Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9NPA1 (KCMB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium-activated potassium channel subunit beta-3
Alternative name(s):
BK channel subunit beta-3
Short name=BKbeta3
Short name=Hbeta3
Calcium-activated potassium channel, subfamily M subunit beta-3
Charybdotoxin receptor subunit beta-3
K(VCA)beta-3
Maxi K channel subunit beta-3
Slo-beta-3
Gene names
Name:KCNMB3
Synonyms:KCNMB2, KCNMBL
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length279 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Alters the functional properties of the current expressed by the KCNMA1 channel. Isoform 2, isoform 3 and isoform 4 partially inactivate the current of KCNBMA. Isoform 4 induces a fast and incomplete inactivation of KCNMA1 channel that is detectable only at large depolarizations. In contrast, isoform 1 does not induce detectable inactivation of KCNMA1. Two or more subunits of KCNMB3 are required to block the KCNMA1 tetramer. Ref.3 Ref.9

Subunit structure

Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB3 per KCNMA1 tetramer. Ref.2

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Isoform 1, isoform 3 and isoform 4 are widely expressed. Isoform 2 is expressed placenta, pancreas, kidney and heart. Isoform 1 and isoform 3 are highly expressed in pancreas and testis. Ref.1 Ref.2 Ref.3

Domain

Isoform 4 cytoplasmic N-terminus domain participates in the partial inactivation of KCNMA1, possibly by binding to a receptor site. Ref.10 Ref.11 Ref.13

The extracellular domain forms gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization. Ref.10 Ref.11 Ref.13

Post-translational modification

N-glycosylated. Ref.4

The extracellular domain contains disulfide bond essential for the gating mechanism.

Sequence similarities

Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB3 subfamily. [View classification]

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NPA1-1)

Also known as: 3d;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9NPA1-2)

Also known as: 3a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MDFSPSSELGFHFVAFILLTRH → MQPFSIPVQITLQGSRRRQG
Isoform 3 (identifier: Q9NPA1-3)

Also known as: 3c;

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MDFSPSSELGFHFVAFILLTRH → MFPLLYELTAVSPSPFPQ
Isoform 4 (identifier: Q9NPA1-4)

Also known as: 3b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.
     23-23: R → M
Isoform 5 (identifier: Q9NPA1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MDFSPSSELGFHFVAFILLTRH → MQPFSIPVQITLQGSRRRQG
     154-175: CFYTPKCHQDRNDLLNSALDIK → RDVTDCRVKEKQTLTVSDEHKQ
     176-279: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 279279Calcium-activated potassium channel subunit beta-3
PRO_0000187054

Regions

Topological domain1 – 6060Cytoplasmic Potential
Transmembrane61 – 8121Helical; Name=1; Potential
Topological domain82 – 207126Extracellular Potential
Transmembrane208 – 22821Helical; Name=2; Potential
Topological domain229 – 27951Cytoplasmic Potential

Amino acid modifications

Glycosylation1311N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 2222MDFSP…LLTRH → MQPFSIPVQITLQGSRRRQG in isoform 2 and isoform 5.
VSP_009827
Alternative sequence1 – 2222MDFSP…LLTRH → MFPLLYELTAVSPSPFPQ in isoform 3.
VSP_009828
Alternative sequence1 – 2222Missing in isoform 4.
VSP_009829
Alternative sequence231R → M in isoform 4.
VSP_009830
Alternative sequence154 – 17522CFYTP…ALDIK → RDVTDCRVKEKQTLTVSDEH KQ in isoform 5.
VSP_046090
Alternative sequence176 – 279104Missing in isoform 5.
VSP_046091
Natural variant441D → G.
Corresponds to variant rs1170672 [ dbSNP | Ensembl ].
VAR_018173
Natural variant531A → T. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5
Corresponds to variant rs7645550 [ dbSNP | Ensembl ].
VAR_018174
Natural variant751L → V. Ref.12
Corresponds to variant rs2276802 [ dbSNP | Ensembl ].
VAR_018175
Natural variant1651N → S. Ref.3 Ref.12
Corresponds to variant rs139527128 [ dbSNP | Ensembl ].
VAR_018176
Natural variant2301M → T. Ref.12
VAR_018177

