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Protein

Potassium voltage-gated channel subfamily B member 1

Gene

Kcnb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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:10024359, PubMed:10618149, PubMed:12451110, PubMed:17379638, PubMed:19276663, PubMed:23878373). Plays also a role in the regulation of exocytosis independently of its electrical function (PubMed:20484665). 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:2770868, PubMed:2206531, PubMed:1875913, PubMed:8083226, PubMed:8978827, PubMed:9351973, PubMed:9565597, PubMed:12560340). 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 (PubMed:20202934). 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 (PubMed:8670833, PubMed:8980147, PubMed:9362476, PubMed:9079713, PubMed:9305895, PubMed:9696692). 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 (PubMed:9362476). 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:12954870, PubMed:19219384). 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 slowly inactivating 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 cells (PubMed:9362476, PubMed:9616203, PubMed:10024359, PubMed:10414968, PubMed:10618149, PubMed:11463864, PubMed:12451110, PubMed:12127166, PubMed:12403834, PubMed:12621036, PubMed:12807875, PubMed:12832499, PubMed:12954870, PubMed:15322114, PubMed:15195093, PubMed:16407566, PubMed:17301173, PubMed:17379638, PubMed:18463252, PubMed:18167541, PubMed:19276663, PubMed:20484665, PubMed:21518833, PubMed:22411134, PubMed:23878373). 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 (PubMed:10618149, PubMed:12451110, PubMed:16319318, PubMed:17379638, PubMed:19276663, PubMed:23878373, PubMed:16917065). Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:11463864). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells (PubMed:9616203). May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval (By similarity). Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury (PubMed:12832499, PubMed:16273079, PubMed:17360683, PubMed:19077057, PubMed:19622611, PubMed:24928958). May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (PubMed:16319318). 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 (PubMed:11463864, PubMed:17301173, PubMed:18167541, PubMed:20484665, PubMed:22411134).By similarity47 Publications

Enzyme regulationi

Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G. spatulata (PubMed:7576642). Inhibited by 100 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S. calceata (PubMed:12065754). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) (PubMed:2770868, PubMed:1875913, PubMed:8083226, PubMed:9362476). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (PubMed:9362476).2 Publications6 Publications

Kineticsi

Homotetrameric channels expressed in xenopus oocytes or in mammalian non-neuronal cells display delayed-rectifier voltage-dependent potassium currents which are activated during membrane depolarization, i.e within a risetime of about 20 msec (PubMed:2770868). After that, inactivate very slowly, i.e within more than 5 sec (PubMed:2206531, PubMed:8083226). Their activation requires low threshold potentials of about -20 to -30 mV, with a midpoint activation at about 10 mV (PubMed:2770868, PubMed:2206531, PubMed:8083226). For inactivation, the voltage at half-maximal amplitude is about -20 mV (PubMed:2206531, PubMed:8083226). The time constant for recovery after inactivation is about 1.6 sec. Channels have an unitary conductance of about 8 pS (PubMed:10414301, PubMed:15858231). The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, the presence or absence of ancillary subunits and post-translational modifications.2 Publications

3 Publications

      GO - Molecular functioni

      • delayed rectifier potassium channel activity Source: UniProtKB
      • ion channel binding Source: UniProtKB
      • outward rectifier potassium channel activity Source: RGD
      • protein heterodimerization activity Source: UniProtKB
      • protein N-terminus binding Source: RGD
      • SNARE binding Source: UniProtKB
      • voltage-gated potassium channel activity Source: MGI

      GO - Biological processi

      • action potential Source: UniProtKB
      • cellular response to glucose stimulus Source: UniProtKB
      • cellular response to nutrient levels Source: UniProtKB
      • glucose homeostasis Source: UniProtKB
      • glutamate receptor signaling pathway Source: UniProtKB
      • negative regulation of insulin secretion Source: UniProtKB
      • positive regulation of calcium ion-dependent exocytosis Source: UniProtKB
      • positive regulation of catecholamine secretion Source: UniProtKB
      • positive regulation of long term synaptic depression Source: UniProtKB
      • positive regulation of norepinephrine secretion Source: UniProtKB
      • positive regulation of protein targeting to membrane Source: UniProtKB
      • potassium ion transmembrane transport Source: UniProtKB
      • potassium ion transport Source: UniProtKB
      • protein homooligomerization Source: InterPro
      • protein oligomerization Source: RGD
      • protein targeting to plasma membrane Source: UniProtKB
      • regulation of action potential Source: UniProtKB
      • regulation of motor neuron apoptotic process Source: UniProtKB
      • vesicle docking involved in exocytosis Source: UniProtKB
      Complete GO annotation...

      Keywords - Molecular functioni

      Ion channel, Potassium channel, Voltage-gated channel

      Keywords - Biological processi

      Exocytosis, Ion transport, Potassium transport, Transport

      Keywords - Ligandi

      Potassium

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium voltage-gated channel subfamily B member 1By similarity
      Alternative name(s):
      Delayed rectifier potassium channel 11 Publication
      Short name:
      DRK11 Publication
      Voltage-gated potassium channel subunit Kv2.1
      Gene namesi
      Name:Kcnb1Imported
      OrganismiRattus norvegicus (Rat)
      Taxonomic identifieri10116 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
      Proteomesi
      • UP000002494 Componenti: Unplaced

      Organism-specific databases

      RGDi2954. Kcnb1.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 186186CytoplasmicBy similarityAdd
      BLAST
      Transmembranei187 – 20822Helical; Name=Segment S1Sequence analysisAdd
      BLAST
      Topological domaini209 – 22820ExtracellularBy similarityAdd
      BLAST
      Transmembranei229 – 25022Helical; Name=Segment S2Sequence analysisAdd
      BLAST
      Topological domaini251 – 2599CytoplasmicBy similarity
      Transmembranei260 – 28021Helical; Name=Segment S3By similarityAdd
      BLAST
      Topological domaini281 – 29414ExtracellularBy similarityAdd
      BLAST
      Transmembranei295 – 31622Helical; Voltage-sensor; Name=Segment S4By similarityAdd
      BLAST
      Topological domaini317 – 33014CytoplasmicBy similarityAdd
      BLAST
      Transmembranei331 – 35121Helical; Name=Segment S5By similarityAdd
      BLAST
      Topological domaini352 – 36413ExtracellularBy similarityAdd
      BLAST
      Intramembranei365 – 37612Helical; Name=Pore helixBy similarityAdd
      BLAST
      Intramembranei377 – 3848By similarity
      Topological domaini385 – 3917ExtracellularBy similarity
      Transmembranei392 – 42029Helical; Name=Segment S6By similarityAdd
      BLAST
      Topological domaini421 – 857437CytoplasmicBy similarityAdd
      BLAST

