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Protein

Potassium voltage-gated channel subfamily B member 1

Gene

KCNB1

Organism
Homo sapiens (Human)
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:23161216). Plays also 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:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340, PubMed:19074135, PubMed:19717558, PubMed:24901643). 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 (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). 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 (By similarity). 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. 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. 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:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. 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 (PubMed:12060745). 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).By similarity10 Publications

Enzyme regulationi

Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (PubMed:14565763). Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata (PubMed:14565763). Modestly sensitive to millimolar levels of tetraethylammonium (TEA) (PubMed:8081723, PubMed:1283219). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).By similarity2 Publications3 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:8081723, PubMed:1283219). After that, inactivate very slowly, i.e within more than 5 sec (PubMed:8081723, PubMed:1283219). Their activation requires low threshold potentials of about -20 to -30 mV, with a midpoint activation at about 10 mV. For inactivation, the voltage at half-maximal amplitude is about -20 mV (PubMed:11852086). The time constant for recovery after inactivation is about 1.6 sec. Channels have an unitary conductance of about 8 pS (PubMed:10484328). 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.By similarity

2 Publications4 Publications

      GO - Molecular functioni

      • delayed rectifier potassium channel activity Source: UniProtKB
      • ion channel binding Source: UniProtKB
      • outward rectifier potassium channel activity Source: Ensembl
      • protein heterodimerization activity Source: UniProtKB
      • ubiquitin-like protein binding Source: UniProtKB

      GO - Biological processi

      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

      Enzyme and pathway databases

      ReactomeiREACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
      REACT_75770. Voltage gated Potassium channels.

      Protein family/group databases

      TCDBi1.A.1.2.11. the voltage-gated ion channel (vic) superfamily.

      Names & Taxonomyi

      Protein namesi
      Recommended name:
      Potassium voltage-gated channel subfamily B member 1Imported
      Alternative name(s):
      Delayed rectifier potassium channel 11 Publication
      Short name:
      DRK11 Publication
      Short name:
      h-DRK11 Publication
      Voltage-gated potassium channel subunit Kv2.11 Publication
      Gene namesi
      Name:KCNB1Imported
      OrganismiHomo sapiens (Human)
      Taxonomic identifieri9606 [NCBI]
      Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
      ProteomesiUP000005640 Componenti: Chromosome 20

      Organism-specific databases

      HGNCiHGNC:6231. KCNB1.

      Subcellular locationi

      Topology

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Topological domaini1 – 186186CytoplasmicBy similarityAdd
      BLAST
      Transmembranei187 – 20822Helical; Name=Segment S1By similarityAdd
      BLAST
      Topological domaini209 – 22820ExtracellularBy similarityAdd
      BLAST
      Transmembranei229 – 25022Helical; Name=Segment S2By similarityAdd
      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 – 858438CytoplasmicBy similarityAdd
      BLAST

      GO - Cellular componenti

      Complete GO annotation...

      Keywords - Cellular componenti

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

      Pathology & Biotechi

      Involvement in diseasei

      Epileptic encephalopathy, early infantile, 26 (EIEE26)1 Publication

      The disease is caused by mutations affecting the gene represented in this entry.

      Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE26 patients manifest multiple types of seizures, delayed psychomotor development, poor or absent speech, hypotonia, hypsarrhythmia.

      See also OMIM:616056
      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Natural varianti347 – 3471S → R in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface. 1 Publication
      VAR_071991
      Natural varianti374 – 3741T → I in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface. 1 Publication
      VAR_071992
      Natural varianti379 – 3791G → R in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface. 1 Publication
      VAR_071993

