ID   KCNJ6_RAT               Reviewed;         425 AA.
AC   P48550;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   24-JAN-2024, entry version 153.
DE   RecName: Full=G protein-activated inward rectifier potassium channel 2;
DE            Short=GIRK-2;
DE   AltName: Full=BIR1;
DE   AltName: Full=Inward rectifier K(+) channel Kir3.2;
DE   AltName: Full=KATP-2;
DE   AltName: Full=Potassium channel, inwardly rectifying subfamily J member 6;
GN   Name=Kcnj6; Synonyms=Girk2, Kcnj7;
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].
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=7601286; DOI=10.1016/0014-5793(95)00497-w;
RA   Bond C.T., Aemmaelae C., Ashfield R., Blair T.A., Gribble F., Khan R.N.,
RA   Lee K., Proks P., Rowe I.C.M., Sakura H., Ashford M.J., Adelman J.P.,
RA   Ashcroft F.M.;
RT   "Cloning and functional expression of the cDNA encoding an inwardly-
RT   rectifying potassium channel expressed in pancreatic beta-cells and in the
RT   brain.";
RL   FEBS Lett. 367:61-66(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7626127; DOI=10.1006/bbrc.1995.2053;
RA   Stoffel M., Tokuyama Y., Trabb J.B., German M.S., Tsaar M.L., Jan L.Y.,
RA   Polonsky K.S., Bell G.I.;
RT   "Cloning of rat KATP-2 channel and decreased expression in pancreatic
RT   islets of male Zucker diabetic fatty rats.";
RL   Biochem. Biophys. Res. Commun. 212:894-899(1995).
RN   [3]
RP   INTERACTION WITH SNX27.
RX   PubMed=17828261; DOI=10.1038/nn1953;
RA   Lunn M.L., Nassirpour R., Arrabit C., Tan J., McLeod I., Arias C.M.,
RA   Sawchenko P.E., Yates J.R. III, Slesinger P.A.;
RT   "A unique sorting nexin regulates trafficking of potassium channels via a
RT   PDZ domain interaction.";
RL   Nat. Neurosci. 10:1249-1259(2007).
CC   -!- FUNCTION: This potassium channel is controlled by G proteins. It may be
CC       involved in the regulation of insulin secretion by glucose and/or
CC       neurotransmitters. Inward rectifier potassium channels are
CC       characterized by a greater tendency to allow potassium to flow into the
CC       cell rather than out of it. Their voltage dependence is regulated by
CC       the concentration of extracellular potassium; as external potassium is
CC       raised, the voltage range of the channel opening shifts to more
CC       positive voltages. The inward rectification is mainly due to the
CC       blockage of outward current by internal magnesium. Can be blocked by
CC       external barium or cesium.
CC   -!- SUBUNIT: Associates with GIRK1 or GIRK4 to form a G-protein-activated
CC       heteromultimer pore-forming unit. The resulting inward current is much
CC       larger (By similarity). Interacts (via PDZ-binding motif) with SNX27
CC       (via PDZ domain); the interaction is required for recycling to the
CC       plasma membrane when endocytosed and prevent degradation in lysosomes.
CC       {ECO:0000250, ECO:0000269|PubMed:17828261}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Pancreatic beta cells and brain.
CC   -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel
CC       (TC 1.A.2.1) family. KCNJ6 subfamily. {ECO:0000305}.
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DR   EMBL; X83583; CAA58566.1; -; mRNA.
DR   EMBL; U21087; AAA87002.1; -; mRNA.
DR   PIR; S66266; S52852.
DR   RefSeq; NP_037324.1; NM_013192.2.
DR   AlphaFoldDB; P48550; -.
DR   SMR; P48550; -.
DR   STRING; 10116.ENSRNOP00000059308; -.
DR   iPTMnet; P48550; -.
DR   PhosphoSitePlus; P48550; -.
DR   PaxDb; 10116-ENSRNOP00000059308; -.
DR   GeneID; 25743; -.
