KCNJ6_MOUSE
ID KCNJ6_MOUSE Reviewed; 425 AA.
AC P48542; O70290; P70216; P70306; P70307; P70308; P70309; P70454; Q9QYH5;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=G protein-activated inward rectifier potassium channel 2;
DE Short=GIRK-2;
DE AltName: Full=Inward rectifier K(+) channel Kir3.2;
DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 6;
GN Name=Kcnj6; Synonyms=Girk2, Kcnj7, W;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GIRK2-1).
RC TISSUE=Brain;
RX PubMed=7926018; DOI=10.1016/0014-5793(94)01007-2;
RA Lesage F., Duprat F., Fink M., Guillemare E., Coppola T., Lazdunski M.,
RA Hugnot J.-P.;
RT "Cloning provides evidence for a family of inward rectifier and G-protein
RT coupled K+ channels in the brain.";
RL FEBS Lett. 353:37-42(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GIRK2A).
RC TISSUE=Brain;
RX PubMed=7499385; DOI=10.1074/jbc.270.48.28660;
RA Lesage F., Guillemare E., Fink M., Duprat F., Heurteaux C., Fosset M.,
RA Romey G., Barhanin J., Lazdunski M.;
RT "Molecular properties of neuronal G-protein-activated inwardly rectifying
RT K+ channels.";
RL J. Biol. Chem. 270:28660-28667(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GIRK2B).
RC TISSUE=Brain;
RX PubMed=8573147; DOI=10.1006/bbrc.1996.0050;
RA Isomoto S., Kondo C., Takahashi N., Matsumoto S., Yamada M., Takumi T.,
RA Horio Y., Kurachi Y.;
RT "A novel ubiquitously distributed isoform of GIRK2 (GIRK2B) enhances GIRK1
RT expression of the G-protein-gated K+ current in Xenopus oocytes.";
RL Biochem. Biophys. Res. Commun. 218:286-291(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND ALTERNATIVE SPLICING.
RC STRAIN=129/SvJ;
RX PubMed=9721208; DOI=10.1006/geno.1998.5369;
RA Wei J., Hodes M.E., Piva R., Feng Y., Wang Y., Ghetti B., Dlouhy S.R.;
RT "Characterization of murine Girk2 transcript isoforms: structure and
RT differential expression.";
RL Genomics 51:379-390(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GIRK2D).
RA Inanobe A., Horio Y., Fujita A., Tanemoto M., Kurachi Y.;
RT "Molecular cloning and characterization of a novel splicing variant of
RT Kir3.2/GIRK2 predominantly expressed in mouse testis.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PROTEIN SEQUENCE OF 379-390, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [7]
RP INVOLVEMENT IN WV PHENOTYPE, AND VARIANT WV SER-156.
RX PubMed=7550338; DOI=10.1038/ng1095-126;
RA Patil N., Cox D.R., Bhat D., Faham M., Myers R.M., Peterson A.S.;
RT "A potassium channel mutation in weaver mice implicates membrane
RT excitability in granule cell differentiation.";
RL Nat. Genet. 11:126-129(1995).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-25, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: This potassium channel is controlled by G proteins. It plays
CC a role in granule cell differentiation, possibly via membrane
CC hyperpolarization. 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.
CC -!- SUBUNIT: May associate with GIRK1 or GIRK4 to form a G-protein-
CC activated heteromultimer pore-forming unit. The resulting inward
CC current is much larger. Interacts (via PDZ-binding motif) with SNX27
CC (via PDZ domain); the interaction is required when endocytosed to
CC prevent degradation in lysosomes and promote recycling to the plasma
CC membrane (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=GIRK2A;
CC IsoId=P48542-1; Sequence=Displayed;
CC Name=GIRK2-1;
CC IsoId=P48542-2; Sequence=VSP_002803;
CC Name=GIRK2B;
CC IsoId=P48542-3; Sequence=VSP_002804, VSP_002805;
CC Name=GIRK2C;
CC IsoId=P48542-4; Sequence=VSP_002806, VSP_002807, VSP_002808;
CC Name=GIRK2D; Synonyms=KIR3.2D;
CC IsoId=P48542-5; Sequence=Not described;
CC -!- TISSUE SPECIFICITY: Cerebellum, testes, cortex and substentia nigra.
CC -!- DISEASE: Note=Defects in Kcnj6 are the cause of the weaver (wv)
CC phenotype. Homozygous animals suffer from severe ataxia that is obvious
CC by about the second postnatal week. The cerebellum of these animals is
CC drastically reduced in size due to depletion of the major cell type of
CC cerebellum, the granule cell neuron. Heterozygous animals are not
CC ataxic but have an intermediate number of surviving granule cells. Male
CC homozygotes are sterile, because of complete failure of sperm
CC production. Both hetero- and homozygous animals undergo sporadic tonic-
CC clonic seizures.
CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC
CC 1.A.2.1) family. KCNJ6 subfamily. {ECO:0000305}.
