KCNJ6_HUMAN
ID KCNJ6_HUMAN Reviewed; 423 AA.
AC P48051; Q3MJ74; Q53WW6;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 184.
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, KATP2, KCNJ7;
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].
RC TISSUE=Insulinoma;
RX PubMed=7592809; DOI=10.1074/jbc.270.44.26086;
RA Ferrer J., Nichols C.G., Makhina E.N., Salkoff L., Bernstein J.,
RA Gerhard D., Wasson J., Ramanadham S., Permutt A.;
RT "Pancreatic islet cells express a family of inwardly rectifying K+ channel
RT subunits which interact to form G-protein-activated channels.";
RL J. Biol. Chem. 270:26086-26091(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hippocampus;
RA Dissmann E., Karschin A.;
RT "Subunit interactions in the assembly of neuronal G protein-activated
RT inwardly rectifying K+ channels.";
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Ohira M., Seki N., Nagase T., Suzuki E., Nomura N., Ohara O., Saito T.,
RA Ichikawa H., Ohki M.;
RT "Gene identification in the 1.6 Mb of the Down syndrome region on
RT chromosome 21.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cerebellum;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 17-423.
RX PubMed=7796919; DOI=10.1016/0014-5793(95)00498-x;
RA Sakura H., Bond C., Warren-Perry M., Horsley S., Kearney L., Tucker S.,
RA Adelman J., Turner R., Ashcroft F.M.;
RT "Characterization and variation of a human inwardly-rectifying-K-channel
RT gene (KCNJ6): a putative ATP-sensitive K-channel subunit.";
RL FEBS Lett. 367:193-197(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 116-211.
RX PubMed=7729621; DOI=10.2337/diab.44.5.592;
RA Tsaur M.-L., Menzel S., Lai F.-P., Espinosa R. III, Concannon P.,
RA Spielman R.S., Hanis C.L., Cox N.J., le Beau M.M., German M.S., Jan L.Y.,
RA Bell G.I., Stoffel M.;
RT "Isolation of a cDNA clone encoding a KATP channel-like protein expressed
RT in insulin-secreting cells, localization of the human gene to chromosome
RT band 21q22.1, and linkage studies with NIDDM.";
RL Diabetes 44:592-596(1995).
RN [8]
RP INVOLVEMENT IN KPLBS, AND VARIANTS KPLBS THR-152 DEL AND SER-154.
RX PubMed=25620207; DOI=10.1016/j.ajhg.2014.12.011;
RA Masotti A., Uva P., Davis-Keppen L., Basel-Vanagaite L., Cohen L.,
RA Pisaneschi E., Celluzzi A., Bencivenga P., Fang M., Tian M., Xu X.,
RA Cappa M., Dallapiccola B.;
RT "Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying
RT K+ channel encoded by KCNJ6.";
RL Am. J. Hum. Genet. 96:295-300(2015).
