ID   KCNJ9_HUMAN             Reviewed;         393 AA.
AC   Q92806; Q5JW75;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   06-FEB-2007, sequence version 2.
DT   24-JAN-2024, entry version 191.
DE   RecName: Full=G protein-activated inward rectifier potassium channel 3;
DE            Short=GIRK-3;
DE   AltName: Full=Inward rectifier K(+) channel Kir3.3;
DE   AltName: Full=Potassium channel, inwardly rectifying subfamily J member 9;
GN   Name=KCNJ9; Synonyms=GIRK3;
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 VAL-366.
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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-366.
RX   PubMed=10913335; DOI=10.1006/bbrc.2000.3136;
RA   Vaughn J., Wolford J.K., Prochazka M., Permana P.A.;
RT   "Genomic structure and expression of human KCNJ9 (Kir3.3/GIRK3).";
RL   Biochem. Biophys. Res. Commun. 274:302-309(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
CC   -!- FUNCTION: This receptor is controlled by G proteins. Inward rectifier
CC       potassium channels are characterized by a greater tendency to allow
CC       potassium to flow into the cell rather than out of it. Their voltage
CC       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 (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Associates with GIRK1 to form a G-protein-activated
CC       heteromultimer pore-forming unit. Interacts (via PDZ-binding motif)
CC       with SNX27 (via PDZ domain); the interaction is required when
CC       endocytosed to prevent degradation in lysosomes and promote recycling
CC       to the plasma membrane (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q92806; Q5SNT2-2: TMEM201; NbExp=3; IntAct=EBI-12822837, EBI-11994282;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- DOMAIN: The PDZ-binding motif specifically binds the PDZ domain of
CC       SNX27: the specificity for SNX27 is provided by the 2 residues located
CC       upstream (Glu-388 and Ser-389) of the PDZ-binding motif. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel
CC       (TC 1.A.2.1) family. KCNJ9 subfamily. {ECO:0000305}.
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DR   EMBL; U52152; AAB07043.1; -; mRNA.
DR   EMBL; AF193615; AAF89098.1; -; Genomic_DNA.
DR   EMBL; AL121987; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS1194.1; -.
DR   RefSeq; NP_004974.2; NM_004983.2.
DR   PDB; 6X23; X-ray; 2.15 A; B=384-393.
DR   PDBsum; 6X23; -.
DR   AlphaFoldDB; Q92806; -.
DR   SMR; Q92806; -.
DR   BioGRID; 109967; 4.
DR   IntAct; Q92806; 1.
DR   STRING; 9606.ENSP00000357067; -.
DR   ChEMBL; CHEMBL3038490; -.
DR   DrugBank; DB00898; Ethanol.
DR   DrugBank; DB11633; Isavuconazole.
DR   TCDB; 1.A.2.1.19; the inward rectifier k(+) channel (irk-c) family.
DR   iPTMnet; Q92806; -.
DR   PhosphoSitePlus; Q92806; -.
DR   BioMuta; KCNJ9; -.
DR   DMDM; 125987834; -.
DR   jPOST; Q92806; -.
DR   MassIVE; Q92806; -.
DR   PaxDb; 9606-ENSP00000357067; -.
DR   PeptideAtlas; Q92806; -.
DR   ProteomicsDB; 75491; -.
DR   ABCD; Q92806; 1 sequenced antibody.
DR   Antibodypedia; 34266; 151 antibodies from 29 providers.
DR   DNASU; 3765; -.
DR   Ensembl; ENST00000368088.4; ENSP00000357067.3; ENSG00000162728.5.
DR   GeneID; 3765; -.
DR   KEGG; hsa:3765; -.
DR   MANE-Select; ENST00000368088.4; ENSP00000357067.3; NM_004983.3; NP_004974.2.
DR   UCSC; uc001fuy.2; human.
DR   AGR; HGNC:6270; -.
DR   CTD; 3765; -.
DR   DisGeNET; 3765; -.
DR   GeneCards; KCNJ9; -.
DR   HGNC; HGNC:6270; KCNJ9.
DR   HPA; ENSG00000162728; Tissue enriched (brain).
DR   MIM; 600932; gene.
