OGR1_HUMAN
ID OGR1_HUMAN Reviewed; 365 AA.
AC Q15743; Q13334; Q4VBB4; Q6IX34;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Ovarian cancer G-protein coupled receptor 1;
DE Short=OGR-1;
DE AltName: Full=G-protein coupled receptor 68;
DE AltName: Full=GPR12A;
DE AltName: Full=Sphingosylphosphorylcholine receptor;
GN Name=GPR68; Synonyms=OGR1;
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].
RX PubMed=7498459; DOI=10.1016/0014-5793(95)01196-l;
RA An S., Tsai C., Goetzl E.J.;
RT "Cloning, sequencing and tissue distribution of two related G protein-
RT coupled receptor candidates expressed prominently in human lung tissue.";
RL FEBS Lett. 375:121-124(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Ovarian carcinoma;
RX PubMed=8661159; DOI=10.1006/geno.1996.0377;
RA Xu Y., Casey G.;
RT "Identification of human OGR1, a novel G protein-coupled receptor that maps
RT to chromosome 14.";
RL Genomics 35:397-402(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RT "Isolation of cDNA coding for human orphan G protein receptor 68.";
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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 [8]
RP PRELIMINARY FUNCTION.
RX PubMed=10806476; DOI=10.1038/35010529;
RA Xu Y., Zhu K., Hong G., Wu W., Baudhuin L.M., Xiao Y.-J., Damron D.S.;
RT "Sphingosylphosphorylcholine is a ligand for ovarian cancer G-protein-
RT coupled receptor 1.";
RL Nat. Cell Biol. 2:261-267(2000).
RN [9]
RP ERRATUM OF PUBMED:10806476, AND RETRACTION NOTICE OF PUBMED:10806476.
RX PubMed=16508674; DOI=10.1038/ncb1377;
RA Xu Y., Zhu K., Hong G., Wu W., Baudhuin L.M., Xiao Y.-J., Damron D.S.;
RL Nat. Cell Biol. 8:299-299(2006).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF HIS-17; HIS-20; HIS-84;
RP HIS-89; HIS-159; HIS-175; HIS-245 AND HIS-269.
RX PubMed=12955148; DOI=10.1038/nature01905;
RA Ludwig M.-G., Vanek M., Guerini D., Gasser J.A., Jones C.E., Junker U.,
RA Hofstetter H., Wolf R.M., Seuwen K.;
RT "Proton-sensing G-protein-coupled receptors.";
RL Nature 425:93-98(2003).
RN [11]
RP INVOLVEMENT IN AI2A6, AND VARIANT AI2A6 PRO-74.
RX PubMed=27693231; DOI=10.1016/j.ajhg.2016.08.020;
RA Parry D.A., Smith C.E., El-Sayed W., Poulter J.A., Shore R.C., Logan C.V.,
RA Mogi C., Sato K., Okajima F., Harada A., Zhang H., Koruyucu M., Seymen F.,
RA Hu J.C., Simmer J.P., Ahmed M., Jafri H., Johnson C.A., Inglehearn C.F.,
RA Mighell A.J.;
RT "Mutations in the pH-sensing G-protein-coupled receptor GPR68 cause
RT amelogenesis imperfecta.";
RL Am. J. Hum. Genet. 99:984-990(2016).
RN [12]
RP VARIANT SER-39.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Proton-sensing receptor involved in pH homeostasis. May
CC represents an osteoblastic pH sensor regulating cell-mediated responses
CC to acidosis in bone. Mediates its action by association with G proteins
CC that stimulates inositol phosphate (IP) production or Ca(2+)
CC mobilization. The receptor is almost silent at pH 7.8 but fully
CC activated at pH 6.8. Also functions as a metastasis suppressor gene in
CC prostate cancer (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:12955148}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Found at low level in a wide range of tissues, but
CC significantly expressed in lung, kidney, bone and nervous system.
CC {ECO:0000269|PubMed:12955148}.
