Lysophosphatidic acid receptor 1
Also known as: EDG2, LPA1, LPAR1
Function
Receptor for lysophosphatidic acid (LPA). Plays a role in the reorganization of the actin cytoskeleton, cell migration, differentiation and proliferation, and thereby contributes to the responses to tissue damage and infectious agents. Activates downstream signaling cascades via the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Signaling inhibits adenylyl cyclase activity and decreases cellular cAMP levels. Signaling triggers an increase of cytoplasmic Ca(2+) levels. Activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate. Signaling mediates activation of down-stream MAP kinases (By similarity). Contributes to the regulation of cell shape. Promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction. Promotes the activation of Rho and the formation of actin stress fibers. Promotes formation of lamellipodia at the leading edge of migrating cells via activation of RAC1 (By similarity). Through its function as LPA receptor, plays a role in chemotaxis and cell migration, including responses to injury and wounding. Plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS) via its interaction with CD14. Promotes cell proliferation in response to LPA (By similarity). Inhibits the intracellular ciliogenesis pathway in response to LPA and through AKT1 activation. Required for normal skeleton development. May play a role in osteoblast differentiation. Required for normal brain development. Required for normal proliferation, survival and maturation of newly formed neurons in the adult dentate gyrus. Plays a role in pain perception and in the initiation of neuropathic pain (By similarity).
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, LPA_rcpt, LPA_rcpt_EDG2
- Functional cluster
- Membrane Transporters & GPCRs
Experimental structures · PDB · 16
- 4Z34 X-ray 3.00A
- 4Z35 X-ray 2.90A
- 4Z36 X-ray 2.90A
- 7TD0 EM 2.83A
- 7TD1 EM 3.08A
- 7TD2 EM 3.11A
- 7YU3 EM 3.40A
- 7YU4 EM 3.30A
- 7YU5 EM 3.30A
- 7YU6 EM 3.50A
- 7YU7 EM 3.80A
- 7YU8 EM 4.50A
- … and 4 more
A predicted model is available from AlphaFold.
Gene Ontology · 43
- GO:0009986 cell surface
- GO:0005737 cytoplasm
- GO:0043198 dendritic shaft
- GO:0043197 dendritic spine
- GO:0005768 endosome
- GO:0098982 GABA-ergic synapse
- GO:0098978 glutamatergic synapse
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0042734 presynaptic membrane
- GO:0004930 G protein-coupled receptor activity
- GO:0001965 G-protein alpha-subunit binding
- GO:0035727 lysophosphatidic acid binding
- GO:0070915 lysophosphatidic acid receptor activity
- GO:0030165 PDZ domain binding
- GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- GO:0060326 cell chemotaxis
- GO:1904566 cellular response to 1-oleoyl-sn-glycerol 3-phosphate
- GO:0071453 cellular response to oxygen levels
- GO:0021549 cerebellum development
- GO:0022038 corpus callosum development
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0042552 myelination
- GO:0141162 negative regulation of cAMP/PKA signal transduction
- GO:1902018 negative regulation of cilium assembly
- GO:0010977 negative regulation of neuron projection development
- GO:0022008 neurogenesis
- GO:0014003 oligodendrocyte development
- GO:0021554 optic nerve development
- GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
- GO:0043065 positive regulation of apoptotic process
- GO:0043123 positive regulation of canonical NF-kappaB signal transduction
- GO:0007204 positive regulation of cytosolic calcium ion concentration
- GO:0060999 positive regulation of dendritic spine development
- GO:0043410 positive regulation of MAPK cascade
- GO:0035025 positive regulation of Rho protein signal transduction
- GO:0071673 positive regulation of smooth muscle cell chemotaxis
- GO:0051496 positive regulation of stress fiber assembly
- GO:0008360 regulation of cell shape
- GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization
- GO:0098693 regulation of synaptic vesicle cycle
Drugs targeting this protein · 1
- BMS-986020 antagonist
Related proteins · sequence + function similarity
- Lysophosphatidic acid receptor 1 1.00
- Lysophosphatidic acid receptor 1 1.00
- Lysophosphatidic acid receptor 1 1.00
- Lysophosphatidic acid receptor 1-B 1.00
- Lysophosphatidic acid receptor 1-A 0.99
- Lysophosphatidic acid receptor 1 0.99
- Lysophosphatidic acid receptor 3 0.96
- Lysophosphatidic acid receptor 3 0.96
- Lysophosphatidic acid receptor 3 0.95
- Sphingosine 1-phosphate receptor 2 0.90
- Sphingosine 1-phosphate receptor 2 0.86
- Sphingosine 1-phosphate receptor 1 0.85
Co-cited proteins · studied together in the literature
- Lysophosphatidic acid receptor 1 3 shared papers
- Lysophosphatidic acid receptor 2 2 shared papers
- Lysophosphatidic acid receptor 3 1 shared papers
- Lysophosphatidic acid receptor 2 1 shared papers
- G protein-coupled receptor kinase 2 1 shared papers
- WD repeat-containing protein 44 1 shared papers
- Ras-related protein Ral-A 1 shared papers
- Rab-3A-interacting protein 1 shared papers
- RAC-beta serine/threonine-protein kinase 1 shared papers
- Rab11 family-interacting protein 3 1 shared papers
- Ras-related protein Rab-11B 1 shared papers
- Ras-related protein Rab-11A 1 shared papers
Literature · 15 cited papers
- Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis. Dev. Cell · 2019
- Crystal structure of antagonist bound human lysophosphatidic acid receptor 1. Cell · 2015
- Comparative analyses of lysophosphatidic acid receptor-mediated signaling. Cell. Mol. Life Sci. · 2015
- Molecular regulation of lysophosphatidic acid receptor 1 trafficking to the cell surface. Cell. Signal. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Lysophosphatidic acid mediates migration of human mesenchymal stem cells stimulated by synovial fluid of patients with rheumatoid arthritis. Biochim. Biophys. Acta · 2010
- Lysophosphatidic acid signals through specific lysophosphatidic acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts. J. Periodontology · 2009
- Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cell. Signal. · 2009
- The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat. Med. · 2008
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- DNA sequence and analysis of human chromosome 9. Nature · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- … and 3 more in the literature graph