KCMB2_HUMAN
ID KCMB2_HUMAN Reviewed; 235 AA.
AC Q9Y691;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Calcium-activated potassium channel subunit beta-2;
DE AltName: Full=BK channel subunit beta-2;
DE Short=BKbeta2;
DE Short=Hbeta2;
DE AltName: Full=Calcium-activated potassium channel, subfamily M subunit beta-2;
DE AltName: Full=Charybdotoxin receptor subunit beta-2;
DE AltName: Full=Hbeta3;
DE AltName: Full=K(VCA)beta-2;
DE AltName: Full=Maxi K channel subunit beta-2;
DE AltName: Full=Slo-beta-2;
GN Name=KCNMB2;
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], FUNCTION, DOMAIN, TISSUE SPECIFICITY, AND
RP INTERACTION WITH KCNMA1.
RC TISSUE=Neuroepithelium;
RX PubMed=10097176; DOI=10.1073/pnas.96.7.4137;
RA Wallner M., Meera P., Toro L.;
RT "Molecular basis of fast inactivation in voltage and Ca2+-activated K+
RT channels: a transmembrane beta-subunit homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4137-4142(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Ovary;
RX PubMed=10692449; DOI=10.1074/jbc.275.9.6453;
RA Brenner R., Jegla T.J., Wickenden A., Liu Y., Aldrich R.W.;
RT "Cloning and functional characterization of novel large conductance
RT calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.";
RL J. Biol. Chem. 275:6453-6461(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic testis;
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 [4]
RP FUNCTION, DOMAIN, AND TISSUE SPECIFICITY.
RX PubMed=10377337; DOI=10.1523/jneurosci.19-13-05255.1999;
RA Xia X.-M., Ding J.-P., Lingle C.J.;
RT "Molecular basis for the inactivation of Ca2+- and voltage-dependent BK
RT channels in adrenal chromaffin cells and rat insulinoma tumor cells.";
RL J. Neurosci. 19:5255-5264(1999).
RN [5]
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 [6]
RP MUTAGENESIS OF 2-PHE--TRP-4.
RX PubMed=12566540; DOI=10.1085/jgp.20028667;
RA Xia X.-M., Ding J.-P., Lingle C.J.;
RT "Inactivation of BK channels by the NH2 terminus of the beta2 auxiliary
RT subunit: an essential role of a terminal peptide segment of three
RT hydrophobic residues.";
RL J. Gen. Physiol. 121:125-148(2003).
RN [7]
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 [8]
RP STRUCTURE BY NMR OF 1-45.
RX PubMed=11517232; DOI=10.1074/jbc.m107118200;
RA Bentrop D., Beyermann M., Wissmann R., Fakler B.;
RT "NMR structure of the 'ball-and-chain' domain of KCNMB2, the beta 2-subunit
RT of large conductance Ca2+- and voltage-activated potassium channels.";
RL J. Biol. Chem. 276:42116-42121(2001).
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. Acts as a
CC negative regulator that confers rapid and complete inactivation of
CC KCNMA1 channel complex. May participate in KCNMA1 inactivation in
CC chromaffin cells of the adrenal gland or in hippocampal CA1 neurons.
CC {ECO:0000269|PubMed:10097176, ECO:0000269|PubMed:10377337}.
CC -!- SUBUNIT: Interacts with KCNMA1 tetramer. There are probably 4 molecules
CC of KCMNB2 per KCNMA1 tetramer. {ECO:0000269|PubMed:10097176}.
CC -!- INTERACTION:
CC Q9Y691; P42858: HTT; NbExp=3; IntAct=EBI-7932244, EBI-466029;
CC Q9Y691; O76024: WFS1; NbExp=3; IntAct=EBI-7932244, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in kidney, heart and brain. Highly
CC expressed in ovary. Expressed at low level in other tissues.
CC {ECO:0000269|PubMed:10097176, ECO:0000269|PubMed:10377337,
CC ECO:0000269|PubMed:10692449}.
CC -!- DOMAIN: The ball and chain domain mediates the inactivation of KCNMA1.
CC It occludes the conduction pathway of KCNMA1 channels, and comprises
CC the pore-blocking ball domain (residues 1-17) and the chain domain
CC (residues 20-45) linking it to the transmembrane segment. The ball
CC domain is made up of a flexible N-terminus anchored at a well ordered
CC loop-helix motif. The chain domain consists of a 4-turn helix with an
CC unfolded linker at its C-terminus. {ECO:0000269|PubMed:10097176,
CC ECO:0000269|PubMed:10377337}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10792058}.
CC -!- SIMILARITY: Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB2
CC subfamily. {ECO:0000305}.
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DR EMBL; AF099137; AAD23380.1; -; mRNA.
DR EMBL; AF209747; AAF36562.1; -; mRNA.
DR EMBL; BC017825; AAH17825.1; -; mRNA.
DR CCDS; CCDS3223.1; -.
DR RefSeq; NP_001265840.1; NM_001278911.1.
DR RefSeq; NP_005823.1; NM_005832.4.
DR RefSeq; NP_852006.1; NM_181361.2.
DR RefSeq; XP_011510627.1; XM_011512325.2.
DR PDB; 1JO6; NMR; -; A=1-45.
DR PDBsum; 1JO6; -.
DR AlphaFoldDB; Q9Y691; -.
DR BMRB; Q9Y691; -.
DR SMR; Q9Y691; -.
DR BioGRID; 115536; 11.
DR IntAct; Q9Y691; 3.
DR MINT; Q9Y691; -.
DR STRING; 9606.ENSP00000407592; -.
DR DrugBank; DB03861; (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidine.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00721; Procaine.
DR DrugBank; DB09089; Trimebutine.
