Top ▲

LPA2 receptor

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 273

Nomenclature: LPA2 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 7 351 19p13.11 LPAR2 lysophosphatidic acid receptor 2 6
Mouse 7 348 8 33.91 cM Lpar2 lysophosphatidic acid receptor 2 6
Rat 7 264 16p14 Lpar2 lysophosphatidic acid receptor 2
Previous and Unofficial Names Click here for help
Edg4 | Pbx4 | pre-B-cell leukemia transcription factor 4 | endothelial differentiation gene 4, lysophosphatidic acid G-protein-coupled receptor 4
Database Links Click here for help
Specialist databases
GPCRdb lpar2_human (Hs), lpar2_mouse (Mm)
Other databases
Alphafold Q9HBW0 (Hs), Q9JL06 (Mm)
ChEMBL Target CHEMBL3724 (Hs), CHEMBL4523464 (Mm)
Ensembl Gene ENSG00000064547 (Hs), ENSMUSG00000031861 (Mm), ENSRNOG00000010758 (Rn)
Entrez Gene 9170 (Hs), 53978 (Mm), 498609 (Rn)
Human Protein Atlas ENSG00000064547 (Hs)
KEGG Gene hsa:9170 (Hs), mmu:53978 (Mm), rno:498609 (Rn)
OMIM 605110 (Hs)
Pharos Q9HBW0 (Hs)
RefSeq Nucleotide NM_004720 (Hs), NM_020028 (Mm), NM_001109109 (Rn)
RefSeq Protein NP_004711 (Hs), NP_064412 (Mm), NP_001102579 (Rn)
UniProtKB Q9HBW0 (Hs), Q9JL06 (Mm)
Wikipedia LPAR2 (Hs)
Natural/Endogenous Ligands Click here for help
farnesyl diphosphate
farnesyl monophosphate
LPA

