ID KCNJ5_HUMAN Reviewed; 419 AA. AC P48544; B2R744; Q6DK13; Q6DK14; Q92807; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 24-JAN-2024, entry version 210. DE RecName: Full=G protein-activated inward rectifier potassium channel 4; DE Short=GIRK-4; DE AltName: Full=Cardiac inward rectifier; DE Short=CIR; DE AltName: Full=Heart KATP channel; DE AltName: Full=Inward rectifier K(+) channel Kir3.4; DE Short=IRK-4; DE AltName: Full=KATP-1; DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 5; GN Name=KCNJ5; Synonyms=GIRK4; 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], AND VARIANT GLU-282. RC TISSUE=Pancreas; RA Chan K.W., Langan M.N., Sui J., Kozak A., Pabon A., Ladias J.A.A., RA Logothetis D.E.; RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], RETRACTED PAPER, AND VARIANT GLU-282. RX PubMed=8047164; DOI=10.1038/370456a0; RA Ashford M.L.J., Bond C.T., Blair T.A., Adelman J.P.; RT "Cloning and functional expression of a rat heart KATP channel."; RL Nature 370:456-459(1994). RN [3] RP ERRATUM OF PUBMED:8047164, AND RETRACTION NOTICE OF PUBMED:8047164. RX PubMed=8524415; DOI=10.1038/378792a0; RA Ashford M.L.J., Bond C.T., Blair T.A., Adelman J.P.; RL Nature 378:792-792(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-282. RX PubMed=8558261; DOI=10.1523/jneurosci.16-03-00930.1996; RA Spauschus A., Lentes K.U., Wischmeyer E., Dissmann E., Karschin C., RA Karschin A.; RT "A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human RT hippocampus associates with other GIRK channels."; RL J. Neurosci. 16:930-938(1996). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-282. RC TISSUE=Pituitary; RX PubMed=10659995; DOI=10.1016/s0898-6568(99)00059-5; RA Schoots O., Wilson J.M., Ethier N., Bigras E., Hebert T.E., Van Tol H.H.M.; RT "Co-expression of human Kir3 subunits can yield channels with different RT functional properties."; RL Cell. Signal. 11:871-883(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLU-282. RC TISSUE=Heart; RX PubMed=8834003; RA Iizuka M., Kubo Y., Tsunenari I., Pan C.X., Akiba I., Kono T.; RT "Functional characterization and localization of a cardiac-type inwardly RT rectifying K+ channel."; RL Recept. Channels 3:299-315(1995). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-282. RC TISSUE=Lung; 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 [10] RP TISSUE SPECIFICITY, VARIANTS HALD3 ARG-151 AND ALA-158, VARIANTS HIS-39; RP ARG-168 AND ILE-210, CHARACTERIZATION OF VARIANT HALD3 ARG-151, RP CHARACTERIZATION OF VARIANT ARG-168, AND INVOLVEMENT IN ALDOSTERONISM RP ASSOCIATED WITH ADRENAL ADENOMAS. RX PubMed=21311022; DOI=10.1126/science.1198785; RA Choi M., Scholl U.I., Yue P., Bjorklund P., Zhao B., Nelson-Williams C., RA Ji W., Cho Y., Patel A., Men C.J., Lolis E., Wisgerhof M.V., Geller D.S., RA Mane S., Hellman P., Westin G., Akerstrom G., Wang W., Carling T., RA Lifton R.P.; RT "K+ channel mutations in adrenal aldosterone-producing adenomas and RT hereditary hypertension."; RL Science 331:768-772(2011). RN [11] RP VARIANT LQT13 ARG-387. RX PubMed=20560207; DOI=10.1016/j.ajhg.2010.04.017; RA Yang Y., Yang Y., Liang B., Liu J., Li J., Grunnet M., Olesen S.P., RA Rasmussen H.B., Ellinor P.T., Gao L., Lin X., Li L., Wang L., Xiao J., RA Liu Y., Liu Y., Zhang S., Liang D., Peng L., Jespersen T., Chen Y.H.; RT "Identification of a Kir3.4 mutation in congenital long QT syndrome."; RL Am. J. Hum. Genet. 