GPR31_HUMAN
ID GPR31_HUMAN Reviewed; 319 AA.
AC O00270; B0M0K2; Q4VBL3; Q9NQ20;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid receptor;
DE Short=12-(S)-HETE receptor {ECO:0000303|PubMed:21712392};
DE Short=12-HETER {ECO:0000303|PubMed:21712392};
DE AltName: Full=G-protein coupled receptor 31 {ECO:0000303|PubMed:9205127};
DE AltName: Full=GPR31/12-HETER {ECO:0000303|PubMed:26965684};
GN Name=GPR31;
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], AND VARIANT ARG-91.
RC TISSUE=Placenta;
RX PubMed=9205127; DOI=10.1006/geno.1997.4754;
RA Zingoni A., Rocchi M., Storlazzi C.T., Bernardini G., Santoni A.,
RA Napolitano M.;
RT "Isolation and chromosomal localization of GPR31, a human gene encoding a
RT putative G protein-coupled receptor.";
RL Genomics 42:519-523(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-91.
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-91.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-91.
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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21712392; DOI=10.1074/jbc.m110.216564;
RA Guo Y., Zhang W., Giroux C., Cai Y., Ekambaram P., Dilly A.K., Hsu A.,
RA Zhou S., Maddipati K.R., Liu J., Joshi S., Tucker S.C., Lee M.J.,
RA Honn K.V.;
RT "Identification of the orphan G protein-coupled receptor GPR31 as a
RT receptor for 12-(S)-hydroxyeicosatetraenoic acid.";
RL J. Biol. Chem. 286:33832-33840(2011).
RN [7]
RP INDUCTION, AND FUNCTION.
RX PubMed=26965684; DOI=10.1096/fj.201500076;
RA Honn K.V., Guo Y., Cai Y., Lee M.J., Dyson G., Zhang W., Tucker S.C.;
RT "12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid
RT receptor, is significantly up-regulated in prostate cancer and plays a
RT critical role in prostate cancer progression.";
RL FASEB J. 30:2360-2369(2016).
RN [8]
RP SUBCELLULAR LOCATION, INTERACTION WITH KRAS, AND FUNCTION.
RX PubMed=28619714; DOI=10.1083/jcb.201609096;
RA Fehrenbacher N., Tojal da Silva I., Ramirez C., Zhou Y., Cho K.J.,
RA Kuchay S., Shi J., Thomas S., Pagano M., Hancock J.F., Bar-Sagi D.,
RA Philips M.R.;
RT "The G protein-coupled receptor GPR31 promotes membrane association of
RT KRAS.";
RL J. Cell Biol. 216:2329-2338(2017).
RN [9]
RP FUNCTION.
RX PubMed=29227475; DOI=10.1038/nm.4451;
RA Zhang X.J., Cheng X., Yan Z.Z., Fang J., Wang X., Wang W., Liu Z.Y.,
RA Shen L.J., Zhang P., Wang P.X., Liao R., Ji Y.X., Wang J.Y., Tian S.,
RA Zhu X.Y., Zhang Y., Tian R.F., Wang L., Ma X.L., Huang Z., She Z.G., Li H.;
RT "An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic
RT ischemia-reperfusion injury.";
RL Nat. Med. 24:73-83(2018).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31119277; DOI=10.1093/jb/mvz042;
RA Mashiko M., Kurosawa A., Tani Y., Tsuji T., Takeda S.;
RT "GPR31 and GPR151 are activated under acidic conditions.";
RL J. Biochem. 0:0-0(2019).
CC -!- FUNCTION: High-affinity receptor for 12-(S)-hydroxy-5,8,10,14-
CC eicosatetraenoic acid (12-S-HETE), with much lower affinities for other
CC HETE isomers (PubMed:21712392, PubMed:29227475). 12-S-HETE is a
CC eicosanoid, a 12-lipoxygenase (ALOX12) metabolite of arachidonic acid,
CC involved in many physiologic and pathologic processes (PubMed:26965684,
CC PubMed:28619714, PubMed:29227475). 12-S-HETE-binding leads to
CC activation of ERK1/2 (MAPK3/MAPK1), MEK, and NF-kappa-B pathways
CC leading to cell growth (PubMed:21712392, PubMed:29227475). Plays a
CC crucial role for proliferation, survival and macropinocytosis of KRAS-
CC dependent cancer cells by mediating the translocation of KRAS from the
CC endoplasmic reticulum to the plasma membrane (PM) and its association
CC with the PM (PubMed:28619714). Contributes to enhanced immune responses
CC by inducing dendrite protrusion of small intestinal CX3CR1(+)
CC phagocytes for the uptake of luminal antigens (By similarity). Acts
CC also as a key receptor for 12-(S)-HETE-mediated liver ischemia
CC reperfusion injury (PubMed:29227475). {ECO:0000250|UniProtKB:F8VQN3,
CC ECO:0000269|PubMed:21712392, ECO:0000269|PubMed:26965684,
CC ECO:0000269|PubMed:28619714, ECO:0000269|PubMed:29227475}.