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
CpY Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.7 pKi 13
⤷ pKi 8.7 (Ki 2x10-9 M) [13]
CpX Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.1 pKi 13
⤷ pKi 7.1 (Ki 7.9x10-8 M) [13]
Radioprotectin-1 Small molecule or natural product Hs Agonist 11.3 pEC50 19
⤷ pEC50 11.3 (EC50 5x10-12 M) [19]
LPA Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Mm Full agonist 8.0 – 8.2 pEC50 1,16
⤷ pEC50 8.0 – 8.2 (EC50 1x10-8 – 6.8x10-9 M) [1,16]
2-oleoyl-LPA Small molecule or natural product Click here for species-specific activity table Hs Agonist 8.0 pEC50 3
⤷ pEC50 8.0 [3]
Radioprotectin-1 Small molecule or natural product Mm Agonist 7.6 pEC50 19
⤷ pEC50 7.6 (EC50 2.5x10-8 M) [19]
NAEPA Small molecule or natural product Click here for species-specific activity table Mm Full agonist 7.5 pEC50 16
⤷ pEC50 7.5 (EC50 3x10-8 M) [16]
CpY Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.5 pEC50 13
⤷ pEC50 7.5 (EC50 3.16x10-8 M) [13]
LPA Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 6.7 – 8.2 pEC50 14,25
⤷ pEC50 6.7 – 8.2 [14,25]
CpX Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.9 pEC50 13
⤷ pEC50 6.9 (EC50 1.26x10-7 M) [13]
oleoyl-thiophosphate Small molecule or natural product Click here for species-specific activity table Mm Partial agonist 6.6 pEC50 10
⤷ pEC50 6.6 (EC50 2.44x10-7 M) [10]
dodecylphosphate Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 pEC50 27
⤷ pEC50 6.2 (EC50 7x10-7 M) [27]
dodecyl-thiophosphate Small molecule or natural product Click here for species-specific activity table Mm Partial agonist 6.0 pEC50 10
⤷ pEC50 6.0 (EC50 1x10-6 M) [10]
decyl dihydrogen phosphate Small molecule or natural product Hs Full agonist 5.4 pEC50 27
⤷ pEC50 5.4 (EC50 3.7x10-6 M) [27]
farnesyl diphosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 5.7 pIC50 28
⤷ pIC50 5.7 [28]
View species-specific agonist tables
Agonist Comments
Virtual screening experiments have shown GRI977143 [18] to be a potent agonist of LPA2.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
UCM-14216 Small molecule or natural product Hs Antagonist 8.9 pKd 17
⤷ pKd 8.9 (Kd 1.3x10-9 M) [17]
BrP-LPA Small molecule or natural product Mm Antagonist 6.6 pKi 29
⤷ pKi 6.6 (Ki 2.45x10-7 M) [29]
Ki16425 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.3 pKi 22
⤷ pKi 5.3 [22]
H2L5186303 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 pIC50 11-12
⤷ pIC50 8.1 (IC50 8.9x10-9 M) [11-12]
compound 15 [PMID: 18178086] Small molecule or natural product Mm Antagonist 7.8 pIC50 4
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [4]
farnesyl monophosphate Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure N/A Antagonist 6.8 pIC50 28
⤷ pIC50 6.8 [28]
BrP-LPA Small molecule or natural product Mm Antagonist 6.3 pIC50 29
⤷ pIC50 6.3 (IC50 4.68x10-7 M) [29]
AM966 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.8 pIC50 26
⤷ pIC50 5.8 [26]
UCM-14216 Small molecule or natural product Hs Antagonist 5.7 pIC50 17
⤷ pIC50 5.7 (IC50 1.9x10-6 M) [17]
AM966 Small molecule or natural product Click here for species-specific activity table Mm Antagonist 4.6 pIC50 26
⤷ pIC50 4.6 [26]
View species-specific antagonist tables
Antagonist Comments
Virtual screening experiments have shown H2L5186303 [11] to be a potent antagonist of LPA2.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family 		Adenylyl cyclase inhibition
Phospholipase A2 stimulation
Comments:  Others include: Phosphatidylinositol-3-Kinase, RAS, Rho, MAP kinase activation. For a detailed review please see [5]
References:  15
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G12/G13 family
References: 
Tissue Distribution Click here for help
Leukocytes, testis, prostate, spleen, thymus, and pancreas
Species:  Human
Technique:  Northern blot
References:  1
Kidney, uterus, testis, lung, stomach, spleen, thymus, postnatal brain, heart, embryonic brain, limb buds, craniofacial regions, and Rathke’s pouch.
Species:  Mouse
Technique:  Northern blot and in situ hybridisation
References:  9,20,23
Abdominal/thoracic aortic vascular smooth muscle cell.
Expression level:  High
Species:  Mouse
Technique:  qRT-PCR
References:  8
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
Cell rounding
Species:  Rat
Tissue:  Neuroblastoma (B103 cell line)
Response measured:  Cell rounding
References:  15
Glycolysis
Species:  Human
Tissue:  Ovarian cancer (Caov-3 and OVCA-432 cell lines)
Response measured:  Altered generation of [3]H water from [3]H glucose.
References:  21
Facilitates DNA damage repair. γ-radiation upregulates LPA2 expression via NF-κB. Pharmacological inhibition of LPA2 delays DNA damage resolution.
Species:  Rat
Tissue:  Small intestine IEC-6 crypt cells.
Response measured:  Expression of Lpar2, DNA damage marker resolution.
References:  2
Physiological Consequences of Altering Gene Expression Click here for help
No obvious phenotypes, but a decrease in PLC activation is observed
Species:  Mouse
Tissue: 
Technique:  Gene targeting:- replacement vector, deletion of half of exon 2
References:  7
LPA2-KO mice showed increased vascular leak, impaired heart function, and increased early mortality.
Species:  Mouse
Tissue: 
Technique:  Gene knockout
References:  24
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
D3Bwg0562etm1Roni|Lpar2tm1Jch D3Bwg0562etm1Roni/D3Bwg0562etm1Roni,Lpar2tm1Jch/Lpar2tm1Jch
involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:106530  MGI:1858422  MP:0004753 abnormal miniature excitatory postsynaptic currents PMID: 19766573 
Lpar2tm1Jch Lpar2tm1Jch/Lpar2tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:1858422  MP:0002169 no abnormal phenotype detected PMID: 12215548 