Experimental info

Sequence conflict241T → P in BAH14265. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (3d) [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: EC5F0D5D3E040C4C

FASTA27931,604
        10         20         30         40         50         60 
MDFSPSSELG FHFVAFILLT RHRTAFPASG KKRETDYSDG DPLDVHKRLP SSAGEDRAVM 

        70         80         90        100        110        120 
LGFAMMGFSV LMFFLLGTTI LKPFMLSIQR EESTCTAIHT DIMDDWLDCA FTCGVHCHGQ 

       130        140        150        160        170        180 
GKYPCLQVFV NLSHPGQKAL LHYNEEAVQI NPKCFYTPKC HQDRNDLLNS ALDIKEFFDH 

       190        200        210        220        230        240 
KNGTPFSCFY SPASQSEDVI LIKKYDQMAI FHCLFWPSLT LLGGALIVGM VRLTQHLSLL 

       250        260        270 
CEKYSTVVRD EVGGKVPYIE QHQFKLCIMR RSKGRAEKS 

« Hide

Isoform 2 (3a) [UniParc].

Checksum: EBF06FF8686F0655
Show »

FASTA27731,351
Isoform 3 (3c) [UniParc].

Checksum: 9C7C5A523D37D5C2
Show »

FASTA27531,089
Isoform 4 (3b) [UniParc].

Checksum: 0B5D59CB0551295D
Show »

FASTA25729,045
Isoform 5 [UniParc].

Checksum: 7EACEF7D7202F1B8
Show »

FASTA17319,474

References

« Hide 'large scale' references
[1]"Identification of a putative regulatory subunit of a calcium-activated potassium channel in the dup(3q) syndrome region and a related sequence on 22q11.2."
Riazi M.A., Brinkman-Mills P., Johnson A., Naylor S.L., Minoshima S., Shimizu N., Baldini A., McDermid H.E.
Genomics 62:90-94(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT THR-53, TISSUE SPECIFICITY.
[2]"Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4."
Brenner R., Jegla T.J., Wickenden A., Liu Y., Aldrich R.W.
J. Biol. Chem. 275:6453-6461(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT THR-53, TISSUE SPECIFICITY, INTERACTION WITH KCNMA1.
Tissue: Brain.
[3]"Cloning and functional expression of two families of Beta-subunits of the large conductance calcium-activated potassium channel."
Uebele V.N., Lagrutta A.A., Wade T., Figueroa D.J., Liu Y., McKenna E., Austin C.P., Bennett P.B., Swanson R.
J. Biol. Chem. 275:23211-23218(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 3 AND 4), FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANTS THR-53 AND SER-165.
Tissue: Spleen.
[4]"A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin."
Meera P., Wallner M., Toro L.
Proc. Natl. Acad. Sci. U.S.A. 97:5562-5567(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT THR-53, GLYCOSYLATION.
[5]"hKCNMB3 and hKCNMB4, cloning and characterization of two members of the large-conductance calcium-activated potassium channel beta subunit family."
Behrens R., Nolting A., Reimann F., Schwarz M., Waldschuetz R., Pongs O.
FEBS Lett. 474:99-106(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), VARIANT THR-53.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
Tissue: Uterus.
[7]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"Rectification and rapid activation at low Ca2+ of Ca2+-activated, voltage-dependent BK currents: consequences of rapid inactivation by a novel beta subunit."
Xia X.-M., Ding J.-P., Zeng X.-H., Duan K.-L., Lingle C.J.
J. Neurosci. 20:4890-4903(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Inactivation of BK channels mediated by the NH(2) terminus of the beta3b auxiliary subunit involves a two-step mechanism: possible separation of binding and blockade."
Lingle C.J., Zeng X.-H., Ding J.-P., Xia X.-M.
J. Gen. Physiol. 117:583-606(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[11]"Gating properties conferred on BK channels by the beta3b auxiliary subunit in the absence of its NH(2)- and COOH termini."
Zeng X.-H., Ding J.-P., Xia X.-M., Lingle C.J.
J. Gen. Physiol. 117:607-628(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN.
[12]"Variants of the KCNMB3 regulatory subunit of maxi BK channels affect channel inactivation."
Hu S., Labuda M.Z., Pandolfo M., Goss G.G., McDermid H.E., Ali D.W.
Physiol. Genomics 15:191-198(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-75; SER-165 AND THR-230.
[13]"Redox-sensitive extracellular gates formed by auxiliary beta subunits of calcium-activated potassium channels."
Zeng X.-H., Xia X.-M., Lingle C.J.
Nat. Struct. Biol. 10:448-454(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS, DOMAIN.
[14]"New disguises for an old channel: MaxiK channel beta-subunits."
Orio P., Rojas P., Ferreira G., Latorre R.
News Physiol. Sci. 17:156-161(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF139471 mRNA. Translation: AAD54771.1.
AF214561 mRNA. Translation: AAF36598.1.
AF204159 Genomic DNA. Translation: AAF97031.1.
AF204160 Genomic DNA. Translation: AAF97032.1.
AF204161 Genomic DNA. Translation: AAF97033.1.
AF204162 Genomic DNA. Translation: AAF97034.1.
AF160968 mRNA. Translation: AAF67811.1.
AF170916 mRNA. Translation: AAF89698.1.
AK304837 mRNA. Translation: BAH14265.1.
AC007823 Genomic DNA. No translation available.
AC076966 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78418.1.
CH471052 Genomic DNA. Translation: EAW78421.1.
RefSeqNP_001157149.1. NM_001163677.1.
NP_055222.3. NM_014407.3.
NP_741979.1. NM_171828.2.
NP_741980.1. NM_171829.2.
NP_741981.1. NM_171830.1.
UniGeneHs.591285.