86:872-880(2010). RN [12] RP CHARACTERIZATION OF VARIANT HALD3 ALA-158, FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=22315453; DOI=10.1210/en.2011-1733; RA Oki K., Plonczynski M.W., Luis Lam M., Gomez-Sanchez E.P., RA Gomez-Sanchez C.E.; RT "Potassium channel mutant KCNJ5 T158A expression in HAC-15 cells increases RT aldosterone synthesis."; RL Endocrinology 153:1774-1782(2012). RN [13] RP VARIANT ARG-168, VARIANTS HALD3 ARG-151; GLU-151 AND ALA-158, RP CHARACTERIZATION OF VARIANT HALD3 GLU-151, AND INVOLVEMENT IN ALDOSTERONISM RP ASSOCIATED WITH ADRENAL ADENOMAS. RX PubMed=22203740; DOI=10.1161/hypertensionaha.111.183996; RA Mulatero P., Tauber P., Zennaro M.C., Monticone S., Lang K., Beuschlein F., RA Fischer E., Tizzani D., Pallauf A., Viola A., Amar L., Williams T.A., RA Strom T.M., Graf E., Bandulik S., Penton D., Plouin P.F., Warth R., RA Allolio B., Jeunemaitre X., Veglio F., Reincke M.; RT "KCNJ5 mutations in European families with nonglucocorticoid remediable RT familial hyperaldosteronism."; RL Hypertension 59:235-240(2012). RN [14] RP VARIANT HALD3 ARG-151, VARIANT ARG-168, AND INVOLVEMENT IN ALDOSTERONISM RP ASSOCIATED WITH ADRENAL ADENOMAS. RX PubMed=22275527; DOI=10.1161/hypertensionaha.111.186478; RA Boulkroun S., Beuschlein F., Rossi G.P., Golib-Dzib J.F., Fischer E., RA Amar L., Mulatero P., Samson-Couterie B., Hahner S., Quinkler M., Fallo F., RA Letizia C., Allolio B., Ceolotto G., Cicala M.V., Lang K., Lefebvre H., RA Lenzini L., Maniero C., Monticone S., Perrocheau M., Pilon C., Plouin P.F., RA Rayes N., Seccia T.M., Veglio F., Williams T.A., Zinnamosca L., Mantero F., RA Benecke A., Jeunemaitre X., Reincke M., Zennaro M.C.; RT "Prevalence, clinical, and molecular correlates of KCNJ5 mutations in RT primary aldosteronism."; RL Hypertension 59:592-598(2012). RN [15] RP VARIANT HALD3 SER-157, CHARACTERIZATION OF VARIANTS HALD3 ARG-151; SER-157 RP AND ALA-158, CHARACTERIZATION OF VARIANT ARG-168, AND FUNCTION. RX PubMed=22628607; DOI=10.1210/jc.2012-1334; RA Charmandari E., Sertedaki A., Kino T., Merakou C., Hoffman D.A., RA Hatch M.M., Hurt D.E., Lin L., Xekouki P., Stratakis C.A., Chrousos G.P.; RT "A novel point mutation in the KCNJ5 gene causing primary RT hyperaldosteronism and early-onset autosomal dominant hypertension."; RL J. Clin. Endocrinol. Metab. 97:E1532-E1539(2012). RN [16] RP VARIANT HALD3 ARG-151, VARIANTS GLN-145 AND ARG-168, AND INVOLVEMENT IN RP ALDOSTERONISM ASSOCIATED WITH ADRENAL ADENOMAS. RX PubMed=22848660; DOI=10.1371/journal.pone.0041926; RA Akerstrom T., Crona J., Delgado Verdugo A., Starker L.F., Cupisti K., RA Willenberg H.S., Knoefel W.T., Saeger W., Feller A., Ip J., Soon P., RA Anlauf M., Alesina P.F., Schmid K.W., Decaussin M., Levillain P., RA Wangberg B., Peix J.L., Robinson B., Zedenius J., Backdahl M., Caramuta S., RA Iwen K.A., Botling J., Stalberg P., Kraimps J.L., Dralle H., Hellman P., RA Sidhu S., Westin G., Lehnert H., Walz M.K., Akerstrom G., Carling T., RA Choi M., Lifton R.P., Bjorklund P.; RT "Comprehensive re-sequencing of adrenal aldosterone producing lesions RT reveal three somatic mutations near the KCNJ5 potassium