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Protein

Sphingosine 1-phosphate receptor 1

Gene

S1pr1

Organism
Mus musculus (Mouse)
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. 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.10 Publications

GO - Molecular functioni

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

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: MGI
  • angiogenesis Source: MGI
  • blood vessel maturation Source: UniProtKB
  • brain development Source: MGI
  • cardiac muscle tissue growth involved in heart morphogenesis Source: UniProtKB
  • cell migration Source: UniProtKB
  • chemotaxis Source: UniProtKB
  • endothelial cell differentiation Source: Ensembl
  • heart trabecula morphogenesis Source: UniProtKB
  • lamellipodium assembly Source: UniProtKB
  • leukocyte chemotaxis Source: MGI
  • negative regulation of stress fiber assembly Source: Ensembl
  • neuron differentiation Source: Ensembl
  • positive regulation of cell migration Source: Ensembl
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: Ensembl
  • positive regulation of GTPase activity Source: Ensembl
  • positive regulation of positive chemotaxis Source: Ensembl
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • regulation of bone mineralization Source: UniProtKB
  • regulation of bone resorption Source: UniProtKB
  • regulation of cell adhesion Source: MGI
  • sphingosine-1-phosphate signaling pathway Source: UniProtKB
  • T cell migration Source: UniProtKB
  • transmission of nerve impulse Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Angiogenesis, Chemotaxis

Enzyme and pathway databases

ReactomeiR-MMU-418594. G alpha (i) signalling events.
R-MMU-419408. Lysosphingolipid and LPA receptors.

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
Lysophospholipid receptor B1
Sphingosine 1-phosphate receptor Edg-1
Short name:
S1P receptor Edg-1
CD_antigen: CD363
Gene namesi
Name:S1pr1
Synonyms:Edg1, Lpb1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1096355. S1pr1.

Subcellular locationi

  • Cell membrane; Multi-pass membrane protein
  • Endosome By similarity
  • Membranecaveola By similarity

  • Note: Recruited to caveolin-enriched plasma membrane microdomains in response to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine. Ligand binding leads to receptor internalization (By similarity).By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 46ExtracellularBy similarityAdd BLAST45
Transmembranei47 – 68Helical; Name=1By similarityAdd BLAST22
Topological domaini69 – 82CytoplasmicBy similarityAdd BLAST14
Transmembranei83 – 104Helical; Name=2By similarityAdd BLAST22
Topological domaini105 – 116ExtracellularBy similarityAdd BLAST12
Transmembranei117 – 138Helical; Name=3By similarityAdd BLAST22
Topological domaini139 – 160CytoplasmicBy similarityAdd BLAST22
Transmembranei161 – 182Helical; Name=4By similarityAdd BLAST22
Topological domaini183 – 196ExtracellularBy similarityAdd BLAST14
Transmembranei197 – 224Helical; Name=5By similarityAdd BLAST28
Topological domaini225 – 257CytoplasmicBy similarityAdd BLAST33
Transmembranei258 – 278Helical; Name=6By similarityAdd BLAST21
Topological domaini279 – 289ExtracellularBy similarityAdd BLAST11
Transmembranei290 – 310Helical; Name=7By similarityAdd BLAST21
Topological domaini311 – 382CytoplasmicBy similarityAdd BLAST72

GO - Cellular componenti

  • caveola Source: UniProtKB-SubCell
  • endosome Source: UniProtKB-SubCell
  • external side of plasma membrane Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • intrinsic component of plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality, due to impaired vascular maturation and defects in heart development. Embryos appear normal up to 11.5 dpc, but after that they display massive hemorrhage. They have a normally arborized vascular network, but present excessive sprouting angiogenesis and severe aberrations in vessel size. Their aorta and other arteries are not properly enveloped by vascular smooth muscle cells, causing hemorrhage. Likewise, small blood vessels show a marked reduction in the number of vascular pericytes. In addition, mutants display defects in heart morphogenesis, with reduced myocardial tissue and altered morphology of the heart wall and the trabeculae. Conditional knockout in endothelial cells leads to the same vascular maturation defect as that seen in homozygous knockout mice. Conditional knockout in fibroblasts leads to defects in chemotaxis, probably due to defects in the activation of SRC and PTK2/FAK1, resulting in defects in the reorganization of the actin cytoskeleton and lamellipodia formation. A T-cell-specific knockout leads to a defect in the egress of mature T-cells from the thymus into the periphery. Conditional knockout in osteoclast precursors leads to osteoporosis, due to impaired migration of osteoclast precursors and increased osteoclast attachment to the bone.8 Publications

Chemistry databases

ChEMBLiCHEMBL1914262.
GuidetoPHARMACOLOGYi275.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000694132 – 382Sphingosine 1-phosphate receptor 1Add BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylvalineCombined sources1
Modified residuei10N6-acetyllysineCombined sources1
Glycosylationi30N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi184 ↔ 191PROSITE-ProRule annotation
Modified residuei236PhosphothreonineBy similarity1
Disulfide bondi282 ↔ 287PROSITE-ProRule annotation
Lipidationi328S-palmitoyl cysteineBy similarity1
Modified residuei351PhosphoserineCombined sources1
Modified residuei353PhosphoserineSequence analysis1

Keywords - PTMi

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

Proteomic databases

MaxQBiO08530.
PaxDbiO08530.
PRIDEiO08530.

PTM databases

iPTMnetiO08530.
PhosphoSitePlusiO08530.