      Mutagenesis

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Mutagenesisi71 – 711E → Q: No effect on channel activity. 1 Publication
      Mutagenesisi74 – 741D → R: Reduces interaction with KCNG1 and self-interaction and impairs plasma membrane subcellular localization, homotetramerization and hetetrotetramerization with KCNG4; when associated with R-75. 2 Publications
      Mutagenesisi75 – 751D → R: Reduces interaction with KCNG1 and self-interaction and impairs plasma membrane subcellular localization, homotetramerization and hetetrotetramerization with KCNG4; when associated with R-74. 2 Publications
      Mutagenesisi79 – 791D → E: Increases channel activity. 1 Publication
      Mutagenesisi105 – 1051H → V or R: Reduces channel activity. Inhibits interaction with KCNG4. Impairs hetetrotetramerization with KCNG1, KCNG3 or KCNG4. Does not impair homotetramerization. 1 Publication

      Keywords - Diseasei

      Disease mutation, Epilepsy

      Organism-specific databases

      MIMi616056. phenotype.
      Orphaneti1934. Early infantile epileptic encephalopathy.
      PharmGKBiPA209.

      Chemistry

      DrugBankiDB06637. Dalfampridine.

      Polymorphism and mutation databases

      BioMutaiKCNB1.
      DMDMi24418854.

      PTM / Processingi

      Molecule processing

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Chaini1 – 858858Potassium voltage-gated channel subfamily B member 1PRO_0000054042Add
      BLAST

      Amino acid modifications

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Modified residuei15 – 151PhosphoserineBy similarity
      Modified residuei128 – 1281Phosphotyrosine; by SrcBy similarity
      Modified residuei457 – 4571PhosphoserineBy similarity
      Cross-linki474 – 474Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
      Modified residuei484 – 4841PhosphoserineBy similarity
      Modified residuei496 – 4961PhosphoserineBy similarity
      Modified residuei503 – 5031PhosphoserineBy similarity
      Modified residuei520 – 5201Phosphoserine; by CDK5; in vitroBy similarity
      Modified residuei541 – 5411PhosphoserineBy similarity
      Modified residuei567 – 5671PhosphoserineBy similarity
      Modified residuei590 – 5901PhosphoserineBy similarity
      Modified residuei607 – 6071Phosphoserine; by CDK5By similarity
      Modified residuei656 – 6561Phosphoserine; by CDK5; in vitroBy similarity
      Modified residuei720 – 7201PhosphoserineBy similarity
      Modified residuei772 – 7721PhosphoserineBy similarity
      Modified residuei800 – 8001PhosphoserineBy similarity
      Modified residuei805 – 8051Phosphoserine; by CDK5, MAPK14; in vitroBy similarity

      Post-translational modificationi

      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-805 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-607, Ser-656 and Ser-805 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-656 and Ser-720 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 Zn2+-dependent manner. Dephosphorylated at Ser-607 by protein phosphatase PPP1CA. Hypoxia-, seizure- or glutamate-induced neuronal activity 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-720 are less dephosphorylated. In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced. Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic nerve tissue (By similarity).By similarity
      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.By similarity
      Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity (PubMed:19223394). 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:19223394). Desumoylated by SENP1 (PubMed:19223394).1 Publication

      Keywords - PTMi

      Isopeptide bond, Phosphoprotein, Ubl conjugation

      Proteomic databases

      PaxDbiQ14721.
      PRIDEiQ14721.

      2D gel databases

      OGPiQ14721.

      PTM databases

      PhosphoSiteiQ14721.

      Expressioni

      Tissue specificityi

      Expressed in neocortical pyramidal cells (PubMed:24477962). Expressed in pancreatic beta cells (at protein level) (PubMed:12403834, PubMed:14988243). Expressed in brain, heart, lung, liver, colon, kidney and adrenal gland (PubMed:19074135). Expressed in the cortex, amygdala, cerebellum, pons, thalamus, hypothalamus, hippocampus and substantia nigra (PubMed:19074135).4 Publications

      Gene expression databases

      BgeeiQ14721.
      CleanExiHS_KCNB1.
      GenevisibleiQ14721. HS.

      Organism-specific databases

      HPAiCAB001979.
      HPA042434.

