Gene/Proteome Database (LMPD)

LMPD ID
LMP002811
Gene ID
Species
Mus musculus (Mouse)
Gene Name
sphingosine-1-phosphate receptor 1
Gene Symbol
Synonyms
AI849002; Edg1; Lpb1; S1p; S1p1
Alternate Names
sphingosine 1-phosphate receptor 1; S1P receptor 1; S1P receptor Edg-1; lysophospholipid receptor B1; sphingosine 1-phosphate receptor Edg-1; endothelial differentiation G-protein coupled receptor 1; endothelial differentiation sphingolipid G-protein-coupled receptor 1
Chromosome
3
Map Location
3 G1|3
Summary
This gene encodes a G-protein-coupled receptor bound by the lysophospholipid, sphingosine 1-phosphate. The gene product functions in endothelial cells and is involved in vascular and heart development. This receptor is highly expressed in T and B lymphocytes, and it plays a role in T cell and B cell export from peripheral lymphoid organs. This protein is bound and downregulated by FTY720, an exogenous immunosuppressant drug studied in mouse disease models for multiple sclerosis in humans. [provided by RefSeq, Jan 2010]
Orthologs

Proteins

sphingosine 1-phosphate receptor 1
Refseq ID NP_031927
Protein GI 21687214
UniProt ID O08530
mRNA ID NM_007901
Length 382
RefSeq Status REVIEWED
MVSTSIPEVKALRSSVSDYGNYDIIVRHYNYTGKLNIGAEKDHGIKLTSVVFILICCFIILENIFVLLTIWKTKKFHRPMYYFIGNLALSDLLAGVAYTANLLLSGATTYKLTPAQWFLREGSMFVALSASVFSLLAIAIERYITMLKMKLHNGSNSSRSFLLISACWVISLILGGLPIMGWNCISSLSSCSTVLPLYHKHYILFCTTVFTLLLLSIVILYCRIYSLVRTRSRRLTFRKNISKASRSSEKSLALLKTVIIVLSVFIACWAPLFILLLLDVGCKAKTCDILYKAEYFLVLAVLNSGTNPIIYTLTNKEMRRAFIRIVSCCKCPNGDSAGKFKRPIIPGMEFSRSKSDNSSHPQKDDGDNPETIMSSGNVNSSS

Gene Information

Entrez Gene ID
Gene Name
sphingosine-1-phosphate receptor 1
Gene Symbol
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005768 IEA:UniProtKB-KW C endosome
GO:0009897 IMP:MGI C external side of plasma membrane
GO:0016021 IEA:UniProtKB-KW C integral component of membrane
GO:0031226 ISS:UniProtKB C intrinsic component of plasma membrane
GO:0046625 IEA:Ensembl F sphingolipid binding
GO:0038036 IMP:UniProtKB F sphingosine-1-phosphate receptor activity
GO:0072678 IMP:UniProtKB P T cell migration
GO:0031532 IMP:UniProtKB P actin cytoskeleton reorganization
GO:0007193 IDA:MGI P adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
GO:0001525 IDA:MGI P angiogenesis
GO:0001955 IMP:UniProtKB P blood vessel maturation
GO:0007420 IMP:MGI P brain development
GO:0003245 IMP:UniProtKB P cardiac muscle tissue growth involved in heart morphogenesis
GO:0016477 IMP:UniProtKB P cell migration
GO:0006935 IMP:UniProtKB P chemotaxis
GO:0045446 IEA:Ensembl P endothelial cell differentiation
GO:0061384 IMP:UniProtKB P heart trabecula morphogenesis
GO:0030032 IMP:UniProtKB P lamellipodium assembly
GO:0051497 IEA:Ensembl P negative regulation of stress fiber assembly
GO:0030182 IEA:Ensembl P neuron differentiation
GO:0032320 IEA:Ensembl P positive regulation of Ras GTPase activity
GO:0030335 IEA:Ensembl P positive regulation of cell migration
GO:0008284 IMP:MGI P positive regulation of cell proliferation
GO:0051482 IEA:Ensembl P positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway
GO:0050927 IEA:Ensembl P positive regulation of positive chemotaxis
GO:0048661 IEA:Ensembl P positive regulation of smooth muscle cell proliferation
GO:0045944 IEA:Ensembl P positive regulation of transcription from RNA polymerase II promoter
GO:0030500 IMP:UniProtKB P regulation of bone mineralization
GO:0045124 IMP:UniProtKB P regulation of bone resorption
GO:0030155 IDA:MGI P regulation of cell adhesion
GO:0003376 IMP:UniProtKB P sphingosine-1-phosphate signaling pathway
GO:0019226 IEA:Ensembl P transmission of nerve impulse

