Top ▲

LPA5 receptor

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 124

Nomenclature: LPA5 receptor

Family: Lysophospholipid (LPA) receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 372 12p13.31 LPAR5 lysophosphatidic acid receptor 5
Mouse 7 372 6 F2 Lpar5 lysophosphatidic acid receptor 5
Rat 7 384 4q42 Lpar5 lysophosphatidic acid receptor 5
Previous and Unofficial Names Click here for help
GPR93 | LPAR5 | GPR92 | G protein-coupled receptor 92
Database Links Click here for help
Specialist databases
GPCRdb lpar5_human (Hs), lpar5_mouse (Mm)
Other databases
Alphafold Q9H1C0 (Hs), Q149R9 (Mm)
ChEMBL Target CHEMBL5700 (Hs)
Ensembl Gene ENSG00000184574 (Hs), ENSMUSG00000067714 (Mm), ENSRNOG00000021401 (Rn)
Entrez Gene 57121 (Hs), 381810 (Mm), 500317 (Rn)
Human Protein Atlas ENSG00000184574 (Hs)
KEGG Gene hsa:57121 (Hs), mmu:381810 (Mm), rno:500317 (Rn)
OMIM 606926 (Hs)
Pharos Q9H1C0 (Hs)
RefSeq Nucleotide NM_020400 (Hs), NM_001163268 (Mm), XM_575667 (Rn)
RefSeq Protein NP_065133 (Hs), NP_001156740 (Mm), XP_575667 (Rn)
UniProtKB Q9H1C0 (Hs), Q149R9 (Mm)
Wikipedia LPAR5 (Hs)
Natural/Endogenous Ligands Click here for help
farnesyl diphosphate
farnesyl monophosphate
LPA
N-arachidonoylglycine
Comments: Proposed ligand, two publications

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LPA Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.2 pKd 6
⤷ pKd 8.2 (Kd 6.4x10-9 M) [6]
alkyl glycerol phosphate 18:1 Small molecule or natural product Rn Full agonist 8.7 pEC50 20
⤷ pEC50 8.7 (EC50 2x10-9 M) [20]
farnesyl monophosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 7.3 pEC50 20
⤷ pEC50 7.3 [20]
farnesyl diphosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 5.8 – 6.5 pEC50 16,20
⤷ pEC50 5.8 – 6.5 (EC50 1.46x10-6 – 2.9x10-7 M) [16,20]
LPA Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 4.3 – 7.9 pEC50 11,16,19
⤷ pEC50 4.3 – 7.9 [11,16,19]
octyl thiophosphatidic acid Small molecule or natural product Rn Partial agonist 5.7 pEC50 20
⤷ pEC50 5.7 (EC50 2.1x10-6 M) [20]
N-arachidonoylglycine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist <4.3 pEC50 16,20
⤷ pEC50 <4.3 (EC50 >5x10-5 M) [16,20]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 66 [PMID: 36126387] Small molecule or natural product Hs Antagonist 7.5 pIC50 22
⤷ pIC50 7.5 [22]
AS2717638 Small molecule or natural product Hs Antagonist 7.4 pIC50 14
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [14]
Description: IC50 value determined in a cAMP accumulation assay.
compound 65 [PMID: 36126387] Small molecule or natural product Hs Antagonist 7.2 pIC50 22
⤷ pIC50 7.2 [22]
TCLPA5 Small molecule or natural product Primary target of this compound Hs Antagonist 6.1 pIC50 7
⤷ pIC50 6.1 (IC50 8x10-7 M) [7]
Description: Inhibitor of KI6425-induced activation of a LPA5-RH7777 cell line.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family
G12/G13 family 		Other - See Comments
Comments:  Increases cAMP, intracellular calcium, conductance change pathway unknown. Others include: Rho. For a detailed review please see [21].
References:  8
Tissue Distribution Click here for help
Mast cells, platelets, spleen, heart, small intestine, placenta, colon, liver
Species:  Human
Technique:  Northern blot and RT-PCR
References:  1,12
Small intestine, lung, heart, stomach, colon, spleen, thymus, skin, liver, platelets, mast cells, gastrointestinal lymphocytes, dorsal root ganglia, early embryonic forebrain, rostral midbrain, hindbrain, choroid plexus, embryonic stem cell, abdominal/thoracic aortic vascular smooth muscle cell.
Species:  Mouse
Technique:  RT-PCR, in situ hybridisation, IHC
References:  2,6,8,16-17
Expression Datasets Click here for help