      Interactioni

      Subunit structurei

      Homotetramer or heterotetramer with KCNB2 (PubMed:8081723, PubMed:1283219). Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19357235, PubMed:19074135, PubMed:19717558, PubMed:24901643). Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (By similarity). Self-associates (via N-terminus and C-terminus) (PubMed:12560340, PubMed:24901643); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (By similarity). 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. 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. Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate. Interacts with CREB1; this promotes channel acetylation in response to stimulation of incretin hormones. Interacts (via N-terminus and C-terminus) with MYL12B. Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface (By similarity). Interacts with SUMO1 (PubMed:19223394). Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells (By similarity).By similarity11 Publications

      Protein-protein interaction databases

      BioGridi109947. 16 interactions.
      IntActiQ14721. 1 interaction.
      STRINGi9606.ENSP00000360806.

      Structurei

      3D structure databases

      ProteinModelPortaliQ14721.
      SMRiQ14721. Positions 30-462.
      ModBaseiSearch...
      MobiDBiSearch...

      Family & Domainsi

      Region

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Regioni59 – 7517Self-associationBy similarityAdd
      BLAST
      Regioni448 – 48134Self-associationBy similarityAdd
      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 biasi701 – 7066Poly-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:11852086, PubMed:12060745, PubMed:12560340, PubMed:19074135, PubMed:24901643). The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subnunits and with ancillary beta subunits (PubMed:24901643). 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. 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 (By similarity).By similarity5 Publications

      Sequence similaritiesi

      Keywords - Domaini

      Transmembrane, Transmembrane helix

      Phylogenomic databases

      eggNOGiCOG1226.
      GeneTreeiENSGT00760000118981.
      HOGENOMiHOG000113206.
      HOVERGENiHBG052225.
      InParanoidiQ14721.
      KOiK04885.
      OMAiTEGVIDM.
      OrthoDBiEOG7CRTPP.
      PhylomeDBiQ14721.
      TreeFamiTF313103.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ-like.
      IPR011333. BTB/POZ_fold.
      IPR027359. Channel_four-helix_dom.
      IPR005821. Ion_trans_dom.
      IPR003091. K_chnl.
      IPR003968. K_chnl_volt-dep_Kv.
      IPR003973. K_chnl_volt-dep_Kv2.
      IPR004350. K_chnl_volt-dep_Kv2.1.
      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. 1 hit.
      [Graphical view]
      PRINTSiPR00169. KCHANNEL.
      PR01514. KV21CHANNEL.
      PR01491. KVCHANNEL.
      PR01495. SHABCHANNEL.
      SMARTiSM00225. BTB. 1 hit.
      [Graphical view]
      SUPFAMiSSF54695. SSF54695. 1 hit.

      Sequencei

      Sequence statusi: Complete.

      Q14721-1 [UniParc]FASTAAdd to basket

      « Hide

              10         20         30         40         50
      MPAGMTKHGS RSTSSLPPEP MEIVRSKACS RRVRLNVGGL AHEVLWRTLD
      60 70 80 90 100
      RLPRTRLGKL RDCNTHDSLL EVCDDYSLDD 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 NMGKKDKVQD NHLSPNKWKW TKRTLSETSS
      510 520 530 540 550
      SKSFETKEQG SPEKARSSSS PQHLNVQQLE DMYNKMAKTQ SQPILNTKES
      560 570 580 590 600
      AAQSKPKEEL EMESIPSPVA PLPTRTEGVI DMRSMSSIDS FISCATDFPE
      610 620 630 640 650
      ATRFSHSPLT SLPSKTGGST APEVGWRGAL GASGGRFVEA NPSPDASQHS
      660 670 680 690 700
      SFFIESPKSS MKTNNPLKLR ALKVNFMEGD PSPLLPVLGM YHDPLRNRGS
      710 720 730 740 750
      AAAAVAGLEC ATLLDKAVLS PESSIYTTAS AKTPPRSPEK HTAIAFNFEA
      760 770 780 790 800
      GVHQYIDADT DDEGQLLYSV DSSPPKSLPG STSPKFSTGT RSEKNHFESS
      810 820 830 840 850
      PLPTSPKFLR QNCIYSTEAL TGKGPSGQEK CKLENHISPD VRVLPGGGAH

