KCNJ3_HUMAN
ID KCNJ3_HUMAN Reviewed; 501 AA.
AC P48549; B4DEW7; Q8TBI0;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=G protein-activated inward rectifier potassium channel 1;
DE Short=GIRK-1;
DE AltName: Full=Inward rectifier K(+) channel Kir3.1;
DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 3;
GN Name=KCNJ3; Synonyms=GIRK1;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8868049; DOI=10.1085/jgp.107.3.381;
RA Chan K.W., Langan M.N., Sui J., Kozak A., Pabon A., Ladias J.A.A.,
RA Logothetis D.E.;
RT "A recombinant inwardly rectifying potassium channel coupled to GTP-binding
RT proteins.";
RL J. Gen. Physiol. 107:381-397(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8804710; DOI=10.1016/0169-328x(95)00349-w;
RA Schoots O., Yue K.T., Macdonald J.F., Hampson D.R., Nobrega J.N.,
RA Dixon L.M., van Tol H.H.M.;
RT "Cloning of a G protein-activated inwardly rectifying potassium channel
RT from human cerebellum.";
RL Brain Res. Mol. Brain Res. 39:23-30(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Wagner V., Gorischek A., Bauernhofer T., Schreibmayer W.;
RT "Splice variant hGIRK1d from human breast cancer cells.";
RL Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 GLYCOSYLATION AT ASN-119.
RX PubMed=10889209; DOI=10.1074/jbc.m005338200;
RA Pabon A., Chan K.W., Sui J.L., Wu X., Logothetis D.E., Thornhill W.B.;
RT "Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different
RT consequences in potassium channel function.";
RL J. Biol. Chem. 275:30677-30682(2000).
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. This receptor plays a crucial role in regulating
CC the heartbeat.
CC -!- SUBUNIT: Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein
CC activated heteromultimer pore-forming unit. The resulting inward
CC current is much larger (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P48549-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P48549-2; Sequence=VSP_045432, VSP_045433;
CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC
CC 1.A.2.1) family. KCNJ3 subfamily. {ECO:0000305}.
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DR EMBL; U39196; AAB53094.1; -; mRNA.
DR EMBL; U50964; AAB42176.1; -; mRNA.
DR EMBL; GU074515; ADB11081.1; -; mRNA.
DR EMBL; AK293824; BAG57228.1; -; mRNA.
DR EMBL; AC061961; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093633; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107060; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022495; AAH22495.1; -; mRNA.
DR CCDS; CCDS2200.1; -. [P48549-1]
DR CCDS; CCDS58733.1; -. [P48549-2]
DR PIR; G02468; G02468.
DR RefSeq; NP_001247437.1; NM_001260508.1. [P48549-2]
DR RefSeq; NP_001247438.1; NM_001260509.1.
DR RefSeq; NP_001247439.1; NM_001260510.1.
DR RefSeq; NP_002230.1; NM_002239.3. [P48549-1]
DR AlphaFoldDB; P48549; -.
DR SMR; P48549; -.
DR BioGRID; 109962; 18.
DR ComplexPortal; CPX-3278; I(KACh) inward rectifier potassium channel complex.
DR IntAct; P48549; 2.
DR STRING; 9606.ENSP00000295101; -.
DR BindingDB; P48549; -.
DR ChEMBL; CHEMBL1914277; -.
DR DrugBank; DB00289; Atomoxetine.
DR DrugBank; DB02451; B-nonylglucoside.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB08954; Ifenprodil.
DR DrugCentral; P48549; -.
DR GuidetoPHARMACOLOGY; 434; -.
DR TCDB; 1.A.2.1.12; the inward rectifier k(+) channel (irk-c) family.
DR GlyGen; P48549; 1 site.
DR iPTMnet; P48549; -.
DR PhosphoSitePlus; P48549; -.
DR BioMuta; KCNJ3; -.
DR DMDM; 1352482; -.
DR MassIVE; P48549; -.
DR PaxDb; P48549; -.
DR PeptideAtlas; P48549; -.
DR PRIDE; P48549; -.
DR ProteomicsDB; 3990; -.
DR ProteomicsDB; 55904; -. [P48549-1]
DR Antibodypedia; 18931; 483 antibodies from 33 providers.
DR DNASU; 3760; -.
DR Ensembl; ENST00000295101.3; ENSP00000295101.2; ENSG00000162989.5. [P48549-1]
DR Ensembl; ENST00000544049.2; ENSP00000438410.1; ENSG00000162989.5. [P48549-2]
DR GeneID; 3760; -.