CC -!- FUNCTION: Proton-sensing G protein-coupled receptor.
CC {ECO:0000269|PubMed:31119277}.
CC -!- SUBUNIT: Interacts with KRAS; in a farnesylation-dependent manner.
CC {ECO:0000269|PubMed:28619714}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21712392,
CC ECO:0000269|PubMed:28619714, ECO:0000269|PubMed:31119277}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- INDUCTION: Up-regulated in prostate cancer.
CC {ECO:0000269|PubMed:26965684}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; U65402; AAC51375.1; -; Genomic_DNA.
DR EMBL; EU432117; ABY87916.1; -; Genomic_DNA.
DR EMBL; AL121935; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47505.1; -; Genomic_DNA.
DR EMBL; BC095537; AAH95537.1; -; mRNA.
DR CCDS; CCDS5299.1; -.
DR RefSeq; NP_005290.2; NM_005299.2.
DR AlphaFoldDB; O00270; -.
DR SMR; O00270; -.
DR BioGRID; 109111; 3.
DR STRING; 9606.ENSP00000355799; -.
DR ChEMBL; CHEMBL4523859; -.
DR GlyGen; O00270; 1 site.
DR BioMuta; GPR31; -.
DR jPOST; O00270; -.
DR PaxDb; O00270; -.
DR PeptideAtlas; O00270; -.
DR PRIDE; O00270; -.
DR Antibodypedia; 2933; 122 antibodies from 26 providers.
DR DNASU; 2853; -.
DR Ensembl; ENST00000366834.2; ENSP00000355799.2; ENSG00000120436.4.
DR GeneID; 2853; -.
DR KEGG; hsa:2853; -.
DR MANE-Select; ENST00000366834.2; ENSP00000355799.2; NM_005299.3; NP_005290.2.
DR UCSC; uc011egq.3; human.
DR CTD; 2853; -.
DR DisGeNET; 2853; -.
DR GeneCards; GPR31; -.
DR HGNC; HGNC:4486; GPR31.
DR HPA; ENSG00000120436; Tissue enhanced (lymphoid).
DR MIM; 602043; gene.
DR neXtProt; NX_O00270; -.
DR OpenTargets; ENSG00000120436; -.
DR PharmGKB; PA28874; -.
DR VEuPathDB; HostDB:ENSG00000120436; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00990000203619; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; O00270; -.
DR OMA; CLPIKAH; -.
DR OrthoDB; 903658at2759; -.
DR PhylomeDB; O00270; -.
DR TreeFam; TF337237; -.
DR PathwayCommons; O00270; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-444209; Free fatty acid receptors.
DR BioGRID-ORCS; 2853; 17 hits in 1067 CRISPR screens.
DR GeneWiki; GPR31; -.
DR GenomeRNAi; 2853; -.
DR Pharos; O00270; Tbio.
DR PRO; PR:O00270; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O00270; protein.
DR Bgee; ENSG00000120436; Expressed in lymph node and 7 other tissues.
DR Genevisible; O00270; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050544; F:arachidonic acid binding; IDA:UniProtKB.
DR GO; GO:0045125; F:bioactive lipid receptor activity; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0050778; P:positive regulation of immune response; IEA:Ensembl.
DR GO; GO:0010447; P:response to acidic pH; IDA:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0002237; P:response to molecule of bacterial origin; ISS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
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; Lipid metabolism;
KW Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..319
FT /note="12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid
FT receptor"
FT /id="PRO_0000069551"
FT TOPO_DOM 1..16
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..52
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 74..91
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..110
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..180
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 181..201
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..240
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 241..265
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..284
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 91
FT /note="H -> R (in dbSNP:rs6902566)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9205127, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.4"
FT /id="VAR_049392"
FT CONFLICT 73
FT /note="F -> L (in Ref. 5; AAH95537)"
FT /evidence="ECO:0000305"
FT CONFLICT 277
FT /note="L -> V (in Ref. 1; AAC51375)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 319 AA; 35075 MW; 2ACD0350AD7FB53A CRC64;
MPFPNCSAPS TVVATAVGVL LGLECGLGLL GNAVALWTFL FRVRVWKPYA VYLLNLALAD
LLLAACLPFL AAFYLSLQAW HLGRVGCWAL HFLLDLSRSV GMAFLAAVAL DRYLRVVHPR
LKVNLLSPQA ALGVSGLVWL LMVALTCPGL LISEAAQNST RCHSFYSRAD GSFSIIWQEA
LSCLQFVLPF GLIVFCNAGI IRALQKRLRE PEKQPKLQRA QALVTLVVVL FALCFLPCFL
ARVLMHIFQN LGSCRALCAV AHTSDVTGSL TYLHSVLNPV VYCFSSPTFR SSYRRVFHTL
RGKGQAAEPP DFNPRDSYS