channel selectivity RT filter."; RL PLoS ONE 7:E41926-E41926(2012). RN [17] RP VARIANTS HALD3 ARG-151 AND GLU-151. RX PubMed=22308486; DOI=10.1073/pnas.1121407109; RA Scholl U.I., Nelson-Williams C., Yue P., Grekin R., Wyatt R.J., RA Dillon M.J., Couch R., Hammer L.K., Harley F.L., Farhi A., Wang W.H., RA Lifton R.P.; RT "Hypertension with or without adrenal hyperplasia due to different RT inherited mutations in the potassium channel KCNJ5."; RL Proc. Natl. Acad. Sci. U.S.A. 109:2533-2538(2012). RN [18] RP VARIANT HALD3 CYS-152, CHARACTERIZATION OF VARIANTS HALD3 GLU-151 AND RP CYS-152, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24037882; DOI=10.1210/jc.2013-2428; RA Monticone S., Hattangady N.G., Penton D., Isales C.M., Edwards M.A., RA Williams T.A., Sterner C., Warth R., Mulatero P., Rainey W.E.; RT "a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism RT type III."; RL J. Clin. Endocrinol. Metab. 98:E1861-E1865(2013). RN [19] RP VARIANTS MET-259 AND ASN-348, CHARACTERIZATION OF VARIANTS MET-259 AND RP ASN-348, INVOLVEMENT IN HYPERTENTION WITH ACTH-DEPENDENT ALDOSTERONE RP HYPERSECRETION, AND FUNCTION. RX PubMed=27293068; DOI=10.1111/cen.13132; RA Sertedaki A., Markou A., Vlachakis D., Kossida S., Campanac E., RA Hoffman D.A., Sierra M.L., Xekouki P., Stratakis C.A., Kaltsas G., RA Piaditis G.P., Chrousos G.P., Charmandari E.; RT "Functional characterization of two novel germline mutations of the KCNJ5 RT gene in hypertensive patients without primary aldosteronism but with ACTH- RT dependent aldosterone hypersecretion."; RL Clin. Endocrinol. (Oxf.) 85:845-851(2016). RN [20] RP CHARACTERIZATION OF VARIANT HALD3 ALA-158, AND FUNCTION. RX PubMed=27099398; DOI=10.1530/jme-15-0324; RA Hattangady N.G., Karashima S., Yuan L., Ponce-Balbuena D., Jalife J., RA Gomez-Sanchez C.E., Auchus R.J., Rainey W.E., Else T.; RT "Mutated KCNJ5 activates the acute and chronic regulatory steps in RT aldosterone production."; RL J. Mol. Endocrinol. 57:1-11(2016). CC -!- FUNCTION: This potassium channel is controlled by G proteins. Inward CC rectifier potassium channels are characterized by a greater tendency to CC allow potassium to flow into the cell rather than out of it. Their CC voltage dependence is regulated by the concentration of extracellular CC potassium; as external potassium is raised, the voltage range of the CC channel opening shifts to more positive voltages. The inward CC rectification is mainly due to the blockage of outward current by CC internal magnesium. Can be blocked by external barium. CC {ECO:0000269|PubMed:22315453, ECO:0000269|PubMed:22628607, CC ECO:0000269|PubMed:24037882, ECO:0000269|PubMed:27099398, CC ECO:0000269|PubMed:27293068}. CC -!- SUBUNIT: May associate with GIRK1 and GIRK2 to form a G-protein- CC activated heteromultimer pore-forming unit. The resulting inward CC current is much larger. {ECO:0000250|UniProtKB:P48548}. CC -!- INTERACTION: CC P48544; Q99712: KCNJ15; NbExp=3; IntAct=EBI-9975563, EBI-7082607; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:22315453, CC ECO:0000269|PubMed:24037882}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Islets, exocrine pancreas and heart. Expressed in CC the adrenal cortex, particularly the zona glomerulosa. CC {ECO:0000269|PubMed:21311022}. CC -!