ECO:0000269|PubMed:24477962}. Cell projection, dendrite {ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}. Membrane; Multi-pass membrane protein. Postsynaptic cell membrane {ECO:0000250|UniProtKB:P15387}. Synapse {ECO:0000250|UniProtKB:P15387}. Synapse, synaptosome {ECO:0000250|UniProtKB:P15387}. Lateral cell membrane {ECO:0000250|UniProtKB:P15387}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P15387}. Note=Localizes to high-density somatodendritic clusters and non-clustered sites on the surface of neocortical and hippocampal pyramidal neurons in a cortical actin cytoskeleton-dependent manner (PubMed:24477962). Also localizes to high-density clusters in the axon initial segment (AIS), at ankyrin-G-deficient sites, on the surface of neocortical and hippocampal pyramidal neurons (PubMed:24477962). KCNB1-containing AIS clusters localize either in close apposition to smooth endoplasmic reticulum cisternal organelles or with GABA-A receptor-containing synapses of hippocampal and cortical pyramidal neurons, respectively (PubMed:24477962). Localizes to high-density clusters on the cell surface of atrial and ventricular myocytes and at the lateral plasma membrane in epithelial cells. Localizes both to the axial and transverse tubules (T tubule) and sarcolemma in ventricular myocytes. Associated with lipid raft domains. In cortical neurons, apoptotic injuries induce de novo plasma membrane insertion in a SNARE-dependent manner causing an apoptotic potassium current surge (By similarity). {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q14721, ECO:0000269|PubMed:19357235, ECO:0000269|PubMed:22056818, ECO:0000269|PubMed:24477962}.
uniprot
proteins
transmembrane_region
TRANSMEM 187..208; /note="Helical; Name=Segment S1"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 229..250; /note="Helical; Name=Segment S2"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 260..280; /note="Helical; Name=Segment S3"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 295..316; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 331..351; /note="Helical; Name=Segment S5"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 392..420; /note="Helical; Name=Segment S6"; /evidence="ECO:0000250|UniProtKB:P63142
uniprot
proteins