      GO - Cellular componenti

      • axon Source: UniProtKB
      • cell junction Source: UniProtKB-KW
      • dendrite Source: UniProtKB
      • dendrite membrane Source: RGD
      • intracellular Source: GOC
      • lateral plasma membrane Source: UniProtKB-SubCell
      • membrane Source: RGD
      • neuronal cell body Source: RGD
      • neuronal cell body membrane Source: UniProtKB
      • perikaryon Source: UniProtKB
      • plasma membrane Source: UniProtKB
      • postsynaptic membrane Source: RGD
      • sarcolemma Source: UniProtKB-SubCell
      • voltage-gated potassium channel complex Source: UniProtKB
      Complete GO annotation...

      Keywords - Cellular componenti

      Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse, Synaptosome

      Pathology & Biotechi

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi15 – 151S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. Additive effect on activation and steady-state inactivation; when associated with A-457. 1 Publication
      Mutagenesisi15 – 151S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi71 – 711Q → E: Reduces channel activity. 1 Publication
      Mutagenesisi79 – 791E → D: No effect on channel activity. 1 Publication
      Mutagenesisi128 – 1281Y → F: Reduces the increase of plasma membrane insertion and apoptotic enhancement of potassium current during cell death program. Significant loss of Src-mediated phosphorylation and channel activity. Reduces interaction with PTPRE. Increases cell viability against apoptotic insults. Abolishes the increase of plasma membrane insertion and apoptotic enhancement of potassium current during cell death program; when associated with D-804. 2 Publications
      Mutagenesisi149 – 1491K → Q: No loss of SUMO-dependent channel activity modulation in hippocampal neurons. 1 Publication
      Mutagenesisi259 – 2591K → Q: No loss of SUMO-dependent channel activity modulation in hippocampal neurons. 1 Publication
      Mutagenesisi369 – 3691W → C: Reduces channel activity. Does not inhibit membrane plasma subcellular localization, interaction with STX1A, pore-independent exocytosis activity and apoptotic enhancement of potassium current during cell death program; when associated with T-384. 7 Publications
      Mutagenesisi384 – 3841Y → T: Reduces channel activity. Does not inhibit membrane plasma subcellular localization, interaction with STX1A, pore-independent exocytosis activity and apoptotic enhancement of potassium current during cell death program; when associated with C-369. 6 Publications
      Mutagenesisi444 – 4441S → A: No effect on Src-mediated phosphorylation. 1 Publication
      Mutagenesisi457 – 4571S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. Additive effect on activation and steady-state inactivation; when associated with A-15. 1 Publication
      Mutagenesisi457 – 4571S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi474 – 4741K → Q: Loss of SUMO-dependent channel activity modulation in hippocampal neurons. 1 Publication
      Mutagenesisi484 – 4841S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi484 – 4841S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi496 – 4961S → A: No effect on Src-mediated phosphorylation. 1 Publication
      Mutagenesisi541 – 5411S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi541 – 5411S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi567 – 5671S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. Larger effect on activation and steady-state inactivation; when associated with A-607. 1 Publication
      Mutagenesisi567 – 5671S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi587 – 5871S → A: Abolishes clustered subcellular distribution in neurons. 1 Publication
      Mutagenesisi590 – 5901S → A: Abolishes clustered subcellular distribution in neurons. Does not affect KCNB1-containing vesicles motility. 2 Publications
      Mutagenesisi591 – 5911F → A: Abolishes clustered subcellular distribution in neurons. 1 Publication
      Mutagenesisi593 – 5931S → A: Abolishes clustered subcellular distribution in neurons. 1 Publication
      Mutagenesisi607 – 6071S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. Larger effect on activation and steady-state inactivation; when associated with A-567. 1 Publication
      Mutagenesisi607 – 6071S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi655 – 6551S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi655 – 6551S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi719 – 7191S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi719 – 7191S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi771 – 7711S → A: Shift in voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi771 – 7711S → D: Resists voltage-dependent gating on calcineurin-dependent activation and steady-state inactivation. 1 Publication
      Mutagenesisi804 – 8041S → A: Reduces the increase of plasma membrane insertion and apoptotic enhancement of potassium current during cell death program. No change in calcineurin-dependent regulation of voltage-dependent gating. Abolishes the increase of plasma membrane insertion and apoptotic enhancement of potassium current during cell death program; when associated with F-128. 3 Publications
      Mutagenesisi804 – 8041S → D: Does not reduce apoptotic enhancement of potassium current during the cell death program. 1 Publication

      Chemistry

      ChEMBLiCHEMBL1075226.
      GuidetoPHARMACOLOGYi546.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 857857Potassium voltage-gated channel subfamily B member 1PRO_0000054046Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Modified residuei15 – 151Phosphoserine2 Publications
      Modified residuei128 – 1281Phosphotyrosine; by Src2 Publications
      Modified residuei444 – 4441PhosphoserineBy similarity
      Modified residuei457 – 4571Phosphoserine3 Publications
      Cross-linki474 – 474Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
      Modified residuei484 – 4841PhosphoserineCombined sources1 Publication
      Modified residuei496 – 4961Phosphoserine1 Publication
      Modified residuei503 – 5031Phosphoserine1 Publication
      Modified residuei519 – 5191PhosphoserineCombined sources
      Modified residuei520 – 5201Phosphoserine; by CDK5; in vitroCombined sources2 Publications
      Modified residuei541 – 5411Phosphoserine2 Publications
      Modified residuei567 – 5671Phosphoserine2 Publications
      Modified residuei590 – 5901Phosphoserine1 Publication
      Modified residuei607 – 6071Phosphoserine; by CDK55 Publications
      Modified residuei655 – 6551Phosphoserine; by CDK5; in vitroCombined sources3 Publications
      Modified residuei719 – 7191Phosphoserine3 Publications
      Modified residuei771 – 7711Phosphoserine1 Publication
      Modified residuei799 – 7991Phosphoserine2 Publications
      Modified residuei804 – 8041Phosphoserine; by CDK5, MAPK14; in vitro4 Publications
      Modified residuei836 – 8361Phosphothreonine2 Publications

