KCJ12_HUMAN
ID KCJ12_HUMAN Reviewed; 433 AA.
AC Q14500; O43401; Q15756; Q8NG63;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=ATP-sensitive inward rectifier potassium channel 12;
DE AltName: Full=Inward rectifier K(+) channel Kir2.2;
DE Short=IRK-2;
DE AltName: Full=Inward rectifier K(+) channel Kir2.2v;
DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 12;
GN Name=KCNJ12; Synonyms=IRK2, KCNJN1;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Heart atrium;
RX PubMed=7859381; DOI=10.1161/01.res.76.3.343;
RA Wible B.A., de Biasi M., Majumder K., Taglialatela M., Brown A.M.;
RT "Cloning and functional expression of an inwardly rectifying K+ channel
RT from human atrium.";
RL Circ. Res. 76:343-350(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP VARIANT VAL-100.
RX PubMed=8647284; DOI=10.1016/0014-5793(96)00445-0;
RA Namba N., Inagaki N., Gonoi T., Seino Y., Seino S.;
RT "Kir2.2v: a possible negative regulator of the inwardly rectifying K+
RT channel Kir2.2.";
RL FEBS Lett. 386:211-214(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12417321; DOI=10.1016/s0014-5793(02)03512-3;
RA Kaibara M., Ishihara K., Doi Y., Hayashi H., Ehara T., Taniyama K.;
RT "Identification of human Kir2.2 (KCNJ12) gene encoding functional inward
RT rectifier potassium channel in both mammalian cells and Xenopus oocytes.";
RL FEBS Lett. 531:250-254(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 161-433.
RC TISSUE=Skeletal muscle;
RX PubMed=9430667; DOI=10.1074/jbc.273.3.1339;
RA Gallagher P.G., Forget B.G.;
RT "An alternate promoter directs expression of a truncated, muscle-specific
RT isoform of the human ankyrin 1 gene.";
RL J. Biol. Chem. 273:1339-1348(1998).
RN [6]
RP INTERACTION WITH KCNJ4.
RX PubMed=12032359; DOI=10.1073/pnas.102609499;
RA Preisig-Muller R., Schlichthorl G., Goerge T., Heinen S., Bruggemann A.,
RA Rajan S., Derst C., Veh R.W., Daut J.;
RT "Heteromerization of Kir2.x potassium channels contributes to the phenotype
RT of Andersen's syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7774-7779(2002).
RN [7]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=20921230; DOI=10.1074/jbc.c110.186692;
RA D'Avanzo N., Cheng W.W., Doyle D.A., Nichols C.G.;
RT "Direct and specific activation of human inward rectifier K+ channels by
RT membrane phosphatidylinositol 4,5-bisphosphate.";
RL J. Biol. Chem. 285:37129-37132(2010).
CC -!- FUNCTION: Inward rectifying potassium channel that is activated by
CC phosphatidylinositol 4,5-bisphosphate and that probably participates in
CC controlling the resting membrane potential in electrically excitable
CC cells. Probably participates in establishing action potential waveform
CC and excitability of neuronal and muscle tissues. 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. {ECO:0000269|PubMed:12417321,
CC ECO:0000269|PubMed:20921230, ECO:0000269|PubMed:7859381,
CC ECO:0000269|PubMed:8647284}.
CC -!- SUBUNIT: Association, via its PDZ-recognition domain, with LIN7A,
CC LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization
CC and trafficking (By similarity). Homotetramer. Forms heteromer with
CC KCNJ4. {ECO:0000250, ECO:0000269|PubMed:20921230}.
CC -!- INTERACTION:
CC Q14500; P50402: EMD; NbExp=3; IntAct=EBI-11794596, EBI-489887;
CC Q14500; Q14160: SCRIB; NbExp=2; IntAct=EBI-11794596, EBI-357345;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC membrane; Multi-pass membrane protein.
CC -!- DOMAIN: Phosphatidylinositol 4,5-bisphosphate binding to the
CC cytoplasmic side of the channel triggers a conformation change leading
CC to channel opening. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC
CC 1.A.2.1) family. KCNJ12 subfamily. {ECO:0000305}.
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DR EMBL; L36069; AAA65122.1; -; mRNA.