      GSTRDQSI
      Length:858
      Mass (Da):95,878
      Last modified:October 25, 2002 - v2
      Checksum:iC4B426174ED0DEE4
      GO

      Sequence cautioni

      The sequence AAA36156.1 differs from that shown. Reason: Erroneous initiation. Curated

      Natural variant

      Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
      Natural varianti347 – 3471S → R in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface. 1 Publication
      VAR_071991
      Natural varianti374 – 3741T → I in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface. 1 Publication
      VAR_071992
      Natural varianti379 – 3791G → R in EIEE26; inhibits ion selectivity and gain of a depolarizing inward cation conductance; trafficks normally to the cell surface. 1 Publication
      VAR_071993
      Natural varianti616 – 6161T → N.
      Corresponds to variant rs2229006 [ dbSNP | Ensembl ].
      VAR_062182
      Natural varianti616 – 6161T → S.
      Corresponds to variant rs2229006 [ dbSNP | Ensembl ].
      VAR_062183
      Natural varianti825 – 8251P → S.
      Corresponds to variant rs34467662 [ dbSNP | Ensembl ].
      VAR_034049
      Natural varianti857 – 8571S → N.
      Corresponds to variant rs34280195 [ dbSNP | Ensembl ].
      VAR_062184

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      X68302 Genomic DNA. Translation: CAA48374.1.
      L02840 mRNA. Translation: AAA36156.1. Different initiation.
      AF026005 mRNA. Translation: AAB88808.1.
      AL035685 Genomic DNA. Translation: CAB89417.1.
      CCDSiCCDS13418.1.
      PIRiS31761.
      RefSeqiNP_004966.1. NM_004975.2.
      XP_006723847.1. XM_006723784.2.
      UniGeneiHs.633143.
      Hs.84244.

      Genome annotation databases

      EnsembliENST00000371741; ENSP00000360806; ENSG00000158445.
      GeneIDi3745.
      KEGGihsa:3745.
      UCSCiuc002xur.1. human.

      Keywords - Coding sequence diversityi

      Polymorphism

      Cross-referencesi

      Sequence databases

      Select the link destinations:
      EMBLi
      GenBanki
      DDBJi
      Links Updated
      X68302 Genomic DNA. Translation: CAA48374.1.
      L02840 mRNA. Translation: AAA36156.1. Different initiation.
      AF026005 mRNA. Translation: AAB88808.1.
      AL035685 Genomic DNA. Translation: CAB89417.1.
      CCDSiCCDS13418.1.
      PIRiS31761.
      RefSeqiNP_004966.1. NM_004975.2.
      XP_006723847.1. XM_006723784.2.
      UniGeneiHs.633143.
      Hs.84244.

      3D structure databases

      ProteinModelPortaliQ14721.
      SMRiQ14721. Positions 30-462.
      ModBaseiSearch...
      MobiDBiSearch...

      Protein-protein interaction databases

      BioGridi109947. 16 interactions.
      IntActiQ14721. 1 interaction.
      STRINGi9606.ENSP00000360806.

      Chemistry

      ChEMBLiCHEMBL2362996.
      DrugBankiDB06637. Dalfampridine.
      GuidetoPHARMACOLOGYi546.

      Protein family/group databases

      TCDBi1.A.1.2.11. the voltage-gated ion channel (vic) superfamily.

      PTM databases

      PhosphoSiteiQ14721.

      Polymorphism and mutation databases

      BioMutaiKCNB1.
      DMDMi24418854.

      2D gel databases

      OGPiQ14721.

      Proteomic databases

      PaxDbiQ14721.
      PRIDEiQ14721.

      Protocols and materials databases

      DNASUi3745.
      Structural Biology KnowledgebaseSearch...

      Genome annotation databases

      EnsembliENST00000371741; ENSP00000360806; ENSG00000158445.
      GeneIDi3745.
      KEGGihsa:3745.
      UCSCiuc002xur.1. human.

