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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 344 | 13q14.2 | LPAR6 | lysophosphatidic acid receptor 6 | 11,15 |
| Mouse | 7 | 344 | 14 D3 | Lpar6 | lysophosphatidic acid receptor 6 | |
| Rat | 7 | 344 | 15q11 | Lpar6 | lysophosphatidic acid receptor 6 | |
| Previous and Unofficial Names |
| P2RY5 | LPA receptor 6 | oleoyl-L-alpha-lysophosphatidic acid receptor | P2Y purinoceptor 5 | purinergic receptor 5 |
| Database Links |
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| Specialist databases | |
| GPCRdb | lpar6_human (Hs), lpar6_mouse (Mm), lpar6_rat (Rn) |
| Other databases | |
| Alphafold | P43657 (Hs), Q8BMC0 (Mm), Q4G072 (Rn) |
| ChEMBL Target | CHEMBL2331058 (Hs) |
| Ensembl Gene | ENSG00000139679 (Hs), ENSMUSG00000033446 (Mm), ENSRNOG00000015577 (Rn) |
| Entrez Gene | 10161 (Hs), 67168 (Mm), 691774 (Rn) |
| Human Protein Atlas | ENSG00000139679 (Hs) |
| KEGG Gene | hsa:10161 (Hs), mmu:67168 (Mm), rno:691774 (Rn) |
| OMIM | 609239 (Hs) |
| Orphanet | ORPHA159166 (Hs) |
| Pharos | P43657 (Hs) |
| RefSeq Nucleotide | NM_005767 (Hs), NM_175116 (Mm), NM_001045843 (Rn) |
| RefSeq Protein | NP_005758 (Hs), NP_780325 (Mm), NP_001039308 (Rn) |
| UniProtKB | P43657 (Hs), Q8BMC0 (Mm), Q4G072 (Rn) |
| Wikipedia | LPAR6 (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| LPA |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| LPA6 was originally reported to bind extracellular nucleotides as ligands [20], although this was not substantiated by additional experiments [6,19]. Alkyl OMPT had similar agonist activity as 1-oleoyl LPA [21]. |
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
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Gs family Gi/Go family G12/G13 family |
Adenylyl cyclase stimulation Phospholipase C stimulation Other - See Comments |
| Comments: Increased intracellular calcium using a promiscuous Gs protein, ERK1/2 activation, and reduced forskolin-stimulated cAMP. G13-Rho pathway [21], and Gα12/13-Rho, PLC, PKC, ROCK, p38, PI3K pathway stimulation [5]. | |
| References: 5,11,21 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Lpar6 knockout mice have not yet been characterized, but are expected to have hypotrichosis/woolly hair. | ||||||||||
| Clinically-Relevant Mutations and Pathophysiology
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| Clinically-Relevant Mutations and Pathophysiology Comments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other distinct missense mutations include E189K [15], as well as deletion (c.172-175delAACT; 177delG; p.N58-L59delinsCfsX88) [18]. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1. Azeem Z, Jelani M, Naz G, Tariq M, Wasif N, Kamran-Ul-Hassan Naqvi S, Ayub M, Yasinzai M, Amin-Ud-Din M, Wali A et al.. (2008) Novel mutations in G protein-coupled receptor gene (P2RY5) in families with autosomal recessive hypotrichosis (LAH3). Hum Genet, 123 (5): 515-9. [PMID:18461368]
2. Azhar A, Tariq M, Baig SM, Dahl N, Klar J. (2012) A novel mutation in lysophosphatidic acid receptor 6 gene in autosomal recessive hypotrichosis and evidence for a founder effect. Eur J Dermatol, 22 (4): 464-6. [PMID:22531990]