      Post-translational modificationi

      Phosphorylated (PubMed:8083226, PubMed:15195093, PubMed:16319318, PubMed:16407566, PubMed:18463252). Differential C-terminal phosphorylation on a subset of serines allows graded activity-dependent regulation of channel gating in hippocampal neurons (PubMed:9351973, PubMed:17192433, PubMed:16917065). Ser-607 and Tyr-128 are significant sites of voltage-gated regulation through phosphorylation/dephosphorylation activities (PubMed:12615930, PubMed:17192433). Tyr-128 can be phosphorylated by Src and dephosphorylated by cytoplasmic form of the phosphatase PTPRE isoform 2 (PubMed:12615930). CDK5-induced Ser-607 phosphorylation increases in response to acute blockade of neuronal activity (PubMed:21712386). 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 (PubMed:17360683, PubMed:19622611). Phosphorylated on Ser-520, Ser-607, Ser-655 and Ser-804 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation (PubMed:21712386). The Ser-607 phosphorylation state differs between KCNB1-containing clusters on the proximal and distal portions of the axon initial segment (AIS) (PubMed:24477962). Highly phosphorylated on serine residues in the C-terminal cytoplasmic tail in resting neurons (PubMed:9351973, PubMed:16917065). Phosphorylated in pancreatic beta cells in response to incretin hormones stimulation in a PKA- and RPS6KA5/MSK1-dependent signaling pathway, promoting beta cell survival (PubMed:21818121). 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 (PubMed:17192433). 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 (PubMed:17192433, PubMed:16917065). Dephosphorylation by phosphatase PTPRE isoform 2 confers neuroprotection by its inhibitory influence on the neuronal apoptotic potassium current surge in a Zn2+-dependent manner (PubMed:19622611). Dephosphorylated at Ser-607 by protein phosphatase PPP1CA (PubMed:21712386). Hypoxia-, seizure- or glutamate-induced neuronal activities promote calcium/calcineurin-dependent dephosphorylation resulting in a loss of KCNB1-containing clustering and enhanced channel activity (PubMed:15195093, PubMed:16319318, PubMed:16407566, PubMed:17192433, PubMed:16917065). In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-719 are less dephosphorylated (PubMed:17192433). In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced (PubMed:17192433). Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic nerve tissue (By similarity).By similarity15 Publications
      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 (PubMed:21818121).1 Publication
      Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity (PubMed:21518833). Sumoylation increases the frequency of repetitive action potential firing at the cell surface of hippocampal neurons and decreases its frequency in pancreatic beta cells (PubMed:21518833). Desumoylated by SENP1 (PubMed:21518833).1 Publication
      Not glycosylated (PubMed:8083226).1 Publication

      Keywords - PTMi

      Isopeptide bond, Phosphoprotein, Ubl conjugation

      Proteomic databases

      PaxDbiP15387.
      PRIDEiP15387.

      PTM databases

      iPTMnetiP15387.
      PhosphoSiteiP15387.

      Expressioni

      Tissue specificityi

      Expressed in brain (PubMed:1740690, PubMed:1961744, PubMed:8508921, PubMed:7623158, PubMed:12954870). Expressed in the hippocampus, cerebral cortex, cerebellum, thalamus, hypothalamus, olfactory bulb, corpus striatum and medial hebenula (PubMed:8463836, PubMed:10414301, PubMed:16319318). Expressed in pancreatic islets (PubMed:12403834). Expressed in heart and skeletal muscle (PubMed:1740690, PubMed:19219384, PubMed:10414301). Levels remain constant throughout postnatal development (PubMed:17192433). Expressed in neocortical pyramidal neurons and inhibitory interneurons (PubMed:1961744, PubMed:9522360, PubMed:10618149, PubMed:12832499, PubMed:17192433, PubMed:17379638, PubMed:19014551, PubMed:20202934, PubMed:24477962). Expressed in the superior cervical ganglion (SCG) neurons (PubMed:12451110). Expressed in globus pallidus neurons (PubMed:10414968). Expressed in pancreatic beta cells (PubMed:11463864, PubMed:22411134). Expressed in cardiomyocytes (PubMed:17965280). Expressed in arterial smooth muscle, alveolar epithelium and parenchyma (at protein level) (PubMed:9362476, PubMed:9616203, PubMed:15322114). Expressed in brain, heart, lung, liver, colon, kidney and adrenal gland (PubMed:8508921, PubMed:9362476, PubMed:19074135). Expressed in pyramidal cells of the cerebral cortex, in Purkinje and granule cells of the cerebellum (PubMed:8463836). Expressed in CA1-CA3 pyramidal cells, dentate granule cells and interneurons of the hippocampus (PubMed:7623158, PubMed:10024359). Expressed in pulmonary artery (PA) smooth muscle cells (PubMed:9362476).27 Publications

      Developmental stagei

      Expressed in embryonic brain at 14 dpc, and thereafter (at protein level) (PubMed:8508921). Expressed in embryonic brain at 14 dpc, and thereafter (PubMed:8508921).1 Publication

      Inductioni

      Down-regulated by angiotensin II in a NFATC3-dependent manner (PubMed:15322114).1 Publication

      Gene expression databases

      GenevisibleiP15387. RN.

