KCNJ5_HUMAN
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 03-AUG-2022, entry version 202.
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], 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 and 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 (TC
CC 1.A.2.1) family. KCNJ5 subfamily. {ECO:0000305}.
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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 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; P48544; -.
DR PeptideAtlas; P48544; -.
DR PRIDE; P48544; -.
DR ProteomicsDB; 55900; -.
DR Antibodypedia; 2997; 203 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 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; 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; ENSGT01040000240379; -.
DR HOGENOM; CLU_022738_11_0_1; -.
DR InParanoid; P48544; -.
DR OMA; FMNQDME; -.
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 1071 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 141 other tissues.
DR ExpressionAtlas; P48544; baseline and differential.
DR Genevisible; P48544; HS.
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 ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0099625; P:ventricular cardiac muscle cell membrane repolarization; IC:BHF-UCL.
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; IPR003277; K_chnl_inward-rec_Kir3.4.
DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR InterPro; IPR040445; Kir_TM.
DR PANTHER; PTHR11767; PTHR11767; 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; SSF81296; 1.
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 aldosterone-
FT producing adrenal adenoma samples; results in loss of
FT channel selectivity and membrane depolarization; increases
FT expression of CYP11B2 and its transcriptional regulators
FT NR4A2 and ATF2; increases aldosterone and hybrid steroids
FT 18-oxocortisol and 18-hydroxycortisol synthesis; increases
FT STAR expression and phosphorylation; 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; unknown
FT pathological 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 (probable disease-associated variant found in
FT patients with hypertension with ACTH-dependent aldosterone
FT hypersecretion; 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