DR EMBL; U53143; AAC50615.1; -; Genomic_DNA.
DR EMBL; AB074970; BAC02718.1; -; Genomic_DNA.
DR EMBL; AB182123; BAD23901.1; -; mRNA.
DR EMBL; BC027982; AAH27982.1; -; mRNA.
DR EMBL; AF005214; AAC01951.1; -; mRNA.
DR CCDS; CCDS11219.1; -.
DR PIR; I52864; I52864.
DR PIR; S71341; S71341.
DR RefSeq; NP_066292.2; NM_021012.4.
DR RefSeq; XP_005256682.1; XM_005256625.4.
DR RefSeq; XP_011522133.1; XM_011523831.2.
DR AlphaFoldDB; Q14500; -.
DR SMR; Q14500; -.
DR BioGRID; 109970; 27.
DR IntAct; Q14500; 3.
DR MINT; Q14500; -.
DR STRING; 9606.ENSP00000463778; -.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB00204; Dofetilide.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB01392; Yohimbine.
DR GuidetoPHARMACOLOGY; 431; -.
DR TCDB; 1.A.2.1.9; the inward rectifier k(+) channel (irk-c) family.
DR iPTMnet; Q14500; -.
DR PhosphoSitePlus; Q14500; -.
DR BioMuta; KCNJ12; -.
DR DMDM; 77416868; -.
DR MassIVE; Q14500; -.
DR PaxDb; Q14500; -.
DR PeptideAtlas; Q14500; -.
DR PRIDE; Q14500; -.
DR ProteomicsDB; 60008; -.
DR Antibodypedia; 26154; 230 antibodies from 27 providers.
DR DNASU; 3768; -.
DR Ensembl; ENST00000331718.5; ENSP00000328150.5; ENSG00000184185.10.
DR Ensembl; ENST00000583088.6; ENSP00000463778.1; ENSG00000184185.10.
DR GeneID; 3768; -.
DR KEGG; hsa:3768; -.
DR MANE-Select; ENST00000583088.6; ENSP00000463778.1; NM_021012.5; NP_066292.2.
DR UCSC; uc002gyv.2; human.
DR CTD; 3768; -.
DR DisGeNET; 3768; -.
DR GeneCards; KCNJ12; -.
DR HGNC; HGNC:6258; KCNJ12.
DR HPA; ENSG00000184185; Group enriched (brain, skeletal muscle, tongue).
DR MIM; 602323; gene.
DR neXtProt; NX_Q14500; -.
DR OpenTargets; ENSG00000184185; -.
DR PharmGKB; PA218; -.
DR VEuPathDB; HostDB:ENSG00000184185; -.
DR eggNOG; KOG3827; Eukaryota.
DR GeneTree; ENSGT01030000234586; -.
DR HOGENOM; CLU_022738_3_0_1; -.
DR InParanoid; Q14500; -.
DR OMA; MHGMNGF; -.
DR OrthoDB; 956263at2759; -.
DR PhylomeDB; Q14500; -.
DR TreeFam; TF313676; -.
DR PathwayCommons; Q14500; -.
DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-HSA-1296053; Classical Kir channels.
DR Reactome; R-HSA-5576886; Phase 4 - resting membrane potential.
DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR SignaLink; Q14500; -.
DR SIGNOR; Q14500; -.
DR BioGRID-ORCS; 3768; 38 hits in 1061 CRISPR screens.
DR ChiTaRS; KCNJ12; human.
DR GeneWiki; KCNJ12; -.
DR GenomeRNAi; 3768; -.
DR Pharos; Q14500; Tchem.
DR PRO; PR:Q14500; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14500; protein.
DR Bgee; ENSG00000184185; Expressed in skeletal muscle tissue of rectus abdominis and 115 other tissues.
DR Genevisible; Q14500; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031224; C:intrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0008016; P:regulation of heart contraction; TAS:ProtInc.
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; IPR003272; K_chnl_inward-rec_Kir2.2.
DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR InterPro; IPR013673; K_chnl_inward-rec_Kir_N.
DR InterPro; IPR040445; Kir_TM.
DR PANTHER; PTHR11767; PTHR11767; 1.