      Interactioni

      Subunit structurei

      Homotetramer or heterotetramer with KCNB2 (PubMed:20202934). Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (PubMed:8670833, PubMed:8980147, PubMed:9362476, PubMed:9079713, PubMed:9305895, PubMed:9696692). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (PubMed:12954870, PubMed:19219384). Self-associates (via N-terminus and C-terminus); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (PubMed:12560340, PubMed:18463252, PubMed:19690160). Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons (PubMed:12621036, PubMed:12807875, PubMed:17301173, PubMed:18167541, PubMed:19077057, PubMed:20484665, PubMed:22411134, PubMed:24928958). Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner (PubMed:12403834, PubMed:12807875, PubMed:19077057). Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate (PubMed:18542995, PubMed:19690160, PubMed:19077057). Interacts with CREB1; this promotes channel acetylation in response to stimulation by incretin hormones (PubMed:21818121). Interacts (via N-terminus and C-terminus) with MYL12B (PubMed:24569993). Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface (PubMed:9565597). Interacts with SUMO1. Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells (By similarity).By similarity25 Publications

      GO - Molecular functioni

      • ion channel binding Source: UniProtKB
      • protein heterodimerization activity Source: UniProtKB
      • protein N-terminus binding Source: RGD
      • SNARE binding Source: UniProtKB

      Protein-protein interaction databases

      BioGridi247764. 5 interactions.
      IntActiP15387. 4 interactions.
      MINTiMINT-8283237.
      STRINGi10116.ENSRNOP00000065961.

      Chemistry

      BindingDBiP15387.

      Structurei

      Secondary structure

      1
      857
      Legend: HelixTurnBeta strand
      Show more details
      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Helixi274 – 2818Combined sources
      Helixi286 – 30217Combined sources
      Helixi303 – 3064Combined sources

      3D structure databases

      Select the link destinations:
      PDBei
      RCSB PDBi
      PDBji
      Links Updated
      EntryMethodResolution (Å)ChainPositionsPDBsum
      2R9RX-ray2.40B/H272-304[»]
      3LNMX-ray2.90B/D272-304[»]
      4JTAX-ray2.50B/Q274-306[»]
      4JTCX-ray2.56B/H274-306[»]
      4JTDX-ray2.54B/H274-306[»]
      ProteinModelPortaliP15387.
      ModBaseiSearch...
      MobiDBiSearch...

      Miscellaneous databases

      EvolutionaryTraceiP15387.

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni59 – 7517Self-association2 PublicationsAdd
      BLAST
      Regioni448 – 48134Self-association2 PublicationsAdd
      BLAST

      Motif

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Motifi377 – 3826Selectivity filterBy similarity

      Compositional bias

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Compositional biasi517 – 5204Poly-Ser
      Compositional biasi700 – 7056Poly-Ala

      Domaini

      The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.By similarity
      The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (PubMed:12560340, PubMed:18463252, PubMed:19690160). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits (PubMed:12954870, PubMed:19219384). The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells (PubMed:8978827, PubMed:10719893). The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons (PubMed:16407566).By similarity8 Publications

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiKOG3713. Eukaryota.
      COG1226. LUCA.
      HOVERGENiHBG052225.
      InParanoidiP15387.
      KOiK04885.
      OMAiTEGVIDM.
      OrthoDBiEOG7CRTPP.
      PhylomeDBiP15387.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ_dom.
      IPR027359. Channel_four-helix_dom.
      IPR005821. Ion_trans_dom.
      IPR003968. K_chnl_volt-dep_Kv.
      IPR003973. K_chnl_volt-dep_Kv2.
      IPR004350. K_chnl_volt-dep_Kv2.1.
      IPR011333. SKP1/BTB/POZ.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 1 hit.
      PfamiPF02214. BTB_2. 1 hit.
      PF00520. Ion_trans. 1 hit.
      PF03521. Kv2channel. 2 hits.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01514. KV21CHANNEL.
      PR01491. KVCHANNEL.
      PR01495. SHABCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.

      Sequencei

      Sequence statusi: Complete.

      P15387-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MPAGMTKHGS RSTSSLPPEP MEIVRSKACS RRVRLNVGGL AHEVLWRTLD
      60 70 80 90 100
      RLPRTRLGKL RDCNTHDSLL QVCDDYSLED NEYFFDRHPG AFTSILNFYR
      110 120 130 140 150
      TGRLHMMEEM CALSFSQELD YWGIDEIYLE SCCQARYHQK KEQMNEELKR
      160 170 180 190 200
      EAETLREREG EEFDNTCCAE KRKKLWDLLE KPNSSVAAKI LAIISIMFIV
      210 220 230 240 250
      LSTIALSLNT LPELQSLDEF GQSTDNPQLA HVEAVCIAWF TMEYLLRFLS
      260 270 280 290 300
      SPKKWKFFKG PLNAIDLLAI LPYYVTIFLT ESNKSVLQFQ NVRRVVQIFR
      310 320 330 340 350
      IMRILRILKL ARHSTGLQSL GFTLRRSYNE LGLLILFLAM GIMIFSSLVF
      360 370 380 390 400
      FAEKDEDDTK FKSIPASFWW ATITMTTVGY GDIYPKTLLG KIVGGLCCIA
      410 420 430 440 450
      GVLVIALPIP IIVNNFSEFY KEQKRQEKAI KRREALERAK RNGSIVSMNM
      460 470 480 490 500
      KDAFARSIEM MDIVVEKNGE SIAKKDKVQD NHLSPNKWKW TKRALSETSS
      510 520 530 540 550
      SKSFETKEQG SPEKARSSSS PQHLNVQQLE DMYSKMAKTQ SQPILNTKEM
      560 570 580 590 600
      APQSKPPEEL EMSSMPSPVA PLPARTEGVI DMRSMSSIDS FISCATDFPE
      610 620 630 640 650
      ATRFSHSPLA SLSSKAGSST APEVGWRGAL GASGGRLTET NPIPETSRSG
      660 670 680 690 700
      FFVESPRSSM KTNNPLKLRA LKVNFVEGDP TPLLPSLGLY HDPLRNRGGA
      710 720 730 740 750
      AAAVAGLECA SLLDKPVLSP ESSIYTTASA RTPPRSPEKH TAIAFNFEAG
      760 770 780 790 800
      VHHYIDTDTD DEGQLLYSVD SSPPKSLHGS TSPKFSTGAR TEKNHFESSP
      810 820 830 840 850
      LPTSPKFLRP NCVYSSEGLT GKGPGAQEKC KLENHTPPDV HMLPGGGAHG

      STRDQSI
      Length:857
      Mass (Da):95,637
      Last modified:October 25, 2002 - v3
      Checksum:iB3C5B0839AB15FD0
      GO

      Sequence cautioni

      The sequence CAA34497.1 differs from that shown. Reason: Erroneous initiation. Curated

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      X16476 mRNA. Translation: CAA34497.1. Different initiation.
      PIRiS05448. CHRTD1.
      RefSeqiNP_037318.1. NM_013186.1.
      UniGeneiRn.26724.

