RAI3_MOUSE
ID RAI3_MOUSE Reviewed; 356 AA.
AC Q8BHL4; Q8K067; Q8K1G5;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 124.
DE RecName: Full=Retinoic acid-induced protein 3;
DE AltName: Full=G-protein coupled receptor family C group 5 member A;
DE AltName: Full=Retinoic acid-induced gene 1 protein;
DE Short=RAIG-1;
GN Name=Gprc5a; Synonyms=Rai3, Raig1;
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 [GENOMIC DNA].
RC STRAIN=129/Sv; TISSUE=Embryonic stem cell;
RX PubMed=14706456; DOI=10.1016/s0888-7543(03)00237-4;
RA Tao Q., Cheng Y., Clifford J., Lotan R.;
RT "Characterization of the murine orphan G-protein-coupled receptor gene Rai3
RT and its regulation by retinoic acid.";
RL Genomics 83:270-280(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-349, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [4]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND
RP 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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND INTERACTION WITH EGFR.
RX PubMed=25744720; DOI=10.1158/0008-5472.can-14-2005;
RA Zhong S., Yin H., Liao Y., Yao F., Li Q., Zhang J., Jiao H., Zhao Y.,
RA Xu D., Liu S., Song H., Gao Y., Liu J., Ma L., Pang Z., Yang R., Ding C.,
RA Sun B., Lin X., Ye X., Guo W., Han B., Zhou B.P., Chin Y.E., Deng J.;
RT "Lung tumor suppressor GPRC5A binds EGFR and restrains its effector
RT signaling.";
RL Cancer Res. 75:1801-1814(2015).
CC -!- FUNCTION: Orphan receptor. Could be involved in modulating
CC differentiation and maintaining homeostasis of epithelial cells. This
CC retinoic acid-inducible GPCR provides evidence for a possible
CC interaction between retinoid and G-protein signaling pathways.
CC Functions as a negative modulator of EGFR signaling (PubMed:25744720).
CC Acts as a lung tumor suppressor (PubMed:18000218).
CC {ECO:0000269|PubMed:18000218, ECO:0000269|PubMed:25744720}.
CC -!- SUBUNIT: Interacts (via its transmembrane domain) with EGFR
CC (PubMed:25744720). {ECO:0000269|PubMed:25744720}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18000218};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in normal fetal and adult
CC lung. Almost undetectable or expressed at very low levels in other
CC tissues. {ECO:0000269|PubMed:18000218}.
CC -!- INDUCTION: By all-trans retinoic acid (ATRA).
CC {ECO:0000269|PubMed:14706456}.
CC -!- PTM: Phosphorylated in two conserved double-tyrosine motifs, TYR-
CC 318/TYR-321 and TYR-346/TYR-349 by EGFR. TYR-318 and TYR-321 are the
CC preferred residues responsible for EGFR-mediated GPRC5A
CC phosphorylation. {ECO:0000250|UniProtKB:Q8NFJ5}.
CC -!- DISRUPTION PHENOTYPE: Homozygous deficient mice developed more lung
CC tumors during 1-2 years than heterozygous or wild-type mice.
CC {ECO:0000269|PubMed:18000218}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL87526.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AH011528; AAL87526.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC034063; AAH34063.1; -; mRNA.
DR EMBL; BC036173; AAH36173.1; -; mRNA.
DR EMBL; BC039217; AAH39217.1; -; mRNA.
DR CCDS; CCDS20644.1; -.
DR AlphaFoldDB; Q8BHL4; -.
DR SMR; Q8BHL4; -.
DR IntAct; Q8BHL4; 3.
DR MINT; Q8BHL4; -.
DR STRING; 10090.ENSMUSP00000061062; -.
DR GlyGen; Q8BHL4; 1 site.
DR iPTMnet; Q8BHL4; -.
DR PhosphoSitePlus; Q8BHL4; -.
DR MaxQB; Q8BHL4; -.
DR PaxDb; Q8BHL4; -.
DR PRIDE; Q8BHL4; -.
DR ProteomicsDB; 254978; -.
DR MGI; MGI:1891250; Gprc5a.
DR eggNOG; ENOG502RRIY; Eukaryota.
DR InParanoid; Q8BHL4; -.
DR PhylomeDB; Q8BHL4; -.
DR ChiTaRS; Gprc5a; mouse.
DR PRO; PR:Q8BHL4; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BHL4; protein.
DR GO; GO:0070062; C:extracellular exosome; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
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; IMP:UniProtKB.
DR InterPro; IPR017978; GPCR_3_C.
DR Pfam; PF00003; 7tm_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; G-protein coupled receptor; Glycoprotein; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix; Tumor suppressor.
FT CHAIN 1..356
FT /note="Retinoic acid-induced protein 3"
FT /id="PRO_0000206896"
FT TOPO_DOM 1..35
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 36..56
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..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..101
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 102..122
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 132..152
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..178
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 179..199
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..214
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 215..235
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..244
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 245..265
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..356
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 336..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFJ5"
FT MOD_RES 318
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFJ5"
FT MOD_RES 321
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFJ5"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFJ5"
FT MOD_RES 346
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFJ5"
FT MOD_RES 349
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 196
FT /note="T -> A (in Ref. 1; AAL87526)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 356 AA; 40101 MW; 08B632F228381C01 CRC64;
MTTPTTAPSG CRSDLDSRYH RLCDLAEGWG IALETLAAVG AVATVACMFA LVFLICKVQD
SNKRKMLPAQ FLFLLGVLGV FGLTFAFIIK LDGATGPTRF FLFGVLFAIC FSCLLAHAFN
LIKLVRGRKP LSWLVILSLA VGFSLVQDVI AIEYLVLTMN RTNVNVFSEL PAPRRNEDFV
MLLIYVLVLM VLTFFTSFLV FCGSFSGWKR HGFHICFTSF LSIAIWVAWI VLLLIPDIDR
KWDDTILSTA LVANGWVFLA FYILPEFRQL PRQRSPTDYP VEDAFCKPQL MKQSYGVENR
AYSQEEITQG LEMGDTLYAP YSTHFQLQNH QKDFSIPRAQ APASPYNDYE GRKGDS