DR PANTHER; PTHR11767:SF14; PTHR11767:SF14; 1.
DR Pfam; PF01007; IRK; 1.
DR Pfam; PF17655; IRK_C; 1.
DR Pfam; PF08466; IRK_N; 1.
DR PRINTS; PR01325; KIR22CHANNEL.
DR PRINTS; PR01320; KIRCHANNEL.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Ion channel; Ion transport; Membrane;
KW Potassium; Potassium transport; Reference proteome; S-nitrosylation;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..433
FT /note="ATP-sensitive inward rectifier potassium channel 12"
FT /id="PRO_0000154962"
FT TOPO_DOM 1..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 83..107
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 108..123
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT INTRAMEM 124..128
FT /evidence="ECO:0000250"
FT INTRAMEM 129..141
FT /note="Helical; Pore-forming; Name=H5"
FT /evidence="ECO:0000250"
FT INTRAMEM 142..151
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TOPO_DOM 152..156
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 157..181
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 182..433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 387..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 79..81
FT /note="Interaction with phosphatidylinositides"
FT /evidence="ECO:0000250"
FT MOTIF 143..148
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT MOTIF 183..190
FT /note="Interaction with phosphatidylinositides"
FT /evidence="ECO:0000250"
FT MOTIF 431..433
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
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 75
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P63252"
FT DISULFID 155
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VARIANT 6
FT /note="R -> Q (in dbSNP:rs3752032)"
FT /id="VAR_024509"
FT VARIANT 15
FT /note="S -> L (in dbSNP:rs1657738)"
FT /id="VAR_049671"
FT VARIANT 100
FT /note="I -> V (in dbSNP:rs8076599)"
FT /evidence="ECO:0000269|PubMed:8647284"
FT /id="VAR_059365"
FT VARIANT 118
FT /note="R -> Q (in dbSNP:rs1657740)"
FT /id="VAR_059366"
FT VARIANT 156
FT /note="P -> L (in dbSNP:rs1714864)"
FT /id="VAR_049672"
FT VARIANT 192
FT /note="Q -> H (in dbSNP:rs1657742)"
FT /id="VAR_059367"
FT VARIANT 249
FT /note="I -> V (in dbSNP:rs4985866)"
FT /id="VAR_049673"
FT VARIANT 430
FT /note="E -> G (in dbSNP:rs5021699)"
FT /id="VAR_059368"
FT CONFLICT 43
FT /note="R -> H (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="M -> I (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="E -> K (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="T -> N (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="G -> S (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="D -> N (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="M -> V (in Ref. 5; AAC01951)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="A -> V (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 211
FT /note="L -> F (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="E -> K (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 261..262
FT /note="RI -> HS (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="Missing (in Ref. 1; AAA65122)"
FT /evidence="ECO:0000305"
FT CONFLICT 289..290
FT /note="ET -> QM (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="V -> I (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="M -> I (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="Missing (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 335
FT /note="Missing (in Ref. 5; AAC01951)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="S -> L (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="S -> R (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="E -> K (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="D -> E (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="S -> I (in Ref. 2; AAC50615)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 433 AA; 49001 MW; 082027A1765B6F4E CRC64;
MTAASRANPY SIVSSEEDGL HLVTMSGANG FGNGKVHTRR RCRNRFVKKN GQCNIEFANM
DEKSQRYLAD MFTTCVDIRW RYMLLIFSLA FLASWLLFGI IFWVIAVAHG DLEPAEGRGR
TPCVMQVHGF MAAFLFSIET QTTIGYGLRC VTEECPVAVF MVVAQSIVGC IIDSFMIGAI
MAKMARPKKR AQTLLFSHNA VVALRDGKLC LMWRVGNLRK SHIVEAHVRA QLIKPRVTEE
GEYIPLDQID IDVGFDKGLD RIFLVSPITI LHEIDEASPL FGISRQDLET DDFEIVVILE
GMVEATAMTT QARSSYLANE ILWGHRFEPV LFEEKNQYKI DYSHFHKTYE VPSTPRCSAK
DLVENKFLLP SANSFCYENE LAFLSRDEED EADGDQDGRS RDGLSPQARH DFDRLQAGGG
VLEQRPYRRE SEI