References

Show »

1. An S, Bleu T, Hallmark OG, Goetzl EJ. (1998) Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid. J Biol Chem, 273 (14): 7906-10. [PMID:9525886]

2. Balogh A, Shimizu Y, Lee SC, Norman DD, Gangwar R, Bavaria M, Moon C, Shukla P, Rao R, Ray R et al.. (2015) The autotaxin-LPA2 GPCR axis is modulated by γ-irradiation and facilitates DNA damage repair. Cell Signal, 27 (9): 1751-62. [PMID:26027517]

3. Bandoh K, Aoki J, Taira A, Tsujimoto M, Arai H, Inoue K. (2000) Lysophosphatidic acid (LPA) receptors of the EDG family are differentially activated by LPA species. Structure-activity relationship of cloned LPA receptors. FEBS Lett, 478 (1-2): 159-65. [PMID:10922489]

4. Beck HP, Kohn T, Rubenstein S, Hedberg C, Schwandner R, Hasslinger K, Dai K, Li C, Liang L, Wesche H et al.. (2008) Discovery of potent LPA2 (EDG4) antagonists as potential anticancer agents. Bioorg Med Chem Lett, 18 (3): 1037-41. [PMID:18178086]

5. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J. (2010) LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol, 50: 157-86. [PMID:20055701]

6. Contos JJ, Chun J. (2000) Genomic characterization of the lysophosphatidic acid receptor gene, lp(A2)/Edg4, and identification of a frameshift mutation in a previously characterized cDNA. Genomics, 64 (2): 155-69. [PMID:10729222]

7. Contos JJ, Fukushima N, Weiner JA, Kaushal D, Chun J. (2000) Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc Natl Acad Sci USA, 97 (24): 13384-9. [PMID:11087877]

8. 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]

9. Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I et al.. (2011) A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol, 9 (1): e1000582. [PMID:21267068]

10. Durgam GG, Virag T, Walker MD, Tsukahara R, Yasuda S, Liliom K, van Meeteren LA, Moolenaar WH, Wilke N, Siess W et al.. (2005) Synthesis, structure-activity relationships, and biological evaluation of fatty alcohol phosphates as lysophosphatidic acid receptor ligands, activators of PPARgamma, and inhibitors of autotaxin. J Med Chem, 48 (15): 4919-30. [PMID:16033271]

11. Fells JI, Tsukahara R, Fujiwara Y, Liu J, Perygin DH, Osborne DA, Tigyi G, Parrill AL. (2008) Identification of non-lipid LPA3 antagonists by virtual screening. Bioorg Med Chem, 16 (11): 6207-17. [PMID:18467108]

12. Fells JI, Tsukahara R, Liu J, Tigyi G, Parrill AL. (2009) Structure-based drug design identifies novel LPA3 antagonists. Bioorg Med Chem, 17 (21): 7457-64. [PMID:19800804]

13. Guillot E, Le Bail JC, Paul P, Fourgous V, Briand P, Partiseti M, Cornet B, Janiak P, Philippo C. (2020) Lysophosphatidic Acid Receptor Agonism: Discovery of Potent Nonlipid Benzofuran Ethanolamine Structures. J Pharmacol Exp Ther, 374 (2): 283-294. [PMID:32409422]

14. Im DS, Heise CE, Harding MA, George SR, O'Dowd BF, Theodorescu D, Lynch KR. (2000) Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate. Mol Pharmacol, 57 (4): 753-9. [PMID:10727522]

15. Ishii I, Contos JJ, Fukushima N, Chun J. (2000) Functional comparisons of the lysophosphatidic acid receptors, LP(A1)/VZG-1/EDG-2, LP(A2)/EDG-4, and LP(A3)/EDG-7 in neuronal cell lines using a retrovirus expression system. Mol Pharmacol, 58 (5): 895-902. [PMID:11040035]