- DISEASE: Long QT syndrome 13 (LQT13) [MIM:613485]: A heart disorder CC characterized by a prolonged QT interval on the ECG and polymorphic CC ventricular arrhythmias. They cause syncope and sudden death in CC response to exercise or emotional stress, and can present with a CC sentinel event of sudden cardiac death in infancy. CC {ECO:0000269|PubMed:20560207}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hyperaldosteronism, familial, 3 (HALD3) [MIM:613677]: A form CC of hyperaldosteronism characterized by hypertension secondary to CC massive adrenal mineralocorticoid production. HALD3 patients present CC with childhood hypertension, elevated aldosteronism levels, and high CC levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. CC Hypertension and aldosteronism are not reversed by administration of CC exogenous glucocorticoids and patients require adrenalectomy to control CC hypertension. {ECO:0000269|PubMed:21311022, CC ECO:0000269|PubMed:22203740, ECO:0000269|PubMed:22275527, CC ECO:0000269|PubMed:22308486, ECO:0000269|PubMed:22315453, CC ECO:0000269|PubMed:22628607, ECO:0000269|PubMed:22848660, CC ECO:0000269|PubMed:24037882, ECO:0000269|PubMed:27099398}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=Somatic mutations in KCNJ5 have been found in CC aldosterone-producing adrenal adenomas and can be responsible for CC aldosteronism associated with cell autonomous proliferation. APAs are CC typically solitary, well circumscribed tumors diagnosed between ages 30 CC and 70. They come to medical attention due to new or worsening CC hypertension, often with hypokalemia. The precise role of KCNJ5 CC mutations in APA is under debate. They produce increased sodium CC conductance and cell depolarization, which in adrenal glomerulosa cells CC produces calcium entry, the signal for aldosterone production and cell CC proliferation. However, they may not be causative of APA development CC but may be a consequence of tumorigenesis, playing only a contributory CC role toward aldosterone overproduction and tumor growth CC (PubMed:22275527). Somatic mutations in KCNJ5 have not been found in CC non-aldosterone secreting adrenal adenomas suggesting that they are CC specifically associated with APA (PubMed:22275527, PubMed:22848660). CC {ECO:0000269|PubMed:21311022, ECO:0000269|PubMed:22203740, CC ECO:0000269|PubMed:22275527, ECO:0000269|PubMed:22848660}. CC -!- DISEASE: Note=Mutations in KCNJ5 are involved in the pathogenesis of CC hypertension without primary aldosteronism but with increased CC aldosterone response to ACTH stimulation. CC {ECO:0000269|PubMed:27293068}. CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel CC (TC 1.A.2.1) family. KCNJ5 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; U39195; AAB53093.1; -; mRNA. DR EMBL; X83582; CAA58565.1; -; mRNA. DR EMBL; L47208; AAB07269.1; -; mRNA. DR EMBL; U52154; AAB07045.1; -; mRNA. DR EMBL; D50134; BAA08814.1; -; mRNA. DR EMBL; AP000920; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK312837; BAG35691.1; -; mRNA. DR EMBL; BC069571; AAH69571.1; -; mRNA. DR EMBL; BC074838; AAH74838.2; -; mRNA. DR EMBL; BC069386; AAH69386.1; -; mRNA. DR EMBL; BC069482; AAH69482.1; -; mRNA. DR EMBL; BC069499; AAH69499.1; -; mRNA. DR EMBL; BC074839; AAH74839.2; -; mRNA. DR CCDS; CCDS8479.1; -. DR PIR; G02232; G02232. DR RefSeq; NP_000881.3; NM_000890.3. DR RefSeq; XP_011541111.1; XM_011542809.2. DR RefSeq; XP_011541112.1; XM_011542810.2. DR AlphaFoldDB; P48544; -. DR EMDB; EMD-22201; -. DR EMDB; EMD-22202; -. DR SMR; P48544; -. DR BioGRID; 109964; 20. DR ComplexPortal; CPX-3278; I(KACh) inward rectifier potassium channel complex. DR IntAct; P48544; 15. DR MINT; P48544; -. DR STRING; 9606.ENSP00000433295; -. DR BindingDB; P48544; -. DR ChEMBL; CHEMBL1914278; -. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB08954; Ifenprodil. DR DrugCentral; P48544; -. DR GuidetoPHARMACOLOGY; 437; -. DR TCDB; 1.A.2.1.3; the inward rectifier k(+) channel (irk-c) family. DR iPTMnet; P48544; -. DR PhosphoSitePlus; P48544; -. DR BioMuta; KCNJ5; -. DR DMDM; 296434543; -. DR jPOST; P48544; -. DR MassIVE; P48544; -. DR PaxDb; 9606-ENSP00000433295; -. DR PeptideAtlas; P48544; -. DR ProteomicsDB; 55900; -. DR Antibodypedia; 2997; 238 antibodies from 29 providers. DR DNASU; 3762; -. DR Ensembl; ENST00000338350.4; ENSP00000339960.4; ENSG00000120457.12. DR Ensembl; ENST00000529694.6; ENSP00000433295.1; ENSG00000120457.12. DR Ensembl; ENST00000533599.1; ENSP00000434266.1; ENSG00000120457.12. DR GeneID; 3762; -. DR KEGG; hsa:3762; -. DR MANE-Select; ENST00000529694.6; ENSP00000433295.1; NM_000890.5; NP_000881.3. DR UCSC; uc001qet.4; human. DR AGR; HGNC:6266; -. DR CTD; 3762; -. DR DisGeNET; 3762; -. DR GeneCards; KCNJ5; -. DR GeneReviews; KCNJ5; -. DR HGNC; HGNC:6266; KCNJ5. DR HPA; ENSG00000120457; Tissue enhanced (adrenal gland, pancreas). DR MalaCards; KCNJ5; -. DR MIM; 600734; gene. DR MIM; 613485; phenotype. DR MIM; 613677; phenotype. DR neXtProt; NX_P48544; -. DR OpenTargets; ENSG00000120457; -. DR Orphanet; 37553; Andersen-Tawil syndrome. DR Orphanet; 334; Familial atrial fibrillation. DR Orphanet; 251274; Familial hyperaldosteronism type III. DR Orphanet; 85142; NON RARE IN EUROPE: Aldosterone-producing adenoma. DR Orphanet; 101016; Romano-Ward syndrome. DR PharmGKB; PA216; -. DR VEuPathDB; HostDB:ENSG00000120457; -. DR eggNOG; KOG3827; Eukaryota. DR GeneTree; ENSGT01080000257365; -. DR HOGENOM; CLU_022738_11_0_1; -. DR InParanoid; P48544; -. DR OMA; FMNQDME; -. DR OrthoDB; 4126787at2759; -. DR PhylomeDB; P48544; -. DR TreeFam; TF313676; -. DR PathwayCommons; P48544; -. DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels. DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits. DR SignaLink; P48544; -. DR SIGNOR; P48544; -. DR BioGRID-ORCS; 3762; 7 hits in 1151 CRISPR screens. DR ChiTaRS; KCNJ5; human. DR GeneWiki; KCNJ5; -. DR GenomeRNAi; 3762; -. DR Pharos; P48544; Tchem. DR PRO; PR:P48544; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P48544; Protein. DR Bgee; ENSG00000120457; Expressed in buccal mucosa cell and 142 other cell types or tissues. DR ExpressionAtlas; P48544; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL. DR GO; GO:0015467; F:G-protein activated inward rectifier potassium channel activity; TAS:UniProtKB. DR GO; GO:0086089; F:voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization; IMP:BHF-UCL. DR GO; GO:1902282; F:voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization; IC:BHF-UCL. DR GO; GO:0098914; P:membrane repolarization during atrial cardiac muscle cell action potential; IMP:BHF-UCL. DR GO; GO:1990573; P:potassium ion import across plasma membrane; IDA:BHF-UCL. DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc. DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL. DR GO; GO:0034765; P:regulation of monoatomic ion transmembrane transport; IBA:GO_Central. DR GO; GO:0099625; P:ventricular cardiac muscle cell membrane repolarization; IC:BHF-UCL. 