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays Click here for help
Receptor internalization
Species:  Rat
Tissue:  Brain
Response measured:  Receptor internalization in B103 neuroblastoma cells
References:  8
Neurite retraction
Species:  Rat
Tissue:  Brain
Response measured:  Neurite retraction in B103 neuroblastoma cells
References:  8
Stress fiber formation
Species:  Rat
Tissue:  Liver
Response measured:  Stress fiber formation in RH7777 hepatoma cells
References:  8
Release of proinflammatory cytokines
Species:  Mouse
Tissue:  Microglia
Response measured:  Increased CD40, CD86, inducible nitric oxide synthase, and COX-2.
References:  18
CD8+ T cell cytotoxicity. n.b.: human and mouse
Species:  Human
Tissue:  CD8+ T cells
Response measured:  Inhibits calcium response, pERK and Nur77 and CD69 expression; potential inhibitory receptor of CD8 T cells.
References:  13,15
Physiological Functions Click here for help
Release of MIP-1β by mast cells
Species:  Human
Tissue:  Immune
References:  12
Chemorepellent for B16 melanoma cells
Species:  Mouse
Tissue:  Skin
References:  5
Sodium dependent water absorption
Species:  Mouse
Tissue:  Intestine
References:  10
Mediation of neuropathic pain
Species:  Mouse
Tissue:  Spinal cord
References:  9
M1 inflammatory polarization.
Species:  Mouse
Tissue:  Microglia
References:  18
Physiological Consequences of Altering Gene Expression Click here for help
LPA5 KO in mice negatively regulates B cell activation and the humoral immune response.
Species:  Mouse
Tissue:  Whole animal
Technique:  Gene knockout
References:  4
LPA5-KO mice exhibit enhanced islet macrophage inflammation, glucose intolerance and severely diminished insulin secretion.
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  3
Mice with receptor knockout are protected from partial sciatic nerve ligation-medated neuropathic pain; no baseline phenotype
Species:  Mouse
Tissue:  Spinal cord: dorsal root ganglia and dorsal horn
Technique:  Gene knockout
References:  9

References

Show »

1. Amisten S, Braun OO, Bengtsson A, Erlinge D. (2008) Gene expression profiling for the identification of G-protein coupled receptors in human platelets. Thromb Res, 122 (1): 47-57. [PMID:17920662]

2. Dancs PT, Ruisanchez É, Balogh A, Panta CR, Miklós Z, Nüsing RM, Aoki J, Chun J, Offermanns S, Tigyi G et al.. (2017) LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. FASEB J, 31 (4): 1547-1555. [PMID:28069828]

3. de Souza CO, Paschoal VA, Sun X, Vishvanath L, Zhang Q, Shao M, Onodera T, Chen S, Joffin N, Bueno LM et al.. (2022) GPR92 activation in islet macrophages controls β cell function in a diet-induced obesity model. J Clin Invest, 132 (21). [PMID:36066975]

4. Hu J, Oda SK, Shotts K, Donovan EE, Strauch P, Pujanauski LM, Victorino F, Al-Shami A, Fujiwara Y, Tigyi G et al.. (2014) Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response. J Immunol, 193 (1): 85-95. [PMID:24890721]

5. Jongsma M, Matas-Rico E, Rzadkowski A, Jalink K, Moolenaar WH. (2011) LPA is a chemorepellent for B16 melanoma cells: action through the cAMP-elevating LPA5 receptor. PLoS ONE, 6 (12): e29260. [PMID:22195035]

6. Kotarsky K, Boketoft A, Bristulf J, Nilsson NE, Norberg A, Hansson S, Owman C, Sillard R, Leeb-Lundberg LM, Olde B. (2006) Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. J Pharmacol Exp Ther, 318 (2): 619-28. [PMID:16651401]

7. Kozian DH, Evers A, Florian P, Wonerow P, Joho S, Nazare M. (2012) Selective non-lipid modulator of LPA5 activity in human platelets. Bioorg Med Chem Lett, 22 (16): 5239-43. [PMID:22801643]