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DR EMBL; U37253; AAA91457.1; -; mRNA.
DR EMBL; U11859; AAA53245.1; -; mRNA.
DR EMBL; U51122; AAC34141.1; -; mRNA.
DR EMBL; U51123; AAC34142.1; -; mRNA.
DR EMBL; U51124; AAC34143.1; -; mRNA.
DR EMBL; U51125; AAC34144.1; -; mRNA.
DR EMBL; U51126; AAC34145.1; -; mRNA.
DR EMBL; AF040049; AAC34286.1; -; Genomic_DNA.
DR EMBL; AF040047; AAC34286.1; JOINED; Genomic_DNA.
DR EMBL; AF040050; AAC34287.1; -; Genomic_DNA.
DR EMBL; AF040049; AAC34287.1; JOINED; Genomic_DNA.
DR EMBL; AF040051; AAC34285.1; -; Genomic_DNA.
DR EMBL; AF040047; AAC34285.1; JOINED; Genomic_DNA.
DR EMBL; AF040049; AAC34285.1; JOINED; Genomic_DNA.
DR EMBL; AF040052; AAC34284.1; -; Genomic_DNA.
DR EMBL; AF040047; AAC34284.1; JOINED; Genomic_DNA.
DR EMBL; AF040049; AAC34284.1; JOINED; Genomic_DNA.
DR EMBL; AF040051; AAC34284.1; JOINED; Genomic_DNA.
DR EMBL; D86040; BAA12972.1; -; mRNA.
DR EMBL; AB029502; BAA88430.1; -; mRNA.
DR CCDS; CCDS37408.1; -. [P48542-2]
DR CCDS; CCDS49921.1; -. [P48542-4]
DR PIR; JC4586; JC4586.
DR PIR; S48738; S48738.
DR RefSeq; NP_001020756.1; NM_001025585.2.
DR RefSeq; NP_001020761.1; NM_001025590.1.
DR RefSeq; NP_034736.2; NM_010606.2.
DR RefSeq; XP_011244406.1; XM_011246104.1.
DR PDB; 2E4F; X-ray; 2.30 A; A=53-74, A=200-381.
DR PDB; 3AGW; X-ray; 2.20 A; A=53-380.
DR PDB; 3AT8; X-ray; 3.30 A; A=53-380.
DR PDB; 3AT9; X-ray; 3.30 A; A=53-380.
DR PDB; 3ATA; X-ray; 3.49 A; A=53-380.
DR PDB; 3ATB; X-ray; 3.51 A; A=53-380.
DR PDB; 3ATD; X-ray; 3.01 A; A=53-380.
DR PDB; 3ATE; X-ray; 3.20 A; A=53-380.
DR PDB; 3ATF; X-ray; 2.95 A; A=53-380.
DR PDB; 3AUW; X-ray; 3.56 A; A/C=53-74, B/D=200-380.
DR PDB; 3SYA; X-ray; 2.98 A; A=52-380.
DR PDB; 3SYC; X-ray; 3.41 A; A=52-380.
DR PDB; 3SYO; X-ray; 3.54 A; A=52-380.
DR PDB; 3SYP; X-ray; 3.12 A; A=52-380.
DR PDB; 3SYQ; X-ray; 3.44 A; A/B=52-380.
DR PDB; 3VSQ; X-ray; 2.00 A; A=53-380.
DR PDB; 4KFM; X-ray; 3.45 A; A=52-380.
DR PDB; 6XIS; EM; 3.90 A; A/B/C/D=52-380.
DR PDB; 6XIT; EM; 3.30 A; A/B/C/D=52-380.
DR PDBsum; 2E4F; -.
DR PDBsum; 3AGW; -.
DR PDBsum; 3AT8; -.
DR PDBsum; 3AT9; -.
DR PDBsum; 3ATA; -.
DR PDBsum; 3ATB; -.
DR PDBsum; 3ATD; -.
DR PDBsum; 3ATE; -.
DR PDBsum; 3ATF; -.
DR PDBsum; 3AUW; -.
DR PDBsum; 3SYA; -.
DR PDBsum; 3SYC; -.
DR PDBsum; 3SYO; -.
DR PDBsum; 3SYP; -.
DR PDBsum; 3SYQ; -.
DR PDBsum; 3VSQ; -.
DR PDBsum; 4KFM; -.
DR PDBsum; 6XIS; -.
DR PDBsum; 6XIT; -.
DR AlphaFoldDB; P48542; -.
DR SMR; P48542; -.
DR CORUM; P48542; -.
DR DIP; DIP-60215N; -.
DR IntAct; P48542; 1.
DR STRING; 10090.ENSMUSP00000097108; -.
DR ChEMBL; CHEMBL4680029; -.
DR DrugCentral; P48542; -.
DR GuidetoPHARMACOLOGY; 435; -.
DR iPTMnet; P48542; -.
DR MaxQB; P48542; -.
DR PaxDb; P48542; -.
DR PeptideAtlas; P48542; -.
