S1PR1_HUMAN
ID S1PR1_HUMAN Reviewed; 382 AA.
AC P21453; D3DT66; Q9BYY4; Q9NYN8;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Sphingosine 1-phosphate receptor 1;
DE Short=S1P receptor 1;
DE Short=S1P1;
DE AltName: Full=Endothelial differentiation G-protein coupled receptor 1;
DE AltName: Full=Sphingosine 1-phosphate receptor Edg-1;
DE Short=S1P receptor Edg-1;
DE AltName: CD_antigen=CD363;
GN Name=S1PR1; Synonyms=CHEDG1, EDG1;
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=Umbilical vein endothelial cell;
RX PubMed=2160972; DOI=10.1016/s0021-9258(19)38849-0;
RA Hla T., Maciag T.;
RT "An abundant transcript induced in differentiating human endothelial cells
RT encodes a polypeptide with structural similarities to G-protein-coupled
RT receptors.";
RL J. Biol. Chem. 265:9308-9313(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=9409733; DOI=10.1016/s0014-5793(97)01301-x;
RA An S., Bleu T., Huang W., Hallmark O.G., Coughlin S.R., Goetzl E.J.;
RT "Identification of cDNAs encoding two G protein-coupled receptors for
RT lysosphingolipids.";
RL FEBS Lett. 417:279-282(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF ARG-120; GLU-121 AND ARG-292.
RX PubMed=10982820; DOI=10.1074/jbc.m007680200;
RA Parrill A.L., Wang D., Bautista D.L., Van Brocklyn J.R., Lorincz Z.,
RA Fischer D.J., Baker D.L., Liliom K., Spiegel S., Tigyi G.;
RT "Identification of Edg1 receptor residues that recognize sphingosine 1-
RT phosphate.";
RL J. Biol. Chem. 275:39379-39384(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Substantia nigra;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [9]
RP FUNCTION, AND INTERACTION WITH GNAI1 AND GNAI3.
RX PubMed=8626678; DOI=10.1074/jbc.271.19.11272;
RA Lee M.-J., Evans M., Hla T.;
RT "The inducible G protein-coupled receptor edg-1 signals via the
RT G(i)/mitogen-activated protein kinase pathway.";
RL J. Biol. Chem. 271:11272-11279(1996).
RN [10]
RP FUNCTION.
RX PubMed=9488656; DOI=10.1126/science.279.5356.1552;
RA Lee M.-J., Van Brocklyn J.R., Thangada S., Liu C.H., Hand A.R.,
RA Menzeleev R., Spiegel S., Hla T.;
RT "Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor
RT EDG-1.";
RL Science 279:1552-1555(1998).
RN [11]
RP PHARMACOLOGICAL CHARACTERIZATION.
RX PubMed=10383399; DOI=10.1074/jbc.274.27.18997;
RA Ancellin N., Hla T.;
RT "Differential pharmacological properties and signal transduction of the
RT sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5.";
RL J. Biol. Chem. 274:18997-19002(1999).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11604399; DOI=10.1074/jbc.m107301200;
RA Wang D.A., Lorincz Z., Bautista D.L., Liliom K., Tigyi G., Parrill A.L.;
RT "A single amino acid determines lysophospholipid specificity of the S1P1
RT (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors.";
RL J. Biol. Chem. 276:49213-49220(2001).
RN [13]
RP FUNCTION IN CHEMOTAXIS, PHOSPHORYLATION AT THR-236, AND MUTAGENESIS OF
RP THR-236.
RX PubMed=11583630; DOI=10.1016/s1097-2765(01)00324-0;
RA Lee M.-J., Thangada S., Paik J.-H., Sapkota G.P., Ancellin N., Chae S.-S.,
RA Wu M., Morales-Ruiz M., Sessa W.C., Alessi D.R., Hla T.;
RT "Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is
RT required for endothelial cell chemotaxis.";
RL Mol. Cell 8:693-704(2001).
RN [14]
RP FUNCTION.
RX PubMed=11230698; DOI=10.1126/science.1057559;
RA Hobson J.P., Rosenfeldt H.M., Barak L.S., Olivera A., Poulton S.,
RA Caron M.G., Milstien S., Spiegel S.;
RT "Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell
RT motility.";
RL Science 291:1800-1803(2001).