CC -!- DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A6 (AI2A6)
CC [MIM:617217]: A defect of enamel formation. The disorder involves both
CC primary and secondary dentitions. The teeth have a shiny agar jelly
CC appearance and the enamel is softer than normal. Brown pigment is
CC present in middle layers of enamel. {ECO:0000269|PubMed:27693231}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Was originally (PubMed:10806476) thought to be a receptor for
CC sphingosylphosphorylcholine (SPC). However, this work has been
CC retracted (PubMed:16508674). {ECO:0000305|PubMed:10806476,
CC ECO:0000305|PubMed:16508674}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH96071.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH96072.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH96073.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH96074.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH98567.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAT38917.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ACG60649.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=EAW81447.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GPR68ID40745ch14q32.html";
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DR EMBL; U35398; AAA79060.1; -; mRNA.
DR EMBL; U48405; AAC50596.1; -; Genomic_DNA.
DR EMBL; EU883575; ACG60649.1; ALT_INIT; mRNA.
DR EMBL; AY615372; AAT38917.1; ALT_INIT; mRNA.
DR EMBL; AL135818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81447.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC067472; AAH67472.1; -; mRNA.
DR EMBL; BC069592; AAH69592.1; -; mRNA.
DR EMBL; BC096071; AAH96071.1; ALT_INIT; mRNA.
DR EMBL; BC096072; AAH96072.1; ALT_INIT; mRNA.
DR EMBL; BC096073; AAH96073.1; ALT_INIT; mRNA.
DR EMBL; BC096074; AAH96074.1; ALT_INIT; mRNA.
DR EMBL; BC098567; AAH98567.1; ALT_INIT; mRNA.
DR CCDS; CCDS9894.2; -.
DR PIR; S68208; S68208.
DR RefSeq; NP_001171147.1; NM_001177676.1.
DR RefSeq; NP_001335366.1; NM_001348437.1.
DR RefSeq; NP_003476.3; NM_003485.3.
DR RefSeq; XP_005268167.1; XM_005268110.4.
DR RefSeq; XP_005268168.1; XM_005268111.3.
DR RefSeq; XP_005268169.1; XM_005268112.3.
DR RefSeq; XP_006720325.1; XM_006720262.3.
DR RefSeq; XP_011535498.1; XM_011537196.2.
DR RefSeq; XP_011535499.1; XM_011537197.2.
DR RefSeq; XP_011535500.1; XM_011537198.2.
DR RefSeq; XP_011535501.1; XM_011537199.2.
DR AlphaFoldDB; Q15743; -.
DR SMR; Q15743; -.
DR STRING; 9606.ENSP00000434045; -.
DR BindingDB; Q15743; -.
DR ChEMBL; CHEMBL3713916; -.
DR GuidetoPHARMACOLOGY; 114; -.
DR GlyGen; Q15743; 2 sites.
DR iPTMnet; Q15743; -.
DR PhosphoSitePlus; Q15743; -.
DR SwissPalm; Q15743; -.
DR BioMuta; GPR68; -.
DR DMDM; 3024266; -.
DR jPOST; Q15743; -.
DR MassIVE; Q15743; -.
DR PaxDb; Q15743; -.
DR PeptideAtlas; Q15743; -.
DR PRIDE; Q15743; -.
DR ProteomicsDB; 60731; -.
DR ABCD; Q15743; 3 sequenced antibodies.
DR Antibodypedia; 13584; 302 antibodies from 30 providers.
DR DNASU; 8111; -.
DR Ensembl; ENST00000531499.2; ENSP00000434045.2; ENSG00000119714.11.
DR Ensembl; ENST00000535815.5; ENSP00000440797.1; ENSG00000119714.11.
DR Ensembl; ENST00000650645.1; ENSP00000498702.1; ENSG00000119714.11.
DR GeneID; 8111; -.
DR KEGG; hsa:8111; -.
DR MANE-Select; ENST00000650645.1; ENSP00000498702.1; NM_001177676.2; NP_001171147.1.
DR UCSC; uc001xzg.4; human.
DR CTD; 8111; -.
DR DisGeNET; 8111; -.
DR GeneCards; GPR68; -.
DR HGNC; HGNC:4519; GPR68.
DR HPA; ENSG00000119714; Tissue enhanced (pituitary).
DR MalaCards; GPR68; -.
DR MIM; 601404; gene.
DR MIM; 617217; phenotype.
DR neXtProt; NX_Q15743; -.
DR OpenTargets; ENSG00000119714; -.
DR Orphanet; 100033; Hypomaturation amelogenesis imperfecta.
DR PharmGKB; PA28911; -.
DR VEuPathDB; HostDB:ENSG00000119714; -.
