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P48050 (IRK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length445 AA.
Sequence statusComplete.
Protein existenceEvidence 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]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 445445Inward rectifier potassium channel 4
PRO_0000154930

Regions

Topological domain1 – 5555Cytoplasmic By similarity
Transmembrane56 – 8025Helical; Name=M1; By similarity
Topological domain81 – 12040Extracellular By similarity
Intramembrane121 – 13212Helical; Pore-forming; Name=H5; By similarity
Intramembrane133 – 1397Pore-forming; By similarity
Topological domain140 – 1489Extracellular By similarity
Transmembrane149 – 17022Helical; Name=M2; By similarity
Topological domain171 – 445275Cytoplasmic By similarity
Region91 – 11121Val/Gly/Ala/Pro stretch
Motif134 – 1396Selectivity filter By similarity
Motif443 – 4453PDZ-binding Potential
Compositional bias102 – 1054Poly-Gly
Compositional bias362 – 3687Poly-Pro
Compositional bias383 – 3908Poly-Glu
Compositional bias391 – 3999Poly-Ala

Sites

Site1641Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium By similarity

Experimental info

Sequence conflict16 – 172KR → NG in AAC60632. Ref.3
Sequence conflict1071A → D in AAA66076. Ref.2
Sequence conflict3501A → G in AAC60632. Ref.3
Sequence conflict3921A → S in AAA66076. Ref.2
Sequence conflict3951A → S in AAA66076. Ref.2
Sequence conflict3961A → R Ref.3
Sequence conflict3981A → G Ref.3

Sequences

Sequence LengthMass (Da)Tools
P48050 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: 893F03365273E8BE

FASTA44549,500
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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.
PIRA54852.
I38521.
RefSeqNP_004972.1. NM_004981.1.
NP_690607.1. NM_152868.2.
UniGeneHs.32505.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3GJ9X-ray2.80C/D436-445[»]
ProteinModelPortalP48050.
SMRP48050. Positions 18-357.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109963. 11 interactions.
IntActP48050. 3 interactions.
MINTMINT-159020.
STRING9606.ENSP00000306497.

Chemistry

ChEMBLCHEMBL2146347.
GuidetoPHARMACOLOGY432.

PTM databases

PhosphoSiteP48050.

Polymorphism databases

DMDM1352483.

Proteomic databases

PaxDbP48050.
PRIDEP48050.

Protocols and materials databases

DNASU3761.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303592; ENSP00000306497; ENSG00000168135.
GeneID3761.
KEGGhsa:3761.
UCSCuc003avs.1. human.

Organism-specific databases

CTD3761.
GeneCardsGC22M038822.
H-InvDBHIX0175381.
HGNCHGNC:6265. KCNJ4.
HPAHPA003270.
MIM600504. gene.
neXtProtNX_P48050.
PharmGKBPA30048.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG72812.
HOGENOMHOG000237325.
HOVERGENHBG006178.
InParanoidP48050.
KOK04998.
OMAKPYMTEE.
OrthoDBEOG7XPZ5K.
PhylomeDBP48050.
TreeFamTF313676.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressP48050.
BgeeP48050.
CleanExHS_KCNJ4.
GenevestigatorP48050.

Family and domain databases

Gene3D2.60.40.1400. 1 hit.
InterProIPR014756. 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]
PANTHERPTHR11767. PTHR11767. 1 hit.
PTHR11767:SF13. PTHR11767:SF13. 1 hit.
PfamPF01007. IRK. 1 hit.
[Graphical view]
PIRSFPIRSF005465. GIRK_kir. 1 hit.
PRINTSPR01326. KIR23CHANNEL.
PR01320. KIRCHANNEL.
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP48050.
GeneWikiKCNJ4.
GenomeRNAi3761.
NextBio14745.
PROP48050.
SOURCESearch...

Entry information

Entry nameIRK4_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM