ID   KCNJ3_RAT               Reviewed;         501 AA.
AC   P63251; P35562;
DT   11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2004, sequence version 1.
DT   10-JUN-2026, entry version 160.
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=KGA;
DE   AltName: Full=KGB1;
DE   AltName: Full=Potassium channel, inwardly rectifying subfamily J member 3;
GN   Name=Kcnj3; Synonyms=Girk1, Kga;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RC   TISSUE=Brain, and Heart atrium;
RX   PubMed=8234283; DOI=10.1073/pnas.90.21.10235;
RA   Dascal N., Schreibmayer W., Lim N.F., Wang W., Chavkin C., Dimagno L.,
RA   Labarca C., Kieffer B.L., Gaveriaux-Ruff C., Trollinger D., Lester H.A.,
RA   Davidson N.;
RT   "Atrial G protein-activated K+ channel: expression cloning and molecular
RT   properties.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:10235-10239(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=8355805; DOI=10.1038/364802a0;
RA   Kubo Y., Reuveny E., Slesinger P.A., Jan Y.N., Jan L.Y.;
RT   "Primary structure and functional expression of a rat G-protein-coupled
RT   muscarinic potassium channel.";
RL   Nature 364:802-806(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7704424; DOI=10.1006/mcne.1994.1063;
RA   Depaoli A.M., Bell G.I., Stoffel M.;
RT   "G protein-activated inwardly rectifying potassium channel (GIRK1/KGA) mRNA
RT   in adult rat heart and brain by in situ hybridization histochemistry.";
RL   Mol. Cell. Neurosci. 5:515-522(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=8642402; DOI=10.1523/jneurosci.16-11-03559.1996;
RA   Karschin C., Dissman E., Stuehmer W., Karschin A.;
RT   "IRK(1-3) and GIRK(1-4) inwardly rectifying K+ channel mRNAs are
RT   differentially expressed in the adult rat brain.";
RL   J. Neurosci. 16:3559-3570(1996).
RN   [5]
RP   FUNCTION, AND SUBUNIT.
RC   TISSUE=Brain;
RX   PubMed=8670306; DOI=10.1006/bbrc.1996.0918;
RA   Dissmann E., Wischmeyer E., Spauschus A., Pfeil D.V., Karschin C.,
RA   Karschin A.;
RT   "Functional expression and cellular mRNA localization of a G protein-
RT   activated K+ inward rectifier isolated from rat brain.";
RL   Biochem. Biophys. Res. Commun. 223:474-479(1996).
RN   [6]
RP   FUNCTION, ACTIVITY REGULATION, AND PIP2-BINDING REGION.
RX   PubMed=9486652; DOI=10.1038/35882;
RA   Huang C.L., Feng S., Hilgemann D.W.;
RT   "Direct activation of inward rectifier potassium channels by PIP2 and its
RT   stabilization by Gbetagamma.";
RL   Nature 391:803-806(1998).
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. This potassium channel is controlled by
CC       G proteins (PubMed:8234283, PubMed:8355805, PubMed:9486652). This
CC       receptor plays a crucial role in regulating the heartbeat
CC       (PubMed:8234283). Forms a functional channel in association with
CC       KCNJ9/GIRK3 (PubMed:8670306). {ECO:0000269|PubMed:8234283,
CC       ECO:0000269|PubMed:8355805, ECO:0000269|PubMed:8670306,
CC       ECO:0000269|PubMed:9486652, ECO:0000303|PubMed:8234283}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103;
CC         Evidence={ECO:0000269|PubMed:8234283, ECO:0000269|PubMed:8355805};
CC   -!- ACTIVITY REGULATION: Heteromultimer composed of KCNJ3/GIRK1 and
CC       KCNJ5/GIRK4 is activated by phosphatidylinositol 4,5 biphosphate
CC       (PtdIns(4,5)P2). {ECO:0000269|PubMed:9486652}.
CC   -!- SUBUNIT: Associates with KCNJ5/GIRK4 or KCNJ6/GIRK2 to form a G protein
CC       activated heteromultimer pore-forming unit. The resulting inward
CC       current is much larger (By similarity). Associates with KCNJ9/GIRK3 to
CC       form a G protein activated heteromultimer pore-forming unit
CC       (PubMed:8670306). {ECO:0000250|UniProtKB:P48549,
CC       ECO:0000250|UniProtKB:P63250, ECO:0000269|PubMed:8670306}.
CC   -!- INTERACTION:
CC       P63251; P00517: PRKACA; Xeno; NbExp=6; IntAct=EBI-7250981, EBI-7251007;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel
CC       (TC 1.A.2.1) family. KCNJ3 subfamily. {ECO:0000305}.
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DR   EMBL; L25264; AAA41226.1; -; mRNA.
DR   EMBL; U01071; AAC52127.1; -; mRNA.
DR   EMBL; U01141; AAC52125.1; -; mRNA.
DR   EMBL; Y12259; CAA72936.1; -; mRNA.
DR   EMBL; U09243; AAA18031.1; -; mRNA.
DR   PIR; I61084; I61084.
DR   RefSeq; NP_113798.1; NM_031610.3.
DR   PDB; 1N9P; X-ray; 1.80 A; A=41-63, A=190-371.
DR   AlphaFoldDB; P63251; -.
DR   SMR; P63251; -.
DR   ComplexPortal; CPX-3276; I(KACh) inward rectifier potassium channel complex.