      Genome annotation databases

      GeneIDi25736.
      KEGGirno:25736.
      UCSCiRGD:2954. rat.

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      X16476 mRNA. Translation: CAA34497.1. Different initiation.
      PIRiS05448. CHRTD1.
      RefSeqiNP_037318.1. NM_013186.1.
      UniGeneiRn.26724.

      3D structure databases

      Select the link destinations:
      PDBei
      RCSB PDBi
      PDBji
      Links Updated
      EntryMethodResolution (Å)ChainPositionsPDBsum
      2R9RX-ray2.40B/H272-304[»]
      3LNMX-ray2.90B/D272-304[»]
      4JTAX-ray2.50B/Q274-306[»]
      4JTCX-ray2.56B/H274-306[»]
      4JTDX-ray2.54B/H274-306[»]
      ProteinModelPortaliP15387.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi247764. 5 interactions.
      IntActiP15387. 4 interactions.
      MINTiMINT-8283237.
      STRINGi10116.ENSRNOP00000065961.

      Chemistry

      BindingDBiP15387.
      ChEMBLiCHEMBL1075226.
      GuidetoPHARMACOLOGYi546.

      PTM databases

      iPTMnetiP15387.
      PhosphoSiteiP15387.

      Proteomic databases

      PaxDbiP15387.
      PRIDEiP15387.

      Protocols and materials databases

      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      GeneIDi25736.
      KEGGirno:25736.
      UCSCiRGD:2954. rat.

      Organism-specific databases

      CTDi3745.
      RGDi2954. Kcnb1.

      Phylogenomic databases

      eggNOGiKOG3713. Eukaryota.
      COG1226. LUCA.
      HOVERGENiHBG052225.
      InParanoidiP15387.
      KOiK04885.
      OMAiTEGVIDM.
      OrthoDBiEOG7CRTPP.
      PhylomeDBiP15387.

      Miscellaneous databases

      EvolutionaryTraceiP15387.
      PROiP15387.

      Gene expression databases

      GenevisibleiP15387. RN.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ_dom.
      IPR027359. Channel_four-helix_dom.
      IPR005821. Ion_trans_dom.
      IPR003968. K_chnl_volt-dep_Kv.
      IPR003973. K_chnl_volt-dep_Kv2.
      IPR004350. K_chnl_volt-dep_Kv2.1.
      IPR011333. SKP1/BTB/POZ.
      IPR003131. T1-type_BTB.
      IPR028325. VG_K_chnl.
      [Graphical view]
      PANTHERiPTHR11537. PTHR11537. 1 hit.
      PfamiPF02214. BTB_2. 1 hit.
      PF00520. Ion_trans. 1 hit.
      PF03521. Kv2channel. 2 hits.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01514. KV21CHANNEL.
      PR01491. KVCHANNEL.
      PR01495. SHABCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.
      ProtoNetiSearch...

