GPC6A_MOUSE
ID GPC6A_MOUSE Reviewed; 928 AA.
AC Q8K4Z6; Q5DK51; Q5DK52;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=G-protein coupled receptor family C group 6 member A;
DE Flags: Precursor;
GN Name=Gprc6a;
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] (ISOFORMS 1; 2 AND 3), SUBCELLULAR LOCATION,
RP SUBUNIT, GLYCOSYLATION, AND TISSUE SPECIFICITY.
RC STRAIN=CD-1;
RX PubMed=15816861; DOI=10.1111/j.1471-4159.2005.03025.x;
RA Kuang D., Yao Y., Lam J., Tsushima R.G., Hampson D.R.;
RT "Cloning and characterization of a family C orphan G-protein coupled
RT receptor.";
RL J. Neurochem. 93:383-391(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster / NIH;
RA Lorenz-Depiereux B., Dorner M., Strom T.M.;
RT "Cloning of a metabotropic glutamate/pheromone receptor (Gprc6a).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [4]
RP FUNCTION.
RX PubMed=15576628; DOI=10.1124/mol.104.007559;
RA Wellendorph P., Hansen K.B., Balsgaard A., Greenwood J.R., Egebjerg J.,
RA Brauener-Osborne H.;
RT "Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with
RT preference for basic amino acids.";
RL Mol. Pharmacol. 67:589-597(2005).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16199532; DOI=10.1074/jbc.m505186200;
RA Pi M., Faber P., Ekema G., Jackson P.D., Ting A., Wang N.,
RA Fontilla-Poole M., Mays R.W., Brunden K.R., Harrington J.J., Quarles L.D.;
RT "Identification of a novel extracellular cation-sensing G-protein-coupled
RT receptor.";
RL J. Biol. Chem. 280:40201-40209(2005).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19050760; DOI=10.1371/journal.pone.0003858;
RA Pi M., Chen L., Huang M.Z., Zhu W., Ringhofer B., Luo J., Christenson L.,
RA Li B., Zhang J., Jackson P.D., Faber P., Brunden K.R., Harrington J.J.,
RA Quarles L.D.;
RT "GPRC6A null mice exhibit osteopenia, feminization and metabolic
RT syndrome.";
RL PLoS ONE 3:E3858-E3858(2008).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20947496; DOI=10.1074/jbc.m110.158063;
RA Pi M., Parrill A.L., Quarles L.D.;
RT "GPRC6A mediates the non-genomic effects of steroids.";
RL J. Biol. Chem. 285:39953-39964(2010).
CC -!- FUNCTION: Receptor activated by amino acids with a preference for basic
CC amino acids such as L-Lys, L-Arg and L-ornithine but also by small and
CC polar amino acids. The L-alpha amino acids respond is augmented by
CC divalent cations Ca(2+) and Mg(2+). Activated by extracellular calcium
CC and osteocalcin. Seems to act through a G(q)/G(11) and G(i)-coupled
CC pathway. Mediates the non-genomic effects of androgens in multiple
CC tissue. May coordinate nutritional and hormonal anabolic signals
CC through the sensing of extracellular amino acids, osteocalcin, divalent
CC ions and its responsiveness to anabolic steroids.
CC {ECO:0000269|PubMed:15576628, ECO:0000269|PubMed:16199532,
CC ECO:0000269|PubMed:19050760, ECO:0000269|PubMed:20947496}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:15816861}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15816861};
CC Multi-pass membrane protein {ECO:0000269|PubMed:15816861}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8K4Z6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8K4Z6-2; Sequence=VSP_016456;
CC Name=3;
CC IsoId=Q8K4Z6-3; Sequence=VSP_016457;
CC -!- TISSUE SPECIFICITY: Expressed at high level in liver, lung, spleen and
CC heart. Expressed at lower level in kidney, skeletal muscle and brain.
CC Expressed in 7 dpc, 11 dpc, 15 dpc and 17 dpc embryos.
CC {ECO:0000269|PubMed:15816861, ECO:0000269|PubMed:16199532}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15816861}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice shown normal body weight, an
CC increased fat mass, decreased lean body, hyperglycemia and insulin
CC resistance, proteinuria, renal calcium, phosphate wasting, impaired
CC bone mineral density and defective testicular function.
CC {ECO:0000269|PubMed:19050760, ECO:0000269|PubMed:20947496}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
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DR EMBL; AY735399; AAW68012.1; -; mRNA.
DR EMBL; AY735400; AAW68013.1; -; mRNA.
DR EMBL; AY735401; AAW68014.1; -; mRNA.
DR EMBL; AY101365; AAM22280.1; -; mRNA.
DR EMBL; BC108998; AAI08999.1; -; mRNA.
DR CCDS; CCDS23834.1; -. [Q8K4Z6-1]
DR RefSeq; NP_694711.1; NM_153071.1. [Q8K4Z6-1]
DR AlphaFoldDB; Q8K4Z6; -.
DR SMR; Q8K4Z6; -.
DR STRING; 10090.ENSMUSP00000020062; -.
DR BindingDB; Q8K4Z6; -.
DR ChEMBL; CHEMBL3347255; -.
DR GuidetoPHARMACOLOGY; 55; -.
DR GlyGen; Q8K4Z6; 3 sites.
DR PhosphoSitePlus; Q8K4Z6; -.
DR PaxDb; Q8K4Z6; -.
DR PRIDE; Q8K4Z6; -.
DR Antibodypedia; 19443; 285 antibodies from 27 providers.
DR DNASU; 210198; -.
