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KCMB1_HUMAN
ID   KCMB1_HUMAN             Reviewed;         191 AA.
AC   Q16558; O00707; O00708; P78475; Q53YR0; Q8TAX3; Q93005;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 5.
DT   03-AUG-2022, entry version 177.
DE   RecName: Full=Calcium-activated potassium channel subunit beta-1;
DE   AltName: Full=BK channel subunit beta-1;
DE            Short=BKbeta;
DE            Short=BKbeta1;
DE            Short=Hbeta1;
DE   AltName: Full=Calcium-activated potassium channel, subfamily M subunit beta-1;
DE            Short=Calcium-activated potassium channel subunit beta;
DE   AltName: Full=Charybdotoxin receptor subunit beta-1;
DE   AltName: Full=K(VCA)beta-1;
DE   AltName: Full=Maxi K channel subunit beta-1;
DE   AltName: Full=Slo-beta-1;
DE            Short=Slo-beta;
GN   Name=KCNMB1;
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] (ISOFORM 1).
RC   TISSUE=Uterus;
RX   PubMed=8612769; DOI=10.1016/0014-5793(96)00151-2;
RA   Meera P., Wallner M., Jiang Z., Toro L.;
RT   "A calcium switch for the functional coupling between alpha (hslo) and beta
RT   subunits (KV,Ca beta) of maxi K channels.";
RL   FEBS Lett. 382:84-88(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Uterus;
RX   PubMed=8764643; DOI=10.1523/jneurosci.16-15-04543.1996;
RA   Dworetzky S.I., Boissard C.G., Lum-Ragan J.T., McKay M.C.,
RA   Post-Munson D.J., Trojnacki J.T., Chang C.P., Gribkoff V.K.;
RT   "Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit
RT   coexpression: changes in blocker sensitivity, activation/relaxation and
RT   inactivation kinetics, and protein kinase A modulation.";
RL   J. Neurosci. 16:4543-4550(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=8799178; DOI=10.1073/pnas.93.17.9200;
RA   Tseng-Crank J., Godinot N., Johansen T.E., Ahring P.K., Strobaek D.,
RA   Mertz R., Foster C.D., Olesen S.P., Reinhart P.H.;
RT   "Cloning, expression, and distribution of a Ca(2+)-activated K+ channel
RT   beta-subunit from human brain.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:9200-9205(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC   TISSUE=Aortic smooth muscle;
RA   Folander K., Biazzo D., Swanson R.;
RT   "Sequence of the gene encoding the beta subunit of a human, large-
RT   conductance, calcium-activate, K+ channel.";
RL   Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Rae J.L., Shepard A.R.;
RT   "Identification of potassium channels in human lens epithelium.";
RL   (In) Civan M.M. (eds.);
RL   The eye's aqueous humor, from secretion to glaucoma, pp.69-104, Academic
RL   Press, San Diego (1998).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Myometrium;
RX   PubMed=12434576;
RA   Mazzone J.N., Kaiser R.A., Buxton I.L.O.;
RT   "Calcium-activated potassium channel expression in human myometrium: effect
RT   of pregnancy.";
RL   Proc. West. Pharmacol. Soc. 45:184-186(2002).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Pluznick J.L., Sansom S.C.;
RT   "Role of the BK-beta1 subunit in human mesangial cells.";
RL   Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Cervix;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Pancreas;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   GLYCOSYLATION.
RX   PubMed=10792058; DOI=10.1073/pnas.100118597;
RA   Meera P., Wallner M., Toro L.;
RT   "A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and
RT   Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:5562-5567(2000).
RN   [12]
RP   BINDING TO E2.
RX   PubMed=10489376; DOI=10.1126/science.285.5435.1929;
RA   Valverde M.A., Rojas P., Amigo J., Cosmelli D., Orio P., Bahamonde M.I.,
RA   Mann G.E., Vergara C., Latorre R.;
RT   "Acute activation of Maxi-K channels (hSlo) by estradiol binding to the
RT   beta subunit.";
RL   Science 285:1929-1931(1999).
RN   [13]
RP   REVIEW.
RX   PubMed=12136044; DOI=10.1152/nips.01387.2002;
RA   Orio P., Rojas P., Ferreira G., Latorre R.;
RT   "New disguises for an old channel: MaxiK channel beta-subunits.";
RL   News Physiol. Sci. 17:156-161(2002).
RN   [14]
RP   VARIANT LYS-65, AND POLYMORPHISM.