3D structure databases

ProteinModelPortalQ9NPA1.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000319370.

Protein family/group databases

TCDB8.A.14.1.4. the ca(2+)-activated k(+) channel auxiliary subunit slowpoke- (slo) family.

Polymorphism databases

DMDM90111824.

Proteomic databases

PaxDbQ9NPA1.
PRIDEQ9NPA1.

Protocols and materials databases

DNASU27094.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314235; ENSP00000319370; ENSG00000171121. [Q9NPA1-1]
ENST00000349697; ENSP00000327866; ENSG00000171121. [Q9NPA1-2]
ENST00000392685; ENSP00000376451; ENSG00000171121. [Q9NPA1-3]
ENST00000392686; ENSP00000376452; ENSG00000171121. [Q9NPA1-4]
ENST00000485523; ENSP00000418536; ENSG00000171121. [Q9NPA1-4]
ENST00000497599; ENSP00000417091; ENSG00000171121. [Q9NPA1-5]
GeneID27094.
KEGGhsa:27094.
UCSCuc003fjm.3. human. [Q9NPA1-1]
uc003fjn.3. human. [Q9NPA1-3]
uc003fjo.3. human. [Q9NPA1-4]
uc003fjp.1. human. [Q9NPA1-2]

Organism-specific databases

CTD27094.
GeneCardsGC03M178957.
HGNCHGNC:6287. KCNMB3.
HPAHPA015665.
HPA019185.
MIM605222. gene.
neXtProtNX_Q9NPA1.
PharmGKBPA30067.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG29303.
HOGENOMHOG000290180.
HOVERGENHBG108059.
InParanoidQ9NPA1.
KOK04939.
OMAKPFMLST.
OrthoDBEOG77WWDC.
PhylomeDBQ9NPA1.
TreeFamTF328589.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_604. Hemostasis.

Gene expression databases

BgeeQ9NPA1.
CleanExHS_KCNMB2.
HS_KCNMB3.
GenevestigatorQ9NPA1.

Family and domain databases

InterProIPR003930. K_chnl_Ca-activ_BK_bsu.
[Graphical view]
PANTHERPTHR10258. PTHR10258. 1 hit.
PfamPF03185. CaKB. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiKCNMB3.
GenomeRNAi27094.
NextBio49727.
PROQ9NPA1.
SOURCESearch...

Entry information

Entry nameKCMB3_HUMAN
AccessionPrimary (citable) accession number: Q9NPA1
Secondary accession number(s): B7Z9C9 expand/collapse secondary AC list , D3DNR2, E9PER5, Q9NPG7, Q9NRM9, Q9UHN3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: March 7, 2006
Last modified: April 16, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM