GPR3_HUMAN
ID GPR3_HUMAN Reviewed; 330 AA.
AC P46089; A8K570;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=G-protein coupled receptor 3;
DE AltName: Full=ACCA orphan receptor;
GN Name=GPR3; Synonyms=ACCA;
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 [GENOMIC DNA].
RX PubMed=8530049; DOI=10.1006/geno.1995.1154;
RA Song Z.-H., Modi W., Bonner T.I.;
RT "Molecular cloning and chromosomal localization of human genes encoding
RT three closely related G protein-coupled receptors.";
RL Genomics 28:347-349(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7698767; DOI=10.1006/geno.1994.1635;
RA Iismaa T.P., Kiefer J., Liu M.L., Baker E., Sutherland G.R., Shine J.;
RT "Isolation and chromosomal localization of a novel human G-protein-coupled
RT receptor (GPR3) expressed predominantly in the central nervous system.";
RL Genomics 24:391-394(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7639700; DOI=10.1042/bj3090837;
RA Eggerickx D., Denef J.F., Labbe O., Hayashi Y., Refetoff S., Vassart G.,
RA Parmentier M., Libert F.;
RT "Molecular cloning of an orphan G-protein-coupled receptor that
RT constitutively activates adenylate cyclase.";
RL Biochem. J. 309:837-843(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-292.
RX PubMed=7851889; DOI=10.1006/geno.1994.1549;
RA Marchese A., Docherty J.M., Nguyen T., Heiber M., Cheng R., Heng H.H.Q.,
RA Tsui L.-C., Shi X., George S.R., O'Dowd B.F.;
RT "Cloning of human genes encoding novel G protein-coupled receptors.";
RL Genomics 23:609-618(1994).
RN [9]
RP PRELIMINARY FUNCTION.
RX PubMed=12220620; DOI=10.1016/s0898-6568(02)00041-4;
RA Uhlenbrock K., Gassenhuber J., Kostenis E.;
RT "Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12
RT family of constitutively active G protein-coupled receptors.";
RL Cell. Signal. 14:941-953(2002).
RN [10]
RP SHOWS THAT IT IS NOT A SPHINGOSINE 1-PHOSPHATE RECEPTOR.
RX PubMed=19286662; DOI=10.1074/jbc.m806516200;
RA Yin H., Chu A., Li W., Wang B., Shelton F., Otero F., Nguyen D.G.,
RA Caldwell J.S., Chen Y.A.;
RT "Lipid G protein-coupled receptor ligand identification using beta-arrestin
RT PathHunter assay.";
RL J. Biol. Chem. 284:12328-12338(2009).
RN [11]
RP FUNCTION.
RX PubMed=19213921; DOI=10.1126/science.1160649;
RA Thathiah A., Spittaels K., Hoffmann M., Staes M., Cohen A., Horre K.,
RA Vanbrabant M., Coun F., Baekelandt V., Delacourte A., Fischer D.F.,
RA Pollet D., De Strooper B., Merchiers P.;
RT "The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide
RT generation in neurons.";
RL Science 323:946-951(2009).
CC -!- FUNCTION: Orphan receptor with constitutive G(s) signaling activity
CC that activate cyclic AMP. Has a potential role in modulating a number
CC of brain functions, including behavioral responses to stress (By
CC similarity), amyloid-beta peptide generation in neurons and neurite
CC outgrowth (By similarity). Maintains also meiotic arrest in oocytes (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:19213921}.
CC -!- INTERACTION:
CC P46089; P05067-4: APP; NbExp=2; IntAct=EBI-3909653, EBI-302641;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the central nervous
CC system, and at low levels in the lung, kidney, testis, ovary and eye.
CC Highly expressed in regions of the brain implicated in the Alzheimer
CC disease.
CC -!- INDUCTION: Overexpression stimulates amyloid-beta production.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Was originally (PubMed:12220620) thought to be a receptor for
CC sphingosine 1-phosphate. PubMed:19286662 demonstrated that it is not
CC the case. {ECO:0000305|PubMed:12220620}.
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DR EMBL; U18550; AAB60402.1; -; Genomic_DNA.
DR EMBL; L32831; AAA73560.1; -; Genomic_DNA.
DR EMBL; X83956; CAA58787.1; -; Genomic_DNA.
DR EMBL; AK291185; BAF83874.1; -; mRNA.
DR EMBL; AK314868; BAG37383.1; -; mRNA.
DR EMBL; AL096774; CAC18517.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07754.1; -; Genomic_DNA.