DR KEGG; hsa:3760; -.
DR MANE-Select; ENST00000295101.3; ENSP00000295101.2; NM_002239.4; NP_002230.1.
DR UCSC; uc002tyv.3; human. [P48549-1]
DR CTD; 3760; -.
DR DisGeNET; 3760; -.
DR GeneCards; KCNJ3; -.
DR HGNC; HGNC:6264; KCNJ3.
DR HPA; ENSG00000162989; Tissue enhanced (brain, heart muscle).
DR MIM; 601534; gene.
DR neXtProt; NX_P48549; -.
DR OpenTargets; ENSG00000162989; -.
DR PharmGKB; PA215; -.
DR VEuPathDB; HostDB:ENSG00000162989; -.
DR eggNOG; KOG3827; Eukaryota.
DR GeneTree; ENSGT01040000240379; -.
DR HOGENOM; CLU_022738_13_0_1; -.
DR InParanoid; P48549; -.
DR OMA; PARMEGN; -.
DR OrthoDB; 956263at2759; -.
DR PhylomeDB; P48549; -.
DR TreeFam; TF313676; -.
DR PathwayCommons; P48549; -.
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; P48549; -.
DR SIGNOR; P48549; -.
DR BioGRID-ORCS; 3760; 16 hits in 1068 CRISPR screens.
DR ChiTaRS; KCNJ3; human.
DR GeneWiki; KCNJ3; -.
DR GenomeRNAi; 3760; -.
DR Pharos; P48549; Tchem.
DR PRO; PR:P48549; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P48549; protein.
DR Bgee; ENSG00000162989; Expressed in endothelial cell and 139 other tissues.
DR ExpressionAtlas; P48549; baseline and differential.
DR Genevisible; P48549; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IEA:Ensembl.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030315; C:T-tubule; IEA:Ensembl.
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:ProtInc.
DR GO; GO:0086089; F:voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarization; IC: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; IC: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; IC:BHF-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
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; IPR003274; K_chnl_inward-rec_Kir3.1.
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 PRINTS; PR01327; KIR31CHANNEL.
DR PRINTS; PR01320; KIRCHANNEL.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..501
FT /note="G protein-activated inward rectifier potassium
FT channel 1"
FT /id="PRO_0000154938"
FT TOPO_DOM 1..80
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 81..105
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 106..129
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT INTRAMEM 130..141
FT /note="Helical; Pore-forming; Name=H5"
FT /evidence="ECO:0000250"
FT INTRAMEM 142..148
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TOPO_DOM 149..157
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 158..179
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 180..501
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 143..148
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 12..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 173
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 385
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63250"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63250"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10889209"
FT VAR_SEQ 235
FT /note="S -> G (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_045432"
FT VAR_SEQ 236..501
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_045433"
FT VARIANT 40
FT /note="K -> R (in dbSNP:rs16838016)"
FT /id="VAR_049669"
FT CONFLICT 271
FT /note="C -> R (in Ref. 6; AAH22495)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="E -> K (in Ref. 6; AAH22495)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 501 AA; 56603 MW; 825A28ACE2873269 CRC64;
MSALRRKFGD DYQVVTTSSS GSGLQPQGPG QDPQQQLVPK KKRQRFVDKN GRCNVQHGNL
GSETSRYLSD LFTTLVDLKW RWNLFIFILT YTVAWLFMAS MWWVIAYTRG DLNKAHVGNY
TPCVANVYNF PSAFLFFIET EATIGYGYRY ITDKCPEGII LFLFQSILGS IVDAFLIGCM
FIKMSQPKKR AETLMFSEHA VISMRDGKLT LMFRVGNLRN SHMVSAQIRC KLLKSRQTPE
GEFLPLDQLE LDVGFSTGAD QLFLVSPLTI CHVIDAKSPF YDLSQRSMQT EQFEIVVILE
GIVETTGMTC QARTSYTEDE VLWGHRFFPV ISLEEGFFKV DYSQFHATFE VPTPPYSVKE
QEEMLLMSSP LIAPAITNSK ERHNSVECLD GLDDITTKLP SKLQKITGRE DFPKKLLRMS
STTSEKAYSL GDLPMKLQRI SSVPGNSEEK LVSKTTKMLS DPMSQSVADL PPKLQKMAGG
AARMEGNLPA KLRKMNSDRF T
