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Protein

Sphingosine 1-phosphate receptor 1

Gene

S1PR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury.By similarity8 Publications

GO - Molecular functioni

  • G-protein coupled receptor activity Source: ProtInc
  • G-protein coupled receptor binding Source: UniProtKB
  • sphingolipid binding Source: Ensembl
  • sphingosine-1-phosphate receptor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processAngiogenesis, Chemotaxis

Enzyme and pathway databases

ReactomeiR-HSA-418594. G alpha (i) signalling events.
R-HSA-419408. Lysosphingolipid and LPA receptors.
R-HSA-6785807. Interleukin-4 and 13 signaling.
SignaLinkiP21453.
SIGNORiP21453.

Protein family/group databases

TCDBi9.A.14.2.1. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sphingosine 1-phosphate receptor 1
Short name:
S1P receptor 1
Short name:
S1P1
Alternative name(s):
Endothelial differentiation G-protein coupled receptor 1
Sphingosine 1-phosphate receptor Edg-1
Short name:
S1P receptor Edg-1
CD_antigen: CD363
Gene namesi
Name:S1PR1
Synonyms:CHEDG1, EDG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000170989.8.
HGNCiHGNC:3165. S1PR1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 46Extracellular1 PublicationAdd BLAST46
Transmembranei47 – 68Helical; Name=1Add BLAST22
Topological domaini69 – 82Cytoplasmic1 PublicationAdd BLAST14
Transmembranei83 – 104Helical; Name=2Add BLAST22
Topological domaini105 – 116Extracellular1 PublicationAdd BLAST12
Transmembranei117 – 138Helical; Name=3Add BLAST22
Topological domaini139 – 160Cytoplasmic1 PublicationAdd BLAST22
Transmembranei161 – 182Helical; Name=4Add BLAST22
Topological domaini183 – 196Extracellular1 PublicationAdd BLAST14
Transmembranei197 – 224Helical; Name=5Add BLAST28
Topological domaini225 – 257Cytoplasmic1 PublicationAdd BLAST33
Transmembranei258 – 278Helical; Name=6Add BLAST21
Topological domaini279 – 289Extracellular1 PublicationAdd BLAST11
Transmembranei290 – 310Helical; Name=7Add BLAST21
Topological domaini311 – 382Cytoplasmic1 PublicationAdd BLAST72

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi120R → A: Drastically reduced affinity for sphingosine 1-phosphate. 1 Publication1
Mutagenesisi121E → A: Drastically reduced affinity for sphingosine 1-phosphate. 1 Publication1
Mutagenesisi121E → Q: Slight activation of the receptor at maximal ligand concentration. 1 Publication1
Mutagenesisi210F → L: Impairs sphingosine 1-phosphate binding and signaling. 1 Publication1
Mutagenesisi236T → A: Acts as a dominant negative GPCR and inhibits S1P-induced Rac activation, chemotaxis, and angiogenesis. 1 Publication1
Mutagenesisi265F → L: Impairs sphingosine 1-phosphate binding and signaling. 1 Publication1
Mutagenesisi269W → F or L: Impairs sphingosine 1-phosphate binding and signaling. 1 Publication1
Mutagenesisi292R → A or V: Drastically reduced affinity for sphingosine 1-phosphate. 1 Publication1

Organism-specific databases

DisGeNETi1901.
OpenTargetsiENSG00000170989.
PharmGKBiPA162402344.

Chemistry databases

ChEMBLiCHEMBL4333.
DrugBankiDB09105. Asfotase Alfa.
GuidetoPHARMACOLOGYi275.

Polymorphism and mutation databases

BioMutaiS1PR1.
DMDMi205371820.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000694121 – 382Sphingosine 1-phosphate receptor 1Add BLAST382

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10N6-acetyllysineBy similarity1
Glycosylationi30N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi36N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi184 ↔ 191PROSITE-ProRule annotation1 Publication
Modified residuei236Phosphothreonine; by PKB/AKT11 Publication1
Disulfide bondi282 ↔ 287PROSITE-ProRule annotation1 Publication
Lipidationi328S-palmitoyl cysteineBy similarity1
Modified residuei351PhosphoserineBy similarity1
Modified residuei353PhosphoserineSequence analysis1

Post-translational modificationi

S1P-induced endothelial cell migration requires the PKB/AKT1-mediated phosphorylation of the third intracellular loop at the Thr-236 residue.2 Publications

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP21453.
PaxDbiP21453.
PeptideAtlasiP21453.
PRIDEiP21453.

PTM databases

iPTMnetiP21453.
PhosphoSitePlusiP21453.
SwissPalmiP21453.

Expressioni

Tissue specificityi

Endothelial cells, and to a lesser extent, in vascular smooth muscle cells, fibroblasts, melanocytes, and cells of epithelioid origin.

Inductioni

By the tumor promoter phorbol 12-myristate 13-acetate (PMA) in the presence of cycloheximide.

Gene expression databases

BgeeiENSG00000170989.
CleanExiHS_S1PR1.
GenevisibleiP21453. HS.