DR   FunCoup; P63251; 1067.
DR   IntAct; P63251; 1.
DR   MINT; P63251; -.
DR   STRING; 10116.ENSRNOP00000007335; -.
DR   BindingDB; P63251; -.
DR   ChEMBL; CHEMBL3832643; -.
DR   GuidetoPHARMACOLOGY; 434; -.
DR   GlyCosmos; P63251; 1 site, No reported glycans.
DR   GlyGen; P63251; 1 site.
DR   iPTMnet; P63251; -.
DR   PhosphoSitePlus; P63251; -.
DR   PaxDb; 10116-ENSRNOP00000007335; -.
DR   Ensembl; ENSRNOT00000116585.2; ENSRNOP00000082842.1; ENSRNOG00000005369.7.
DR   Ensembl; ENSRNOT00055001216; ENSRNOP00055000971; ENSRNOG00055000706.
DR   Ensembl; ENSRNOT00060013520; ENSRNOP00060010298; ENSRNOG00060008163.
DR   Ensembl; ENSRNOT00065013133; ENSRNOP00065009704; ENSRNOG00065008281.
DR   GeneID; 50599; -.
DR   KEGG; rno:50599; -.
DR   UCSC; RGD:2958; rat.
DR   AGR; RGD:2958; -.
DR   CTD; 3760; -.
DR   RGD; 2958; Kcnj3.
DR   eggNOG; KOG3827; Eukaryota.
DR   GeneTree; ENSGT01080000257365; -.
DR   HOGENOM; CLU_022738_13_0_1; -.
DR   InParanoid; P63251; -.
DR   OMA; ITNSKDR; -.
DR   OrthoDB; 273257at2759; -.
DR   PhylomeDB; P63251; -.
DR   Reactome; R-RNO-1296041; Activation of G protein gated Potassium channels.
DR   Reactome; R-RNO-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR   PRO; PR:P63251; -.
DR   Proteomes; UP000002494; Chromosome 3.
DR   Bgee; ENSRNOG00000005369; Expressed in frontal cortex and 11 other cell types or tissues.
DR   ExpressionAtlas; P63251; baseline and differential.
DR   GO; GO:0009986; C:cell surface; IDA:RGD.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR   GO; GO:1902937; C:inward rectifier potassium channel complex; ISO:RGD.
DR   GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0042734; C:presynaptic membrane; ISO:RGD.
DR   GO; GO:0030315; C:T-tubule; IDA:RGD.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; ISO:RGD.
DR   GO; GO:0015467; F:G-protein activated inward rectifier potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR   GO; GO:0099508; F:voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IDA:SynGO.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:RGD.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; NAS:ComplexPortal.
DR   GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR   FunFam; 1.10.287.70:FF:000019; G protein-activated inward rectifier potassium channel 1; 1.
DR   FunFam; 2.60.40.1400:FF:000006; G protein-activated inward rectifier potassium channel 1; 1.
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; IPR003274; K_chnl_inward-rec_Kir3.1.
DR   InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR   InterPro; IPR040445; Kir_TM.
DR   PANTHER; PTHR11767:SF16; G PROTEIN-ACTIVATED INWARD RECTIFIER POTASSIUM CHANNEL 1; 1.
DR   PANTHER; PTHR11767; INWARD RECTIFIER POTASSIUM CHANNEL; 1.
DR   Pfam; PF01007; IRK; 1.
DR   Pfam; PF17655; IRK_C; 1.
DR   PRINTS; PR01327; KIR31CHANNEL.
DR   PRINTS; PR01320; KIRCHANNEL.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   PDBsum; 1N9P; -.
PE   1: Evidence at protein level;
KW   3D-structure; 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_0000154940"
FT   TOPO_DOM        1..80
FT                   /note="Cytoplasmic"
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   REGION          1..40
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          182..209
FT                   /note="Polyphosphoinositide (PIP2)-binding"
FT                   /evidence="ECO:0000269|PubMed:9486652"
FT   REGION          456..501
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           143..148
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        18..37
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        456..467
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:0000255"
FT   STRAND          194..196
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          200..205
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          208..215
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          219..221
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          223..237
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          243..250
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   TURN            255..260
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          261..263
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          268..273
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   TURN            279..282
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   HELIX           287..289
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          294..303
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   TURN            304..306
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          312..317
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   HELIX           318..320
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          321..323
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          325..327
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          331..336
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          338..340
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   HELIX           342..344
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   STRAND          348..350
FT                   /evidence="ECO:0007829|PDB:1N9P"
FT   HELIX           358..368
FT                   /evidence="ECO:0007829|PDB:1N9P"
SQ   SEQUENCE   501 AA;  56573 MW;  AB8910E9CC08FFEC CRC64;
     MSALRRKFGD DYQVVTTSSS GSGLQPQGPG QGPQQQLVPK 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 EQFEVVVILE
     GIVETTGMTC QARTSYTEDE VLWGHRFFPV ISLEEGFFKV DYSQFHATFE VPTPPYSVKE
     QEEMLLMSSP LIAPAITNSK ERHNSVECLD GLDDISTKLP SKLQKITGRE DFPKKLLRMS
     STTSEKAYSL GDLPMKLQRI SSVPGNSEEK LVSKTTKMLS DPMSQSVADL PPKLQKMAGG
     PTRMEGNLPA KLRKMNSDRF T
//