      Publicationsi

      « Hide 'large scale' publications
      1. "A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning."
        Frech G.C., Vandongen A.M.J., Schuster G., Brown A.M., Joho R.H.
        Nature 340:642-645(1989) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-857, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
        Tissue: Brain.
      2. Frech G.C.
        Submitted (FEB-1990) to the EMBL/GenBank/DDBJ databases
        Cited for: SEQUENCE REVISION.
      3. "Distinct spatial and temporal expression patterns of K+ channel mRNAs from different subfamilies."
        Drewe J.A., Verma S., Frech G.C., Joho R.H.
        J. Neurosci. 12:538-548(1992) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-575, TISSUE SPECIFICITY.
      4. "Alteration and restoration of K+ channel function by deletions at the N- and C-termini."
        VanDongen A.M., Frech G.C., Drewe J.A., Joho R.H., Brown A.M.
        Neuron 5:433-443(1990) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
      5. "Patterns of internal and external tetraethylammonium block in four homologous K+ channels."
        Taglialatela M., Vandongen A.M., Drewe J.A., Joho R.H., Brown A.M., Kirsch G.E.
        Mol. Pharmacol. 40:299-307(1991) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, ENZYME REGULATION.
      6. "Immunological identification and characterization of a delayed rectifier K+ channel polypeptide in rat brain."
        Trimmer J.S.
        Proc. Natl. Acad. Sci. U.S.A. 88:10764-10768(1991) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      7. "Expression of Kv2.1 delayed rectifier K+ channel isoforms in the developing rat brain."
        Trimmer J.S.
        FEBS Lett. 324:205-210(1993) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      8. "Contrasting immunohistochemical localizations in rat brain of two novel K+ channels of the Shab subfamily."
        Hwang P.M., Fotuhi M., Bredt D.S., Cunningham A.M., Snyder S.H.
        J. Neurosci. 13:1569-1576(1993) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      9. "Properties of Kv2.1 K+ channels expressed in transfected mammalian cells."
        Shi G., Kleinklaus A.K., Marrion N.V., Trimmer J.S.
        J. Biol. Chem. 269:23204-23211(1994) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, PHOSPHORYLATION, ENZYME REGULATION, SUBCELLULAR LOCATION, ABSENCE OF GLYCOSYLATION.
      10. "Association and colocalization of K+ channel alpha- and beta-subunit polypeptides in rat brain."
        Rhodes K.J., Keilbaugh S.A., Barrezueta N.X., Lopez K.L., Trimmer J.S.
        J. Neurosci. 15:5360-5371(1995) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ABSENCE OF INTERACTION WITH KCNAB1 AND KCNAB2.
      11. "An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula."
        Swartz K.J., MacKinnon R.
        Neuron 15:941-949(1995) [PubMed] [Europe PMC] [Abstract]
        Cited for: ENZYME REGULATION.
      12. "Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel."
        Scannevin R.H., Murakoshi H., Rhodes K.J., Trimmer J.S.
        J. Cell Biol. 135:1619-1632(1996) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN.
      13. "Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards Shab and Shaw channels."
        Hugnot J.-P., Salinas M., Lesage F., Guillemare E., de Weille J., Heurteaux C., Mattei M.-G., Lazdunski M.
        EMBO J. 15:3322-3331(1996) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNV1, SUBCELLULAR LOCATION.
      14. "Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current."
        Post M.A., Kirsch G.E., Brown A.M.
        FEBS Lett. 399:177-182(1996) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNG1, SUBCELLULAR LOCATION.
      15. "Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes."
        Patel A.J., Lazdunski M., Honore E.
        EMBO J. 16:6615-6625(1997) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNS3, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY.
      16. "Modes of regulation of shab K+ channel activity by the Kv8.1 subunit."
        Salinas M., de Weille J., Guillemare E., Lazdunski M., Hugnot J.-P.
        J. Biol. Chem. 272:8774-8780(1997) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
      17. "New modulatory alpha subunits for mammalian Shab K+ channels."
        Salinas M., Duprat F., Heurteaux C., Hugnot J.-P., Lazdunski M.
        J. Biol. Chem. 272:24371-24379(1997) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
      18. "Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation."
        Murakoshi H., Shi G., Scannevin R.H., Trimmer J.S.
        Mol. Pharmacol. 52:821-828(1997) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION, FUNCTION, MUTAGENESIS OF SER-444 AND SER-496.
      19. "Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits."
        Kramer J.W., Post M.A., Brown A.M., Kirsch G.E.
        Am. J. Physiol. 274:C1501-C1510(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNF1 AND KCNG1, SUBCELLULAR LOCATION.
      20. "Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes."
        Archer S.L., Souil E., Dinh-Xuan A.T., Schremmer B., Mercier J.C., El Yaagoubi A., Nguyen-Huu L., Reeve H.L., Hampl V.
        J. Clin. Invest. 101:2319-2330(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      21. "Cloning and expression of a novel K+ channel regulatory protein, KChAP."
        Wible B.A., Yang Q., Kuryshev Y.A., Accili E.A., Brown A.M.
        J. Biol. Chem. 273:11745-11751(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH PIAS3.
      22. "The K+ channel, Kv2.1, is apposed to astrocytic processes and is associated with inhibitory postsynaptic membranes in hippocampal and cortical principal neurons and inhibitory interneurons."
        Du J., Tao-Cheng J.H., Zerfas P., McBain C.J.
        Neuroscience 84:37-48(1998) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      23. Cited for: REVIEW.
      24. "Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons."
        Murakoshi H., Trimmer J.S.
        J. Neurosci. 19:1728-1735(1999) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      25. "Delayed rectifier currents in rat globus pallidus neurons are attributable to Kv2.1 and Kv3.1/3.2 K(+) channels."
        Baranauskas G., Tkatch T., Surmeier D.J.
        J. Neurosci. 19:6394-6404(1999) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      26. "Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1."
        Du J., Haak L.L., Phillips-Tansey E., Russell J.T., McBain C.J.
        J. Physiol. (Lond.) 522:19-31(2000) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      27. "A novel targeting signal for proximal clustering of the Kv2.1 K+ channel in hippocampal neurons."
        Lim S.T., Antonucci D.E., Scannevin R.H., Trimmer J.S.
        Neuron 25:385-397(2000) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF SER-587; SER-590; PHE-591 AND SER-593.
      28. "Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion."
        MacDonald P.E., Ha X.F., Wang J., Smukler S.R., Sun A.M., Gaisano H.Y., Salapatek A.M., Backx P.H., Wheeler M.B.
        Mol. Endocrinol. 15:1423-1435(2001) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, TISSUE SPECIFICITY.
      29. "Delayed rectifier K+ currents, IK, are encoded by Kv2 alpha-subunits and regulate tonic firing in mammalian sympathetic neurons."
        Malin S.A., Nerbonne J.M.
        J. Neurosci. 22:10094-10105(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF TRP-369 AND TYR-384.
      30. "Contributions of Kv1.2, Kv1.5 and Kv2.1 subunits to the native delayed rectifier K(+) current in rat mesenteric artery smooth muscle cells."
        Lu Y., Hanna S.T., Tang G., Wang R.
        Life Sci. 71:1465-1473(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION.
      31. "Synaptosome-associated protein of 25 kilodaltons modulates Kv2.1 voltage-dependent K(+) channels in neuroendocrine islet beta-cells through an interaction with the channel N terminus."
