LMPD Database

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LMP002811

UniProt Annotations

Entry Information
Gene Namesphingosine-1-phosphate receptor 1
Protein EntryS1PR1_MOUSE
UniProt IDO08530
SpeciesMouse
Comments
Comment typeDescription
Disruption PhenotypeEmbryonic 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}.
FunctionG-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}.
SimilarityBelongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.
Subcellular LocationCell 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}.
SubunitInteracts with GNAI1 and GNAI3. {ECO:0000250}.
Tissue SpecificityExpressed 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}.