DR Ensembl; ENSMUST00000020062; ENSMUSP00000020062; ENSMUSG00000019905. [Q8K4Z6-1]
DR Ensembl; ENSMUST00000218684; ENSMUSP00000152031; ENSMUSG00000019905. [Q8K4Z6-2]
DR Ensembl; ENSMUST00000219286; ENSMUSP00000151341; ENSMUSG00000019905. [Q8K4Z6-3]
DR GeneID; 210198; -.
DR KEGG; mmu:210198; -.
DR UCSC; uc007fau.1; mouse. [Q8K4Z6-1]
DR UCSC; uc007fav.1; mouse. [Q8K4Z6-2]
DR UCSC; uc007faw.1; mouse. [Q8K4Z6-3]
DR CTD; 222545; -.
DR MGI; MGI:2429498; Gprc6a.
DR VEuPathDB; HostDB:ENSMUSG00000019905; -.
DR eggNOG; KOG1056; Eukaryota.
DR GeneTree; ENSGT00940000158416; -.
DR HOGENOM; CLU_005389_1_0_1; -.
DR InParanoid; Q8K4Z6; -.
DR OMA; VFIITDQ; -.
DR OrthoDB; 119538at2759; -.
DR PhylomeDB; Q8K4Z6; -.
DR TreeFam; TF331269; -.
DR Reactome; R-MMU-416476; G alpha (q) signalling events.
DR Reactome; R-MMU-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR BioGRID-ORCS; 210198; 0 hits in 73 CRISPR screens.
DR PRO; PR:Q8K4Z6; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8K4Z6; protein.
DR Bgee; ENSMUSG00000019905; Expressed in left lung lobe and 2 other tissues.
DR Genevisible; Q8K4Z6; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0043200; P:response to amino acid; IDA:UniProtKB.
DR Gene3D; 2.10.50.30; -; 1.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR000337; GPCR_3.
DR InterPro; IPR011500; GPCR_3_9-Cys_dom.
DR InterPro; IPR038550; GPCR_3_9-Cys_sf.
DR InterPro; IPR017978; GPCR_3_C.
DR InterPro; IPR000068; GPCR_3_Ca_sens_rcpt-rel.
DR InterPro; IPR017979; GPCR_3_CS.
DR InterPro; IPR028082; Peripla_BP_I.
DR PANTHER; PTHR24061; PTHR24061; 1.
DR Pfam; PF00003; 7tm_3; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF07562; NCD3G; 1.
DR PRINTS; PR00592; CASENSINGR.
DR PRINTS; PR00248; GPCRMGR.
DR SUPFAM; SSF53822; SSF53822; 1.
DR PROSITE; PS00980; G_PROTEIN_RECEP_F3_2; 1.
DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..928
FT /note="G-protein coupled receptor family C group 6 member
FT A"
FT /id="PRO_0000043197"
FT TOPO_DOM 21..594
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 595..615
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 616..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 631..651
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 652..669
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 670..690
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 691..706
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 707..727
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 728..750
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 751..771
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 772..784
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 785..805
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 806..812
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 813..833
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 834..928
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 555
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 131
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 271..445
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15816861"
FT /id="VSP_016456"
FT VAR_SEQ 446..516
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15816861"
FT /id="VSP_016457"
SQ SEQUENCE 928 AA; 104213 MW; D670E3FEC700BD9B CRC64;
MALLITVVTC FMIILDTSQS CHTPDDFVAI TSPGHIMIGG LFAIHEKMLS SDDHPRRPQI
QKCAGFEISV FLQTLAMIHS IEMINNSTLL SGVKLGYEIY DTCTEVTAAM AATLRFLSKF
NCSRETVVFQ CDYSSYMPRV KAVIGAGYSE TSIAVSRMLN LQLMPQVSYE STAEILSDKI
RFPSFLRTVP SDFYQTKAMA HLIRQSGWNW IGAITTDDDY GRLALNTFAI QAAENNVCIA
FKEVLPAFLS DNTIEVRINQ TLEKIIAEAQ VNVIVVFLRK FHVFNLFTKA IERKISKIWI
ASDNWSTATK IITIPNVKKL GKVVGFAFRR GNTSSFHSFL QTLHMYPNDN NKPLHEFAML
VSACKYIKDG DLSQCISNYS QATLTYDTTK TIENHLFKRN DFLWHYTEPG LIYSIQLAVF
ALGHAIRDLC QARDCKKPNA FQPWELLAVL KNVTFTDGRN SFHFDAHGDL NTGYDVVLWK
ETNGLMTVTK MAEYDLQRDV FITTNQETKH EFRKLKQILS KCSKECSPGQ MKKATGSQHS
CCYECVSCPE NHYSNETDMD HCLLCNNETH WAPVRSTTCF EKEVEYLDWD DSLALLLIAL
SLLGIAFVLA IGIIFTRNLK TPVVKSSGGL VVCYVMLICH ALNFASTGFF IGEPQDFACK
TRQTLFGVSF TLCVSCILTK SLKILLAFSF DPKLTMFLKC LYRPVPIVLT CTGIQVVICT
LWLVLAAPSV EENISLPRVI ILECEEGSAL AFGTMLGYIT VLAFICFVFA FKGRKLPENY
NEAKFLTFGM LIYFIAWITF IPVYTTTFGK YLPAVEIIVI LISNYGILCC IFFPKCYIIL
CKQKTNTKSA FLQMVYNYSA HSVDSLALSH VSLDSTSYDT ATTNQSPGNK MTACQNDNHL
PAQVLPHTGT AKTIKASKTL RQKRSSSI