      Organism-specific databases

      CTDi3745.
      GeneCardsiGC20M047984.
      HGNCiHGNC:6231. KCNB1.
      HPAiCAB001979.
      HPA042434.
      MIMi600397. gene.
      616056. phenotype.
      neXtProtiNX_Q14721.
      Orphaneti1934. Early infantile epileptic encephalopathy.
      PharmGKBiPA209.
      GenAtlasiSearch...

      Phylogenomic databases

      eggNOGiCOG1226.
      GeneTreeiENSGT00760000118981.
      HOGENOMiHOG000113206.
      HOVERGENiHBG052225.
      InParanoidiQ14721.
      KOiK04885.
      OMAiTEGVIDM.
      OrthoDBiEOG7CRTPP.
      PhylomeDBiQ14721.
      TreeFamiTF313103.

      Enzyme and pathway databases

      ReactomeiREACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
      REACT_75770. Voltage gated Potassium channels.

      Miscellaneous databases

      GeneWikiiKCNB1.
      GenomeRNAii3745.
      NextBioi14655.
      PROiQ14721.
      SOURCEiSearch...

      Gene expression databases

      BgeeiQ14721.
      CleanExiHS_KCNB1.
      GenevisibleiQ14721. HS.

      Family and domain databases

      Gene3Di1.20.120.350. 1 hit.
      InterProiIPR000210. BTB/POZ-like.
      IPR011333. BTB/POZ_fold.
      IPR027359. Channel_four-helix_dom.
      IPR005821. Ion_trans_dom.
      IPR003091. K_chnl.
      IPR003968. K_chnl_volt-dep_Kv.
      IPR003973. K_chnl_volt-dep_Kv2.
      IPR004350. K_chnl_volt-dep_Kv2.1.
      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. 1 hit.
      [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. "Cloning and characterization of a human delayed rectifier potassium channel gene."
        Albrecht B., Lorra C., Stocker K., Pongs O.
        Recept. Channels 1:99-110(1993) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBCELLULAR LOCATION.
      2. "Heterologous expression of the human potassium channel Kv2.1 in clonal mammalian cells by direct cytoplasmic microinjection of cRNA."
        Ikeda S.R., Soler F., Zuhlke R.D., Joho R.H., Lewis D.L.
        Pflugers Arch. 422:201-203(1992) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBCELLULAR LOCATION.
        Tissue: Brain cortex.
      3. "Identification of potassium channels in human lens epithelium."
        Rae J.L., Shepard A.R.
        (In) Civan M.M. (eds.); The eye's aqueous humor-from secretion to glaucoma, pp.69-104, Academic Press, San Diego (1998)
        Cited for: NUCLEOTIDE SEQUENCE [MRNA].
        Tissue: Lens epithelium.
      4. "The DNA sequence and comparative analysis of human chromosome 20."
        Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
        , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
        Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
        Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      5. "Electrically silent potassium channel subunits from human lens epithelium."
        Shepard A.R., Rae J.L.
        Am. J. Physiol. 277:C412-C424(1999) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
      6. Cited for: REVIEW.
      7. "Molecular cloning and characterization of Kv6.3, a novel modulatory subunit for voltage-gated K(+) channel Kv2.1."
        Sano Y., Mochizuki S., Miyake A., Kitada C., Inamura K., Yokoi H., Nozawa K., Matsushime H., Furuichi K.
        FEBS Lett. 512:230-234(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNG3, SELF-ASSOCIATION, DOMAIN, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
      8. "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: TISSUE SPECIFICITY.
      9. "Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome."
        Ottschytsch N., Raes A., Van Hoorick D., Snyders D.J.
        Proc. Natl. Acad. Sci. U.S.A. 99:7986-7991(2002) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNG3; KCNH1 AND KCNH2, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION.
      10. "Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels."
        Shiau Y.S., Huang P.T., Liou H.H., Liaw Y.C., Shiau Y.Y., Lou K.L.
        Chem. Res. Toxicol. 16:1217-1225(2003) [PubMed] [Europe PMC] [Abstract]
        Cited for: ENZYME REGULATION.
      11. "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 GLU-71 AND ASP-79.