Expressioni

Tissue specificityi

Expressed in a wide variety of tissues with highest levels in brain, heart and spleen. Lower levels found in kidney, liver, lung, muscle, placenta, thymus, and uterus. Very low levels in intestine, stomach and testis. According to PubMed:9931453, expressed modestly in apparent endothelial cells surrounding some blood vessels (e.g. aortic trunk).2 Publications

Gene expression databases

BgeeiENSMUSG00000045092.
GenevisibleiO08530. MM.

Interactioni

Subunit structurei

Interacts with GNAI1 and GNAI3.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199373. 2 interactors.
DIPiDIP-32248N.
IntActiO08530. 1 interactor.
STRINGi10090.ENSMUSP00000050897.

Chemistry databases

BindingDBiO08530.

Structurei

3D structure databases

ProteinModelPortaliO08530.
SMRiO08530.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni120 – 121Sphingosine 1-phosphate bindingBy similarity2
Regioni265 – 269Sphingosine 1-phosphate bindingBy similarity5

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.
InParanoidiO08530.
KOiK04288.
OMAiIGGMEFS.
OrthoDBiEOG091G0DD4.
TreeFamiTF330052.

Family and domain databases

InterProiIPR000987. EDG1_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004061. S1P_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00642. EDG1RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01523. S1PRECEPTOR.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O08530-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVSTSIPEVK ALRSSVSDYG NYDIIVRHYN YTGKLNIGAE KDHGIKLTSV
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
LHNGSNSSRS FLLISACWVI SLILGGLPIM GWNCISSLSS CSTVLPLYHK
210 220 230 240 250
HYILFCTTVF TLLLLSIVIL YCRIYSLVRT RSRRLTFRKN ISKASRSSEK
260 270 280 290 300
SLALLKTVII VLSVFIACWA PLFILLLLDV GCKAKTCDIL YKAEYFLVLA
310 320 330 340 350
VLNSGTNPII YTLTNKEMRR AFIRIVSCCK CPNGDSAGKF KRPIIPGMEF
360 370 380
SRSKSDNSSH PQKDDGDNPE TIMSSGNVNS SS
Length:382
Mass (Da):42,639
Last modified:July 27, 2011 - v3
Checksum:i5FE4C9A2BD65CB2A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti179I → S in AAC53294 (PubMed:9226368).Curated1
Sequence conflicti179I → S in AAD16975 (PubMed:9931453).Curated1
Sequence conflicti218V → A in AAC53294 (PubMed:9226368).Curated1
Sequence conflicti244A → G in AAC53294 (PubMed:9226368).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40811 Genomic DNA. Translation: AAC53294.1.
AF108019 Genomic DNA. Translation: AAD16975.1.
AK004591 mRNA. Translation: BAB23393.1.
AK146501 mRNA. Translation: BAE27216.1.
CH466532 Genomic DNA. Translation: EDL12402.1.
BC049094 mRNA. Translation: AAH49094.1.
BC051023 mRNA. Translation: AAH51023.1.
CCDSiCCDS17781.1.
RefSeqiNP_031927.2. NM_007901.5.
UniGeneiMm.982.

Genome annotation databases

EnsembliENSMUST00000055676; ENSMUSP00000050897; ENSMUSG00000045092.
GeneIDi13609.
KEGGimmu:13609.
UCSCiuc008rbo.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40811 Genomic DNA. Translation: AAC53294.1.
AF108019 Genomic DNA. Translation: AAD16975.1.
AK004591 mRNA. Translation: BAB23393.1.
AK146501 mRNA. Translation: BAE27216.1.
CH466532 Genomic DNA. Translation: EDL12402.1.
BC049094 mRNA. Translation: AAH49094.1.
BC051023 mRNA. Translation: AAH51023.1.
CCDSiCCDS17781.1.
RefSeqiNP_031927.2. NM_007901.5.
UniGeneiMm.982.

3D structure databases

ProteinModelPortaliO08530.
SMRiO08530.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199373. 2 interactors.
DIPiDIP-32248N.
IntActiO08530. 1 interactor.
STRINGi10090.ENSMUSP00000050897.

Chemistry databases

BindingDBiO08530.
ChEMBLiCHEMBL1914262.
GuidetoPHARMACOLOGYi275.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO08530.
PhosphoSitePlusiO08530.

Proteomic databases

MaxQBiO08530.
PaxDbiO08530.
PRIDEiO08530.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000055676; ENSMUSP00000050897; ENSMUSG00000045092.
GeneIDi13609.
KEGGimmu:13609.
UCSCiuc008rbo.2. mouse.

Organism-specific databases

CTDi1901.
MGIiMGI:1096355. S1pr1.

Phylogenomic databases

eggNOGiENOG410IIA7. Eukaryota.
ENOG410XQD3. LUCA.
GeneTreeiENSGT00760000118804.
HOGENOMiHOG000233501.
HOVERGENiHBG103071.
InParanoidiO08530.
KOiK04288.
OMAiIGGMEFS.
OrthoDBiEOG091G0DD4.
TreeFamiTF330052.

Enzyme and pathway databases

ReactomeiR-MMU-418594. G alpha (i) signalling events.
R-MMU-419408. Lysosphingolipid and LPA receptors.

Miscellaneous databases

PROiO08530.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000045092.
GenevisibleiO08530. MM.

Family and domain databases

InterProiIPR000987. EDG1_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR004061. S1P_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00642. EDG1RECEPTOR.
PR00237. GPCRRHODOPSN.
PR01523. S1PRECEPTOR.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS1PR1_MOUSE
AccessioniPrimary (citable) accession number: O08530
Secondary accession number(s): Q9DC35, Q9R235
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.