Reviewed, UniProtKB/Swiss-Prot P22460 (KCNA5_HUMAN)

Names and origin

Protein names

Recommended name:
    Potassium voltage-gated channel subfamily A member 5
Alternative name(s):
    Voltage-gated potassium channel subunit Kv1.5
    HK2
    HPCN1

Gene names

Name:

KCNA5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 potasssium ions may pass in accordance with their electrochemical gradient. 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
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.
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 by SUMO3. Sumoylation regulates the voltage sensitivity of the channel. Ref.8
Involvement in disease	Defects in KCNA5 are the cause of atrial fibrillation familial type 7 (ATFB7) [MIM:612240]. Atrial fibrillation is a common disorder of cardiac rhythm that is hereditary in a small subgroup of patients. It is characterized by disorganized atrial electrical activity, progressive deterioration of atrial electromechanical function and ineffective pumping of blood into the ventricles. It can be associated with palpitations, syncope, thromboembolic stroke, and congestive heart failure. Ref.7
Sequence similarities	Belongs to the potassium channel family. A (Shaker) subfamily.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Atrial fibrillation
Domain	Repeat Transmembrane
Ligand	Potassium
Molecular function	Ionic channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Isopeptide bond Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	potassium ion transport Ref.2 Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Inferred from direct assay. Source: UniProtKB voltage-gated potassium channel complex Ref.2 Traceable author statement. Source: ProtInc
Molecular function	delayed rectifier potassium channel activity Ref.2 Traceable author statement. Source: ProtInc potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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	Segment S1
	Transmembrane	325 – 345	21	Segment S2
	Transmembrane	356 – 377	22	Segment S3
	Transmembrane	398 – 419	22	Segment S4
	Transmembrane	434 – 455	22	Segment S5
	Transmembrane	495 – 516	22	Segment S6
	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.8
	Cross-link	536		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.8
Natural variations
	Alternative sequence	1 – 209	209	Missing in isoform 2.		VSP_037110
	Natural variant	228	1	P → S: dbSNP rs1056464.		VAR_053856
	Natural variant	300	1	G → S in a breast cancer sample; somatic mutation. Ref.9		VAR_035770
	Natural variant	578	1	R → K: dbSNP rs12720445.		VAR_054786
Experimental info
	Mutagenesis	15	1	T → A: Loss of DLG1 effect on channel current. Ref.6
	Mutagenesis	220	1	I → N: Reduces sumoylation; when associated with N-535. Ref.8
	Mutagenesis	221	1	K → R: Abolishes sumoylation; when associated with R-536. Ref.8
	Mutagenesis	535	1	L → N: Reduces sumoylation; when associated with N-220. Ref.8
	Mutagenesis	536	1	K → R: Abolishes sumoylation; when associated with R-221. Ref.8
	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
	Sequence conflict	579 – 613	35	GSCPL…RETDL → QLPPREV in AAA60146. Ref.3

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). 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: 2001794] [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: 1986382] [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: 1349297] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"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: 11524461] [Abstract] Cited for: FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2).
[6]	"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: 16466689] [Abstract] Cited for: INTERACTION WITH DLG1, MUTAGENESIS OF THR-15.
[7]	"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: 16772329] [Abstract] Cited for: INVOLVEMENT IN ATFB7.
[8]	"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: 17261810] [Abstract] Cited for: SUMOYLATION AT LYS-221 AND LYS-536, INTERACTION WITH UBE2I, MUTAGENESIS OF ILE-220; LYS-221; LEU-535 AND LYS-536.
[9]	"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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-300.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M60451 mRNA. Translation: AAA61276.1. M55513 mRNA. Translation: AAA36422.1. M83254 mRNA. Translation: AAA60146.1. BC096357 mRNA. Translation: AAH96357.1. BC096358 mRNA. Translation: AAH96358.3. BC099665 mRNA. Translation: AAH99665.3. BC099666 mRNA. Translation: AAH99666.3.
IPI	IPI00304594.
PIR	A56031.
RefSeq	NP_002225.2.
UniGene	Hs.150208
3D structure databases
HSSP	HSSP built from PDB template 1HO2 based on UniProtKB P08510.
SMR	P22460. Positions 322-527.
ModBase	Search...
Protein family/group databases
TCDB	1.A.1.2.4. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	P22460.
Proteomic databases
PRIDE	P22460.
Genome annotation databases
Ensembl	ENSG00000130037. Homo sapiens. [Contig view]
GeneID	3741.
KEGG	hsa:3741.
Organism-specific databases
GeneCards	GC12P005023.
HGNC	HGNC:6224. KCNA5.
MIM	176267. gene. 612240. phenotype.
Orphanet	334. Atrial fibrillation, familial.
PharmGKB	PA208.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P22460.
HOVERGEN	P22460.
OMA	P22460. KRLRYFD.
Gene expression databases
ArrayExpress	P22460.
Bgee	P22460.
CleanEx	HS_KCNA5.
GermOnline	ENSG00000130037. Homo sapiens.
Family and domain databases
InterPro	IPR000210. BTB/POZ-like. IPR011333. BTB/POZ_fold. IPR005821. Ion_trans. IPR003091. K_chnl. IPR003968. K_chnl_volt-dep_Kv. IPR003972. K_chnl_volt-dep_Kv1. IPR004052. K_chnl_volt-dep_Kv1.5. IPR003131. K_chnl_volt-dep_Kv_tetra. [Graphical view]
Gene3D	G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit.
PANTHER	PTHR11537:SF25. KV15channel. 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]
ProtoNet	Search...
Other Resources
NextBio	14639.
SOURCE	Search...

Entry information

Entry name

KCNA5_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	May 1, 2007
Last modified:	June 16, 2009
This is version 90 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)