      12. "Expression of voltage-gated potassium channels in human and rhesus pancreatic islets."
        Yan L., Figueroa D.J., Austin C.P., Liu Y., Bugianesi R.M., Slaughter R.S., Kaczorowski G.J., Kohler M.G.
        Diabetes 53:597-607(2004) [PubMed] [Europe PMC] [Abstract]
        Cited for: TISSUE SPECIFICITY.
      13. "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.
      14. "Kv2.1 and silent Kv subunits underlie the delayed rectifier K+ current in cultured small mouse DRG neurons."
        Bocksteins E., Raes A.L., Van de Vijver G., Bruyns T., Van Bogaert P.P., Snyders D.J.
        Am. J. Physiol. 296:C1271-C1278(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: SUBUNIT.
      15. "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: FUNCTION, SUBUNIT, INTERACTION WITH KCNG4, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-105, TISSUE SPECIFICITY.
      16. "Conserved negative charges in the N-terminal tetramerization domain mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels."
        Bocksteins E., Labro A.J., Mayeur E., Bruyns T., Timmermans J.P., Adriaensen D., Snyders D.J.
        J. Biol. Chem. 284:31625-31634(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-74 AND ASP-75.
      17. "SUMOylation regulates Kv2.1 and modulates pancreatic beta-cell excitability."
        Dai X.Q., Kolic J., Marchi P., Sipione S., Macdonald P.E.
        J. Cell Sci. 122:775-779(2009) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUMOYLATION, DESUMOYLATION, INTERACTION WITH SUMO1, SUBCELLULAR LOCATION.
      18. "The role of voltage-gated potassium channels Kv2.1 and Kv2.2 in the regulation of insulin and somatostatin release from pancreatic islets."
        Li X.N., Herrington J., Petrov A., Ge L., Eiermann G., Xiong Y., Jensen M.V., Hohmeier H.E., Newgard C.B., Garcia M.L., Wagner M., Zhang B.B., Thornberry N.A., Howard A.D., Kaczorowski G.J., Zhou Y.P.
        J. Pharmacol. Exp. Ther. 344:407-416(2013) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION.
      19. "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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      20. "The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits is determined by interactions between the N- and C-termini."
        Bocksteins E., Mayeur E., Van Tilborg A., Regnier G., Timmermans J.P., Snyders D.J.
        PLoS ONE 9:E98960-E98960(2014) [PubMed] [Europe PMC] [Abstract]
        Cited for: FUNCTION, SUBUNIT, INTERACTION WITH KCNG4, SELF-ASSOCIATION, DOMAIN, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-74 AND ASP-75.
      21. Cited for: VARIANTS EIEE26 ARG-347; ILE-374 AND ARG-379, CHARACTERIZATION OF VARIANTS EIEE26 ARG-347; ILE-374 AND ARG-379, INVOLVEMENT IN EIEE26.

      Entry informationi

      Entry nameiKCNB1_HUMAN
      AccessioniPrimary (citable) accession number: Q14721
      Secondary accession number(s): Q14193
      Entry historyi
      Integrated into UniProtKB/Swiss-Prot: July 15, 1998
      Last sequence update: October 25, 2002
      Last modified: June 24, 2015
      This is version 133 of the entry and version 2 of the sequence. [Complete history]
      Entry statusiReviewed (UniProtKB/Swiss-Prot)
      Annotation programChordata Protein Annotation Program
      DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

      Miscellaneousi

      Keywords - Technical termi

      Complete proteome, Reference proteome

      Documents

      1. Human chromosome 20
        Human chromosome 20: entries, gene names and cross-references to MIM
      2. Human entries with polymorphisms or disease mutations
        List of human entries with polymorphisms or disease mutations
      3. Human polymorphisms and disease mutations
        Index of human polymorphisms and disease mutations
      4. MIM cross-references
        Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
      5. SIMILARITY comments
        Index of protein domains and families

      External Data

      Dasty 3

      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 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.