RN [15]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION AT ASN-30.
RX PubMed=15750791; DOI=10.1007/s10719-004-5540-8;
RA Kohno T., Igarashi Y.;
RT "Roles for N-glycosylation in the dynamics of Edg-1/S1P1 in sphingosine 1-
RT phosphate-stimulated cells.";
RL Glycoconj. J. 21:497-501(2004).
RN [16]
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=19286607; DOI=10.1161/circresaha.108.193367;
RA Singleton P.A., Chatchavalvanich S., Fu P., Xing J., Birukova A.A.,
RA Fortune J.A., Klibanov A.M., Garcia J.G., Birukov K.G.;
RT "Akt-mediated transactivation of the S1P1 receptor in caveolin-enriched
RT microdomains regulates endothelial barrier enhancement by oxidized
RT phospholipids.";
RL Circ. Res. 104:978-986(2009).
RN [17]
RP SUBCELLULAR LOCATION, AND PALMITOYLATION BY ZDHHC5.
RX PubMed=29185452; DOI=10.1038/s41598-017-16457-4;
RA Badawy S.M.M., Okada T., Kajimoto T., Ijuin T., Nakamura S.I.;
RT "DHHC5-mediated palmitoylation of S1P receptor subtype 1 determines G-
RT protein coupling.";
RL Sci. Rep. 7:16552-16552(2017).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 2-326 IN COMPLEX WITH SPHINGOLIPID
RP ANALOG, FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, MUTAGENESIS OF
RP PHE-210; PHE-265 AND TRP-269, GLYCOSYLATION AT ASN-30, AND DISULFIDE BONDS.
RX PubMed=22344443; DOI=10.1126/science.1215904;
RA Hanson M.A., Roth C.B., Jo E., Griffith M.T., Scott F.L., Reinhart G.,
RA Desale H., Clemons B., Cahalan S.M., Schuerer S.C., Sanna M.G., Han G.W.,
RA Kuhn P., Rosen H., Stevens R.C.;
RT "Crystal structure of a lipid G protein-coupled receptor.";
RL Science 335:851-855(2012).
CC -!- FUNCTION: G-protein coupled receptor for the bioactive lysosphingolipid
CC sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i)
CC subclass of heteromeric G proteins. Signaling leads to the activation
CC of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in
CC cell migration, probably via its role in the reorganization of the
CC actin cytoskeleton and the formation of lamellipodia in response to
CC stimuli that increase the activity of the sphingosine kinase SPHK1.
CC Required for normal chemotaxis toward sphingosine 1-phosphate. Required
CC for normal embryonic heart development and normal cardiac
CC morphogenesis. Plays an important role in the regulation of sprouting
CC angiogenesis and vascular maturation. Inhibits sprouting angiogenesis
CC to prevent excessive sprouting during blood vessel development.
CC Required for normal egress of mature T-cells from the thymus into the
CC blood stream and into peripheral lymphoid organs. Plays a role in the
CC migration of osteoclast precursor cells, the regulation of bone
CC mineralization and bone homeostasis (By similarity). Plays a role in
CC responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-
CC phosphocholine by pulmonary endothelial cells and in the protection
CC against ventilator-induced lung injury. {ECO:0000250,
CC ECO:0000269|PubMed:10982820, ECO:0000269|PubMed:11230698,
CC ECO:0000269|PubMed:11583630, ECO:0000269|PubMed:11604399,
CC ECO:0000269|PubMed:19286607, ECO:0000269|PubMed:22344443,
CC ECO:0000269|PubMed:8626678, ECO:0000269|PubMed:9488656}.
CC -!- SUBUNIT: Interacts with GNAI1 and GNAI3. {ECO:0000269|PubMed:22344443,
CC ECO:0000269|PubMed:8626678}.
CC -!- INTERACTION:
CC P21453; Q07108: CD69; NbExp=2; IntAct=EBI-2681920, EBI-2836595;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29185452};
CC Multi-pass membrane protein. Endosome. Membrane raft. Note=Recruited to
CC caveolin-enriched plasma membrane microdomains in response to oxidized
CC 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine. Ligand binding
CC leads to receptor internalization.
