P22459 (KCNA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Potassium voltage-gated channel subfamily A member 4

Alternative name(s):
HPCN2
Voltage-gated K(+) channel HuKII
Voltage-gated potassium channel HBK4
Voltage-gated potassium channel HK1
Voltage-gated potassium channel subunit Kv1.4

Gene names

Name:	KCNA4
Synonyms:	KCNA4L

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	653 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.
Subunit structure	Heterotetramer of potassium channel proteins. Binds PDZ domains of DLG1, DLG2 and DLG4. Interacts with SIGMAR1 By similarity. Part of a complex containing KCNA1, KCNAB1 and LGI1 By similarity.
Subcellular location	Membrane; Multi-pass membrane protein.
Domain	The N-terminus may be important in determining the rate of inactivation of the channel while the tail 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.
Sequence similarities	Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein homooligomerization Inferred from electronic annotation. Source: InterPro synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	voltage-gated potassium channel complex Traceable author statement Ref.2. Source: ProtInc
Molecular_function	potassium ion binding Inferred from electronic annotation. Source: InterPro voltage-gated potassium channel activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 653	653	Potassium voltage-gated channel subfamily A member 4		PRO_0000053981
Regions
	Transmembrane	308 – 326	19	Helical; Name=Segment S1; Potential
	Transmembrane	371 – 392	22	Helical; Name=Segment S2; Potential
	Transmembrane	404 – 424	21	Helical; Name=Segment S3; Potential
	Transmembrane	443 – 461	19	Helical; Voltage-sensor; Name=Segment S4; Potential
	Transmembrane	478 – 497	20	Helical; Name=Segment S5; Potential
	Transmembrane	539 – 561	23	Helical; Name=Segment S6; Potential
	Motif	524 – 529	6	Selectivity filter By similarity
	Motif	651 – 653	3	PDZ-binding By similarity
	Compositional bias	62 – 65	4	Poly-His
	Compositional bias	123 – 137	15	Poly-Glu
	Compositional bias	162 – 165	4	Poly-Gly
	Compositional bias	433 – 436	4	Poly-Gln
Amino acid modifications
	Modified residue	90	1	Phosphoserine; by PKA Potential
	Modified residue	122	1	Phosphoserine By similarity
	Modified residue	599	1	Phosphoserine; by PKA Potential
	Glycosylation	181	1	N-linked (GlcNAc...) Potential
	Glycosylation	352	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	38	1	A → R in AAA60034. Ref.1
	Sequence conflict	42	1	A → R in AAA60034. Ref.1
	Sequence conflict	84 – 88	5	RRRRQ → EEEAT in AAA60034. Ref.1
	Sequence conflict	304	1	S → D in AAA60034. Ref.1
	Sequence conflict	542	1	S → V in AAA60034. Ref.1
	Sequence conflict	631	1	G → A in AAA60034. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P22459 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 5E511DB704CCA013	FASTA	653	73,257
	10 20 30 40 50 60 MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA VEGSGGSGGG 70 80 90 100 110 120 SHHHHQSRGA CTSHDPQSSR GSRRRRRQRS EKKKAHYRQS SFPHCSDLMP SGSEEKILRE 130 140 150 160 170 180 LSEEEEDEEE EEEEEEEGRF YYSEDDHGDE CSYTDLLPQD EGGGGYSSVR YSDCCERVVI 190 200 210 220 230 240 NVSGLRFETQ MKTLAQFPET LLGDPEKRTQ YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR 250 260 270 280 290 300 LKRPVNVPFD IFTEEVKFYQ LGEEALLKFR EDEGFVREEE DRALPENEFK KQIWLLFEYP 310 320 330 340 350 360 ESSSPARGIA IVSVLVILIS IVIFCLETLP EFRDDRDLVM ALSAGGHGGL LNDTSAPHLE 370 380 390 400 410 420 NSGHTIFNDP FFIVETVCIV