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 24-JAN-2024, entry version 205. 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 CC (TC 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; 13. 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; 9606-ENSP00000306497; -. DR PeptideAtlas; P48050; -. DR ProteomicsDB; 55841; -. DR Antibodypedia; 327; 335 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 AGR; HGNC:6265; -. 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; YMTAEGE; -. DR OrthoDB; 4126787at2759; -. 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; 49 hits in 1147 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 88 other cell types or tissues. DR ExpressionAtlas; P48050; baseline and differential. 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 monoatomic ion transmembrane transport; IBA:GO_Central. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 2.60.40.1400; G protein-activated inward rectifier potassium channel 1; 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; INWARD RECTIFIER POTASSIUM CHANNEL; 1. DR PANTHER; PTHR11767:SF53; INWARD RECTIFIER POTASSIUM CHANNEL 4; 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; E set domains; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; P48050; HS. 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 //