RX   PubMed=15057310; DOI=10.1172/jci200420347;
RA   Fernandez-Fernandez J.M., Tomas M., Vazquez E., Orio P., Latorre R.,
RA   Senti M., Marrugat J., Valverde M.A.;
RT   "Gain-of-function mutation in the KCNMB1 potassium channel subunit is
RT   associated with low prevalence of diastolic hypertension.";
RL   J. Clin. Invest. 113:1032-1039(2004).
CC   -!- FUNCTION: Regulatory subunit of the calcium activated potassium KCNMA1
CC       (maxiK) channel. Modulates the calcium sensitivity and gating kinetics
CC       of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases
CC       the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also
CC       modifies KCNMA1 channel kinetics and alters its pharmacological
CC       properties. It slows down the activation and the deactivation kinetics
CC       of the channel. Acts as a negative regulator of smooth muscle
CC       contraction by enhancing the calcium sensitivity to KCNMA1. Its
CC       presence is also a requirement for internal binding of the KCNMA1
CC       channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and
CC       for external binding of the agonist hormone 17-beta-estradiol (E2).
CC       Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1
CC       peptide blocker by increasing the CTX association rate and decreasing
CC       the dissociation rate.
CC   -!- SUBUNIT: Interacts with KCNMA1 tetramer. There are probably 4 molecules
CC       of KCMNB1 per KCNMA1 tetramer.
CC   -!- INTERACTION:
CC       Q16558-2; Q9UNK0: STX8; NbExp=3; IntAct=EBI-17703887, EBI-727240;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q16558-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q16558-2; Sequence=VSP_009822, VSP_009823;
CC   -!- TISSUE SPECIFICITY: Abundantly expressed in smooth muscle. Low levels
CC       of expression in most other tissues. Within the brain, relatively high
CC       levels found in hippocampus and corpus callosum.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10792058}.
CC   -!- POLYMORPHISM: Genetic variation in KCNMB1 can influence the severity of
CC       diastolic hypertension (PubMed:15057310).
CC       {ECO:0000269|PubMed:15057310}.
CC   -!- SIMILARITY: Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; U25138; AAB02394.1; -; mRNA.
DR   EMBL; U38907; AAA81327.1; -; mRNA.
DR   EMBL; U42600; AAB16827.1; -; mRNA.
DR   EMBL; U42601; AAB16825.1; -; Genomic_DNA.
DR   EMBL; U42603; AAB16826.1; -; Genomic_DNA.
DR   EMBL; U42602; AAB16826.1; JOINED; Genomic_DNA.
DR   EMBL; U61536; AAB61396.1; -; mRNA.
DR   EMBL; U61537; AAB61397.1; -; Genomic_DNA.
DR   EMBL; AF026002; AAB88805.1; -; mRNA.
DR   EMBL; AY044441; AAK95827.1; -; mRNA.
DR   EMBL; AY515264; AAS20193.1; -; mRNA.
DR   EMBL; AK313979; BAG36693.1; -; mRNA.
DR   EMBL; CH471062; EAW61474.1; -; Genomic_DNA.
DR   EMBL; BC025707; AAH25707.1; -; mRNA.
DR   CCDS; CCDS4373.1; -. [Q16558-1]
DR   PIR; S68842; S68842.
DR   RefSeq; NP_004128.1; NM_004137.3. [Q16558-1]
DR   AlphaFoldDB; Q16558; -.
DR   SMR; Q16558; -.
DR   BioGRID; 109980; 7.
DR   IntAct; Q16558; 2.
DR   STRING; 9606.ENSP00000274629; -.
DR   BindingDB; Q16558; -.
DR   ChEMBL; CHEMBL5078; -.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB00721; Procaine.
DR   DrugBank; DB09089; Trimebutine.
DR   TCDB; 8.A.14.1.2; the ca(2+)-activated k(+) channel auxiliary subunit slowpoke-Beta (sloBeta) family.
DR   GlyGen; Q16558; 2 sites.
DR   PhosphoSitePlus; Q16558; -.
DR   BioMuta; KCNMB1; -.
DR   DMDM; 292495100; -.
DR   MassIVE; Q16558; -.
DR   PaxDb; Q16558; -.
DR   PeptideAtlas; Q16558; -.
DR   PRIDE; Q16558; -.
DR   ProteomicsDB; 60914; -. [Q16558-1]
DR   ProteomicsDB; 60915; -. [Q16558-2]
DR   Antibodypedia; 16897; 190 antibodies from 27 providers.
DR   DNASU; 3779; -.
DR   Ensembl; ENST00000274629.9; ENSP00000274629.3; ENSG00000145936.9. [Q16558-1]
DR   Ensembl; ENST00000521859.1; ENSP00000427940.1; ENSG00000145936.9. [Q16558-2]
DR   GeneID; 3779; -.