CC -!- TISSUE SPECIFICITY: Endothelial cells, and to a lesser extent, in
CC vascular smooth muscle cells, fibroblasts, melanocytes, and cells of
CC epithelioid origin.
CC -!- INDUCTION: By the tumor promoter phorbol 12-myristate 13-acetate (PMA)
CC in the presence of cycloheximide.
CC -!- PTM: S1P-induced endothelial cell migration requires the PKB/AKT1-
CC mediated phosphorylation of the third intracellular loop at the Thr-236
CC residue. {ECO:0000269|PubMed:11583630, ECO:0000269|PubMed:19286607}.
CC -!- PTM: Palmitoylated by ZDHHC5. Palmitoylation is required for targeting
CC to plasma membrane, enabling G(i) coupling.
CC {ECO:0000269|PubMed:29185452}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; M31210; AAA52336.1; -; mRNA.
DR EMBL; AF022137; AAC51905.1; -; mRNA.
DR EMBL; AF233365; AAF43420.1; -; mRNA.
DR EMBL; AK312493; BAG35395.1; -; mRNA.
DR EMBL; CR541786; CAG46585.1; -; mRNA.
DR EMBL; CR542269; CAG47065.1; -; mRNA.
DR EMBL; AL109741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW72927.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW72928.1; -; Genomic_DNA.
DR EMBL; BC018650; AAH18650.1; -; mRNA.
DR CCDS; CCDS777.1; -.
DR PIR; A35300; A35300.
DR RefSeq; NP_001307659.1; NM_001320730.1.
DR RefSeq; NP_001391.2; NM_001400.4.
DR PDB; 3V2W; X-ray; 3.35 A; A=2-231, A=244-326.
DR PDB; 3V2Y; X-ray; 2.80 A; A=2-231, A=244-326.
DR PDB; 7EO2; EM; 2.89 A; A=1-339.
DR PDB; 7EO4; EM; 2.86 A; A=1-382.
DR PDB; 7EVY; EM; 2.98 A; D=1-337.
DR PDB; 7EVZ; EM; 3.07 A; D=1-337.
DR PDB; 7EW0; EM; 3.42 A; D=1-337.
DR PDB; 7EW7; EM; 3.27 A; D=1-337.
DR PDB; 7TD3; EM; 3.00 A; R=2-382.
DR PDB; 7TD4; EM; 2.60 A; R=2-382.
DR PDB; 7WF7; EM; 3.40 A; A=1-382.
DR PDBsum; 3V2W; -.
DR PDBsum; 3V2Y; -.
DR PDBsum; 7EO2; -.
DR PDBsum; 7EO4; -.
DR PDBsum; 7EVY; -.
DR PDBsum; 7EVZ; -.
DR PDBsum; 7EW0; -.
DR PDBsum; 7EW7; -.
DR PDBsum; 7TD3; -.
DR PDBsum; 7TD4; -.
DR PDBsum; 7WF7; -.
DR AlphaFoldDB; P21453; -.
DR SMR; P21453; -.
DR BioGRID; 108225; 119.
DR CORUM; P21453; -.
DR DIP; DIP-60427N; -.
DR IntAct; P21453; 23.
DR STRING; 9606.ENSP00000305416; -.
DR BindingDB; P21453; -.
DR ChEMBL; CHEMBL4333; -.
DR DrugBank; DB08868; Fingolimod.
DR DrugBank; DB12612; Ozanimod.
DR DrugBank; DB12016; Ponesimod.
DR DrugBank; DB12371; Siponimod.
DR DrugCentral; P21453; -.
DR GuidetoPHARMACOLOGY; 275; -.
DR TCDB; 9.A.14.2.1; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; P21453; 2 sites.
DR iPTMnet; P21453; -.
DR PhosphoSitePlus; P21453; -.
DR SwissPalm; P21453; -.
DR BioMuta; S1PR1; -.
DR DMDM; 205371820; -.
DR EPD; P21453; -.
DR jPOST; P21453; -.
DR MassIVE; P21453; -.
DR PaxDb; P21453; -.
DR PeptideAtlas; P21453; -.
DR PRIDE; P21453; -.
DR ProteomicsDB; 53871; -.
DR Antibodypedia; 4111; 768 antibodies from 45 providers.
