S1pr1

The protein encoded by this gene is structurally similar to G protein-coupled receptors and is highly expressed in endothelial cells. It binds the ligand sphingosine-1-phosphate with high affinity and high specificity, and suggested to be involved in the processes that regulate the differentiation of endothelial cells. Activation of this receptor induces cell-cell adhesion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

Sphingosine-1-Phosphate Receptor 1

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.

Biological Process actin cytoskeleton reorganizationISS:UniProtKB
Biological Process adenylate cyclase-activating G protein-coupled receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Biological Process adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayIEA:Ensembl
Biological Process angiogenesisManual Assertion Based On ExperimentIBA:GO_Central
Biological Process blood vessel maturationISS:UniProtKB
Biological Process brain developmentIEA:Ensembl
Biological Process cardiac muscle tissue growth involved in heart morphogenesisISS:UniProtKB
Biological Process cell adhesionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process cell migrationISS:UniProtKB
Biological Process cell population proliferationIEA:Ensembl
Biological Process chemotaxisISS:UniProtKB
Biological Process endothelial cell differentiationIEA:Ensembl
Biological Process G protein-coupled receptor signaling pathwayManual Assertion Based On ExperimentTAS:ProtInc
Biological Process heart trabecula morphogenesisISS:UniProtKB
Biological Process lamellipodium assemblyISS:UniProtKB
Biological Process leukocyte chemotaxisIEA:Ensembl
Biological Process negative regulation of stress fiber assemblyIEA:Ensembl
Biological Process neuron differentiationIEA:Ensembl
Biological Process positive regulation of cell migrationIEA:Ensembl
Biological Process positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathwayIEA:Ensembl
Biological Process positive regulation of GTPase activityIEA:Ensembl
Biological Process positive regulation of positive chemotaxisIEA:Ensembl
Biological Process positive regulation of smooth muscle cell proliferationIEA:Ensembl
Biological Process positive regulation of transcription by RNA polymerase IIIEA:Ensembl
Biological Process regulation of bone mineralizationISS:UniProtKB
Biological Process regulation of bone resorptionISS:UniProtKB
Biological Process regulation of cell adhesionIEA:Ensembl
Biological Process regulation of metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process sphingosine-1-phosphate receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process T cell migrationISS:UniProtKB
Biological Process transmission of nerve impulseIEA:Ensembl

Extracellular: 1-46
Helical: 47-68
Cytoplasmic: 69-82
Helical: 83-104
Extracellular: 105-116
Helical: 117-138
Cytoplasmic: 139-160
Helical: 161-182
Extracellular: 183-196
Helical: 197-224
Cytoplasmic: 225-257
Helical: 258-278
Extracellular: 279-289
Helical: 290-310
Cytoplasmic: 311-382

S1P-induced endothelial cell migration requires the PKB/AKT1-mediated phosphorylation of the third intracellular loop at the Thr-236 residue.
Palmitoylated by ZDHHC5. Palmitoylation is required for targeting to plasma membrane, enabling G(i) coupling.