KCNJ4_HUMAN
ID KCNJ4_HUMAN Reviewed; 445 AA.
AC P48050; Q14D44;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Inward rectifier potassium channel 4;
DE AltName: Full=HIRK2;
DE AltName: Full=HRK1;
DE AltName: Full=Hippocampal inward rectifier;
DE Short=HIR;
DE AltName: Full=Inward rectifier K(+) channel Kir2.3;
DE Short=IRK-3;
DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 4;
GN Name=KCNJ4; Synonyms=IRK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hippocampus;
RX PubMed=8016146; DOI=10.1073/pnas.91.13.6240;
RA Perier F., Radeke C.M., Vandenberg C.A.;
RT "Primary structure and characterization of a small-conductance inwardly
RT rectifying potassium channel from human hippocampus.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6240-6244(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=8034048; DOI=10.1016/0014-5793(94)00612-1;
RA Tang W., Yang X.-C.;
RT "Cloning a novel human brain inward rectifier potassium channel and its
RT functional expression in Xenopus oocytes.";
RL FEBS Lett. 348:239-243(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hippocampus;
RX PubMed=8051145; DOI=10.1016/s0021-9258(17)32016-1;
RA Makhina E.N., Kelly A.J., Lopatin A.N., Mercer R.W., Nichols C.G.;
RT "Cloning and expression of a novel human brain inward rectifier potassium
RT channel.";
RL J. Biol. Chem. 269:20468-20474(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP MUTAGENESIS OF HIS-117.
RX PubMed=7576658; DOI=10.1016/0896-6273(95)90103-5;
RA Coulter K.L., Perier F., Radeke C.M., Vandenberg C.A.;
RT "Identification and molecular localization of a pH-sensing domain for the
RT inward rectifier potassium channel HIR.";
RL Neuron 15:1157-1168(1995).
RN [8]
RP INTERACTION WITH KCNJ2 AND KCNJ12.
RX PubMed=12032359; DOI=10.1073/pnas.102609499;
RA Preisig-Muller R., Schlichthorl G., Goerge T., Heinen S., Bruggemann A.,
RA Rajan S., Derst C., Veh R.W., Daut J.;
RT "Heteromerization of Kir2.x potassium channels contributes to the phenotype
RT of Andersen's syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7774-7779(2002).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 436-445 IN COMPLEX WITH TAX1BP3,
RP AND INTERACTION WITH TAX1BP3.
RX PubMed=19635485; DOI=10.1016/j.jmb.2009.07.060;
RA Yan X., Zhou H., Zhang J., Shi C., Xie X., Wu Y., Tian C., Shen Y.,
RA Long J.;
RT "Molecular mechanism of inward rectifier potassium channel 2.3 regulation
RT by tax-interacting protein-1.";
RL J. Mol. Biol. 392:967-976(2009).
CC -!- FUNCTION: Inward rectifier potassium channels are characterized by a
CC greater tendency to allow potassium to flow into the cell rather than
CC out of it. Their voltage dependence is regulated by the concentration
CC of extracellular potassium; as external potassium is raised, the
CC voltage range of the channel opening shifts to more positive voltages.
CC The inward rectification is mainly due to the blockage of outward
CC current by internal magnesium. Can be blocked by extracellular barium
CC and cesium (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homomultimeric and heteromultimeric association with KCNJ2 and
CC KCNJ12. Association, via its PDZ-recognition domain, with LIN7A, LIN7B,
CC LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and
CC trafficking (By similarity). Interacts with TAX1BP3. TAX1BP3 competes
CC with LIN7 family members for KCNJ4 binding. {ECO:0000250,
CC ECO:0000269|PubMed:12032359, ECO:0000269|PubMed:19635485}.
CC -!- INTERACTION:
CC P48050; Q14160: SCRIB; NbExp=2; IntAct=EBI-706117, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Postsynaptic cell membrane {ECO:0000250}; Multi-pass membrane protein
CC {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}. Note=TAX1BP3
CC binding promotes dissociation of KCNJ4 from LIN7 famaly members and
CC KCNJ4 internalization. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Heart, skeletal muscle, and several different brain
CC regions including the hippocampus.
CC -!- DOMAIN: The Val/Gly/Ala/Pro stretch may have a functional role in the
CC conductance or permeation properties.
CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC
CC 1.A.2.1) family. KCNJ4 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U07364; AAA19962.1; -; mRNA.
DR EMBL; U24056; AAA66076.1; -; mRNA.
DR EMBL; S72503; AAC60632.1; -; mRNA.
DR EMBL; CR456507; CAG30393.1; -; mRNA.
DR EMBL; Z97056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113506; AAI13507.1; -; mRNA.
DR EMBL; BC113508; AAI13509.1; -; mRNA.
DR CCDS; CCDS13971.1; -.
DR PIR; A54852; A54852.
DR PIR; I38521; I38521.
DR RefSeq; NP_004972.1; NM_004981.1.
DR RefSeq; NP_690607.1; NM_152868.2.
DR PDB; 3GJ9; X-ray; 2.80 A; C/D=436-445.
DR PDBsum; 3GJ9; -.
DR AlphaFoldDB; P48050; -.
DR SMR; P48050; -.
DR BioGRID; 109963; 12.
DR ELM; P48050; -.
DR IntAct; P48050; 6.
DR MINT; P48050; -.
DR STRING; 9606.ENSP00000306497; -.
DR BindingDB; P48050; -.
DR ChEMBL; CHEMBL2146347; -.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00243; Ranolazine.
DR DrugCentral; P48050; -.
DR GuidetoPHARMACOLOGY; 432; -.
DR TCDB; 1.A.2.1.18; the inward rectifier k(+) channel (irk-c) family.
DR iPTMnet; P48050; -.