        MacDonald P.E., Wang G., Tsuk S., Dodo C., Kang Y., Tang L., Wheeler M.B., Cattral M.S., Lakey J.R., Salapatek A.M., Lotan I., Gaisano H.Y.
        Mol. Endocrinol. 16:2452-2461(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH SNAP25, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      32. "Novel tarantula toxins for subtypes of voltage-dependent potassium channels in the Kv2 and Kv4 subfamilies."
        Escoubas P., Diochot S., Celerier M.-L., Nakajima T., Lazdunski M.
        Mol. Pharmacol. 62:48-57(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: ENZYME REGULATION.
      33. "The Roles of N- and C-terminal determinants in the activation of the Kv2.1 potassium channel."
        Ju M., Stevens L., Leadbitter E., Wray D.
        J. Biol. Chem. 278:12769-12778(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION, MUTAGENESIS OF GLN-71 AND GLU-79.
      34. "Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase epsilon."
        Tiran Z., Peretz A., Attali B., Elson A.
        J. Biol. Chem. 278:17509-17514(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT TYR-128, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-128.
      35. "Syntaxin 1A binds to the cytoplasmic C terminus of Kv2.1 to regulate channel gating and trafficking."
        Leung Y.M., Kang Y., Gao X., Xia F., Xie H., Sheu L., Tsuk S., Lotan I., Tsushima R.G., Gaisano H.Y.
        J. Biol. Chem. 278:17532-17538(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH STX1A, SUBCELLULAR LOCATION.
      36. "Direct interaction of target SNAREs with the Kv2.1 channel. Modal regulation of channel activation and inactivation gating."
        Michaelevski I., Chikvashvili D., Tsuk S., Singer-Lahat D., Kang Y., Linial M., Gaisano H.Y., Fili O., Lotan I.
        J. Biol. Chem. 278:34320-34330(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH SNP25 AND STX1A, SUBCELLULAR LOCATION.
      37. "Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels."
        Pal S., Hartnett K.A., Nerbonne J.M., Levitan E.S., Aizenman E.
        J. Neurosci. 23:4798-4802(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF TRP-369 AND TYR-384.
      38. "MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain."
        McCrossan Z.A., Lewis A., Panaghie G., Jordan P.N., Christini D.J., Lerner D.J., Abbott G.W.
        J. Neurosci. 23:8077-8091(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNE3, SUBCELLULAR LOCATION, DOMAIN, TISSUE SPECIFICITY.
      39. "NFATc3 regulates Kv2.1 expression in arterial smooth muscle."
        Amberg G.C., Rossow C.F., Navedo M.F., Santana L.F.
        J. Biol. Chem. 279:47326-47334(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
      40. "Regulation of ion channel localization and phosphorylation by neuronal activity."
        Misonou H., Mohapatra D.P., Park E.W., Leung V., Zhen D., Misonou K., Anderson A.E., Trimmer J.S.
        Nat. Neurosci. 7:711-718(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, PHOSPHORYLATION, DEPHOSPHORYLATION, SUBCELLULAR LOCATION.
      41. "Molecular determinants of voltage-gated potassium currents in vascular smooth muscle."
        Cox R.H.
        Cell Biochem. Biophys. 42:167-195(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: REVIEW.
      42. "Targeting of voltage-gated potassium channel isoforms to distinct cell surface microdomains."
        O'Connell K.M., Tamkun M.M.
        J. Cell Sci. 118:2155-2166(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION.
      43. "Calcium- and metabolic state-dependent modulation of the voltage-dependent Kv2.1 channel regulates neuronal excitability in response to ischemia."
        Misonou H., Mohapatra D.P., Menegola M., Trimmer J.S.
        J. Neurosci. 25:11184-11193(2005) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, PHOSPHORYLATION, DEPHOSPHORYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      44. Cited for: FUNCTION, SUBCELLULAR LOCATION.
      45. "The Kv2.1 C terminus can autonomously transfer Kv2.1-like phosphorylation-dependent localization, voltage-dependent gating, and muscarinic modulation to diverse Kv channels."
        Mohapatra D.P., Trimmer J.S.
        J. Neurosci. 26:685-695(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, PHOSPHORYLATION, DEPHOSPHORYLATION, DOMAIN, SUBCELLULAR LOCATION.
      46. "Kv2.1 potassium channels are retained within dynamic cell surface microdomains that are defined by a perimeter fence."
        O'Connell K.M., Rolig A.S., Whitesell J.D., Tamkun M.M.
        J. Neurosci. 26:9609-9618(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION.
      47. "Bidirectional activity-dependent regulation of neuronal ion channel phosphorylation."
        Misonou H., Menegola M., Mohapatra D.P., Guy L.K., Park K.-S., Trimmer J.S.
        J. Neurosci. 26:13505-13514(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT SER-457; SER-567; SER-607 AND SER-719, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, FUNCTION.
      48. "Graded regulation of the Kv2.1 potassium channel by variable phosphorylation."
        Park K.-S., Mohapatra D.P., Misonou H., Trimmer J.S.
        Science 313:976-979(2006) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT SER-15; SER-457; SER-484; SER-496; SER-503; SER-520; SER-541; SER-567; SER-590; SER-607; SER-655; SER-719; SER-771; SER-799; SER-804 AND THR-836, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-15; SER-457; SER-484; SER-541; SER-567; SER-607; SER-655; SER-719; SER-771 AND SER-804.
      49. "Proteomic analyses of K(v)2.1 channel phosphorylation sites determining cell background specific differences in function."
        Park K.S., Mohapatra D.P., Trimmer J.S.
        Channels 1:59-61(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT SER-15; SER-457; SER-541; SER-607; SER-655; SER-719; SER-799; SER-804 AND THR-836, IDENTIFICATION BY MASS SPECTROMETRY.
      50. "A cytoskeletal-based perimeter fence selectively corrals a sub-population of cell surface Kv2.1 channels."
        Tamkun M.M., O'connell K.M., Rolig A.S.
        J. Cell Sci. 120:2413-2423(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION.
      51. Cited for: FUNCTION, INTERACTION WITH STX1A, SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-369 AND TYR-384.
      52. "Kv2 subunits underlie slowly inactivating potassium current in rat neocortical pyramidal neurons."
        Guan D., Tkatch T., Surmeier D.J., Armstrong W.E., Foehring R.C.
        J. Physiol. (Lond.) 581:941-960(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      53. "Apoptotic surge of potassium currents is mediated by p38 phosphorylation of Kv2.1."
        Redman P.T., He K., Hartnett K.A., Jefferson B.S., Hu L., Rosenberg P.A., Levitan E.S., Aizenman E.
        Proc. Natl. Acad. Sci. U.S.A. 104:3568-3573(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT SER-804, MUTAGENESIS OF TRP-369; TYR-384 AND SER-804, FUNCTION, SUBCELLULAR LOCATION.
      54. "Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes."
        O'Connell K.M., Whitesell J.D., Tamkun M.M.
        Am. J. Physiol. 294:H229-H237(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      55. "The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ."
        Sarmiere P.D., Weigle C.M., Tamkun M.M.
        BMC Neurosci. 9:112-112(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      56. "Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel."
        Mohapatra D.P., Siino D.F., Trimmer J.S.
        J. Neurosci. 28:4982-4994(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SELF-ASSOCIATION, SUBCELLULAR LOCATION, PHOSPHORYLATION, DOMAIN.
      57. "VAMP2 interacts directly with the N terminus of Kv2.1 to enhance channel inactivation."
        Lvov A., Chikvashvili D., Michaelevski I., Lotan I.
        Pflugers Arch. 456:1121-1136(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH VAMP2, SUBCELLULAR LOCATION.
      58. "Direct interaction of endogenous Kv channels with syntaxin enhances exocytosis by neuroendocrine cells."
        Singer-Lahat D., Chikvashvili D., Lotan I.
        PLoS ONE 3:E1381-E1381(2008) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH STX1A, SUBCELLULAR LOCATION.
      59. "Regulation of intrinsic excitability in hippocampal neurons by activity-dependent modulation of the KV2.1 potassium channel."
        Mohapatra D.P., Misonou H., Pan S.J., Held J.E., Surmeier D.J., Trimmer J.S.
        Channels 3:46-56(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION.
      60. "Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4."
        Mederos y Schnitzler M., Rinne S., Skrobek L., Renigunta V., Schlichthorl G., Derst C., Gudermann T., Daut J., Preisig-Muller R.
        J. Biol. Chem. 284:4695-4704(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY.
      61. "Rearrangements in the relative orientation of cytoplasmic domains induced by a membrane-anchored protein mediate modulations in Kv channel gating."
        Lvov A., Greitzer D., Berlin S., Chikvashvili D., Tsuk S., Lotan I., Michaelevski I.
        J. Biol. Chem. 284:28276-28291(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH VAMP2, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION.
      62. "Regulation of the Kv2.1 potassium channel by MinK and MiRP1."
        McCrossan Z.A., Roepke T.K., Lewis A., Panaghie G., Abbott G.W.
        J. Membr. Biol. 228:1-14(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNE1 AND KCNE2, SUBCELLULAR LOCATION, DOMAIN, TISSUE SPECIFICITY.
      63. "The Kv2.1 channels mediate neuronal apoptosis induced by excitotoxicity."
        Yao H., Zhou K., Yan D., Li M., Wang Y.
        J. Neurochem. 108:909-919(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SNAP25; STX1A AND VAMP2.
      64. "Regulation of apoptotic potassium currents by coordinated zinc-dependent signalling."
        Redman P.T., Hartnett K.A., Aras M.A., Levitan E.S., Aizenman E.
        J. Physiol. (Lond.) 587:4393-4404(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, PHOSPHORYLATION AT TYR-128, DEPHOSPHORYLATION, MUTAGENESIS OF TYR-128 AND SER-804.
      65. "Formation of heteromeric Kv2 channels in mammalian brain neurons."
        Kihira Y., Hermanstyne T.O., Misonou H.
        J. Biol. Chem. 285:15048-15055(2010) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNB2, SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-369 AND TYR-384, TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY.
      66. "Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells."
        Feinshreiber L., Singer-Lahat D., Friedrich R., Matti U., Sheinin A., Yizhar O., Nachman R., Chikvashvili D., Rettig J., Ashery U., Lotan I.
        J. Cell Sci. 123:1940-1947(2010) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH STX1A, SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-369 AND TYR-384.
      67. "Activity-dependent phosphorylation of neuronal Kv2.1 potassium channels by CDK5."
        Cerda O., Trimmer J.S.
        J. Biol. Chem. 286:28738-28748(2011) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT SER-520; SER-655; SER-607 AND SER-804, DEPHOSPHORYLATION AT SER-607, SUBCELLULAR LOCATION.
      68. "SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons."
        Plant L.D., Dowdell E.J., Dementieva I.S., Marks J.D., Goldstein S.A.
        J. Gen. Physiol. 137:441-454(2011) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUMOYLATION AT LYS-474, DESUMOYLATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-149; LYS-259 AND LYS-474, IDENTIFICATION BY MASS SPECTROMETRY.
      69. "Pancreatic beta-cell prosurvival effects of the incretin hormones involve post-translational modification of Kv2.1 delayed rectifier channels."
        Kim S.J., Widenmaier S.B., Choi W.S., Nian C., Ao Z., Warnock G., McIntosh C.H.
        Cell Death Differ. 19:333-344(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION, ACETYLATION, INTERACTION WITH CREB1.
      70. "The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function."
        Dai X.Q., Manning Fox J.E., Chikvashvili D., Casimir M., Plummer G., Hajmrle C., Spigelman A.F., Kin T., Singer-Lahat D., Kang Y., Shapiro A.M., Gaisano H.Y., Lotan I., Macdonald P.E.
        Diabetologia 55:1709-1720(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH STX1A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF TRP-369 AND TYR-384.
      71. "Kv2.1 cell surface clusters are insertion platforms for ion channel delivery to the plasma membrane."
        Deutsch E., Weigel A.V., Akin E.J., Fox P., Hansen G., Haberkorn C.J., Loftus R., Krapf D., Tamkun M.M.
        Mol. Biol. Cell 23:2917-2929(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBCELLULAR LOCATION.
      72. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
        Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
        Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; SER-519; SER-520 AND SER-655, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      73. "Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor cortex."
        Guan D., Armstrong W.E., Foehring R.C.
        J. Physiol. (Lond.) 591:4807-4825(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBCELLULAR LOCATION.
      74. "Specific sorting and post-Golgi trafficking of dendritic potassium channels in living neurons."
        Jensen C.S., Watanabe S., Rasmussen H.B., Schmitt N., Olesen S.P., Frost N.A., Blanpied T.A., Misonou H.
        J. Biol. Chem. 289:10566-10581(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: INTERACTION WITH MYL12B, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-590.
      75. "A unique ion channel clustering domain on the axon initial segment of mammalian neurons."
        King A.N., Manning C.F., Trimmer J.S.
        J. Comp. Neurol. 522:2594-2608(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: PHOSPHORYLATION AT SER-607, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      76. "Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+ currents."
        McCord M.C., Kullmann P.H., He K., Hartnett K.A., Horn J.P., Lotan I., Aizenman E.
        J. Physiol. (Lond.) 592:3511-3521(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, INTERACTION WITH STX1A, SUBCELLULAR LOCATION.
      77. "Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment."
        Long S.B., Tao X., Campbell E.B., MacKinnon R.
        Nature 450:376-382(2007) [PubMed] [Europe PMC] [Abstract]
        Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 272-304.
      78. "A gating charge transfer center in voltage sensors."
        Tao X., Lee A., Limapichat W., Dougherty D.A., MacKinnon R.
        Science 328:67-73(2010) [PubMed] [Europe PMC] [Abstract]
        Cited for: X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 272-304.
      79. "Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K(+) channel."
        Banerjee A., Lee A., Campbell E., Mackinnon R.
        Elife 2:E00594-E00594(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 272-304.

      Entry informationi

      Entry nameiKCNB1_RAT
      AccessioniPrimary (citable) accession number: P15387
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: April 1, 1990
      Last sequence update: October 25, 2002
      Last modified: July 6, 2016
      This is version 143 of the entry and version 3 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program

      Miscellaneousi

      Keywords - Technical termi

      3D-structure, Complete proteome, Reference proteome

      Documents

      1. PDB cross-references
        Index of Protein Data Bank (PDB) cross-references
      2. SIMILARITY comments
        Index of protein domains and families

      Similar proteinsi

      Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
      100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
      90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
      50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.