8. Lee CW, Rivera R, Gardell S, Dubin AE, Chun J. (2006) GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J Biol Chem, 281 (33): 23589-97. [PMID:16774927]

9. Lin ME, Rivera RR, Chun J. (2012) Targeted deletion of LPA5 identifies novel roles for lysophosphatidic acid signaling in development of neuropathic pain. J Biol Chem, 287 (21): 17608-17. [PMID:22461625]

10. Lin S, Yeruva S, He P, Singh AK, Zhang H, Chen M, Lamprecht G, de Jonge HR, Tse M, Donowitz M, Hogema BM, Chun J, Seidler U, Yun CC. (2010) Lysophosphatidic acid stimulates the intestinal brush border Na(+)/H(+) exchanger 3 and fluid absorption via LPA(5) and NHERF2. Gastroenterology, 138 (2): 649-58. [PMID:19800338]

11. Lu Y, Wang Z, Li CM, Chen J, Dalton JT, Li W, Miller DD. (2010) Synthesis, in vitro structure-activity relationship, and in vivo studies of 2-arylthiazolidine-4-carboxylic acid amides as anticancer agents. Bioorg Med Chem, 18 (2): 477-95. [PMID:20056548]

12. Lundequist A, Boyce JA. (2011) LPA5 is abundantly expressed by human mast cells and important for lysophosphatidic acid induced MIP-1β release. PLoS ONE, 6 (3): e18192. [PMID:21464938]

13. Mathew D, Kremer KN, Strauch P, Tigyi G, Pelanda R, Torres RM. (2019) LPA5 Is an Inhibitory Receptor That Suppresses CD8 T-Cell Cytotoxic Function via Disruption of Early TCR Signaling. Front Immunol, 10: 1159. [PMID:31231367]

14. Murai N, Hiyama H, Kiso T, Sekizawa T, Watabiki T, Oka H, Aoki T. (2017) Analgesic effects of novel lysophosphatidic acid receptor 5 antagonist AS2717638 in rodents. Neuropharmacology, 126: 97-107. [PMID:28859883]

15. Oda SK, Strauch P, Fujiwara Y, Al-Shami A, Oravecz T, Tigyi G, Pelanda R, Torres RM. (2013) Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression. Cancer Immunol Res, 1 (4): 245-55. [PMID:24455753]

16. Oh DY, Yoon JM, Moon MJ, Hwang JI, Choe H, Lee JY, Kim JI, Kim S, Rhim H, O'Dell DK, Walker JM, Na HS, Lee MG, Kwon HB, Kim K, Seong JY. (2008) Identification of farnesyl pyrophosphate and N-arachidonylglycine as endogenous ligands for GPR92. J Biol Chem, 283 (30): 21054-64. [PMID:18499677]

17. Ohuchi H, Hamada A, Matsuda H, Takagi A, Tanaka M, Aoki J, Arai H, Noji S. (2008) Expression patterns of the lysophospholipid receptor genes during mouse early development. Dev Dyn, 237 (11): 3280-94. [PMID:18924241]

18. Plastira I, Bernhart E, Goeritzer M, Reicher H, Kumble VB, Kogelnik N, Wintersperger A, Hammer A, Schlager S, Jandl K et al.. (2016) 1-Oleyl-lysophosphatidic acid (LPA) promotes polarization of BV-2 and primary murine microglia towards an M1-like phenotype. J Neuroinflammation, 13 (1): 205. [PMID:27565558]

19. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]

20. Williams JR, Khandoga AL, Goyal P, Fells JI, Perygin DH, Siess W, Parrill AL, Tigyi G, Fujiwara Y. (2009) Unique ligand selectivity of the GPR92/LPA5 lysophosphatidate receptor indicates role in human platelet activation. J Biol Chem, 284 (25): 17304-19. [PMID:19366702]

21. Yung YC, Stoddard NC, Chun J. (2014) LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res, 55 (7): 1192-1214. [PMID:24643338]

22. Zhang D, Decker AM, Woodhouse K, Snyder R, Patel P, Harris DL, Tao YX, Li JX, Zhang Y. (2022) Isoquinolone derivatives as lysophosphatidic acid receptor 5 (LPA5) antagonists: Investigation of structure-activity relationships, ADME properties and analgesic effects. Eur J Med Chem, 243: 114741. [PMID:36126387]

Contributors

Show »

How to cite this page