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P22460 (KCNA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium voltage-gated channel subfamily A member 5
Alternative name(s):
HPCN1
Voltage-gated potassium channel HK2
Voltage-gated potassium channel subunit Kv1.5
Gene names
Name:KCNA5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length613 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. This channel displays rapid activation and slow inactivation. May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation. Ref.5 Ref.6

Subunit structure

Heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 By similarity. Interacts with UBE2I. Ref.7 Ref.9

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Pancreatic islets and insulinoma.

Domain

The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Post-translational modification

Sumoylated on Lys-221, and Lys-536, preferentially with SUMO3. Sumoylation regulates the voltage sensitivity of the channel. Ref.9

Involvement in disease

Atrial fibrillation, familial, 7 (ATFB7) [MIM:612240]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily. [View classification]

Sequence caution

The sequence AAA60146.1 differs from that shown. Reason: Frameshift at position 579.

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAtrial fibrillation
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Potassium channel
Voltage-gated channel
   PTMGlycoprotein
Isopeptide bond
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processatrial cardiac muscle cell action potential

Inferred from mutant phenotype PubMed 19343045. Source: BHF-UCL

membrane hyperpolarization

Inferred from mutant phenotype PubMed 16236819. Source: BHF-UCL

negative regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

negative regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of G1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

positive regulation of myoblast proliferation

Inferred from electronic annotation. Source: Ensembl

potassium ion export

Inferred from direct assay PubMed 12970345Ref.2. Source: BHF-UCL

potassium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Inferred from direct assay PubMed 8576199. Source: MGI

protein homooligomerization

Inferred from electronic annotation. Source: InterPro

regulation of atrial cardiac muscle cell membrane repolarization

Inferred from mutant phenotype PubMed 19343045. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype PubMed 19343045. Source: BHF-UCL

regulation of insulin secretion

Traceable author statement Ref.2. Source: BHF-UCL

regulation of membrane potential

Inferred from direct assay Ref.2. Source: BHF-UCL

regulation of potassium ion transport

Inferred from mutant phenotype PubMed 12021261. Source: BHF-UCL

regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 16780588. Source: UniProtKB

Z disc

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from electronic annotation. Source: Ensembl

intercalated disc

Inferred from direct assay PubMed 7615797. Source: BHF-UCL

intracellular canaliculus

Inferred from electronic annotation. Source: Ensembl

membrane raft

Inferred from direct assay PubMed 18218624. Source: BHF-UCL

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay PubMed 16780588. Source: UniProtKB

voltage-gated potassium channel complex

Inferred from direct assay Ref.2. Source: BHF-UCL

   Molecular_functionalpha-actinin binding

Inferred from physical interaction PubMed 10812072. Source: BHF-UCL

delayed rectifier potassium channel activity

Inferred from direct assay Ref.2. Source: BHF-UCL

outward rectifier potassium channel activity

Inferred from direct assay PubMed 12970345. Source: BHF-UCL

potassium channel inhibitor activity

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 10812072PubMed 11389904. Source: IntAct

protein kinase binding

Inferred from physical interaction PubMed 8953041. Source: BHF-UCL

scaffold protein binding

Inferred from physical interaction PubMed 12970345PubMed 18281375. Source: BHF-UCL

voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization

Inferred from mutant phenotype PubMed 19343045. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ACTN2P356096EBI-6426121,EBI-77797

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22460-1)

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: P22460-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-209: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 613613Potassium voltage-gated channel subfamily A member 5
PRO_0000053985

Regions

Transmembrane251 – 26919Helical; Name=Segment S1; Potential
Transmembrane325 – 34521Helical; Name=Segment S2; Potential
Transmembrane356 – 37722Helical; Name=Segment S3; Potential
Transmembrane398 – 41922Helical; Voltage-sensor; Name=Segment S4; Potential
Transmembrane434 – 45522Helical; Name=Segment S5; Potential
Transmembrane495 – 51622Helical; Name=Segment S6; Potential
Repeat61 – 71111
Repeat72 – 82112
Region61 – 82222 X 11 AA tandem repeat of D-[SP]-G-V-R-P-L-P-P-L-P
Motif480 – 4856Selectivity filter By similarity
Motif611 – 6133PDZ-binding By similarity
Compositional bias94 – 996Poly-Glu
Compositional bias382 – 3876Poly-Gly