DR TCDB; 8.A.14.1.3; the ca(2+)-activated k(+) channel auxiliary subunit slowpoke-Beta (sloBeta) family.
DR GlyGen; Q9Y691; 3 sites.
DR iPTMnet; Q9Y691; -.
DR PhosphoSitePlus; Q9Y691; -.
DR BioMuta; KCNMB2; -.
DR DMDM; 46396054; -.
DR jPOST; Q9Y691; -.
DR MassIVE; Q9Y691; -.
DR PaxDb; Q9Y691; -.
DR PeptideAtlas; Q9Y691; -.
DR PRIDE; Q9Y691; -.
DR ProteomicsDB; 86624; -.
DR ABCD; Q9Y691; 1 sequenced antibody.
DR Antibodypedia; 33738; 254 antibodies from 29 providers.
DR DNASU; 10242; -.
DR Ensembl; ENST00000358316.7; ENSP00000351068.3; ENSG00000197584.13.
DR Ensembl; ENST00000420517.6; ENSP00000408252.2; ENSG00000197584.13.
DR Ensembl; ENST00000432997.5; ENSP00000407592.1; ENSG00000197584.13.
DR Ensembl; ENST00000452583.6; ENSP00000397483.1; ENSG00000197584.13.
DR GeneID; 10242; -.
DR KEGG; hsa:10242; -.
DR MANE-Select; ENST00000452583.6; ENSP00000397483.1; NM_181361.3; NP_852006.1.
DR UCSC; uc003fjd.5; human.
DR CTD; 10242; -.
DR DisGeNET; 10242; -.
DR GeneCards; KCNMB2; -.
DR HGNC; HGNC:6286; KCNMB2.
DR HPA; ENSG00000197584; Tissue enhanced (epididymis, fallopian tube, ovary).
DR MIM; 605214; gene.
DR neXtProt; NX_Q9Y691; -.
DR OpenTargets; ENSG00000197584; -.
DR OpenTargets; ENSG00000275163; -.
DR PharmGKB; PA30066; -.
DR VEuPathDB; HostDB:ENSG00000197584; -.
DR eggNOG; ENOG502QSCP; Eukaryota.
DR GeneTree; ENSGT00950000183039; -.
DR HOGENOM; CLU_085739_1_1_1; -.
DR InParanoid; Q9Y691; -.
DR OMA; FACYSDP; -.
DR OrthoDB; 1178937at2759; -.
DR PhylomeDB; Q9Y691; -.
DR TreeFam; TF328589; -.
DR PathwayCommons; Q9Y691; -.
DR Reactome; R-HSA-1296052; Ca2+ activated K+ channels.
DR Reactome; R-HSA-418457; cGMP effects.
DR SignaLink; Q9Y691; -.
DR BioGRID-ORCS; 10242; 12 hits in 1070 CRISPR screens.
DR ChiTaRS; KCNMB2; human.
DR EvolutionaryTrace; Q9Y691; -.
DR GeneWiki; KCNMB2; -.
DR GenomeRNAi; 10242; -.
DR Pharos; Q9Y691; Tbio.
DR PRO; PR:Q9Y691; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y691; protein.
DR Bgee; ENSG00000197584; Expressed in islet of Langerhans and 114 other tissues.
DR ExpressionAtlas; Q9Y691; baseline and differential.
DR Genevisible; Q9Y691; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0008200; F:ion channel inhibitor activity; TAS:ProtInc.
DR GO; GO:0015459; F:potassium channel regulator activity; IBA:GO_Central.
DR GO; GO:0001508; P:action potential; IDA:UniProtKB.
DR GO; GO:0005513; P:detection of calcium ion; IDA:UniProtKB.
DR GO; GO:0019228; P:neuronal action potential; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB.
DR GO; GO:0019229; P:regulation of vasoconstriction; TAS:UniProtKB.
DR Gene3D; 4.10.81.20; -; 1.
DR InterPro; IPR003930; K_chnl_Ca-activ_BK_bsu.
DR InterPro; IPR037096; KCNMB2_ball/chain_dom_sf.
DR InterPro; IPR015382; KCNMB2_ball_chain_dom.
DR PANTHER; PTHR10258; PTHR10258; 1.
DR Pfam; PF03185; CaKB; 1.
DR Pfam; PF09303; KcnmB2_inactiv; 1.
DR PRINTS; PR01450; BKCHANNELB.
PE 1: Evidence at protein level;
KW 3D-structure; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..235
FT /note="Calcium-activated potassium channel subunit beta-2"
FT /id="PRO_0000187051"
FT TOPO_DOM 1..46
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..67
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..194
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..45
FT /note="Ball and chain"
FT CARBOHYD 88
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 2..4
FT /note="FIW->GGG: Abolishes inactivation of KCNMA1 channel."
FT /evidence="ECO:0000269|PubMed:12566540"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:1JO6"
FT HELIX 22..29
FT /evidence="ECO:0007829|PDB:1JO6"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:1JO6"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:1JO6"
SQ SEQUENCE 235 AA; 27130 MW; 5752021DF27D8CF5 CRC64;
MFIWTSGRTS SSYRHDEKRN IYQKIRDHDL LDKRKTVTAL KAGEDRAILL GLAMMVCSIM
MYFLLGITLL RSYMQSVWTE ESQCTLLNAS ITETFNCSFS CGPDCWKLSQ YPCLQVYVNL
TSSGEKLLLY HTEETIKINQ KCSYIPKCGK NFEESMSLVN VVMENFRKYQ HFSCYSDPEG
NQKSVILTKL YSSNVLFHSL FWPTCMMAGG VAIVAMVKLT QYLSLLCERI QRINR