CC -!- FUNCTION: This potassium channel may be involved in the regulation of
CC insulin secretion by glucose and/or neurotransmitters acting through G-
CC protein-coupled receptors. 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: Associates with GIRK1 or GIRK4 to form a G-protein-activated
CC heteromultimer pore-forming unit. The resulting inward current is much
CC larger. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain);
CC the interaction is required when endocytosed to prevent degradation in
CC lysosomes and promote recycling to the plasma membrane (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P48051; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-12017638, EBI-11957045;
CC P48051; P05090: APOD; NbExp=3; IntAct=EBI-12017638, EBI-715495;
CC P48051; Q92843: BCL2L2; NbExp=3; IntAct=EBI-12017638, EBI-707714;
CC P48051; O15155: BET1; NbExp=3; IntAct=EBI-12017638, EBI-749204;
CC P48051; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-12017638, EBI-11522780;
CC P48051; Q9BT09: CNPY3; NbExp=3; IntAct=EBI-12017638, EBI-2835965;
CC P48051; P29400-2: COL4A5; NbExp=3; IntAct=EBI-12017638, EBI-12211159;
CC P48051; P56851: EDDM3B; NbExp=3; IntAct=EBI-12017638, EBI-10215665;
CC P48051; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-12017638, EBI-711490;
CC P48051; O75063: FAM20B; NbExp=3; IntAct=EBI-12017638, EBI-11090967;
CC P48051; Q9Y3D6: FIS1; NbExp=3; IntAct=EBI-12017638, EBI-3385283;
CC P48051; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-12017638, EBI-714482;
CC P48051; Q9H0Q3: FXYD6; NbExp=3; IntAct=EBI-12017638, EBI-713304;
CC P48051; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-12017638, EBI-14103818;
CC P48051; P30519: HMOX2; NbExp=3; IntAct=EBI-12017638, EBI-712096;
CC P48051; O60725: ICMT; NbExp=3; IntAct=EBI-12017638, EBI-11721771;
CC P48051; P11215: ITGAM; NbExp=3; IntAct=EBI-12017638, EBI-2568251;
CC P48051; O95214: LEPROTL1; NbExp=3; IntAct=EBI-12017638, EBI-750776;
CC P48051; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-12017638, EBI-12033434;
CC P48051; Q7L5N7: LPCAT2; NbExp=3; IntAct=EBI-12017638, EBI-4280011;
CC P48051; P30301: MIP; NbExp=3; IntAct=EBI-12017638, EBI-8449636;
CC P48051; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-12017638, EBI-10317425;
CC P48051; Q8N912: NRAC; NbExp=3; IntAct=EBI-12017638, EBI-12051377;
CC P48051; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-12017638, EBI-11075081;
CC P48051; Q96HA9: PEX11G; NbExp=3; IntAct=EBI-12017638, EBI-17284886;
CC P48051; Q9Y5Y5: PEX16; NbExp=3; IntAct=EBI-12017638, EBI-981985;
CC P48051; Q9Y342: PLLP; NbExp=3; IntAct=EBI-12017638, EBI-3919291;
CC P48051; Q01453: PMP22; NbExp=3; IntAct=EBI-12017638, EBI-2845982;
CC P48051; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-12017638, EBI-8652812;
CC P48051; Q9NS64: RPRM; NbExp=3; IntAct=EBI-12017638, EBI-1052363;
CC P48051; Q5QGT7: RTP2; NbExp=3; IntAct=EBI-12017638, EBI-10244780;
CC P48051; Q969E2: SCAMP4; NbExp=3; IntAct=EBI-12017638, EBI-4403649;
CC P48051; Q14162: SCARF1; NbExp=3; IntAct=EBI-12017638, EBI-12056025;
CC P48051; O00767: SCD; NbExp=3; IntAct=EBI-12017638, EBI-2684237;
CC P48051; A2A2V5: SERTM1; NbExp=3; IntAct=EBI-12017638, EBI-17284533;
CC P48051; P02808: STATH; NbExp=3; IntAct=EBI-12017638, EBI-738687;
CC P48051; P0DN84: STRIT1; NbExp=3; IntAct=EBI-12017638, EBI-12200293;
CC P48051; Q9BQG1: SYT3; NbExp=3; IntAct=EBI-12017638, EBI-17284568;
CC P48051; C9JKN6: THSD7B; NbExp=3; IntAct=EBI-12017638, EBI-17192156;
CC P48051; Q9BZW4: TM6SF2; NbExp=3; IntAct=EBI-12017638, EBI-13082040;
CC P48051; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-12017638, EBI-12845616;
CC P48051; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-12017638, EBI-10171534;
CC P48051; Q969S6: TMEM203; NbExp=3; IntAct=EBI-12017638, EBI-12274070;
CC P48051; Q9BTX3: TMEM208; NbExp=3; IntAct=EBI-12017638, EBI-12876824;
CC P48051; A2RU14: TMEM218; NbExp=3; IntAct=EBI-12017638, EBI-10173151;
CC P48051; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-12017638, EBI-11724433;
CC P48051; O14798: TNFRSF10C; NbExp=3; IntAct=EBI-12017638, EBI-717441;
CC P48051; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-12017638, EBI-12195249;
CC P48051; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-12017638, EBI-2819725;
CC P48051; Q53HI1: UNC50; NbExp=3; IntAct=EBI-12017638, EBI-7601760;
CC P48051; O75841: UPK1B; NbExp=3; IntAct=EBI-12017638, EBI-12237619;
CC P48051; Q6UX27-3: VSTM1; NbExp=3; IntAct=EBI-12017638, EBI-12190699;
CC P48051; Q9Y548: YIPF1; NbExp=3; IntAct=EBI-12017638, EBI-7850136;
CC P48051; Q96EC8: YIPF6; NbExp=3; IntAct=EBI-12017638, EBI-751210;
CC P48051; Q6UX98: ZDHHC24; NbExp=3; IntAct=EBI-12017638, EBI-10254561;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Most abundant in cerebellum, and to a lesser degree
CC in islets and exocrine pancreas.