Amino acid modifications

Modified residue5571Phosphoserine; by PKA Potential
Lipidation3461S-palmitoyl cysteine Potential
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1901N-linked (GlcNAc...) Potential
Cross-link221Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.9
Cross-link536Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.9

Natural variations

Alternative sequence1 – 209209Missing in isoform 2.
VSP_037110
Natural variant2281P → S.
Corresponds to variant rs1056464 [ dbSNP | Ensembl ].
VAR_053856
Natural variant3001G → S in a breast cancer sample; somatic mutation. Ref.10
VAR_035770
Natural variant5781R → K.
Corresponds to variant rs12720445 [ dbSNP | Ensembl ].
VAR_054786

Experimental info

Mutagenesis151T → A: Loss of DLG1 effect on channel current. Ref.7
Mutagenesis2201I → N: Reduces sumoylation; when associated with N-535. Ref.9
Mutagenesis2211K → R: Abolishes sumoylation; when associated with R-536. Ref.9
Mutagenesis5351L → N: Reduces sumoylation; when associated with N-220. Ref.9
Mutagenesis5361K → R: Abolishes sumoylation; when associated with R-221. Ref.9
Sequence conflict551Missing in AAA61276. Ref.1
Sequence conflict1381L → Q in AAA36422. Ref.2
Sequence conflict1541R → P in AAA61276. Ref.1
Sequence conflict1541R → P in AAA36422. Ref.2
Sequence conflict187 – 1882RP → G in AAA61276. Ref.1
Sequence conflict2141R → G in AAA36422. Ref.2
Sequence conflict2281P → V in AAA36422. Ref.2
Sequence conflict2821L → V in AAA60146. Ref.3
Sequence conflict3071P → A in AAA61276. Ref.1

Sequences

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

Last modified May 1, 2007. Version 4.
Checksum: A5B02B27F8396E3D

FASTA61367,228
        10         20         30         40         50         60 
MEIALVPLEN GGAMTVRGGD EARAGCGQAT GGELQCPPTA GLSDGPKEPA PKGRGAQRDA 

        70         80         90        100        110        120 
DSGVRPLPPL PDPGVRPLPP LPEELPRPRR PPPEDEEEEG DPGLGTVEDQ ALGTASLHHQ 

       130        140        150        160        170        180 
RVHINISGLR FETQLGTLAQ FPNTLLGDPA KRLRYFDPLR NEYFFDRNRP SFDGILYYYQ 

       190        200        210        220        230        240 
SGGRLRRPVN VSLDVFADEI RFYQLGDEAM ERFREDEGFI KEEEKPLPRN EFQRQVWLIF 

       250        260        270        280        290        300 
EYPESSGSAR AIAIVSVLVI LISIITFCLE TLPEFRDERE LLRHPPAPHQ PPAPAPGANG 

       310        320        330        340        350        360 
SGVMAPPSGP TVAPLLPRTL ADPFFIVETT CVIWFTFELL VRFFACPSKA GFSRNIMNII 

       370        380        390        400        410        420 
DVVAIFPYFI TLGTELAEQQ PGGGGGGQNG QQAMSLAILR VIRLVRVFRI FKLSRHSKGL 

       430        440        450        460        470        480 
QILGKTLQAS MRELGLLIFF LFIGVILFSS AVYFAEADNQ GTHFSSIPDA FWWAVVTMTT 

       490        500        510        520        530        540 
VGYGDMRPIT VGGKIVGSLC AIAGVLTIAL PVPVIVSNFN YFYHRETDHE EPAVLKEEQG 

       550        560        570        580        590        600 
TQSQGPGLDR GVQRKVSGSR GSFCKAGGTL ENADSARRGS CPLEKCNVKA KSNVDLRRSL 

       610 
YALCLDTSRE TDL 

« Hide

Isoform 2 (Short) [UniParc].