DR DNASU; 1901; -.
DR Ensembl; ENST00000305352.7; ENSP00000305416.6; ENSG00000170989.10.
DR Ensembl; ENST00000475289.2; ENSP00000498038.1; ENSG00000170989.10.
DR Ensembl; ENST00000648480.1; ENSP00000497478.1; ENSG00000170989.10.
DR Ensembl; ENST00000649383.1; ENSP00000497175.1; ENSG00000170989.10.
DR GeneID; 1901; -.
DR KEGG; hsa:1901; -.
DR MANE-Select; ENST00000305352.7; ENSP00000305416.6; NM_001400.5; NP_001391.2.
DR UCSC; uc001dud.3; human.
DR CTD; 1901; -.
DR DisGeNET; 1901; -.
DR GeneCards; S1PR1; -.
DR HGNC; HGNC:3165; S1PR1.
DR HPA; ENSG00000170989; Low tissue specificity.
DR MIM; 601974; gene.
DR neXtProt; NX_P21453; -.
DR OpenTargets; ENSG00000170989; -.
DR PharmGKB; PA162402344; -.
DR VEuPathDB; HostDB:ENSG00000170989; -.
DR eggNOG; ENOG502QSFG; Eukaryota.
DR GeneTree; ENSGT01050000244887; -.
DR HOGENOM; CLU_047979_1_0_1; -.
DR InParanoid; P21453; -.
DR OMA; HPNKEEV; -.
DR OrthoDB; 981486at2759; -.
DR PhylomeDB; P21453; -.
DR TreeFam; TF330052; -.
DR PathwayCommons; P21453; -.
DR Reactome; R-HSA-419408; Lysosphingolipid and LPA receptors.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; P21453; -.
DR SIGNOR; P21453; -.
DR BioGRID-ORCS; 1901; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; S1PR1; human.
DR GeneWiki; S1PR1; -.
DR GenomeRNAi; 1901; -.
DR Pharos; P21453; Tclin.
DR PRO; PR:P21453; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P21453; protein.
DR Bgee; ENSG00000170989; Expressed in right lung and 153 other tissues.
DR ExpressionAtlas; P21453; baseline and differential.
DR Genevisible; P21453; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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:0046625; F:sphingolipid binding; IEA:Ensembl.
DR GO; GO:0038036; F:sphingosine-1-phosphate receptor activity; IDA:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0001955; P:blood vessel maturation; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0003245; P:cardiac muscle tissue growth involved in heart morphogenesis; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0006935; P:chemotaxis; ISS:UniProtKB.
DR GO; GO:0045446; P:endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0061384; P:heart trabecula morphogenesis; ISS:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0030595; P:leukocyte chemotaxis; IEA:Ensembl.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IEA:Ensembl.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0030500; P:regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0045124; P:regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0019222; P:regulation of metabolic process; IBA:GO_Central.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0072678; P:T cell migration; ISS:UniProtKB.
DR GO; GO:0019226; P:transmission of nerve impulse; IEA:Ensembl.
DR InterPro; IPR000987; EDG1_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR004061; S1P_rcpt.
DR PANTHER; PTHR22750:SF16; PTHR22750:SF16; 1.
DR Pfam; PF00001; 7tm_1; 1.
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; Acetylation; Angiogenesis; Cell membrane; Chemotaxis;
KW Disulfide bond; Endosome; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..382
FT /note="Sphingosine 1-phosphate receptor 1"
FT /id="PRO_0000069412"
FT TOPO_DOM 1..46
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 47..68
FT /note="Helical; Name=1"
FT TOPO_DOM 69..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 83..104
FT /note="Helical; Name=2"
FT TOPO_DOM 105..116
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 117..138
FT /note="Helical; Name=3"
FT TOPO_DOM 139..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 161..182
FT /note="Helical; Name=4"
FT TOPO_DOM 183..196
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 197..224
FT /note="Helical; Name=5"
FT TOPO_DOM 225..257
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 258..278
FT /note="Helical; Name=6"
FT TOPO_DOM 279..289
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:15750791"
FT TRANSMEM 290..310
FT /note="Helical; Name=7"
FT TOPO_DOM 311..382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15750791"
FT REGION 350..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 120..121
FT /ligand="sphing-4-enine 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:60119"
FT BINDING 265..269
FT /ligand="sphing-4-enine 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:60119"
FT MOD_RES 10
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O08530"
FT MOD_RES 236
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:11583630"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08530"
FT MOD_RES 353
FT /note="Phosphoserine"
FT /evidence="ECO:0000255"
FT LIPID 328
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 30
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15750791,
FT ECO:0000269|PubMed:22344443"
FT CARBOHYD 36
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 184..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:22344443"
FT DISULFID 282..287
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:22344443"
FT VARIANT 15
FT /note="S -> L (in dbSNP:rs4987250)"
FT /id="VAR_046158"
FT VARIANT 115
FT /note="A -> T (in dbSNP:rs11542632)"
FT /id="VAR_046159"
FT VARIANT 332
FT /note="P -> R (in dbSNP:rs7549921)"
FT /id="VAR_046160"
FT MUTAGEN 120
FT /note="R->A: Drastically reduced affinity for sphingosine
FT 1-phosphate."
