Reviewed, UniProtKB/Swiss-Prot P22459 (KCNA4_HUMAN)

Names and origin

Protein names

Recommended name:
    Potassium voltage-gated channel subfamily A member 4
Alternative name(s):
    Voltage-gated potassium channel subunit Kv1.4
      Short name=HK1
    HPCN2
    HBK4
    HUKII

Gene names

Name:	KCNA4
Synonyms:	KCNA4L

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	653 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 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 OPRS1 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) subfamily.

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Domain	Transmembrane
Ligand	Potassium
Molecular function	Ionic channel Potassium channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	potassium ion transport Ref.3 Traceable author statement. Source: ProtInc
Cellular component	voltage-gated potassium channel complex Ref.3 Traceable author statement. Source: ProtInc
Molecular function	potassium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct voltage-gated potassium channel activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Dlg4	P31016	1	EBI-631235,EBI-375655	From a different organism.

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	Segment S1 Potential
	Transmembrane	371 – 392	22	Segment S2 Potential
	Transmembrane	404 – 424	21	Segment S3 Potential
	Transmembrane	443 – 461	19	Segment S4 Potential
	Transmembrane	478 – 497	20	Segment S5 Potential
	Transmembrane	539 – 561	23	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	R → A Ref.3
	Sequence conflict	38	1	R → A Ref.4
	Sequence conflict	42	1	R → A Ref.3
	Sequence conflict	42	1	R → A Ref.4
	Sequence conflict	84 – 88	5	EEEAT → RRRRQ Ref.3
	Sequence conflict	84 – 88	5	EEEAT → RRRRQ Ref.4
	Sequence conflict	304	1	D → S Ref.3
	Sequence conflict	304	1	D → S Ref.4
	Sequence conflict	542	1	V → S Ref.3
	Sequence conflict	542	1	V → S Ref.4
	Sequence conflict	631	1	A → G Ref.3
	Sequence conflict	631	1	A → G Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P22459-1 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 7A66781F827D6F27	FASTA	653	73,288
	10 20 30 40 50 60 MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRRAA ARAVAAATAA VEGSGGSGGG 70 80 90 100 110 120 SHHHHQSRGA CTSHDPQSSR GSREEEATRS 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 ESSDPARGIA 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 GVLCAIAGVL TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS 610 620 630 640 650 TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ AKGDDSETDK NNCSNAKAVE TDV

References

[1]	"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]. Tissue: Skeletal muscle.
[2]	"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: 2263489] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[3]	"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]. Tissue: Heart.
[4]	"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.
[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: 9000078] [Abstract] Cited for: STRUCTURE BY NMR OF 1-37.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M55514 mRNA. Translation: AAA60034.1. M60450 mRNA. Translation: AAA61275.1. L02751 mRNA. Translation: AAA36140.1.
IPI	IPI00304582.
PIR	A39922.
RefSeq	NP_002224.1.
UniGene	Hs.592002
3D structure databases
SMR	P22459. Positions 1-75, 175-274, 369-571.
ModBase	Search...
Protein-protein interaction databases
IntAct	P22459. 3 interactions.
PTM databases
PhosphoSite	P22459.
Proteomic databases
PRIDE	P22459.
Genome annotation databases
Ensembl	ENSG00000182255. Homo sapiens. [Contig view]
GeneID	3739.
KEGG	hsa:3739.
Organism-specific databases
GeneCards	GC11M029988.
H-InvDB	HIX0036152.
HGNC	HGNC:6222. KCNA4.
HPA	CAB001977. HPA016422.
MIM	176266. gene.
PharmGKB	PA207.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P22459.
HOVERGEN	P22459.
Gene expression databases
ArrayExpress	P22459.
Bgee	P22459.
CleanEx	HS_KCNA4.
GermOnline	ENSG00000182255. 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. IPR012897. K_chnl_volt-dep_Kv1.4_TID. IPR003131. K_chnl_volt-dep_Kv_tetra. [Graphical view]
Gene3D	G3DSA:3.30.710.10. BTB/POZ_fold. 1 hit. G3DSA:1.20.5.600. K_channel_TID. 1 hit.
Pfam	PF00520. Ion_trans. 1 hit. PF07941. K_channel_TID. 1 hit. PF02214. K_tetra. 1 hit. [Graphical view]
PRINTS	PR00169. KCHANNEL. PR01491. KVCHANNEL. PR01496. SHAKERCHANEL.
SMART	SM00225. BTB. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	August 1, 1991
Last modified:	June 16, 2009
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)