P48050 (IRK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inward rectifier potassium channel 4

Alternative name(s):
HIRK2
HRK1
Hippocampal inward rectifier
Short name=HIR
Inward rectifier K(+) channel Kir2.3
Short name=IRK-3
Potassium channel, inwardly rectifying subfamily J member 4

Gene names

Name:	KCNJ4
Synonyms:	IRK3

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	445 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium By similarity.
Subunit structure	Homomultimeric and heteromultimeric association with Kir2.1, resulting in an enhanced G-protein-induced current. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking By similarity. Interacts with TAX1BP3. TAX1BP3 competes with LIN7 family members for KCNJ4 binding. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein. Cytoplasmic vesicle membrane By similarity. Note: TAX1BP3 binding promotes dissociation of KCNJ4 from LIN7 famaly members and KCNJ4 internalization By similarity.
Tissue specificity	Heart, skeletal muscle, and several different brain regions including the hippocampus.
Domain	The Val/Gly/Ala/Pro stretch may have a functional role in the conductance or permeation properties.
Sequence similarities	Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ4 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ion channel Voltage-gated channel
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	basolateral plasma membrane Inferred from direct assay PubMed 16855024. Source: UniProtKB cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell voltage-gated potassium channel complex Traceable author statement Ref.3. Source: ProtInc
Molecular_function	inward rectifier potassium channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 445	445	Inward rectifier potassium channel 4		PRO_0000154930
Regions
	Topological domain	1 – 55	55	Cytoplasmic By similarity
	Transmembrane	56 – 80	25	Helical; Name=M1; By similarity
	Topological domain	81 – 120	40	Extracellular By similarity
	Intramembrane	121 – 132	12	Helical; Pore-forming; Name=H5; By similarity
	Intramembrane	133 – 139	7	Pore-forming; By similarity
	Topological domain	140 – 148	9	Extracellular By similarity
	Transmembrane	149 – 170	22	Helical; Name=M2; By similarity
	Topological domain	171 – 445	275	Cytoplasmic By similarity
	Region	91 – 111	21	Val/Gly/Ala/Pro stretch
	Motif	134 – 139	6	Selectivity filter By similarity
	Motif	443 – 445	3	PDZ-binding Potential
	Compositional bias	102 – 105	4	Poly-Gly
	Compositional bias	362 – 368	7	Poly-Pro
	Compositional bias	383 – 390	8	Poly-Glu
	Compositional bias	391 – 399	9	Poly-Ala
Sites
	Site	164	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity
Experimental info
	Sequence conflict	16 – 17	2	KR → NG in AAC60632. Ref.3
	Sequence conflict	107	1	A → D in AAA66076. Ref.2
	Sequence conflict	350	1	A → G in AAC60632. Ref.3
	Sequence conflict	392	1	A → S in AAA66076. Ref.2
	Sequence conflict	395	1	A → S in AAA66076. Ref.2
	Sequence conflict	396	1	A → R Ref.3
	Sequence conflict	398	1	A → G Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P48050 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 893F03365273E8BE	FASTA	445	49,500
	10 20 30 40 50 60 MHGHSRNGQA HVPRRKRRNR FVKKNGQCNV YFANLSNKSQ RYMADIFTTC VDTRWRYMLM 70 80 90 100 110 120 IFSAAFLVSW LFFGLLFWCI AFFHGDLEAS PGVPAAGGPA AGGGGAAPVA PKPCIMHVNG 130 140 150 160 170 180 FLGAFLFSVE TQTTIGYGFR CVTEECPLAV IAVVVQSIVG CVIDSFMIGT IMAKMARPKK 190 200 210 220 230 240 RAQTLLFSHH AVISVRDGKL CLMWRVGNLR KSHIVEAHVR AQLIKPYMTQ EGEYLPLDQR 250 260 270 280 290 300 DLNVGYDIGL DRIFLVSPII IVHEIDEDSP LYGMGKEELE SEDFEIVVIL EGMVEATAMT 310 320 330 340 350 360 TQARSSYLAS EILWGHRFEP VVFEEKSHYK VDYSRFHKTY EVAGTPCCSA RELQESKITV 370 380 390 400 410 420 LPAPPPPPSA FCYENELALM SQEEEEMEEE AAAAAAVAAG LGLEAGSKEE AGIIRMLEFG 430 440 SHLDLERMQA SLPLDNISYR RESAI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure and characterization of a small-conductance inwardly rectifying potassium channel from human hippocampus." Perier F., Radeke C.M., Vandenberg C.A. Proc. Natl. Acad. Sci. U.S.A. 91:6240-6244(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hippocampus.
[2]	"Cloning a novel human brain inward rectifier potassium channel and its functional expression in Xenopus oocytes." Tang W., Yang X.-C. FEBS Lett. 348:239-243(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"Cloning and expression of a novel human brain inward rectifier potassium channel." Makhina E.N., Kelly A.J., Lopatin A.N., Mercer R.W., Nichols C.G. J. Biol. Chem. 269:20468-20474(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hippocampus.
[4]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Brain.
[7]	"Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1." Yan X., Zhou H., Zhang J., Shi C., Xie X., Wu Y., Tian C., Shen Y., Long J. J. Mol. Biol. 392:967-976(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 436-445 IN COMPLEX WITH TAX1BP3, INTERACTION WITH TAX1BP3.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U07364 mRNA. Translation: AAA19962.1.
U24056 mRNA. Translation: AAA66076.1.
S72503 mRNA. Translation: AAC60632.1.
CR456507 mRNA. Translation: CAG30393.1.
Z97056 Genomic DNA. Translation: CAB09790.1.
BC113506 mRNA. Translation: AAI13507.1.
BC113508 mRNA. Translation: AAI13509.1.

