S1PR2_HUMAN
ID S1PR2_HUMAN Reviewed; 353 AA.
AC O95136; Q86UN8;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Sphingosine 1-phosphate receptor 2;
DE Short=S1P receptor 2;
DE Short=S1P2;
DE AltName: Full=Endothelial differentiation G-protein coupled receptor 5;
DE AltName: Full=Sphingosine 1-phosphate receptor Edg-5;
DE Short=S1P receptor Edg-5;
GN Name=S1PR2; Synonyms=EDG5;
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], AND FUNCTION.
RC TISSUE=Fetal brain;
RX PubMed=10617617; DOI=10.1074/jbc.275.1.288;
RA An S., Zheng Y., Bleu T.;
RT "Sphingosine 1-phosphate-induced cell proliferation, survival, and related
RT signaling events mediated by G protein-coupled receptors Edg3 and Edg5.";
RL J. Biol. Chem. 275:288-296(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kopatz S.A., 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 (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP VARIANTS DFNB68 PRO-108 AND CYS-140.
RX PubMed=26805784; DOI=10.1016/j.ajhg.2015.12.004;
RG University of Washington Center for Mendelian Genomics;
RA Santos-Cortez R.L., Faridi R., Rehman A.U., Lee K., Ansar M., Wang X.,
RA Morell R.J., Isaacson R., Belyantseva I.A., Dai H., Acharya A.,
RA Qaiser T.A., Muhammad D., Ali R.A., Shams S., Hassan M.J., Shahzad S.,
RA Raza S.I., Bashir Z.E., Smith J.D., Nickerson D.A., Bamshad M.J.,
RA Riazuddin S., Ahmad W., Friedman T.B., Leal S.M.;
RT "Autosomal-recessive hearing impairment due to rare missense variants
RT within S1PR2.";
RL Am. J. Hum. Genet. 98:331-338(2016).
RN [5]
RP FUNCTION.
RX PubMed=29453251; DOI=10.1161/circulationaha.117.032398;
RA Wang Y., Chen D., Zhang Y., Wang P., Zheng C., Zhang S., Yu B., Zhang L.,
RA Zhao G., Ma B., Cai Z., Xie N., Huang S., Liu Z., Mo X., Guan Y., Wang X.,
RA Fu Y., Ma D., Wang Y., Kong W.;
RT "Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury
RT Through Sphingosine-1-Phosphate Receptor 2.";
RL Circulation 138:48-63(2018).
CC -!- FUNCTION: Receptor for the lysosphingolipid sphingosine 1-phosphate
CC (S1P) (PubMed:10617617). S1P is a bioactive lysophospholipid that
CC elicits diverse physiological effects on most types of cells and
CC tissues (PubMed:10617617). When expressed in rat HTC4 hepatoma cells,
CC is capable of mediating S1P-induced cell proliferation and suppression
CC of apoptosis (PubMed:10617617). Receptor for the chemokine-like protein
CC FAM19A5 (PubMed:29453251). Mediates the inhibitory effect of FAM19A5 on
CC vascular smooth muscle cell proliferation and migration (By
CC similarity). {ECO:0000250|UniProtKB:P47752,
CC ECO:0000269|PubMed:10617617, ECO:0000269|PubMed:29453251}.
CC -!- INTERACTION:
CC O95136; P16144: ITGB4; NbExp=2; IntAct=EBI-10634606, EBI-948678;
CC O95136; Q9JK11-1: Rtn4; Xeno; NbExp=2; IntAct=EBI-10634606, EBI-919989;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- DISEASE: Deafness, autosomal recessive, 68 (DFNB68) [MIM:610419]: A
CC form of non-syndromic sensorineural hearing loss. Sensorineural
CC deafness results from damage to the neural receptors of the inner ear,
CC the nerve pathways to the brain, or the area of the brain that receives
CC sound information. {ECO:0000269|PubMed:26805784}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AF034780; AAC98919.1; -; mRNA.
DR EMBL; AY262688; AAP20652.1; -; Genomic_DNA.
DR EMBL; BC069598; AAH69598.1; -; mRNA.
DR CCDS; CCDS12229.1; -.
DR RefSeq; NP_004221.3; NM_004230.3.
DR PDB; 7T6B; EM; 3.19 A; R=1-353.
DR PDBsum; 7T6B; -.
DR AlphaFoldDB; O95136; -.
DR SMR; O95136; -.
DR BioGRID; 114708; 49.
DR CORUM; O95136; -.
DR DIP; DIP-60682N; -.
DR IntAct; O95136; 26.
DR STRING; 9606.ENSP00000466933; -.
DR BindingDB; O95136; -.
DR ChEMBL; CHEMBL2955; -.
DR DrugCentral; O95136; -.
DR GuidetoPHARMACOLOGY; 276; -.
DR GlyGen; O95136; 1 site.
DR iPTMnet; O95136; -.
DR PhosphoSitePlus; O95136; -.
DR SwissPalm; O95136; -.
DR BioMuta; S1PR2; -.
DR jPOST; O95136; -.