Organism-specific databases

HPAiCAB010104.
HPA075568.

Interactioni

Subunit structurei

Interacts with GNAI1 and GNAI3.2 Publications

GO - Molecular functioni

  • G-protein coupled receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108225. 30 interactors.
CORUMiP21453.
DIPiDIP-60427N.
IntActiP21453. 3 interactors.
STRINGi9606.ENSP00000305416.

Chemistry databases

BindingDBiP21453.

Structurei

Secondary structure

1382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 31Combined sources9
Helixi36 – 39Combined sources4
Helixi42 – 72Combined sources31
Helixi74 – 76Combined sources3
Helixi79 – 104Combined sources26
Helixi106 – 109Combined sources4
Helixi114 – 146Combined sources33
Helixi158 – 176Combined sources19
Turni177 – 181Combined sources5
Helixi188 – 190Combined sources3
Beta strandi193 – 195Combined sources3
Helixi200 – 231Combined sources32
Turni247 – 249Combined sources3
Helixi251 – 280Combined sources30
Turni284 – 286Combined sources3
Turni289 – 291Combined sources3
Helixi294 – 302Combined sources9
Helixi303 – 305Combined sources3
Helixi307 – 314Combined sources8
Helixi316 – 322Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3V2WX-ray3.35A2-231[»]
A244-326[»]
3V2YX-ray2.80A2-231[»]
A244-326[»]
ProteinModelPortaliP21453.
SMRiP21453.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni120 – 121Sphingosine 1-phosphate binding2
Regioni265 – 269Sphingosine 1-phosphate binding5

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIA7. Eukaryota.
ENOG410XQD3. LUCA.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000233501.
HOVERGENiHBG103071.
InParanoidiP21453.
KOiK04288.
OMAiCFIACWA.
OrthoDBiEOG091G0DD4.
PhylomeDBiP21453.
TreeFamiTF330052.

Family and domain databases

InterProiView protein in InterPro
IPR000987. EDG1_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004061. S1P_rcpt.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00642. EDG1RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01523. S1PRECEPTOR.
SMARTiView protein in SMART
SM01381. 7TM_GPCR_Srsx. 1 hit.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P21453-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV
60 70 80 90 100
VFILICCFII LENIFVLLTI WKTKKFHRPM YYFIGNLALS DLLAGVAYTA
110 120 130 140 150
NLLLSGATTY KLTPAQWFLR EGSMFVALSA SVFSLLAIAI ERYITMLKMK
160 170 180 190 200
LHNGSNNFRL FLLISACWVI SLILGGLPIM GWNCISALSS CSTVLPLYHK
210 220 230 240 250
HYILFCTTVF TLLLLSIVIL YCRIYSLVRT RSRRLTFRKN ISKASRSSEK
260 270 280 290 300
SLALLKTVII VLSVFIACWA PLFILLLLDV GCKVKTCDIL FRAEYFLVLA
310 320 330 340 350
VLNSGTNPII YTLTNKEMRR AFIRIMSCCK CPSGDSAGKF KRPIIAGMEF
360 370 380
SRSKSDNSSH PQKDEGDNPE TIMSSGNVNS SS
Length:382
Mass (Da):42,811
Last modified:September 2, 2008 - v2
Checksum:i0CCE8685A5E1BAD2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti250 – 252KSL → NV in AAA52336 (PubMed:2160972).Curated3
Sequence conflicti250 – 252KSL → NV in AAC51905 (PubMed:9409733).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04615815S → L. Corresponds to variant dbSNP:rs4987250Ensembl.1
Natural variantiVAR_046159115A → T. Corresponds to variant dbSNP:rs11542632Ensembl.1
Natural variantiVAR_046160332P → R. Corresponds to variant dbSNP:rs7549921Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31210 mRNA. Translation: AAA52336.1.
AF022137 mRNA. Translation: AAC51905.1.
AF233365 mRNA. Translation: AAF43420.1.
AK312493 mRNA. Translation: BAG35395.1.
CR541786 mRNA. Translation: CAG46585.1.
CR542269 mRNA. Translation: CAG47065.1.
AL109741 Genomic DNA. Translation: CAI21861.1.
CH471097 Genomic DNA. Translation: EAW72927.1.
CH471097 Genomic DNA. Translation: EAW72928.1.
BC018650 mRNA. Translation: AAH18650.1.
CCDSiCCDS777.1.
PIRiA35300.
RefSeqiNP_001307659.1. NM_001320730.1.
NP_001391.2. NM_001400.4.
UniGeneiHs.154210.

Genome annotation databases

EnsembliENST00000305352; ENSP00000305416; ENSG00000170989.
GeneIDi1901.
KEGGihsa:1901.
UCSCiuc001dud.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiS1PR1_HUMAN
AccessioniPrimary (citable) accession number: P21453
Secondary accession number(s): D3DT66, Q9BYY4, Q9NYN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: September 2, 2008
Last modified: September 27, 2017
This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  8. SIMILARITY comments
    Index of protein domains and families