WFSFEFVVRC FACPSQALFF KNIMNIIDIV SILPYFITLG 430 440 450 460 470 480 TDLAQQQGGG NGQQQQAMSF AILRIIRLVR VFRIFKLSRH SKGLQILGHT LRASMRELGL 490 500 510 520 530 540 LIFFLFIGVI LFSSAVYFAE ADEPTTHFQS IPDAFWWAVV TMTTVGYGDM KPITVGGKIV 550 560 570 580 590 600 GSLCAIAGVL TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS 610 620 630 640 650 TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ GKGDDSETDK NNCSNAKAVE TDV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4." Philipson L.H., Schaefer K., Lamendola J., Bell G.I., Steiner D.F. Nucleic Acids Res. 18:7160-7160(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"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]. Tissue: Heart.
[3]	"Human potassium channel genes: molecular cloning and functional expression." Ramaswami M., Gautam M., Kamb A., Rudy B., Tanouye M.A., Mathew M.K. Mol. Cell. Neurosci. 1:214-223(1990) Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"NMR structure of inactivation gates from mammalian voltage-dependent potassium channels." Antz C., Geyer M., Fakler B., Schott M.K., Guy H.R., Frank R., Ruppersberg J.P., Kalbitzer H.R. Nature 385:272-275(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-37.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M55514 mRNA. Translation: AAA60034.1. M60450 mRNA. Translation: AAA61275.1. L02751 mRNA. Translation: AAA36140.1. AC124657 Genomic DNA. No translation available.
IPI	IPI00304582.
PIR	A39922.
RefSeq	NP_002224.1. NM_002233.3.
UniGene	Hs.592002.
3D structure databases
ProteinModelPortal	P22459.
SMR	P22459. Positions 1-75, 175-571.
ModBase	Search...
Protein-protein interaction databases
IntAct	P22459. 3 interactions.
MINT	MINT-200816.
STRING	9606.ENSP00000328511.
PTM databases
PhosphoSite	P22459.
Polymorphism databases
DMDM	116430.
Proteomic databases
PaxDb	P22459.
PRIDE	P22459.
Protocols and materials databases
DNASU	3739.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328224; ENSP00000328511; ENSG00000182255.
GeneID	3739.
KEGG	hsa:3739.
UCSC	uc001msk.3. human.
Organism-specific databases
CTD	3739.
GeneCards	GC11M030031.
H-InvDB	HIX0036152.
HGNC	HGNC:6222. KCNA4.
HPA	CAB001977. HPA016422.
MIM	176266. gene.
neXtProt	NX_P22459.
PharmGKB	PA207.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1226.
HOGENOM	HOG000231015.
HOVERGEN	HBG052230.
InParanoid	P22459.
KO	K04877.
OMA	DPQSGRG.
OrthoDB	EOG4QRH3T.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	P22459.
CleanEx	HS_KCNA4.
Genevestigator	P22459.
GermOnline	ENSG00000182255. Homo sapiens.
Family and domain databases
Gene3D	1.20.5.600. 1 hit. 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. IPR020467. K_chnl_volt-dep_Kv1.4. IPR012897. K_chnl_volt-dep_Kv1.4_TID. IPR003131. T1-type_BTB. [Graphical view]
PANTHER	PTHR11537. PTHR11537. 1 hit.
Pfam	PF00520. Ion_trans. 1 hit. PF07941. K_channel_TID. 1 hit. PF02214. K_tetra. 1 hit. [Graphical view]
PRINTS	PR00169. KCHANNEL. PR01511. KV14CHANNEL. PR01491. KVCHANNEL. PR01496. SHAKERCHANEL.
SMART	SM00225. BTB. 1 hit. [Graphical view]
SUPFAM	SSF54695. BTB/POZ_fold. 1 hit.
ProtoNet	Search...
Other
BindingDB	P22459.
ChEMBL	CHEMBL4205.
GenomeRNAi	3739.
NextBio	14635.
SOURCE	Search...

Entry information

Entry name

KCNA4_HUMAN

Accession

Primary (citable) accession number: P22459

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	November 30, 2010
Last modified:	April 3, 2013
This is version 126 of the entry and version 2 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.