CC -!- DISEASE: Keppen-Lubinsky syndrome (KPLBS) [MIM:614098]: A rare disease
CC characterized by severe developmental delay, intellectual disability,
CC severe generalized lipodystrophy, dysmorphic features including
CC microcephaly, large prominent eyes, narrow nasal bridge, tented upper
CC lip, high palate, open mouth, tightly adherent skin, and aged
CC appearance. {ECO:0000269|PubMed:25620207}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
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; U24660; AAC50258.1; -; mRNA.
DR EMBL; L78480; AAB02277.1; -; mRNA.
DR EMBL; D87327; BAA13331.1; -; mRNA.
DR EMBL; U52153; AAB07044.1; -; mRNA.
DR EMBL; BC101547; AAI01548.1; -; mRNA.
DR EMBL; S78685; AAB34738.2; -; Genomic_DNA.
DR EMBL; S78684; AAB34738.2; JOINED; Genomic_DNA.
DR EMBL; G02354; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS42927.1; -.
DR PIR; I38979; I38979.
DR RefSeq; NP_002231.1; NM_002240.4.
DR AlphaFoldDB; P48051; -.
DR SMR; P48051; -.
DR BioGRID; 109965; 74.
DR IntAct; P48051; 64.
DR MINT; P48051; -.
DR STRING; 9606.ENSP00000477437; -.
DR BindingDB; P48051; -.
DR ChEMBL; CHEMBL2406895; -.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB08954; Ifenprodil.
DR DrugBank; DB11633; Isavuconazole.
DR DrugCentral; P48051; -.
DR GuidetoPHARMACOLOGY; 435; -.
DR TCDB; 1.A.2.1.10; the inward rectifier k(+) channel (irk-c) family.
DR iPTMnet; P48051; -.
DR PhosphoSitePlus; P48051; -.
DR BioMuta; KCNJ6; -.
DR DMDM; 1352487; -.
DR jPOST; P48051; -.
DR MassIVE; P48051; -.
DR PaxDb; P48051; -.
DR PeptideAtlas; P48051; -.
DR PRIDE; P48051; -.
DR ProteomicsDB; 55842; -.
DR Antibodypedia; 23226; 283 antibodies from 35 providers.
DR DNASU; 3763; -.
DR Ensembl; ENST00000609713.2; ENSP00000477437.1; ENSG00000157542.11.
DR Ensembl; ENST00000645093.1; ENSP00000493772.1; ENSG00000157542.11.
DR GeneID; 3763; -.
DR KEGG; hsa:3763; -.
DR MANE-Select; ENST00000609713.2; ENSP00000477437.1; NM_002240.5; NP_002231.1.
DR UCSC; uc002ywn.2; human.
DR CTD; 3763; -.
DR DisGeNET; 3763; -.