IPI

IPI00007626.

PIR

A54852.
I38521.

RefSeq

NP_004972.1. NM_004981.1.
NP_690607.1. NM_152868.2.

UniGene

Hs.32505.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GJ9	X-ray	2.80	C/D	436-445	[»]

ProteinModelPortal

P48050.

ModBase

Search...

Protein-protein interaction databases

IntAct

P48050. 3 interactions.

MINT

MINT-159020.

STRING

9606.ENSP00000306497.

PTM databases

PhosphoSite

P48050.

Polymorphism databases

DMDM

1352483.

Proteomic databases

PaxDb

P48050.

PRIDE

P48050.

Protocols and materials databases

DNASU

3761.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000303592; ENSP00000306497; ENSG00000168135.

GeneID

3761.

KEGG

hsa:3761.

UCSC

uc003avs.1. human.

Organism-specific databases

CTD

3761.

GeneCards

GC22M038822.

H-InvDB

HIX0175381.

HGNC

HGNC:6265. KCNJ4.

HPA

HPA003270.

MIM

600504. gene.

neXtProt

NX_P48050.

PharmGKB

PA30048.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG72812.

HOGENOM

HOG000237325.

HOVERGEN

HBG006178.

InParanoid

P48050.

KO

K04998.

OMA

PYMTEEG.

OrthoDB

EOG40GCR0.

PhylomeDB

P48050.

Enzyme and pathway databases

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

P48050.

Bgee

P48050.

CleanEx

HS_KCNJ4.

Genevestigator

P48050.

GermOnline

ENSG00000168135. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.1400. 1 hit.

InterPro

IPR014756. Ig_E-set.
IPR016449. K_chnl_inward-rec_Kir.
IPR003273. K_chnl_inward-rec_Kir2.3.
IPR013518. K_chnl_inward-rec_Kir_cyto.
[Graphical view]

PANTHER

PTHR11767. PTHR11767. 1 hit.
PTHR11767:SF13. PTHR11767:SF13. 1 hit.

Pfam

PF01007. IRK. 1 hit.
[Graphical view]

PIRSF

PIRSF005465. GIRK_kir. 1 hit.

PRINTS

PR01326. KIR23CHANNEL.
PR01320. KIRCHANNEL.

SUPFAM

SSF81296. Ig_E-set. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P48050.

GenomeRNAi

3761.

NextBio

14745.

SOURCE

Search...

Entry information

Entry name

IRK4_HUMAN

Accession

Primary (citable) accession number: P48050
Secondary accession number(s): Q14D44

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 126 of the entry and version 1 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.