Nomenclature: LPA3 receptor

Family: Lysophospholipid (LPA) receptors

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 353 1p22.3 LPAR3 lysophosphatidic acid receptor 3
Mouse 7 354 3 71.03 cM Lpar3 lysophosphatidic acid receptor 3
Rat 7 354 1q55 Lpar3 lysophosphatidic acid receptor 3
Previous and Unofficial Names
Edg7
lp A3
LP-A3
Edg-7
RP4-678I3
HOFNH30
LPA3
endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 7
LPA receptor 3
LPA-3
endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor 7
lysophosphatidic acid receptor 3
lysophosphatidic acid receptor Edg-7
putative G protein-coupled receptor snGPCR32
snGPCR32
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
LPA
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LPA Hs Agonist 6.69 pKd 1
pKd 6.69 [1]
Ki16425 Hs Agonist 6.44 pKi 17
pKi 6.44 (Ki 3.6x10-7 M) [17]
α-fluoromethylenephosphonate Hs Agonist 9.3 pEC50 24
pEC50 9.3 [24]
T13 Mm Agonist 9.3 pEC50 14
pEC50 9.3 (EC50 5x10-10 M) [14]
2-oleoyl-LPA Hs Agonist 8.0 pEC50 2
pEC50 8.0 [2]
alkyl OMPT Hs Agonist 7.21 pEC50 20
pEC50 7.21 [20]
OMPT Hs Agonist 7.17 pEC50 9
pEC50 7.17 [9]
LPA Mm Agonist 6.6 pEC50 14
pEC50 6.6 (EC50 2.53x10-7 M) [14]
oleoyl-thiophosphate Mm Partial agonist 6.26 pEC50 5
pEC50 6.26 (EC50 5.46x10-7 M) [5]
NAEPA Mm Agonist <5.3 pEC50 14
pEC50 <5.3 (EC50 >5x10-6 M) [14]
dioctanoy​lglycerol​ pyrophos​phate Hs Agonist 6.97 pIC50 7
pIC50 6.97 (IC50 1.06x10-7 M) [7]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
farnesyl monophosphate Hs Antagonist 7.32 pKd 15
pKd 7.32 [15]
farnesyl diphosphate Hs Antagonist 6.81 pKd 15
pKd 6.81 [15]
dodecyl-thiophosphate Mm Antagonist 7.89 pKi 5
pKi 7.89 (Ki 1.3x10-8 M) [5]
dodecylphosphate Hs Antagonist 7.05 pKi 22
pKi 7.05 [22]
Ki16425 N/A Antagonist 6.44 pKi 17
pKi 6.44 [17]
VPC12249 Hs Antagonist 6.37 pKi 11
pKi 6.37 [11]
dioctanoy​lglycerol​ pyrophos​phate Hs Antagonist 5.5 – 7.0 pKi 7,17
pKi 5.5 – 7.0 (Ki 3.33x10-6 M) [7,17]
farnesyl diphosphate Hs Antagonist 6.81 pIC50 23
pIC50 6.81 [23]
AM966 Mm Antagonist 6.8 pIC50 21
pIC50 6.8 [21]
VPC32183 Hs Antagonist 6.76 pIC50 10
pIC50 6.76 [10]
pIC50 6.76 (IC50 1.75x10-7 M) [10]
farnesyl monophosphate Hs Antagonist 6.3 pIC50 23
pIC50 6.3 [23]
VPC12249 Hs Antagonist 5.19 – 6.37 pIC50 11,14
pIC50 5.19 – 6.37 (IC50 4.28x10-7 – 6.4x10-6 M) [11,14]
AM966 Hs Antagonist 5.7 pIC50 21
pIC50 5.7 [21]
compound 12 [PMID:19800804] Mm Antagonist 5.52 pIC50 6
pIC50 5.52 (IC50 2.992x10-6 M) [6]
View species-specific antagonist tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
Adenylate cyclase inhibition
Phospholipase A2 stimulation
Comments:  Others include: phosphatidylinositol-3-kinase, RAS, and MAP kinase activation. For a detailed review please see [3].
References:  13
Tissue Distribution
Heart, testis, prostate, pancreas, lung, ovary, brain
Species:  Human
Technique:  Northern blot
References:  12
Lung, kidney, uterus, oviduct, and testis, small intestine, brain, heart, stomach, placenta, spleen, thymus, embryonic heart, embryonic mesonephros, embryonic otic vesicle
Species:  Mouse
Technique:  Northern blot and in situ hybridisation
References:  16,18,25
Kidney, testis
Species:  Rat
Technique:  Northern blot
References:  12
Expression Datasets

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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
Neurite elongation
Species:  Rat
Tissue:  Neuroblastoma (B103 cell line)
Response measured: 
References:  13
Physiological Functions
Maintenance of proper embryo implantation and spacing
Species:  Mouse
Tissue:  Uterus
References:  4,8,25
Blockade of LPA3 reduces renal ischemia-reperfusion injury
Species:  Mouse
Tissue:  Kidney
References:  19
Physiological Consequences of Altering Gene Expression
Mice with receptor deletion have altered embryo implantation and spacing
Species:  Mouse
Tissue:  Uterus
Technique:  Gene knockouts
References:  4,8,25
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Lpar3tm1Jch Lpar3tm1Jch/Lpar3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1929469  MP:0001727 abnormal embryo implantation PMID: 15875025 
Lpar3tm1Jch Lpar3tm1Jch/Lpar3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1929469  MP:0001711 abnormal placenta morphology PMID: 15875025 
Lpar3tm1Jch Lpar3tm1Jch/Lpar3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1929469  MP:0001935 decreased litter size PMID: 15875025 
Lpar3tm1Jch Lpar3tm1Jch/Lpar3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1929469  MP:0009815 decreased prostaglandin level PMID: 15875025 
Lpar3tm1Jch Lpar3tm1Jch/Lpar3tm1Jch
involves: 129S1/Sv * 129X1/SvJ * C57BL/6
MGI:1929469  MP:0002293 long gestation period PMID: 15875025 
Available Assays
DiscoveRx PathHunter® CHO-K1 EDG7 β-Arrestin Cell Line (Cat no. 93-0636C2)
PathHunter® eXpress EDG7 CHO-K1 β-Arrestin GPCR Assay (Cat no. 93-0636E2CP13M)
more info

REFERENCES

1. Bandoh K, Aoki J, Hosono H, Kobayashi S, Kobayashi T, Murakami-Murofushi K, Tsujimoto M, Arai H, Inoue K. (1999) Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J. Biol. Chem.274 (39): 27776-85. [PMID:10488122]

2. 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]

3. 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]

4. Diao H, Aplin JD, Xiao S, Chun J, Li Z, Chen S, Ye X. (2011) Altered spatiotemporal expression of collagen types I, III, IV, and VI in Lpar3-deficient peri-implantation mouse uterus. Biol. Reprod.84 (2): 255-65. [PMID:20864640]

5. 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]

6. 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]

7. Fischer DJ, Nusser N, Virag T, Yokoyama K, Wang Da, Baker DL, Bautista D, Parrill AL, Tigyi G. (2001) Short-chain phosphatidates are subtype-selective antagonists of lysophosphatidic acid receptors. Mol. Pharmacol.60 (4): 776-84. [PMID:11562440]

8. Hama K, Aoki J, Inoue A, Endo T, Amano T, Motoki R, Kanai M, Ye X, Chun J, Matsuki N et al.. (2007) Embryo spacing and implantation timing are differentially regulated by LPA3-mediated lysophosphatidic acid signaling in mice. Biol. Reprod.77 (6): 954-9. [PMID:17823089]

9. Hasegawa Y, Erickson JR, Goddard GJ, Yu S, Liu S, Cheng KW, Eder A, Bandoh K, Aoki J, Jarosz R et al.. (2003) Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J. Biol. Chem.278 (14): 11962-9. [PMID:12554733]

10. Heasley BH, Jarosz R, Lynch KR, Macdonald TL. (2004) Initial structure-activity relationships of lysophosphatidic acid receptor antagonists: discovery of a high-affinity LPA1/LPA3 receptor antagonist. Bioorg. Med. Chem. Lett.14 (11): 2735-40. [PMID:15125924]

11. Heise CE, Santos WL, Schreihofer AM, Heasley BH, Mukhin YV, Macdonald TL, Lynch KR. (2001) Activity of 2-substituted lysophosphatidic acid (LPA) analogs at LPA receptors: discovery of a LPA1/LPA3 receptor antagonist. Mol. Pharmacol.60 (6): 1173-80. [PMID:11723223]

12. 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]

13. 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]

14. 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]

15. Liliom K, Tsukahara T, Tsukahara R, Zelman-Femiak M, Swiezewska E, Tigyi G. (2006) Farnesyl phosphates are endogenous ligands of lysophosphatidic acid receptors: inhibition of LPA GPCR and activation of PPARs. Biochim. Biophys. Acta1761 (12): 1506-14. [PMID:17092771]

16. 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]

17. 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]

18. 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]

19. Okusa MD, Ye H, Huang L, Sigismund L, Macdonald T, Lynch KR. (2003) Selective blockade of lysophosphatidic acid LPA3 receptors reduces murine renal ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol.285 (3): F565-74. [PMID:12770838]

20. Qian L, Xu Y, Simper T, Jiang G, Aoki J, Umezu-Goto M, Arai H, Yu S, Mills GB, Tsukahara R et al.. (2006) Phosphorothioate analogues of alkyl lysophosphatidic acid as LPA3 receptor-selective agonists. ChemMedChem1 (3): 376-83. [PMID:16892372]

21. 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]

22. 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]

23. 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]

24. Xu Y, Aoki J, Shimizu K, Umezu-Goto M, Hama K, Takanezawa Y, Yu S, Mills GB, Arai H, Qian L et al.. (2005) Structure-activity relationships of fluorinated lysophosphatidic acid analogues. J. Med. Chem.48 (9): 3319-27. [PMID:15857137]

25. Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H et al.. (2005) LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature435 (7038): 104-8. [PMID:15875025]

To cite this database page, please use the following:

Yun C. Yung, Jerold Chun, Chido Mpamhanga.
Lysophospholipid (LPA) receptors: LPA3 receptor. Last modified on 28/01/2014. Accessed on 23/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=274.

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