Checksum: 75826108B430EAC1
Show »

FASTA40444,427

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle."
Tamkun M.M., Knoth K.M., Walbridge J.A., Kroemer H., Roden D.M., Glover D.M.
FASEB J. 5:331-337(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[2]"Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel."
Philipson L.H., Hice R.E., Schaefer K., Lamendola J., Bell G.I., Nelson D.J., Steiner D.F.
Proc. Natl. Acad. Sci. U.S.A. 88:53-57(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Insulinoma.
[3]"Molecular cloning, characterization, and genomic localization of a human potassium channel gene."
Curran M.E., Landes G.M., Keating M.T.
Genomics 12:729-737(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression."
Snyders D.J., Tamkun M.M., Bennett P.B.
J. Gen. Physiol. 101:513-543(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Altered state dependence of c-type inactivation in the long and short forms of human Kv1.5."
Kurata H.T., Soon G.S., Fedida D.
J. Gen. Physiol. 118:315-332(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[7]"A specific N-terminal residue in Kv1.5 is required for upregulation of the channel by SAP97."
Mathur R., Choi W.S., Eldstrom J., Wang Z., Kim J., Steele D.F., Fedida D.
Biochem. Biophys. Res. Commun. 342:1-8(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DLG1, MUTAGENESIS OF THR-15.
[8]"Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation."
Olson T.M., Alekseev A.E., Liu X.K., Park S., Zingman L.V., Bienengraeber M., Sattiraju S., Ballew J.D., Jahangir A., Terzic A.
Hum. Mol. Genet. 15:2185-2191(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ATFB7.
[9]"SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5."
Benson M.D., Li Q.J., Kieckhafer K., Dudek D., Whorton M.R., Sunahara R.K., Iniguez-Lluhi J.A., Martens J.R.
Proc. Natl. Acad. Sci. U.S.A. 104:1805-1810(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-221 AND LYS-536, INTERACTION WITH UBE2I, MUTAGENESIS OF ILE-220; LYS-221; LEU-535 AND LYS-536.
[10]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-300.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M60451 mRNA. Translation: AAA61276.1.
M55513 mRNA. Translation: AAA36422.1.
M83254 mRNA. Translation: AAA60146.1. Frameshift.
BC096357 mRNA. Translation: AAH96357.1.
BC096358 mRNA. Translation: AAH96358.3.
BC099665 mRNA. Translation: AAH99665.3.
BC099666 mRNA. Translation: AAH99666.3.
CCDSCCDS8536.1. [P22460-1]
PIRA56031.
RefSeqNP_002225.2. NM_002234.3. [P22460-1]
UniGeneHs.150208.
Hs.741439.

3D structure databases

ProteinModelPortalP22460.
SMRP22460. Positions 120-527.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109943. 27 interactions.
DIPDIP-42010N.
IntActP22460. 2 interactions.
MINTMINT-200758.
STRING9606.ENSP00000252321.

Chemistry

BindingDBP22460.
ChEMBLCHEMBL2362996.
GuidetoPHARMACOLOGY542.

Protein family/group databases

TCDB1.A.1.2.4. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteP22460.

Polymorphism databases

DMDM146345443.

Proteomic databases

PaxDbP22460.
PRIDEP22460.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252321; ENSP00000252321; ENSG00000130037. [P22460-1]
GeneID3741.
KEGGhsa:3741.
UCSCuc001qni.4. human. [P22460-1]

Organism-specific databases

CTD3741.
GeneCardsGC12P005153.
HGNCHGNC:6224. KCNA5.
HPACAB022562.
HPA021516.
MIM176267. gene.
612240. phenotype.
neXtProtNX_P22460.
Orphanet334. Familial atrial fibrillation.
PharmGKBPA208.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231015.
HOVERGENHBG052230.
InParanoidP22460.
KOK04878.
OMAGGELQCP.
OrthoDBEOG7M0NRD.
PhylomeDBP22460.
TreeFamTF313103.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeP22460.
CleanExHS_KCNA5.
GenevestigatorP22460.

Family and domain databases

Gene3D1.20.120.350. 1 hit.
3.30.710.10. 1 hit.
InterProIPR000210. 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.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004052. K_chnl_volt-dep_Kv1.5.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERPTHR11537. PTHR11537. 1 hit.
PTHR11537:SF25. PTHR11537:SF25. 1 hit.
PfamPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSPR00169. KCHANNEL.
PR01512. KV15CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMSSF54695. SSF54695. 1 hit.
ProtoNetSearch...

Other

GeneWikiKCNA5.
GenomeRNAi3741.
NextBio14639.
PROP22460.
SOURCESearch...

Entry information

Entry nameKCNA5_HUMAN
AccessionPrimary (citable) accession number: P22460
Secondary accession number(s): Q4KKT8 expand/collapse secondary AC list , Q4VAJ1, Q4VAJ2, Q9UDA4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 1, 2007
Last modified: July 9, 2014
This is version 143 of the entry and version 4 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 12

Human chromosome 12: entries, gene names and cross-references to MIM