DR   KEGG; hsa:3779; -.
DR   MANE-Select; ENST00000274629.9; ENSP00000274629.3; NM_004137.4; NP_004128.1.
DR   UCSC; uc003maq.3; human. [Q16558-1]
DR   CTD; 3779; -.
DR   DisGeNET; 3779; -.
DR   GeneCards; KCNMB1; -.
DR   HGNC; HGNC:6285; KCNMB1.
DR   HPA; ENSG00000145936; Tissue enhanced (endometrium, intestine, seminal vesicle, smooth muscle).
DR   MalaCards; KCNMB1; -.
DR   MIM; 603951; gene.
DR   MIM; 608622; phenotype.
DR   neXtProt; NX_Q16558; -.
DR   OpenTargets; ENSG00000145936; -.
DR   PharmGKB; PA221; -.
DR   VEuPathDB; HostDB:ENSG00000145936; -.
DR   eggNOG; ENOG502RZA0; Eukaryota.
DR   GeneTree; ENSGT00950000183039; -.
DR   HOGENOM; CLU_085739_1_1_1; -.
DR   InParanoid; Q16558; -.
DR   OMA; FPYPCLQ; -.
DR   OrthoDB; 1178937at2759; -.
DR   PhylomeDB; Q16558; -.
DR   TreeFam; TF328589; -.
DR   PathwayCommons; Q16558; -.
DR   Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR   Reactome; R-HSA-418457; cGMP effects.
DR   Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR   Reactome; R-HSA-9667769; Acetylcholine inhibits contraction of outer hair cells.
DR   SignaLink; Q16558; -.
DR   BioGRID-ORCS; 3779; 11 hits in 1068 CRISPR screens.
DR   ChiTaRS; KCNMB1; human.
DR   GeneWiki; KCNMB1; -.
DR   GenomeRNAi; 3779; -.
DR   Pharos; Q16558; Tbio.
DR   PRO; PR:Q16558; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q16558; protein.
DR   Bgee; ENSG00000145936; Expressed in blood vessel layer and 123 other tissues.
DR   Genevisible; Q16558; HS.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; IBA:GO_Central.
DR   GO; GO:0015269; F:calcium-activated potassium channel activity; IBA:GO_Central.
DR   GO; GO:0015459; F:potassium channel regulator activity; IBA:GO_Central.
DR   GO; GO:0007568; P:aging; IEA:Ensembl.
DR   GO; GO:1903413; P:cellular response to bile acid; IEA:Ensembl.
DR   GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR   GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR   GO; GO:0005513; P:detection of calcium ion; IBA:GO_Central.
DR   GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; IEA:Ensembl.
DR   GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR   GO; GO:0042311; P:vasodilation; IEA:Ensembl.
DR   InterPro; IPR003930; K_chnl_Ca-activ_BK_bsu.
DR   PANTHER; PTHR10258; PTHR10258; 1.
DR   Pfam; PF03185; CaKB; 1.
DR   PRINTS; PR01450; BKCHANNELB.
PE   1: Evidence at protein level;
KW   Alternative splicing; Glycoprotein; Ion channel; Ion transport; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..191
FT                   /note="Calcium-activated potassium channel subunit beta-1"
FT                   /id="PRO_0000187046"
FT   TOPO_DOM        1..18
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        19..39
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        40..157
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        158..178
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        179..191
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        80
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         103..130
FT                   /note="CSYIPGSVDNYQTARADVEKVRAKFQEQ -> VLNWRDGDTSLYPCQVCEPV
FT                   PNCPCPRG (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_009822"
FT   VAR_SEQ         131..191
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_009823"
FT   VARIANT         65
FT                   /note="E -> K (has a protective effect against diastolic
FT                   hypertension; dbSNP:rs11739136)"
FT                   /evidence="ECO:0000269|PubMed:15057310"
FT                   /id="VAR_019325"
FT   VARIANT         110
FT                   /note="V -> L (in dbSNP:rs2301149)"
FT                   /id="VAR_047009"
SQ   SEQUENCE   191 AA;  21797 MW;  547432FF194E770D CRC64;
     MVKKLVMAQK RGETRALCLG VTMVVCAVIT YYILVTTVLP LYQKSVWTQE SKCHLIETNI
     RDQEELKGKK VPQYPCLWVN VSAAGRWAVL YHTEDTRDQN QQCSYIPGSV DNYQTARADV
     EKVRAKFQEQ QVFYCFSAPR GNETSVLFQR LYGPQALLFS LFWPTFLLTG GLLIIAMVKS
     NQYLSILAAQ K
 
 
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