DR PRIDE; P48542; -.
DR ProteomicsDB; 263498; -. [P48542-1]
DR ProteomicsDB; 263499; -. [P48542-2]
DR ProteomicsDB; 263500; -. [P48542-3]
DR ProteomicsDB; 263501; -. [P48542-4]
DR DNASU; 16522; -.
DR GeneID; 16522; -.
DR KEGG; mmu:16522; -.
DR CTD; 3763; -.
DR MGI; MGI:104781; Kcnj6.
DR eggNOG; KOG3827; Eukaryota.
DR InParanoid; P48542; -.
DR OrthoDB; 956263at2759; -.
DR PhylomeDB; P48542; -.
DR Reactome; R-MMU-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-MMU-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR BioGRID-ORCS; 16522; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Kcnj6; mouse.
DR EvolutionaryTrace; P48542; -.
DR PRO; PR:P48542; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P48542; protein.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:0032809; C:neuronal cell body membrane; ISO:MGI.
DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015467; F:G-protein activated inward rectifier potassium channel activity; IDA:MGI.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; ISO:MGI.
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 ion transmembrane transport; IBA:GO_Central.
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; IPR003275; K_chnl_inward-rec_Kir3.2.
DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR InterPro; IPR040445; Kir_TM.
DR PANTHER; PTHR11767; PTHR11767; 1.
DR PANTHER; PTHR11767:SF19; PTHR11767:SF19; 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; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Potassium; 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_0000154944"
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:0007744|PubMed:21183079"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..18
FT /note="Missing (in isoform GIRK2C)"
FT /evidence="ECO:0000305"
FT /id="VSP_002806"
FT VAR_SEQ 319..327
FT /note="MTCQARSSY -> KMGFALGFL (in isoform GIRK2B)"
FT /evidence="ECO:0000303|PubMed:8573147"
FT /id="VSP_002804"
FT VAR_SEQ 319..320
FT /note="MT -> QF (in isoform GIRK2C)"
FT /evidence="ECO:0000305"
FT /id="VSP_002807"
FT VAR_SEQ 321..425
FT /note="Missing (in isoform GIRK2C)"
FT /evidence="ECO:0000305"
FT /id="VSP_002808"
FT VAR_SEQ 328..425
FT /note="Missing (in isoform GIRK2B)"
FT /evidence="ECO:0000303|PubMed:8573147"
FT /id="VSP_002805"
FT VAR_SEQ 415..425
FT /note="Missing (in isoform GIRK2-1)"
FT /evidence="ECO:0000303|PubMed:7926018"
FT /id="VSP_002803"
FT VARIANT 156
FT /note="G -> S (in wv)"
FT /evidence="ECO:0000269|PubMed:7550338"
FT VARIANT 313
FT /note="I -> M"
FT VARIANT 344
FT /note="M -> L"
FT CONFLICT 67
FT /note="V -> C (in Ref. 3 and 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="S -> T (in Ref. 3; BAA12972, 4; AAC34145 and 5;
FT BAA88430)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="V -> L (in Ref. 5; BAA88430)"
FT /evidence="ECO:0000305"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6XIT"
FT HELIX 76..80
FT /evidence="ECO:0007829|PDB:3SYA"
FT HELIX 82..88
FT /evidence="ECO:0007829|PDB:3SYA"
FT HELIX 91..119
FT /evidence="ECO:0007829|PDB:3SYA"
FT TURN 120..124
FT /evidence="ECO:0007829|PDB:3SYA"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:4KFM"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:3SYA"
FT HELIX 143..152
FT /evidence="ECO:0007829|PDB:3SYA"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:3SYA"
FT HELIX 167..196
FT /evidence="ECO:0007829|PDB:3SYA"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:3SYP"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:3SYA"
FT STRAND 234..248
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 254..262
FT /evidence="ECO:0007829|PDB:3VSQ"
FT TURN 266..271
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:3SYP"
FT STRAND 279..284
FT /evidence="ECO:0007829|PDB:3VSQ"
FT TURN 290..293
FT /evidence="ECO:0007829|PDB:3VSQ"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:3VSQ"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 305..314
FT /evidence="ECO:0007829|PDB:3VSQ"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 320..328
FT /evidence="ECO:0007829|PDB:3VSQ"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 348..352
FT /evidence="ECO:0007829|PDB:3VSQ"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:3VSQ"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:3VSQ"
FT HELIX 369..377
FT /evidence="ECO:0007829|PDB:3VSQ"
SQ SEQUENCE 425 AA; 48652 MW; 2E5153DCB1B60331 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 EGEFIPLNQS DINVGYYTGD DRLFLVSPLI ISHEINQQSP FWEISKAQLP
KEELEIVVIL EGIVEATGMT CQARSSYITS EILWGYRFTP VLTMEDGFYE VDYNSFHETY
ETSTPSLSAK ELAELANRAE VPLSWSVSSK LNQHAELETE EEEKNPEELT ERNGDVANLE
NESKV
