Sphingosine 1-phosphate receptor 1
Also known as: CHEDG1, EDG1, S1PR1
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 (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.
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- EDG1, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, S1P_rcpt
- Functional cluster
- Ribosomal Proteins & RNA-Processing Enzymes
Experimental structures · PDB · 17
- 3V2W X-ray 3.35A
- 3V2Y X-ray 2.80A
- 7EO2 EM 2.89A
- 7EO4 EM 2.86A
- 7EVY EM 2.98A
- 7EVZ EM 3.07A
- 7EW0 EM 3.42A
- 7EW7 EM 3.27A
- 7TD3 EM 3.00A
- 7TD4 EM 2.60A
- 7VIE EM 2.86A
- 7VIF EM 2.83A
- … and 5 more
A predicted model is available from AlphaFold.
Gene Ontology · 35
- GO:0005737 cytoplasm
- GO:0005768 endosome
- GO:0009897 external side of plasma membrane
- GO:0045121 membrane raft
- GO:0005886 plasma membrane
- GO:0098793 presynapse
- GO:0004930 G protein-coupled receptor activity
- GO:0001664 G protein-coupled receptor binding
- GO:0046625 sphingolipid binding
- GO:0038036 sphingosine-1-phosphate receptor activity
- GO:0030036 actin cytoskeleton organization
- GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- GO:0001525 angiogenesis
- GO:0001955 blood vessel maturation
- GO:0003245 cardiac muscle tissue growth involved in heart morphogenesis
- GO:0007155 cell adhesion
- GO:0016477 cell migration
- GO:0006935 chemotaxis
- GO:0045446 endothelial cell differentiation
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0061384 heart trabecula morphogenesis
- GO:0030032 lamellipodium assembly
- GO:0051497 negative regulation of stress fiber assembly
- GO:0030182 neuron differentiation
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0030335 positive regulation of cell migration
- GO:0050927 positive regulation of positive chemotaxis
- GO:0048661 positive regulation of smooth muscle cell proliferation
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0030500 regulation of bone mineralization
- GO:0045124 regulation of bone resorption
- GO:0003376 sphingosine-1-phosphate receptor signaling pathway
- GO:0072678 T cell migration
- GO:0019226 transmission of nerve impulse
Drugs targeting this protein · 11
- PONESIMOD agonist
- MOCRAVIMOD agonist
- SIPONIMOD agonist
- ETRASIMOD agonist
- OZANIMOD HYDROCHLORIDE modulator
- AMISELIMOD HYDROCHLORIDE modulator
- ETRASIMOD ARGININE modulator
- CENERIMOD modulator
- SIPONIMOD FUMARIC ACID agonist
- FINGOLIMOD LAURYL SULFATE binding agent
- FINGOLIMOD HYDROCHLORIDE agonist
Related proteins · sequence + function similarity
- Sphingosine 1-phosphate receptor 1 1.00
- Sphingosine 1-phosphate receptor 1 1.00
- Sphingosine 1-phosphate receptor 1 1.00
- Sphingosine 1-phosphate receptor 1 0.98
- Sphingosine 1-phosphate receptor 3 0.96
- Sphingosine 1-phosphate receptor 3 0.95
- Sphingosine 1-phosphate receptor 2 0.94
- Sphingosine 1-phosphate receptor 3 0.89
- Lysophosphatidic acid receptor 3 0.86
- Lysophosphatidic acid receptor 3 0.86
- Cannabinoid receptor type 1B 0.85
- Cannabinoid receptor 1 0.85
Co-cited proteins · studied together in the literature
- Sphingosine 1-phosphate receptor 1 2 shared papers
- Sphingosine 1-phosphate receptor 2 2 shared papers
- Sphingosine 1-phosphate receptor 3 2 shared papers
- Early activation antigen CD69 1 shared papers
- Palmitoyltransferase ZDHHC5 1 shared papers
Literature · 17 cited papers
- Transmembrane protein CD69 acts as an S1PR1 agonist. Elife · 2023
- DHHC5-mediated palmitoylation of S1P receptor subtype 1 determines G-protein coupling. Sci. Rep. · 2017
- Crystal structure of a lipid G protein-coupled receptor. Science · 2012
- Akt-mediated transactivation of the S1P1 receptor in caveolin-enriched microdomains regulates endothelial barrier enhancement by oxidized phospholipids. Circ. Res. · 2009
- The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
- Roles for N-glycosylation in the dynamics of Edg-1/S1P1 in sphingosine 1-phosphate-stimulated cells. Glycoconj. J. · 2004
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- A single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors. J. Biol. Chem. · 2001
- Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Mol. Cell · 2001
- Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science · 2001
- Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate. J. Biol. Chem. · 2000
- … and 5 more in the literature graph