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; IPR003277; K_chnl_inward-rec_Kir3.4. DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto. DR InterPro; IPR040445; Kir_TM. DR PANTHER; PTHR11767:SF52; G PROTEIN-ACTIVATED INWARD RECTIFIER POTASSIUM CHANNEL 4; 1. DR PANTHER; PTHR11767; INWARD RECTIFIER POTASSIUM CHANNEL; 1. DR Pfam; PF01007; IRK; 1. DR Pfam; PF17655; IRK_C; 1. DR PIRSF; PIRSF005465; GIRK_kir; 1. DR PRINTS; PR01330; KIR34CHANNEL. DR PRINTS; PR01320; KIRCHANNEL. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR Genevisible; P48544; HS. PE 1: Evidence at protein level; KW Disease variant; Ion channel; Ion transport; Long QT syndrome; Membrane; KW Phosphoprotein; Potassium; Potassium transport; Reference proteome; KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1..419 FT /note="G protein-activated inward rectifier potassium FT channel 4" FT /id="PRO_0000154934" FT TOPO_DOM 1..86 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT TRANSMEM 87..111 FT /note="Helical; Name=M1" FT /evidence="ECO:0000250" FT TOPO_DOM 112..135 FT /note="Extracellular" FT /evidence="ECO:0000250" FT INTRAMEM 136..147 FT /note="Helical; Pore-forming; Name=H5" FT /evidence="ECO:0000250" FT INTRAMEM 148..154 FT /note="Pore-forming" FT /evidence="ECO:0000250" FT TOPO_DOM 155..163 FT /note="Extracellular" FT /evidence="ECO:0000250" FT TRANSMEM 164..185 FT /note="Helical; Name=M2" FT /evidence="ECO:0000250" FT TOPO_DOM 186..419 FT /note="Cytoplasmic" FT /evidence="ECO:0000250" FT REGION 390..419 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 149..154 FT /note="Selectivity filter" FT /evidence="ECO:0000250" FT SITE 179 FT /note="Role in the control of polyamine-mediated channel FT gating and in the blocking by intracellular magnesium" FT /evidence="ECO:0000250" FT MOD_RES 5 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48542" FT VARIANT 39 FT /note="R -> H (in dbSNP:rs560269341)" FT /evidence="ECO:0000269|PubMed:21311022" FT /id="VAR_065929" FT VARIANT 145 FT /note="E -> Q (found in aldosterone-producing adrenal FT adenoma samples; somatic mutation)" FT /evidence="ECO:0000269|PubMed:22848660" FT /id="VAR_069182" FT VARIANT 151 FT /note="G -> E (in HALD3; results in a profound alteration FT of channel function with loss of channel selectivity and FT membrane depolarization; dbSNP:rs587777437)" FT /evidence="ECO:0000269|PubMed:22203740, FT ECO:0000269|PubMed:22308486, ECO:0000269|PubMed:24037882" FT /id="VAR_067090" FT VARIANT 151 FT /note="G -> R (in HALD3; detected as germline mutation in a FT kindred with severe primary aldosteronism and FT adrenocortical hyperplasia; also found as somatic mutation FT in aldosterone-producing adrenal adenoma samples; results FT in loss of channel selectivity and membrane depolarization; FT dbSNP:rs386352319)" FT /evidence="ECO:0000269|PubMed:21311022, FT