KCNB2_HUMAN
ID KCNB2_HUMAN Reviewed; 911 AA.
AC Q92953; Q7Z7D0; Q9BXD3;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Potassium voltage-gated channel subfamily B member 2 {ECO:0000312|HGNC:HGNC:6232};
DE AltName: Full=Voltage-gated potassium channel subunit Kv2.2;
GN Name=KCNB2 {ECO:0000312|HGNC:HGNC:6232};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Preisig-Mueller R., Derst C., Schnitzler M.M., Daut J.;
RT "Cloning and characterization of two novel gamma Kv subunits.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Rae J.L.;
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-811.
RX PubMed=9612272; DOI=10.1152/ajpgi.1998.274.5.g901;
RA Schmalz F., Kinsella J., Koh S.D., Vogalis F., Schneider A., Flynn E.R.,
RA Kenyon J.L., Horowitz B.;
RT "Molecular identification of a component of delayed rectifier current in
RT gastrointestinal smooth muscles.";
RL Am. J. Physiol. 274:G901-G911(1998).
RN [4]
RP REVIEW.
RX PubMed=10414301; DOI=10.1111/j.1749-6632.1999.tb11293.x;
RA Coetzee W.A., Amarillo Y., Chiu J., Chow A., Lau D., McCormack T.,
RA Moreno H., Nadal M.S., Ozaita A., Pountney D., Saganich M.,
RA Vega-Saenz de Miera E., Rudy B.;
RT "Molecular diversity of K+ channels.";
RL Ann. N. Y. Acad. Sci. 868:233-285(1999).
RN [5]
RP VARIANT [LARGE SCALE ANALYSIS] ILE-450.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes, primarily in the brain and
CC smooth muscle cells. Channels open or close in response to the voltage
CC difference across the membrane, letting potassium ions pass in
CC accordance with their electrochemical gradient. Homotetrameric channels
CC mediate a delayed-rectifier voltage-dependent outward potassium current
CC that display rapid activation and slow inactivation in response to
CC membrane depolarization. Can form functional homotetrameric and
CC heterotetrameric channels that contain variable proportions of KCNB1;
CC channel properties depend on the type of alpha subunits that are part
CC of the channel. Can also form functional heterotetrameric channels with
CC other alpha subunits that are non-conducting when expressed alone, such
CC as KCNS1 and KCNS2, creating a functionally diverse range of channel
CC complexes. In vivo, membranes probably contain a mixture of heteromeric
CC potassium channel complexes, making it difficult to assign currents
CC observed in intact tissues to any particular potassium channel family
CC member. Contributes to the delayed-rectifier voltage-gated potassium
CC current in cortical pyramidal neurons and smooth muscle cells.
CC {ECO:0000250|UniProtKB:A6H8H5, ECO:0000250|UniProtKB:Q63099}.
CC -!- ACTIVITY REGULATION: Inhibited by quinine at micromolar levels.
CC Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and
CC 4-aminopyridine (4-AP). {ECO:0000250|UniProtKB:Q63099,
CC ECO:0000250|UniProtKB:Q95167, ECO:0000305|PubMed:10414301}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=Homotetrameric channels expressed in xenopus oocytes or in
CC mammalian non-neuronal cells display delayed-rectifier voltage-
CC dependent potassium currents which are activated during membrane
CC depolarization, i.e within a risetime of about 20 msec. After that,
CC inactivate very slowly. Their activation requires low threshold
CC potentials of about -20 to -30 mV, with a midpoint activation at
CC about 10 mV. For inactivation, the voltage at half-maximal amplitude
CC is about -30 mV. Channels have an unitary conductance of about 14 pS.
CC The voltage-dependence of activation and inactivation and other
CC channel characteristics vary depending on the experimental
CC conditions, the expression system and post-translational
CC modifications. {ECO:0000305|PubMed:10414301};
CC -!- SUBUNIT: Homotetramer or heterotetramer with KCNB1. Heterotetramer with
CC KCNS1 and KCNS2. {ECO:0000250|UniProtKB:Q63099}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q63099};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q63099}. Perikaryon
CC {ECO:0000250|UniProtKB:Q63099}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q63099}. Note=Localized uniformly throughout
CC cell bodies and dendrites. Colocalizes with KCNB1 to high-density
CC somatodendritic clusters on cortical pyramidal neurons.
CC {ECO:0000250|UniProtKB:Q63099}.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q63099}.
CC -!- SIMILARITY: Belongs to the potassium channel family. B (Shab) (TC
CC 1.A.1.2) subfamily. Kv2.2/KCNB2 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB08433.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF450111; AAP46292.1; -; mRNA.
DR EMBL; AF338730; AAK16585.1; -; mRNA.
DR EMBL; U69962; AAB08433.1; ALT_FRAME; mRNA.
DR CCDS; CCDS6209.1; -.
DR RefSeq; NP_004761.2; NM_004770.2.
DR AlphaFoldDB; Q92953; -.
DR SMR; Q92953; -.
DR BioGRID; 114724; 58.
DR IntAct; Q92953; 8.
DR MINT; Q92953; -.
DR STRING; 9606.ENSP00000430846; -.
DR BindingDB; Q92953; -.
DR ChEMBL; CHEMBL2321618; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q92953; -.
DR GuidetoPHARMACOLOGY; 547; -.
DR TCDB; 1.A.1.2.25; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q92953; 1 site.
DR iPTMnet; Q92953; -.
DR PhosphoSitePlus; Q92953; -.
DR BioMuta; KCNB2; -.
DR DMDM; 24418855; -.
DR MassIVE; Q92953; -.
DR PaxDb; Q92953; -.
DR PeptideAtlas; Q92953; -.
DR PRIDE; Q92953; -.
DR ProteomicsDB; 75623; -.
DR ABCD; Q92953; 2 sequenced antibodies.
DR Antibodypedia; 63986; 131 antibodies from 26 providers.
DR DNASU; 9312; -.
DR Ensembl; ENST00000523207.2; ENSP00000430846.1; ENSG00000182674.6.
DR GeneID; 9312; -.
DR KEGG; hsa:9312; -.
DR MANE-Select; ENST00000523207.2; ENSP00000430846.1; NM_004770.3; NP_004761.2.
DR UCSC; uc003xzb.3; human.
DR CTD; 9312; -.
DR DisGeNET; 9312; -.
DR GeneCards; KCNB2; -.
DR HGNC; HGNC:6232; KCNB2.
DR HPA; ENSG00000182674; Tissue enhanced (brain, lymphoid tissue, retina).
DR MIM; 607738; gene.
DR neXtProt; NX_Q92953; -.
DR OpenTargets; ENSG00000182674; -.
DR PharmGKB; PA30025; -.
DR VEuPathDB; HostDB:ENSG00000182674; -.
DR eggNOG; KOG3713; Eukaryota.
DR GeneTree; ENSGT00940000161902; -.
DR HOGENOM; CLU_011722_2_0_1; -.
DR InParanoid; Q92953; -.
DR OMA; YNPINRA; -.
DR OrthoDB; 203440at2759; -.
DR PhylomeDB; Q92953; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; Q92953; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q92953; -.
DR SIGNOR; Q92953; -.
DR BioGRID-ORCS; 9312; 7 hits in 1060 CRISPR screens.
DR ChiTaRS; KCNB2; human.
DR GeneWiki; KCNB2; -.
DR GenomeRNAi; 9312; -.
DR Pharos; Q92953; Tclin.
DR PRO; PR:Q92953; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q92953; protein.
DR Bgee; ENSG00000182674; Expressed in buccal mucosa cell and 74 other tissues.
DR Genevisible; Q92953; HS.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; TAS:ProtInc.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003973; K_chnl_volt-dep_Kv2.
DR InterPro; IPR005826; K_chnl_volt-dep_Kv2.2.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03521; Kv2channel; 1.
DR PRINTS; PR01515; KV22CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01495; SHABCHANNEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..911
FT /note="Potassium voltage-gated channel subfamily B member
FT 2"
FT /id="PRO_0000054048"
FT TOPO_DOM 1..190
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 191..212
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 213..232
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 233..254
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 255..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 266..284
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 285..296
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 297..317
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 318..332
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 333..354
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 355..368
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 369..380
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 381..388
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 389..395
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 396..424
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 425..911
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..534
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 549..571
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 637..665
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 685..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 760..865
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 892..911
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 381..386
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT COMPBIAS 519..534
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..570
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 794..824
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63099"
FT CARBOHYD 287
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 450
FT /note="V -> I (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs770305852)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035774"
FT VARIANT 657
FT /note="E -> G (in dbSNP:rs16938507)"
FT /id="VAR_034050"
FT CONFLICT 161..162
FT /note="ER -> DG (in Ref. 1; AAP46292)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="S -> F (in Ref. 1; AAP46292)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 911 AA; 102563 MW; 2261D7D6280CF81A CRC64;
MAEKAPPGLN RKTSRSTLSL PPEPVDIIRS KTCSRRVKIN VGGLNHEVLW RTLDRLPRTR
LGKLRDCNTH ESLLEVCDDY NLNENEYFFD RHPGAFTSIL NFYRTGKLHM MEEMCALSFG
QELDYWGIDE IYLESCCQAR YHQKKEQMNE ELRREAETMR EREGEEFDNT CCPDKRKKLW
DLLEKPNSSV AAKILAIVSI LFIVLSTIAL SLNTLPELQE TDEFGQLNDN RQLAHVEAVC
IAWFTMEYLL RFLSSPNKWK FFKGPLNVID LLAILPYYVT IFLTESNKSV LQFQNVRRVV
QIFRIMRILR ILKLARHSTG LQSLGFTLRR SYNELGLLIL FLAMGIMIFS SLVFFAEKDE
DATKFTSIPA SFWWATITMT TVGYGDIYPK TLLGKIVGGL CCIAGVLVIA LPIPIIVNNF
SEFYKEQKRQ EKAIKRREAL ERAKRNGSIV SMNLKDAFAR SMELIDVAVE KAGESANTKD
SADDNHLSPS RWKWARKALS ETSSNKSFEN KYQEVSQKDS HEQLNNTSSS SPQHLSAQKL
EMLYNEITKT QPHSHPNPDC QEKPERPSAY EEEIEMEEVV CPQEQLAVAQ TEVIVDMKST
SSIDSFTSCA TDFTETERSP LPPPSASHLQ MKFPTDLPGT EEHQRARGPP FLTLSREKGP
AARDGTLEYA PVDITVNLDA SGSQCGLHSP LQSDNATDSP KSSLKGSNPL KSRSLKVNFK
ENRGSAPQTP PSTARPLPVT TADFSLTTPQ HISTILLEET PSQGDRPLLG TEVSAPCQGP
SKGLSPRFPK QKLFPFSSRE RRSFTEIDTG DDEDFLELPG AREEKQVDSS PNCFADKPSD
GRDPLREEGS VGSSSPQDTG HNCRQDIYHA VSEVKKDSSQ EGCKMENHLF APEIHSNPGD
TGYCPTRETS M