DR GeneCards; KCNJ6; -.
DR HGNC; HGNC:6267; KCNJ6.
DR HPA; ENSG00000157542; Tissue enriched (brain).
DR MalaCards; KCNJ6; -.
DR MIM; 600877; gene.
DR MIM; 614098; phenotype.
DR neXtProt; NX_P48051; -.
DR OpenTargets; ENSG00000157542; -.
DR Orphanet; 435628; Keppen-Lubinsky syndrome.
DR PharmGKB; PA30049; -.
DR VEuPathDB; HostDB:ENSG00000157542; -.
DR eggNOG; KOG3827; Eukaryota.
DR GeneTree; ENSGT01040000240379; -.
DR HOGENOM; CLU_022738_11_0_1; -.
DR InParanoid; P48051; -.
DR OMA; HIEDPTW; -.
DR OrthoDB; 956263at2759; -.
DR PhylomeDB; P48051; -.
DR TreeFam; TF313676; -.
DR PathwayCommons; P48051; -.
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; P48051; -.
DR BioGRID-ORCS; 3763; 12 hits in 1024 CRISPR screens.
DR ChiTaRS; KCNJ6; human.
DR GeneWiki; KCNJ6; -.
DR GenomeRNAi; 3763; -.
DR Pharos; P48051; Tchem.
DR PRO; PR:P48051; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P48051; protein.
DR Bgee; ENSG00000157542; Expressed in substantia nigra pars reticulata and 80 other tissues.
DR Genevisible; P48051; HS.
DR GO; GO:0005794; C:Golgi apparatus; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; HDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc.
DR GO; GO:0015467; F:G-protein activated inward rectifier potassium channel activity; TAS:ProtInc.
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:0006813; P:potassium ion transport; 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; 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 Congenital generalized lipodystrophy; Disease variant;
KW Intellectual disability; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..423
FT /note="G protein-activated inward rectifier potassium
FT channel 2"
FT /id="PRO_0000154942"
FT TOPO_DOM 1..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 90..114
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 115..138
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT INTRAMEM 139..150
FT /note="Helical; Pore-forming; Name=H5"
FT /evidence="ECO:0000250"
FT INTRAMEM 151..157
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TOPO_DOM 158..166
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 167..188
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 189..423
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 390..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 152..157
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT MOTIF 420..423
FT /note="PDZ-binding"
FT COMPBIAS 392..423
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 182
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 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48542"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48542"
FT VARIANT 152
FT /note="Missing (in KPLBS)"
FT /evidence="ECO:0000269|PubMed:25620207"
FT /id="VAR_073430"
FT VARIANT 154
FT /note="G -> S (in KPLBS; dbSNP:rs786204795)"
FT /evidence="ECO:0000269|PubMed:25620207"
FT /id="VAR_073431"
SQ SEQUENCE 423 AA; 48451 MW; 7A02F6B0FBF8B7D4 CRC64;
MAKLTESMTN VLEGDSMDQD VESPVAIHQP KLPKQARDDL PRHISRDRTK RKIQRYVRKD
GKCNVHHGNV RETYRYLTDI FTTLVDLKWR FNLLIFVMVY TVTWLFFGMI WWLIAYIRGD
MDHIEDPSWT PCVTNLNGFV SAFLFSIETE TTIGYGYRVI TDKCPEGIIL LLIQSVLGSI
VNAFMVGCMF VKISQPKKRA ETLVFSTHAV ISMRDGKLCL MFRVGDLRNS HIVEASIRAK
LIKSKQTSEG EFIPLNQTDI NVGYYTGDDR LFLVSPLIIS HEINQQSPFW EISKAQLPKE
ELEIVVILEG MVEATGMTCQ ARSSYITSEI LWGYRFTPVL TLEDGFYEVD YNSFHETYET
STPSLSAKEL AELASRAELP LSWSVSSKLN QHAELETEEE EKNLEEQTER NGDVANLENE
SKV
