P22460 (KCNA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Familial atrial fibrillation 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 process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Atrial fibrillation
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Isopeptide bond Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	membrane hyperpolarization Inferred from mutant phenotype PubMed 16236819. Source: BHF-UCL negative regulation of potassium ion transport Inferred from electronic annotation. Source: Compara potassium ion export Inferred from direct assay PubMed 12970345Ref.2. Source: BHF-UCL potassium ion homeostasis Inferred from electronic annotation. Source: Compara protein homooligomerization Inferred from electronic annotation. Source: InterPro reduction of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara 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 potassium ion transport Inferred from mutant phenotype PubMed 12021261. Source: BHF-UCL regulation of vasoconstriction Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from direct assay PubMed 16780588. Source: UniProtKB intercalated disc Inferred from direct assay PubMed 7615797. Source: BHF-UCL membrane raft Inferred from direct assay PubMed 18218624. Source: BHF-UCL voltage-gated potassium channel complex Inferred from direct assay Ref.2. Source: BHF-UCL
Molecular_function	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: Compara 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...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 613	613	Potassium voltage-gated channel subfamily A member 5		PRO_0000053985
Regions
	Transmembrane	251 – 269	19	Helical; Name=Segment S1; Potential
	Transmembrane	325 – 345	21	Helical; Name=Segment S2; Potential
	Transmembrane	356 – 377	22	Helical; Name=Segment S3; Potential
	Transmembrane	398 – 419	22	Helical; Voltage-sensor; Name=Segment S4; Potential
	Transmembrane	434 – 455	22	Helical; Name=Segment S5; Potential
	Transmembrane	495 – 516	22	Helical; Name=Segment S6; Potential
	Repeat	61 – 71	11	1
	Repeat	72 – 82	11	2
	Region	61 – 82	22	2 X 11 AA tandem repeat of D-[SP]-G-V-R-P-L-P-P-L-P
	Motif	480 – 485	6	Selectivity filter By similarity
	Motif	611 – 613	3	PDZ-binding By similarity
	Compositional bias	94 – 99	6	Poly-Glu
	Compositional bias	382 – 387	6	Poly-Gly
Amino acid modifications
	Modified residue	557	1	Phosphoserine; by PKA Potential
	Lipidation	346	1	S-palmitoyl cysteine Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	190	1	N-linked (GlcNAc...) Potential
	Cross-link	221		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.9
	Cross-link	536		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.9
Natural variations
	Alternative sequence	1 – 209	209	Missing in isoform 2.		VSP_037110
	Natural variant	228	1	P → S. Corresponds to variant rs1056464 [ dbSNP | Ensembl ].		VAR_053856
	Natural variant	300	1	G → S in a breast cancer sample; somatic mutation. Ref.10		VAR_035770
	Natural variant	578	1	R → K. Corresponds to variant rs12720445 [ dbSNP | Ensembl ].		VAR_054786
Experimental info
	Mutagenesis	15	1	T → A: Loss of DLG1 effect on channel current. Ref.7
	Mutagenesis	220	1	I → N: Reduces sumoylation; when associated with N-535. Ref.9
	Mutagenesis	221	1	K → R: Abolishes sumoylation; when associated with R-536. Ref.9
	Mutagenesis	535	1	L → N: Reduces sumoylation; when associated with N-220. Ref.9
	Mutagenesis	536	1	K → R: Abolishes sumoylation; when associated with R-221. Ref.9
	Sequence conflict	55	1	Missing in AAA61276. Ref.1
	Sequence conflict	138	1	L → Q in AAA36422. Ref.2
	Sequence conflict	154	1	R → P in AAA61276. Ref.1
	Sequence conflict	154	1	R → P in AAA36422. Ref.2
	Sequence conflict	187 – 188	2	RP → G in AAA61276. Ref.1
	Sequence conflict	214	1	R → G in AAA36422. Ref.2
	Sequence conflict	228	1	P → V in AAA36422. Ref.2
	Sequence conflict	282	1	L → V in AAA60146. Ref.3
	Sequence conflict	307	1	P → A in AAA61276. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2007. Version 4. Checksum: A5B02B27F8396E3D	FASTA	613	67,228
	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
	Isoform 2 (Short) [UniParc]. Checksum: 75826108B430EAC1	FASTA	404	44,427
	10 20 30 40 50 60 MERFREDEGF IKEEEKPLPR NEFQRQVWLI FEYPESSGSA RAIAIVSVLV ILISIITFCL 70 80 90 100 110 120 ETLPEFRDER ELLRHPPAPH QPPAPAPGAN GSGVMAPPSG PTVAPLLPRT LADPFFIVET 130 140 150 160 170 180 TCVIWFTFEL LVRFFACPSK AGFSRNIMNI IDVVAIFPYF ITLGTELAEQ QPGGGGGGQN 190 200 210 220 230 240 GQQAMSLAIL RVIRLVRVFR IFKLSRHSKG LQILGKTLQA SMRELGLLIF FLFIGVILFS 250 260 270 280 290 300 SAVYFAEADN QGTHFSSIPD AFWWAVVTMT TVGYGDMRPI TVGGKIVGSL CAIAGVLTIA 310 320 330 340 350 360 LPVPVIVSNF NYFYHRETDH EEPAVLKEEQ GTQSQGPGLD RGVQRKVSGS RGSFCKAGGT 370 380 390 400 LENADSARRG SCPLEKCNVK AKSNVDLRRS LYALCLDTSR ETDL