DR PhosphoSitePlus; P48050; -.
DR BioMuta; KCNJ4; -.
DR DMDM; 1352483; -.
DR MassIVE; P48050; -.
DR PaxDb; P48050; -.
DR PeptideAtlas; P48050; -.
DR PRIDE; P48050; -.
DR ProteomicsDB; 55841; -.
DR Antibodypedia; 327; 313 antibodies from 29 providers.
DR DNASU; 3761; -.
DR Ensembl; ENST00000303592.3; ENSP00000306497.3; ENSG00000168135.4.
DR GeneID; 3761; -.
DR KEGG; hsa:3761; -.
DR MANE-Select; ENST00000303592.3; ENSP00000306497.3; NM_152868.3; NP_690607.1.
DR UCSC; uc003avt.3; human.
DR CTD; 3761; -.
DR DisGeNET; 3761; -.
DR GeneCards; KCNJ4; -.
DR HGNC; HGNC:6265; KCNJ4.
DR HPA; ENSG00000168135; Group enriched (brain, heart muscle).
DR MIM; 600504; gene.
DR neXtProt; NX_P48050; -.
DR OpenTargets; ENSG00000168135; -.
DR PharmGKB; PA30048; -.
DR VEuPathDB; HostDB:ENSG00000168135; -.
DR eggNOG; KOG3827; Eukaryota.
DR GeneTree; ENSGT01030000234586; -.
DR HOGENOM; CLU_022738_11_1_1; -.
DR InParanoid; P48050; -.
DR OMA; VKPCIMH; -.
DR OrthoDB; 956263at2759; -.
DR PhylomeDB; P48050; -.
DR TreeFam; TF313676; -.
DR PathwayCommons; P48050; -.
DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-HSA-1296053; Classical Kir channels.
DR Reactome; R-HSA-5576886; Phase 4 - resting membrane potential.
DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR SignaLink; P48050; -.
DR SIGNOR; P48050; -.
DR BioGRID-ORCS; 3761; 45 hits in 1068 CRISPR screens.
DR ChiTaRS; KCNJ4; human.
DR EvolutionaryTrace; P48050; -.
DR GeneWiki; KCNJ4; -.
DR GenomeRNAi; 3761; -.
DR Pharos; P48050; Tchem.
DR PRO; PR:P48050; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P48050; protein.
DR Bgee; ENSG00000168135; Expressed in endothelial cell and 87 other tissues.
DR ExpressionAtlas; P48050; baseline and differential.
DR Genevisible; P48050; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IBA:GO_Central.
DR Gene3D; 2.60.40.1400; -; 1.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR041647; IRK_C.
DR InterPro; IPR016449; K_chnl_inward-rec_Kir.
DR InterPro; IPR003273; K_chnl_inward-rec_Kir2.3.
DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR InterPro; IPR040445; Kir_TM.
DR PANTHER; PTHR11767; PTHR11767; 1.
DR PANTHER; PTHR11767:SF53; PTHR11767:SF53; 1.
DR Pfam; PF01007; IRK; 1.
DR Pfam; PF17655; IRK_C; 1.
DR PIRSF; PIRSF005465; GIRK_kir; 1.
DR PRINTS; PR01326; KIR23CHANNEL.
DR PRINTS; PR01320; KIRCHANNEL.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; Ion channel;
KW Ion transport; Membrane; Postsynaptic cell membrane; Potassium;
KW Potassium transport; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..445
FT /note="Inward rectifier potassium channel 4"
FT /id="PRO_0000154930"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 56..80
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 81..120
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT INTRAMEM 121..132
FT /note="Helical; Pore-forming; Name=H5"
FT /evidence="ECO:0000250"
FT INTRAMEM 133..139
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TOPO_DOM 140..148
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 149..170
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 171..445
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 91..111
FT /note="Val/Gly/Ala/Pro stretch"
FT MOTIF 134..139
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT MOTIF 443..445
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT SITE 164
FT /note="Role in the control of polyamine-mediated channel
FT gating and in the blocking by intracellular magnesium"
FT /evidence="ECO:0000250"
FT MUTAGEN 117
FT /note="H->E: Loss of pH-sensitivity."
FT /evidence="ECO:0000269|PubMed:7576658"
FT CONFLICT 16..17
FT /note="KR -> NG (in Ref. 3; AAC60632)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="A -> D (in Ref. 2; AAA66076)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="A -> G (in Ref. 3; AAC60632)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="A -> S (in Ref. 2; AAA66076)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="A -> S (in Ref. 2; AAA66076)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="A -> R (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 398
FT /note="A -> G (in Ref. 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 445 AA; 49500 MW; 893F03365273E8BE CRC64;
MHGHSRNGQA HVPRRKRRNR FVKKNGQCNV YFANLSNKSQ RYMADIFTTC VDTRWRYMLM
IFSAAFLVSW LFFGLLFWCI AFFHGDLEAS PGVPAAGGPA AGGGGAAPVA PKPCIMHVNG
FLGAFLFSVE TQTTIGYGFR CVTEECPLAV IAVVVQSIVG CVIDSFMIGT IMAKMARPKK
RAQTLLFSHH AVISVRDGKL CLMWRVGNLR KSHIVEAHVR AQLIKPYMTQ EGEYLPLDQR
DLNVGYDIGL DRIFLVSPII IVHEIDEDSP LYGMGKEELE SEDFEIVVIL EGMVEATAMT
TQARSSYLAS EILWGHRFEP VVFEEKSHYK VDYSRFHKTY EVAGTPCCSA RELQESKITV
LPAPPPPPSA FCYENELALM SQEEEEMEEE AAAAAAVAAG LGLEAGSKEE AGIIRMLEFG
SHLDLERMQA SLPLDNISYR RESAI