ECO:0000269|PubMed:22203740, ECO:0000269|PubMed:22275527, FT ECO:0000269|PubMed:22308486, ECO:0000269|PubMed:22628607, FT ECO:0000269|PubMed:22848660" FT /id="VAR_065930" FT VARIANT 152 FT /note="Y -> C (in HALD3; results in alteration of channel FT function with reduced channel selectivity and membrane FT depolarization; increases expression of CYP11B2 and its FT transcriptional regulator NR4A2)" FT /evidence="ECO:0000269|PubMed:24037882" FT /id="VAR_077577" FT VARIANT 157 FT /note="I -> S (in HALD3; loss of channel selectivity; FT dbSNP:rs587777438)" FT /evidence="ECO:0000269|PubMed:22628607" FT /id="VAR_077578" FT VARIANT 158 FT /note="T -> A (in HALD3; also found in FT aldosterone-producing adrenal adenoma samples; results in FT loss of channel selectivity and membrane depolarization; FT increases expression of CYP11B2 and its transcriptional FT regulators NR4A2 and ATF2; increases aldosterone and hybrid FT steroids 18-oxocortisol and 18-hydroxycortisol synthesis; FT increases STAR expression and phosphorylation; FT dbSNP:rs387906778)" FT /evidence="ECO:0000269|PubMed:21311022, FT ECO:0000269|PubMed:22203740, ECO:0000269|PubMed:22315453, FT ECO:0000269|PubMed:22628607, ECO:0000269|PubMed:27099398" FT /id="VAR_065931" FT VARIANT 168 FT /note="L -> R (found in aldosterone-producing adrenal FT adenoma samples; somatic mutation; results in loss of FT channel selectivity and membrane depolarization; FT dbSNP:rs386352318)" FT /evidence="ECO:0000269|PubMed:21311022, FT ECO:0000269|PubMed:22203740, ECO:0000269|PubMed:22275527, FT ECO:0000269|PubMed:22628607, ECO:0000269|PubMed:22848660" FT /id="VAR_065932" FT VARIANT 210 FT /note="M -> I (in dbSNP:rs138295501)" FT /evidence="ECO:0000269|PubMed:21311022" FT /id="VAR_065933" FT VARIANT 259 FT /note="V -> M (found in patients with hypertension with FT ACTH-dependent aldosterone hypersecretion; uncertain FT significance; no effect on channel function; FT dbSNP:rs759363415)" FT /evidence="ECO:0000269|PubMed:27293068" FT /id="VAR_077579" FT VARIANT 282 FT /note="Q -> E (in dbSNP:rs7102584)" FT /evidence="ECO:0000269|PubMed:10659995, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8047164, FT ECO:0000269|PubMed:8558261, ECO:0000269|PubMed:8834003, FT ECO:0000269|Ref.1" FT /id="VAR_063107" FT VARIANT 348 FT /note="Y -> N (found in patients with hypertension with FT ACTH-dependent aldosterone hypersecretion; likely FT pathogenic; loss of channel selectivity)" FT /evidence="ECO:0000269|PubMed:27293068" FT /id="VAR_077580" FT VARIANT 387 FT /note="G -> R (in LQT13; dbSNP:rs199830292)" FT /evidence="ECO:0000269|PubMed:20560207" FT /id="VAR_063766" FT CONFLICT 35 FT /note="I -> T (in Ref. 5; AAB07045)" FT /evidence="ECO:0000305" FT CONFLICT 388 FT /note="G -> R (in Ref. 2; CAA58565)" FT /evidence="ECO:0000305" SQ SEQUENCE 419 AA; 47668 MW; 7C14A6B0B7EA0FD4 CRC64; MAGDSRNAMN QDMEIGVTPW DPKKIPKQAR DYVPIATDRT RLLAEGKKPR QRYMEKSGKC NVHHGNVQET YRYLSDLFTT LVDLKWRFNL LVFTMVYTVT WLFFGFIWWL IAYIRGDLDH VGDQEWIPCV ENLSGFVSAF LFSIETETTI GYGFRVITEK CPEGIILLLV QAILGSIVNA FMVGCMFVKI SQPKKRAETL MFSNNAVISM RDEKLCLMFR VGDLRNSHIV EASIRAKLIK SRQTKEGEFI PLNQTDINVG FDTGDDRLFL VSPLIISHEI NQKSPFWEMS QAQLHQEEFE VVVILEGMVE ATGMTCQARS SYMDTEVLWG HRFTPVLTLE KGFYEVDYNT FHDTYETNTP SCCAKELAEM KREGRLLQYL PSPPLLGGCA EAGLDAEAEQ NEEDEPKGLG GSREARGSV //