FT /evidence="ECO:0000269|PubMed:10982820"
FT MUTAGEN 121
FT /note="E->A: Drastically reduced affinity for sphingosine
FT 1-phosphate."
FT /evidence="ECO:0000269|PubMed:10982820"
FT MUTAGEN 121
FT /note="E->Q: Slight activation of the receptor at maximal
FT ligand concentration."
FT /evidence="ECO:0000269|PubMed:10982820"
FT MUTAGEN 210
FT /note="F->L: Impairs sphingosine 1-phosphate binding and
FT signaling."
FT /evidence="ECO:0000269|PubMed:22344443"
FT MUTAGEN 236
FT /note="T->A: Acts as a dominant negative GPCR and inhibits
FT S1P-induced Rac activation, chemotaxis, and angiogenesis."
FT /evidence="ECO:0000269|PubMed:11583630"
FT MUTAGEN 265
FT /note="F->L: Impairs sphingosine 1-phosphate binding and
FT signaling."
FT /evidence="ECO:0000269|PubMed:22344443"
FT MUTAGEN 269
FT /note="W->F,L: Impairs sphingosine 1-phosphate binding and
FT signaling."
FT /evidence="ECO:0000269|PubMed:22344443"
FT MUTAGEN 292
FT /note="R->A,V: Drastically reduced affinity for sphingosine
FT 1-phosphate."
FT /evidence="ECO:0000269|PubMed:10982820"
FT CONFLICT 250..252
FT /note="KSL -> NV (in Ref. 1; AAA52336 and 2; AAC51905)"
FT /evidence="ECO:0000305"
FT HELIX 23..31
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 42..72
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:7EO4"
FT HELIX 79..104
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 106..109
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 114..146
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 158..176
FT /evidence="ECO:0007829|PDB:3V2Y"
FT TURN 177..181
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:3V2Y"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 200..231
FT /evidence="ECO:0007829|PDB:3V2Y"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:7WF7"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 251..280
FT /evidence="ECO:0007829|PDB:3V2Y"
FT TURN 284..286
FT /evidence="ECO:0007829|PDB:3V2Y"
FT TURN 289..291
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 294..302
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 307..314
FT /evidence="ECO:0007829|PDB:3V2Y"
FT HELIX 316..323
FT /evidence="ECO:0007829|PDB:3V2Y"
SQ SEQUENCE 382 AA; 42811 MW; 0CCE8685A5E1BAD2 CRC64;
MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII
LENIFVLLTI WKTKKFHRPM YYFIGNLALS DLLAGVAYTA NLLLSGATTY KLTPAQWFLR
EGSMFVALSA SVFSLLAIAI ERYITMLKMK LHNGSNNFRL FLLISACWVI SLILGGLPIM
GWNCISALSS CSTVLPLYHK HYILFCTTVF TLLLLSIVIL YCRIYSLVRT RSRRLTFRKN
ISKASRSSEK SLALLKTVII VLSVFIACWA PLFILLLLDV GCKVKTCDIL FRAEYFLVLA
VLNSGTNPII YTLTNKEMRR AFIRIMSCCK CPSGDSAGKF KRPIIAGMEF SRSKSDNSSH
PQKDEGDNPE TIMSSGNVNS SS
