RAI3_HUMAN
ID RAI3_HUMAN Reviewed; 357 AA.
AC Q8NFJ5; B3KV45; O95357;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Retinoic acid-induced protein 3;
DE AltName: Full=G-protein coupled receptor family C group 5 member A;
DE AltName: Full=Phorbol ester induced gene 1 {ECO:0000303|PubMed:8832110};
DE Short=PEIG-1;
DE AltName: Full=Retinoic acid-induced gene 1 protein;
DE Short=RAIG-1;
GN Name=GPRC5A; Synonyms=GPCR5A, RAI3, RAIG1;
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=Colon carcinoma;
RX PubMed=8832110;
RA Cafferata E.G., Gonzalez-Guerrico A.M., Pivetta O.H., Santa-Coloma T.A.;
RT "Identification by differential display of a mRNA specifically induced by
RT 12-O-tetradecanoylphorbol-13-acetate (TPA) in T84 human colon carcinoma
RT cells.";
RL Cell. Mol. Biol. 42:797-804(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INDUCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=9857033; DOI=10.1074/jbc.273.52.35008;
RA Cheng Y., Lotan R.;
RT "Molecular cloning and characterization of a novel retinoic acid-inducible
RT gene that encodes a putative G protein-coupled receptor.";
RL J. Biol. Chem. 273:35008-35015(1998).
RN [3]
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 [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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 TISSUE SPECIFICITY.
RX PubMed=10783259; DOI=10.1006/geno.2000.6164;
RA Braeuner-Osborne H., Krogsgaard-Larsen P.;
RT "Sequence and expression pattern of a novel human orphan G-protein-coupled
RT receptor, GPRC5B, a family C receptor with a short amino-terminal domain.";
RL Genomics 65:121-128(2000).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=10945465; DOI=10.1006/geno.2000.6226;
RA Robbins M.J., Michalovich D., Hill J., Calver A.R., Medhurst A.D.,
RA Gloger I., Sims M.A., Middlemiss D.N., Pangalos M.N.;
RT "Molecular cloning and characterization of two novel retinoic acid-
RT inducible orphan G-protein-coupled receptors (GPRC5B and GPRC5C).";
RL Genomics 67:8-18(2000).
RN [8]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=18000218; DOI=10.1093/jnci/djm208;
RA Tao Q., Fujimoto J., Men T., Ye X., Deng J., Lacroix L., Clifford J.L.,
RA Mao L., Van Pelt C.S., Lee J.J., Lotan D., Lotan R.;
RT "Identification of the retinoic acid-inducible Gprc5a as a new lung tumor
RT suppressor gene.";
RL J. Natl. Cancer Inst. 99:1668-1682(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-345, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301 AND SER-345, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-345 AND TYR-347, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INTERACTION WITH EGFR, AND PHOSPHORYLATION AT TYR-317; TYR-320; TYR-347 AND
RP TYR-350 BY EGFR.
RX PubMed=25311788; DOI=10.1186/1476-4598-13-233;
RA Lin X., Zhong S., Ye X., Liao Y., Yao F., Yang X., Sun B., Zhang J., Li Q.,
RA Gao Y., Wang Y., Liu J., Han B., Chin Y.E., Zhou B.P., Deng J.;
RT "EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung
RT cancer.";
RL Mol. Cancer 13:233-233(2014).
CC -!- FUNCTION: Orphan receptor. Could be involved in modulating
CC differentiation and maintaining homeostasis of epithelial cells. This
CC retinoic acid-inducible GPCR provide evidence for a possible
CC interaction between retinoid and G-protein signaling pathways.
CC Functions as a negative modulator of EGFR signaling (By similarity).
CC May act as a lung tumor suppressor (PubMed:18000218).
CC {ECO:0000250|UniProtKB:Q8BHL4, ECO:0000269|PubMed:18000218}.
CC -!- SUBUNIT: Interacts (via its transmembrane domain) with EGFR.
CC {ECO:0000269|PubMed:25311788}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9857033};
CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:9857033}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localized in perinuclear vesicles, probably Golgi-
CC associated vesicles. {ECO:0000269|PubMed:18000218}.
CC -!- TISSUE SPECIFICITY: Expressed at high level in fetal and adult lung
CC tissues but repressed in most human lung cancers (PubMed:9857033,
CC PubMed:18000218). Constitutively expressed in fetal kidney and adult
CC placenta, kidney, prostate, testis, ovary, small intestine, colon,
CC stomach, and spinal cord at low to moderate levels. Not detectable in
CC fetal heart, brain, and liver and adult heart, brain, liver, skeletal
CC muscle, pancreas, spleen, thymus, and peripheral leukocytes. According
CC to PubMed:10783259, expressed at low but detectable level in pancreas
CC and heart. {ECO:0000269|PubMed:10783259, ECO:0000269|PubMed:10945465,
CC ECO:0000269|PubMed:18000218, ECO:0000269|PubMed:9857033}.
CC -!- INDUCTION: By all-trans retinoic acid (ATRA).
CC {ECO:0000269|PubMed:9857033}.
CC -!- PTM: Phosphorylated in two conserved double-tyrosine motifs, TYR-
CC 317/TYR-320 and TYR-347/TYR-350, by EGFR; leading to inactivation of
CC the tumor suppressive function of GPRC5A in lung cancer cells. TYR-317
CC and TYR-320 are the preferred residues responsible for EGFR-mediated
CC GPRC5A phosphorylation. {ECO:0000269|PubMed:25311788}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF506289; AAM77594.1; -; mRNA.
DR EMBL; AF095448; AAC98506.1; -; mRNA.
DR EMBL; AK001761; BAA91890.1; -; mRNA.