DR MassIVE; O95136; -.
DR PaxDb; O95136; -.
DR PeptideAtlas; O95136; -.
DR PRIDE; O95136; -.
DR ProteomicsDB; 50657; -.
DR Antibodypedia; 65016; 327 antibodies from 34 providers.
DR DNASU; 9294; -.
DR Ensembl; ENST00000646641.1; ENSP00000496438.1; ENSG00000267534.4.
DR GeneID; 9294; -.
DR KEGG; hsa:9294; -.
DR MANE-Select; ENST00000646641.1; ENSP00000496438.1; NM_004230.4; NP_004221.3.
DR UCSC; uc002mnl.3; human.
DR CTD; 9294; -.
DR DisGeNET; 9294; -.
DR GeneCards; S1PR2; -.
DR HGNC; HGNC:3169; S1PR2.
DR HPA; ENSG00000267534; Low tissue specificity.
DR MalaCards; S1PR2; -.
DR MIM; 605111; gene.
DR MIM; 610419; phenotype.
DR neXtProt; NX_O95136; -.
DR OpenTargets; ENSG00000267534; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA162402353; -.
DR VEuPathDB; HostDB:ENSG00000267534; -.
DR eggNOG; ENOG502QVQY; Eukaryota.
DR GeneTree; ENSGT01050000244887; -.
DR HOGENOM; CLU_047979_1_0_1; -.
DR InParanoid; O95136; -.
DR OMA; CPVRACP; -.
DR OrthoDB; 981486at2759; -.
DR PhylomeDB; O95136; -.
DR PathwayCommons; O95136; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-419408; Lysosphingolipid and LPA receptors.
DR SignaLink; O95136; -.
DR SIGNOR; O95136; -.
DR BioGRID-ORCS; 9294; 8 hits in 1073 CRISPR screens.
DR ChiTaRS; S1PR2; human.
DR GeneWiki; S1PR2; -.
DR GenomeRNAi; 9294; -.
DR Pharos; O95136; Tchem.
DR PRO; PR:O95136; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O95136; protein.
DR Bgee; ENSG00000267534; Expressed in heart right ventricle and 165 other tissues.
DR ExpressionAtlas; O95136; baseline and differential.
DR Genevisible; O95136; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IPI:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0008289; F:lipid binding; TAS:ProtInc.
DR GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; IDA:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0046847; P:filopodium assembly; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0090394; P:negative regulation of excitatory postsynaptic potential; IEA:Ensembl.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:1903142; P:positive regulation of establishment of endothelial barrier; IMP:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:UniProtKB.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:UniProtKB.
DR InterPro; IPR004063; EDG5_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR004061; S1P_rcpt.
DR PANTHER; PTHR22750:SF17; PTHR22750:SF17; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01525; EDG5RECEPTOR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01523; S1PRECEPTOR.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
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 3D-structure; Cell membrane; Deafness; Disease variant;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane;
KW Non-syndromic deafness; Palmitate; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..353
FT /note="Sphingosine 1-phosphate receptor 2"
FT /id="PRO_0000069427"
FT TOPO_DOM 1..34
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 35..59
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 60..66
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 67..95
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 96..109
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 110..128
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250"
FT TOPO_DOM 129..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 148..173
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250"
FT TOPO_DOM 174..189
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 190..210
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250"
FT TOPO_DOM 211..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 234..255
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250"
FT TOPO_DOM 256..271
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 272..292
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250"
FT TOPO_DOM 293..353
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT LIPID 305
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 19
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 108
FT /note="R -> P (in DFNB68; dbSNP:rs869312749)"
FT /evidence="ECO:0000269|PubMed:26805784"
FT /id="VAR_076391"
FT VARIANT 140
FT /note="Y -> C (in DFNB68; dbSNP:rs869312750)"
FT /evidence="ECO:0000269|PubMed:26805784"
FT /id="VAR_076392"
FT CONFLICT 113
FT /note="F -> S (in Ref. 1; AAC98919)"
FT /evidence="ECO:0000305"
FT CONFLICT 318
FT /note="G -> V (in Ref. 1; AAC98919)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 353 AA; 38867 MW; 8E37084284ABF7E8 CRC64;
MGSLYSEYLN PNKVQEHYNY TKETLETQET TSRQVASAFI VILCCAIVVE NLLVLIAVAR
NSKFHSAMYL FLGNLAASDL LAGVAFVANT LLSGSVTLRL TPVQWFAREG SAFITLSASV
FSLLAIAIER HVAIAKVKLY GSDKSCRMLL LIGASWLISL VLGGLPILGW NCLGHLEACS
TVLPLYAKHY VLCVVTIFSI ILLAIVALYV RIYCVVRSSH ADMAAPQTLA LLKTVTIVLG
VFIVCWLPAF SILLLDYACP VHSCPILYKA HYFFAVSTLN SLLNPVIYTW RSRDLRREVL
RPLQCWRPGV GVQGRRRGGT PGHHLLPLRS SSSLERGMHM PTSPTFLEGN TVV