DR   neXtProt; NX_Q92806; -.
DR   OpenTargets; ENSG00000162728; -.
DR   PharmGKB; PA30051; -.
DR   VEuPathDB; HostDB:ENSG00000162728; -.
DR   eggNOG; KOG3827; Eukaryota.
DR   GeneTree; ENSGT01080000257365; -.
DR   HOGENOM; CLU_022738_11_0_1; -.
DR   InParanoid; Q92806; -.
DR   OMA; RFSPMML; -.
DR   OrthoDB; 4126787at2759; -.
DR   PhylomeDB; Q92806; -.
DR   TreeFam; TF313676; -.
DR   PathwayCommons; Q92806; -.
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; Q92806; -.
DR   BioGRID-ORCS; 3765; 90 hits in 1137 CRISPR screens.
DR   GeneWiki; KCNJ9; -.
DR   GenomeRNAi; 3765; -.
DR   Pharos; Q92806; Tbio.
DR   PRO; PR:Q92806; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q92806; Protein.
DR   Bgee; ENSG00000162728; Expressed in middle temporal gyrus and 88 other cell types or tissues.
DR   GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW.
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:0042734; C:presynaptic membrane; IEA:Ensembl.
DR   GO; GO:0015467; F:G-protein activated inward rectifier potassium channel activity; IEA:InterPro.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR   GO; GO:0034765; P:regulation of monoatomic ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0099505; P:regulation of presynaptic membrane potential; IEA:Ensembl.
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; IPR003276; K_chnl_inward-rec_Kir3.3.
DR   InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR   InterPro; IPR040445; Kir_TM.
DR   PANTHER; PTHR11767:SF17; G PROTEIN-ACTIVATED INWARD RECTIFIER POTASSIUM CHANNEL 3; 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; PR01329; KIR33CHANNEL.
DR   PRINTS; PR01320; KIRCHANNEL.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   Genevisible; Q92806; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Ion channel; Ion transport; Membrane; Potassium;
KW   Potassium transport; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..393
FT                   /note="G protein-activated inward rectifier potassium
FT                   channel 3"
FT                   /id="PRO_0000154950"
FT   TOPO_DOM        1..57
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        58..82
FT                   /note="Helical; Name=M1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        83..106
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        107..118
FT                   /note="Helical; Pore-forming; Name=H5"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        119..125
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        126..134
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        135..156
FT                   /note="Helical; Name=M2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        157..393
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          1..23
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          360..393
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           120..125
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   MOTIF           390..393
FT                   /note="PDZ-binding"
FT   SITE            150
FT                   /note="Role in the control of polyamine-mediated channel
FT                   gating and in the blocking by intracellular magnesium"
FT                   /evidence="ECO:0000250"
FT   VARIANT         366
FT                   /note="A -> V (in dbSNP:rs3001040)"
FT                   /evidence="ECO:0000269|PubMed:10659995,
FT                   ECO:0000269|PubMed:10913335"
FT                   /id="VAR_023568"
FT   STRAND          389..392
FT                   /evidence="ECO:0007829|PDB:6X23"
SQ   SEQUENCE   393 AA;  44020 MW;  C6F79F80A37B01C9 CRC64;
     MAQENAAFSP GQEEPPRRRG RQRYVEKDGR CNVQQGNVRE TYRYLTDLFT TLVDLQWRLS
     LLFFVLAYAL TWLFFGAIWW LIAYGRGDLE HLEDTAWTPC VNNLNGFVAA FLFSIETETT
     IGYGHRVITD QCPEGIVLLL LQAILGSMVN AFMVGCMFVK ISQPNKRAAT LVFSSHAVVS
     LRDGRLCLMF RVGDLRSSHI VEASIRAKLI RSRQTLEGEF IPLHQTDLSV GFDTGDDRLF
     LVSPLVISHE IDAASPFWEA SRRALERDDF EIVVILEGMV EATGMTCQAR SSYLVDEVLW
     GHRFTSVLTL EDGFYEVDYA SFHETFEVPT PSCSARELAE AAARLDAHLY WSIPSRLDEK
     VEEEGAGEGA GGEAGADKEQ NGCLPPPESE SKV
//