DR   KEGG; rno:25743; -.
DR   UCSC; RGD:2959; rat.
DR   AGR; RGD:2959; -.
DR   CTD; 3763; -.
DR   RGD; 2959; Kcnj6.
DR   eggNOG; KOG3827; Eukaryota.
DR   InParanoid; P48550; -.
DR   OrthoDB; 4126787at2759; -.
DR   PhylomeDB; P48550; -.
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:P48550; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0030424; C:axon; IDA:RGD.
DR   GO; GO:0009986; C:cell surface; IDA:RGD.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0032809; C:neuronal cell body membrane; IDA: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:0015467; F:G-protein activated inward rectifier potassium channel activity; ISO:RGD.
DR   GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:RGD.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR   GO; GO:0005267; F:potassium channel activity; ISO:RGD.
DR   GO; GO:0099508; F:voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; ISO:RGD.
DR   GO; GO:0071315; P:cellular response to morphine; IEP:RGD.
DR   GO; GO:0034220; P:monoatomic ion transmembrane transport; ISO:RGD.
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; ISO:RGD.
DR   GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; ISO:RGD.
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; IPR003275; K_chnl_inward-rec_Kir3.2.
DR   InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR   InterPro; IPR040445; Kir_TM.
DR   PANTHER; PTHR11767:SF19; G PROTEIN-ACTIVATED INWARD RECTIFIER POTASSIUM CHANNEL 2; 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; PR01328; KIR32CHANNEL.
DR   PRINTS; PR01320; KIRCHANNEL.
DR   SUPFAM; SSF81296; E set domains; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
PE   1: Evidence at protein level;
KW   Ion channel; Ion transport; Membrane; Phosphoprotein; Potassium;
KW   Potassium transport; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..425
FT                   /note="G protein-activated inward rectifier potassium
FT                   channel 2"
FT                   /id="PRO_0000154946"
FT   TOPO_DOM        1..91
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        92..116
FT                   /note="Helical; Name=M1"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        117..140
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        141..152
FT                   /note="Helical; Pore-forming; Name=H5"
FT                   /evidence="ECO:0000250"
FT   INTRAMEM        153..159
FT                   /note="Pore-forming"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        160..168
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250"
FT   TRANSMEM        169..190
FT                   /note="Helical; Name=M2"
FT                   /evidence="ECO:0000250"
FT   TOPO_DOM        191..425
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250"
FT   REGION          392..425
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           154..159
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   MOTIF           422..425
FT                   /note="PDZ-binding"
FT   COMPBIAS        394..425
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            184
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         18
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P48542"
FT   MOD_RES         25
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P48542"
FT   CONFLICT        328
FT                   /note="V -> I (in Ref. 2; AAA87002)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        360
FT                   /note="H -> Y (in Ref. 2; AAA87002)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   425 AA;  48640 MW;  66CE9599A4AE38D3 CRC64;
     MTMAKLTESM TNVLEGDSMD QDVESPVAIH QPKLPKQARD DLPRHISRDR TKRKIQRYVR
     KDGKCNVHHG NVRETYRYLT DIFTTLVDLK WRFNLLIFVM VYTVTWLFFG MIWWLIAYIR
     GDMDHIEDPS WTPCVTNLNG FVSAFLFSIE TETTIGYGYR VITDKCPEGI ILLLIQSVLG
     SIVNAFMVGC MFVKISQPKK RAETLVFSTH AVISMRDGKL CLMFRVGDLR NSHIVEASIR
     AKLIKSKQTS EGEFIPLNQT DINVGYYTGD DRLFLVSPLI ISHEINQQSP FWEISKAQLP
     KEELEIVVIL EGMVEATGMT CQARSSYVTS EILWGYRFTP VLTLEDGFYE VDYNSFHETH
     ETSTPSLSAK ELAELANRAE LPLSWSVSSK LNQHAELETE EEEKNPEELT ERNGDVANLE
     NESKV
//