DR eggNOG; ENOG502QQJA; Eukaryota.
DR GeneTree; ENSGT00950000183136; -.
DR InParanoid; Q15743; -.
DR OMA; FLTCART; -.
DR OrthoDB; 716326at2759; -.
DR PhylomeDB; Q15743; -.
DR TreeFam; TF331803; -.
DR PathwayCommons; Q15743; -.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR BioGRID-ORCS; 8111; 15 hits in 1075 CRISPR screens.
DR ChiTaRS; GPR68; human.
DR GeneWiki; GPR68; -.
DR GenomeRNAi; 8111; -.
DR Pharos; Q15743; Tchem.
DR PRO; PR:Q15743; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q15743; protein.
DR Bgee; ENSG00000119714; Expressed in tendon of biceps brachii and 147 other tissues.
DR ExpressionAtlas; Q15743; baseline and differential.
DR Genevisible; Q15743; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc.
DR GO; GO:0071467; P:cellular response to pH; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0030224; P:monocyte differentiation; IEA:Ensembl.
DR GO; GO:0045656; P:negative regulation of monocyte differentiation; IEA:Ensembl.
DR GO; GO:0036035; P:osteoclast development; IEA:Ensembl.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:2001206; P:positive regulation of osteoclast development; IEA:Ensembl.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR005389; OGR1_rcpt.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01564; OGR1RECEPTOR.
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 Amelogenesis imperfecta; Cell membrane; Disease variant; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix;
KW Tumor suppressor.
FT CHAIN 1..365
FT /note="Ovarian cancer G-protein coupled receptor 1"
FT /id="PRO_0000070113"
FT TOPO_DOM 1..21
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..46
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..58
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 59..80
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..95
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..117
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..136
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..158
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..183
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..205
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..263
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 345..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 8
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 94..172
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 39
FT /note="N -> S (found in a renal cell carcinoma case;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064716"
FT VARIANT 53
FT /note="R -> Q (in dbSNP:rs2230339)"
FT /id="VAR_058714"
FT VARIANT 74
FT /note="L -> P (in AI2A6; dbSNP:rs1057517672)"
FT /evidence="ECO:0000269|PubMed:27693231"
FT /id="VAR_077874"
FT MUTAGEN 17
FT /note="H->F: Failed to stimulate IP formation at pH 6.8,
FT activity is restored at more acid pH."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 20
FT /note="H->F: Failed to stimulate IP formation at pH 6.8,
FT activity is restored at more acid pH."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 84
FT /note="H->F: Failed to stimulate IP formation at pH 6.8,
FT activity is restored at more acid pH."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 89
FT /note="H->F: No effect on pH-sensing activity."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 159
FT /note="H->F: No effect on pH-sensing activity."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 169
FT /note="H->F: Failed to stimulate IP formation at pH 6.8,
FT activity is restored at more acid pH."
FT MUTAGEN 175
FT /note="H->F: No effect on pH-sensing activity."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 245
FT /note="H->F: Severe loss pH-sensing activity."
FT /evidence="ECO:0000269|PubMed:12955148"
FT MUTAGEN 269
FT /note="H->F: Failed to stimulate IP formation at pH 6.8,
FT activity is restored at more acid pH."
FT /evidence="ECO:0000269|PubMed:12955148"
FT CONFLICT 140..142
FT /note="GVS -> RVT (in Ref. 1; AAA79060)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 365 AA; 41077 MW; 05919AFD5B842CCD CRC64;
MGNITADNSS MSCTIDHTIH QTLAPVVYVT VLVVGFPANC LSLYFGYLQI KARNELGVYL
CNLTVADLFY ICSLPFWLQY VLQHDNWSHG DLSCQVCGIL LYENIYISVG FLCCISVDRY
LAVAHPFRFH QFRTLKAAVG VSVVIWAKEL LTSIYFLMHE EVIEDENQHR VCFEHYPIQA
WQRAINYYRF LVGFLFPICL LLASYQGILR AVRRSHGTQK SRKDQIQRLV LSTVVIFLAC
FLPYHVLLLV RSVWEASCDF AKGVFNAYHF SLLLTSFNCV ADPVLYCFVS ETTHRDLARL
RGACLAFLTC SRTGRAREAY PLGAPEASGK SGAQGEEPEL LTKLHPAFQT PNSPGSGGFP
TGRLA