DR EMBL; BC032702; AAH32702.1; -; mRNA.
DR EMBL; U13668; AAA64594.1; -; Genomic_DNA.
DR CCDS; CCDS303.1; -.
DR PIR; A55689; A55689.
DR RefSeq; NP_005272.1; NM_005281.3.
DR AlphaFoldDB; P46089; -.
DR SMR; P46089; -.
DR BioGRID; 109088; 11.
DR IntAct; P46089; 11.
DR STRING; 9606.ENSP00000363136; -.
DR ChEMBL; CHEMBL4523856; -.
DR GuidetoPHARMACOLOGY; 83; -.
DR TCDB; 9.A.14.2.7; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P46089; 1 site.
DR iPTMnet; P46089; -.
DR PhosphoSitePlus; P46089; -.
DR BioMuta; GPR3; -.
DR DMDM; 1170006; -.
DR MassIVE; P46089; -.
DR PaxDb; P46089; -.
DR PeptideAtlas; P46089; -.
DR PRIDE; P46089; -.
DR ProteomicsDB; 55716; -.
DR Antibodypedia; 3339; 371 antibodies from 39 providers.
DR DNASU; 2827; -.
DR Ensembl; ENST00000374024.4; ENSP00000363136.3; ENSG00000181773.7.
DR GeneID; 2827; -.
DR KEGG; hsa:2827; -.
DR MANE-Select; ENST00000374024.4; ENSP00000363136.3; NM_005281.4; NP_005272.1.
DR UCSC; uc001bod.5; human.
DR CTD; 2827; -.
DR DisGeNET; 2827; -.
DR GeneCards; GPR3; -.
DR HGNC; HGNC:4484; GPR3.
DR HPA; ENSG00000181773; Tissue enhanced (brain).
DR MIM; 600241; gene.
DR neXtProt; NX_P46089; -.
DR OpenTargets; ENSG00000181773; -.
DR PharmGKB; PA28872; -.
DR VEuPathDB; HostDB:ENSG00000181773; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01000000214392; -.
DR HOGENOM; CLU_065071_0_0_1; -.
DR InParanoid; P46089; -.
DR OMA; GTFASCW; -.
DR OrthoDB; 903801at2759; -.
DR PhylomeDB; P46089; -.
DR TreeFam; TF330052; -.
DR PathwayCommons; P46089; -.
DR SignaLink; P46089; -.
DR BioGRID-ORCS; 2827; 7 hits in 1075 CRISPR screens.
DR GeneWiki; GPR3; -.
DR GenomeRNAi; 2827; -.
DR Pharos; P46089; Tchem.
DR PRO; PR:P46089; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P46089; protein.
DR Bgee; ENSG00000181773; Expressed in secondary oocyte and 97 other tissues.
DR ExpressionAtlas; P46089; baseline and differential.
DR Genevisible; P46089; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0040020; P:regulation of meiotic nuclear division; IEA:Ensembl.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000984; GPR3.
DR InterPro; IPR000723; GPR_3/6/12_orphan.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00648; GPR3ORPHANR.
DR PRINTS; PR00644; GPRORPHANR.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; G-protein coupled receptor; Glycoprotein; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..330
FT /note="G-protein coupled receptor 3"
FT /id="PRO_0000069510"
FT TOPO_DOM 1..42
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..62
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..74
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..98
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 99..110
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..132
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 154..173
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..198
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..217
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 218..245
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 246..272
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..277
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..299
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 300..330
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT LIPID 313
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 222
FT /note="R -> H (in dbSNP:rs734852)"
FT /id="VAR_011859"
SQ SEQUENCE 330 AA; 35010 MW; 0F82E89200968D1E CRC64;
MMWGAGSPLA WLSAGSGNVN VSSVGPAEGP TGPAAPLPSP KAWDVVLCIS GTLVSCENAL
VVAIIVGTPA FRAPMFLLVG SLAVADLLAG LGLVLHFAAV FCIGSAEMSL VLVGVLAMAF
TASIGSLLAI TVDRYLSLYN ALTYYSETTV TRTYVMLALV WGGALGLGLL PVLAWNCLDG
LTTCGVVYPL SKNHLVVLAI AFFMVFGIML QLYAQICRIV CRHAQQIALQ RHLLPASHYV
ATRKGIATLA VVLGAFAACW LPFTVYCLLG DAHSPPLYTY LTLLPATYNS MINPIIYAFR
NQDVQKVLWA VCCCCSSSKI PFRSRSPSDV