DR EMBL; AK122672; BAG53657.1; -; mRNA.
DR EMBL; CH471094; EAW96289.1; -; Genomic_DNA.
DR EMBL; BC003665; AAH03665.1; -; mRNA.
DR CCDS; CCDS8657.1; -.
DR RefSeq; NP_003970.1; NM_003979.3.
DR AlphaFoldDB; Q8NFJ5; -.
DR SMR; Q8NFJ5; -.
DR BioGRID; 114514; 81.
DR IntAct; Q8NFJ5; 33.
DR MINT; Q8NFJ5; -.
DR STRING; 9606.ENSP00000014914; -.
DR ChEMBL; CHEMBL4523896; -.
DR DrugBank; DB00755; Tretinoin.
DR GlyGen; Q8NFJ5; 1 site.
DR iPTMnet; Q8NFJ5; -.
DR PhosphoSitePlus; Q8NFJ5; -.
DR SwissPalm; Q8NFJ5; -.
DR BioMuta; GPRC5A; -.
DR DMDM; 46396943; -.
DR EPD; Q8NFJ5; -.
DR jPOST; Q8NFJ5; -.
DR MassIVE; Q8NFJ5; -.
DR MaxQB; Q8NFJ5; -.
DR PaxDb; Q8NFJ5; -.
DR PeptideAtlas; Q8NFJ5; -.
DR PRIDE; Q8NFJ5; -.
DR ProteomicsDB; 73316; -.
DR Antibodypedia; 1914; 421 antibodies from 36 providers.
DR DNASU; 9052; -.
DR Ensembl; ENST00000014914.6; ENSP00000014914.6; ENSG00000013588.9.
DR GeneID; 9052; -.
DR KEGG; hsa:9052; -.
DR MANE-Select; ENST00000014914.6; ENSP00000014914.6; NM_003979.4; NP_003970.1.
DR UCSC; uc001rba.4; human.
DR CTD; 9052; -.
DR DisGeNET; 9052; -.
DR GeneCards; GPRC5A; -.
DR HGNC; HGNC:9836; GPRC5A.
DR HPA; ENSG00000013588; Tissue enhanced (lung, urinary bladder).
DR MIM; 604138; gene.
DR neXtProt; NX_Q8NFJ5; -.
DR OpenTargets; ENSG00000013588; -.
DR PharmGKB; PA34194; -.
DR VEuPathDB; HostDB:ENSG00000013588; -.
DR eggNOG; ENOG502RRIY; Eukaryota.
DR GeneTree; ENSGT00950000182961; -.
DR HOGENOM; CLU_044162_0_0_1; -.
DR InParanoid; Q8NFJ5; -.
DR OMA; YHRLCDT; -.
DR OrthoDB; 807909at2759; -.
DR PhylomeDB; Q8NFJ5; -.
DR TreeFam; TF321410; -.
DR PathwayCommons; Q8NFJ5; -.
DR SignaLink; Q8NFJ5; -.
DR BioGRID-ORCS; 9052; 17 hits in 1075 CRISPR screens.
DR ChiTaRS; GPRC5A; human.
DR GeneWiki; GPRC5A; -.
DR GenomeRNAi; 9052; -.
DR Pharos; Q8NFJ5; Tbio.
DR PRO; PR:Q8NFJ5; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8NFJ5; protein.
DR Bgee; ENSG00000013588; Expressed in amniotic fluid and 161 other tissues.
DR ExpressionAtlas; Q8NFJ5; baseline and differential.
DR Genevisible; Q8NFJ5; HS.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IDA:BHF-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR GO; GO:0030295; F:protein kinase activator activity; IBA:GO_Central.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR017978; GPCR_3_C.
DR Pfam; PF00003; 7tm_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasmic vesicle; G-protein coupled receptor;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix; Tumor suppressor.
FT CHAIN 1..357
FT /note="Retinoic acid-induced protein 3"
FT /id="PRO_0000206895"
FT TOPO_DOM 1..33
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 34..54
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 69..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..97
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 98..118
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..129
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 130..150
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 151..176
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 177..197
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 213..233
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 234..247
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 248..268
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 269..357
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 317
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25311788"
FT MOD_RES 320
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25311788"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 347
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25311788,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 350
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:25311788"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 9
FT /note="C -> F (in dbSNP:rs11550683)"
FT /id="VAR_049281"
FT VARIANT 118
FT /note="S -> G (in dbSNP:rs850932)"
FT /id="VAR_018296"
FT VARIANT 182
FT /note="T -> A (in dbSNP:rs12368599)"
FT /id="VAR_049282"
FT CONFLICT 292
FT /note="S -> G (in Ref. 1; AAM77594)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 357 AA; 40251 MW; 7BEB524BF6F307E5 CRC64;
MATTVPDGCR NGLKSKYYRL CDKAEAWGIV LETVATAGVV TSVAFMLTLP ILVCKVQDSN
RRKMLPTQFL FLLGVLGIFG LTFAFIIGLD GSTGPTRFFL FGILFSICFS CLLAHAVSLT
KLVRGRKPLS LLVILGLAVG FSLVQDVIAI EYIVLTMNRT NVNVFSELSA PRRNEDFVLL
LTYVLFLMAL TFLMSSFTFC GSFTGWKRHG AHIYLTMLLS IAIWVAWITL LMLPDFDRRW
DDTILSSALA ANGWVFLLAY VSPEFWLLTK QRNPMDYPVE DAFCKPQLVK KSYGVENRAY
SQEEITQGFE ETGDTLYAPY STHFQLQNQP PQKEFSIPRA HAWPSPYKDY EVKKEGS