KEGG Pathway Links

KEGG Pathway ID Description
mmu04068 FoxO signaling pathway

REACTOME Pathway Links

REACTOME Pathway ID Description
5893663 G alpha (i) signalling events

Domain Information

InterPro Annotations

Accession Description
IPR000987 EDG-1 sphingosine 1-phosphate receptor
IPR000276 G protein-coupled receptor, rhodopsin-like
IPR017452 GPCR, rhodopsin-like, 7TM
IPR004061 Sphingosine 1-phosphate receptor

UniProt Annotations

Entry Information

Gene Name
sphingosine-1-phosphate receptor 1
Protein Entry
S1PR1_MOUSE
UniProt ID
Species
Mouse

Comments

Comment Type Description
Disruption Phenotype 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. {ECO:0000269|PubMed:11032855, ECO:0000269|PubMed:11726541, ECO:0000269|PubMed:12869509, ECO:0000269|PubMed:14732704, ECO:0000269|PubMed:14737169, ECO:0000269|PubMed:19204730, ECO:0000269|PubMed:21668976, ECO:0000269|PubMed:22951644}.
Function 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. {ECO:0000269|PubMed:11032855, ECO:0000269|PubMed:11230698, ECO:0000269|PubMed:11726541, ECO:0000269|PubMed:12869509, ECO:0000269|PubMed:14732704, ECO:0000269|PubMed:14737169, ECO:0000269|PubMed:19204730, ECO:0000269|PubMed:19286607, ECO:0000269|PubMed:21668976, ECO:0000269|PubMed:22951644}.
Similarity Belongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.
Subcellular Location Cell membrane; Multi-pass membrane protein. Endosome {ECO:0000250}. Membrane, caveola {ECO:0000250}. 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). {ECO:0000250}.
Subunit Interacts with GNAI1 and GNAI3. {ECO:0000250}.
Tissue Specificity 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). {ECO:0000269|PubMed:11032855, ECO:0000269|PubMed:9931453}.

Identical and Related Proteins

Unique RefSeq proteins for LMP002811 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
21687214 RefSeq NP_031927 382 sphingosine 1-phosphate receptor 1

Identical Sequences to LMP002811 proteins

Reference Database Accession Length Protein Name
GI:21687214 DBBJ BAE27216.1 382 unnamed protein product [Mus musculus]
GI:21687214 GenBank AAH49094.1 382 Sphingosine-1-phosphate receptor 1 [Mus musculus]
GI:21687214 GenBank AAH51023.1 382 Sphingosine-1-phosphate receptor 1 [Mus musculus]
GI:21687214 GenBank EDL12402.1 382 endothelial differentiation sphingolipid G-protein-coupled receptor 1 [Mus musculus]
GI:21687214 GenBank AED45321.1 382 Sequence 783 from patent US 7892730
GI:21687214 SwissProt O08530.3 382 RecName: Full=Sphingosine 1-phosphate receptor 1; Short=S1P receptor 1; Short=S1P1; AltName: Full=Endothelial differentiation G-protein coupled receptor 1; AltName: Full=Lysophospholipid receptor B1; AltName: Full=Sphingosine 1-phosphate receptor Edg-1; Short=S1P receptor Edg-1; AltName: CD_antigen=CD363 [Mus musculus]

Related Sequences to LMP002811 proteins

Reference Database Accession Length Protein Name
GI:21687214 DBBJ BAE23622.1 382 unnamed protein product [Mus musculus]
GI:21687214 GenBank AAC53294.1 382 orphan G-protein-coupled receptor [Mus musculus]
GI:21687214 GenBank AAD16975.1 382 lysophospholipid receptor B1 [Mus musculus]
GI:21687214 GenBank AEF78471.1 382 Sequence 26 from patent US 7943732
GI:21687214 GenBank AFS96219.1 382 Sequence 26 from patent US 8263357
GI:21687214 GenBank AFX82592.1 382 sphingosine 1-phosphate receptor 1 [Mus musculus]