16. Kano K, Arima N, Ohgami M, Aoki J. (2008) LPA and its analogs-attractive tools for elucidation of LPA biology and drug development. Curr Med Chem, 15 (21): 2122-31. [PMID:18781939]

17. Khiar-Fernández N, Zian D, Vázquez-Villa H, Martínez RF, Escobar-Peña A, Foronda-Sainz R, Ray M, Puigdomenech-Poch M, Cincilla G, Sánchez-Martínez M et al.. (2022) Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice. J Med Chem, 65 (16): 10956-10974. [PMID:35948083]

18. Kiss GN, Fells JI, Gupte R, Lee SC, Liu J, Nusser N, Lim KG, Ray RM, Lin FT, Parrill AL et al.. (2012) Virtual screening for LPA2-specific agonists identifies a nonlipid compound with antiapoptotic actions. Mol Pharmacol, 82 (6): 1162-73. [PMID:22968304]

19. Kuo B, Szabó E, Lee SC, Balogh A, Norman D, Inoue A, Ono Y, Aoki J, Tigyi G. (2018) The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids. Cell Signal, 51: 23-33. [PMID:30063964]

20. McGiffert C, Contos JJ, Friedman B, Chun J. (2002) Embryonic brain expression analysis of lysophospholipid receptor genes suggests roles for s1p(1) in neurogenesis and s1p(1-3) in angiogenesis. FEBS Lett, 531 (1): 103-8. [PMID:12401212]

21. Mukherjee A, Ma Y, Yuan F, Gong Y, Fang Z, Mohamed EM, Berrios E, Shao H, Fang X. (2015) Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells. Neoplasia, 17 (9): 723-34. [PMID:26476080]

22. Ohta H, Sato K, Murata N, Damirin A, Malchinkhuu E, Kon J, Kimura T, Tobo M, Yamazaki Y, Watanabe T, Yagi M, Sato M, Suzuki R, Murooka H, Sakai T, Nishitoba T, Im DS, Nochi H, Tamoto K, Tomura H, Okajima F. (2003) Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol, 64 (4): 994-1005. [PMID:14500756]

23. 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]

24. Pei J, Cai L, Wang F, Xu C, Pei S, Guo H, Sun X, Chun J, Cong X, Zhu W et al.. (2022) LPA2 Contributes to Vascular Endothelium Homeostasis and Cardiac Remodeling After Myocardial Infarction. Circ Res, 131 (5): 388-403. [PMID:35920162]

25. Santos WL, Heasley BH, Jarosz R, Carter KM, Lynch KR, Macdonald TL. (2004) Synthesis and biological evaluation of phosphonic and thiophosphoric acid derivatives of lysophosphatidic acid. Bioorg Med Chem Lett, 14 (13): 3473-6. [PMID:15177455]

26. Swaney JS, Chapman C, Correa LD, Stebbins KJ, Bundey RA, Prodanovich PC, Fagan P, Baccei CS, Santini AM, Hutchinson JH et al.. (2010) A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol, 160 (7): 1699-713. [PMID:20649573]

27. Virag T, Elrod DB, Liliom K, Sardar VM, Parrill AL, Yokoyama K, Durgam G, Deng W, Miller DD, Tigyi G. (2003) Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors. Mol Pharmacol, 63 (5): 1032-42. [PMID:12695531]

28. 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]

29. Zhang H, Xu X, Gajewiak J, Tsukahara R, Fujiwara Y, Liu J, Fells JI, Perygin D, Parrill AL, Tigyi G et al.. (2009) Dual activity lysophosphatidic acid receptor pan-antagonist/autotaxin inhibitor reduces breast cancer cell migration in vitro and causes tumor regression in vivo. Cancer Res, 69 (13): 5441-9. [PMID:19509223]

Contributors

Show »

How to cite this page