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00304594. IPI00929686.
PIR	A56031.
RefSeq	NP_002225.2. NM_002234.3.
UniGene	Hs.150208. Hs.741439.
3D structure databases
ProteinModelPortal	P22460.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-42010N.
IntAct	P22460. 1 interaction.
MINT	MINT-200758.
STRING	9606.ENSP00000252321.
Protein family/group databases
TCDB	1.A.1.2.4. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	P22460.
Polymorphism databases
DMDM	146345443.
Proteomic databases
PaxDb	P22460.
PRIDE	P22460.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000252321; ENSP00000252321; ENSG00000130037.
GeneID	3741.
KEGG	hsa:3741.
UCSC	uc001qni.3. human.
Organism-specific databases
CTD	3741.
GeneCards	GC12P005153.
HGNC	HGNC:6224. KCNA5.
MIM	176267. gene. 612240. phenotype.
neXtProt	NX_P22460.
Orphanet	334. Familial atrial fibrillation.
PharmGKB	PA208.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1226.
HOGENOM	HOG000231015.
HOVERGEN	HBG052230.
InParanoid	P22460.
KO	K04878.
OMA	KRLRYFD.
OrthoDB	EOG4R502V.
PhylomeDB	P22460.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	P22460.
CleanEx	HS_KCNA5.
Genevestigator	P22460.
GermOnline	ENSG00000130037. Homo sapiens.
Family and domain databases
Gene3D	3.30.710.10. 1 hit.
InterPro	IPR000210. BTB/POZ-like. IPR011333. BTB/POZ_fold. 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. [Graphical view]
PANTHER	PTHR11537. PTHR11537. 1 hit. PTHR11537:SF25. PTHR11537:SF25. 1 hit.
Pfam	PF00520. Ion_trans. 1 hit. PF02214. K_tetra. 1 hit. [Graphical view]
PRINTS	PR00169. KCHANNEL. PR01512. KV15CHANNEL. PR01491. KVCHANNEL. PR01496. SHAKERCHANEL.
SMART	SM00225. BTB. 1 hit. [Graphical view]
SUPFAM	SSF54695. BTB/POZ_fold. 1 hit.
ProtoNet	Search...
Other
BindingDB	P22460.
ChEMBL	CHEMBL4306.
GenomeRNAi	3741.
NextBio	14639.
SOURCE	Search...

Entry information

Entry name

KCNA5_HUMAN

Accession

Primary (citable) accession number: P22460
Secondary accession number(s): Q4KKT8 , Q4VAJ1, Q4VAJ2, Q9UDA4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 129 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.