3. Horev L, Saad-Edin B, Ingber A, Zlotogorski A. (2010) A novel deletion mutation in P2RY5/LPA(6) gene cause autosomal recessive woolly hair with hypotrichosis. J Eur Acad Dermatol Venereol, 24 (7): 858-9. [PMID:20015179]
4. Kano K, Matsumoto H, Inoue A, Yukiura H, Kanai M, Chun J, Ishii S, Shimizu T, Aoki J. (2019) Molecular mechanism of lysophosphatidic acid-induced hypertensive response. Sci Rep, 9 (1): 2662. [PMID:30804442]
5. Lee M, Choi S, Halldén G, Yo SJ, Schichnes D, Aponte GW. (2009) P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion. Am J Physiol Gastrointest Liver Physiol, 297 (4): G641-54. [PMID:19679818]
6. Li Q, Schachter JB, Harden TK, Nicholas RA. (1997) The 6H1 orphan receptor, claimed to be the p2y5 receptor, does not mediate nucleotide-promoted second messenger responses. Biochem Biophys Res Commun, 236 (2): 455-60. [PMID:9240460]
7. Mahmoudi H, Tug E, Parlak AH, Atasoy HI, Ludwig M, Polat M, Pasternack SM, Betz RC. (2012) Identification of an Alu-mediated 12.2-kb deletion of the complete LPAR6 (P2RY5) gene in a Turkish family with hypotrichosis and woolly hair. Exp Dermatol, 21 (6): 469-71. [PMID:22621192]
8. Masago K, Kihara Y, Yanagida K, Hamano F, Nakagawa S, Niwa M, Shimizu T. (2018) Lysophosphatidic acid receptor, LPA6, regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy. Biochem Biophys Res Commun, 501 (4): 1048-1054. [PMID:29778535]
9. Nakamura M, Tokura Y. (2009) Congenital woolly hair without P2RY5 mutation. Dermatoendocrinol, 1 (1): 58-9. [PMID:20046591]
10. Pasternack SM, Murugusundram S, Eigelshoven S, Müller M, Kruse R, Lehmann P, Betz RC. (2009) Novel mutations in the P2RY5 gene in one Turkish and two Indian patients presenting with hypotrichosis and woolly hair. Arch Dermatol Res, 301 (8): 621-4. [PMID:19529952]
11. Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC. (2008) G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat Genet, 40 (3): 329-34. [PMID:18297070]
12. Pasternack SM, von Kügelgen I, Müller M, Oji V, Traupe H, Sprecher E, Nöthen MM, Janecke AR, Betz RC. (2009) In vitro analysis of LIPH mutations causing hypotrichosis simplex: evidence confirming the role of lipase H and lysophosphatidic acid in hair growth. J Invest Dermatol, 129 (12): 2772-6. [PMID:19536142]
13. Petukhova L, Sousa Jr EC, Martinez-Mir A, Vitebsky A, Dos Santos LG, Shapiro L, Haynes C, Gordon D, Shimomura Y, Christiano AM. (2008) Genome-wide linkage analysis of an autosomal recessive hypotrichosis identifies a novel P2RY5 mutation. Genomics, 92 (5): 273-8. [PMID:18692127]
14. Shimomura Y, Garzon MC, Kristal L, Shapiro L, Christiano AM. (2009) Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene. Exp Dermatol, 18 (3): 218-21. [PMID:18803659]
15. Shimomura Y, Wajid M, Ishii Y, Shapiro L, Petukhova L, Gordon D, Christiano AM. (2008) Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nat Genet, 40 (3): 335-9. [PMID:18297072]
16. Spencer SA, Suárez-Pozos E, Soto-Verdugo J, Wang H, Afshari FS, Li G, Manam S, Yasuda D, Ortega A, Lister JA et al.. (2022) Lysophosphatidic acid signaling via LPA6 : A negative modulator of developmental oligodendrocyte maturation. J Neurochem, 163 (6): 478-499. [PMID:36153691]
17. Taniguchi R, Inoue A, Sayama M, Uwamizu A, Yamashita K, Hirata K, Yoshida M, Tanaka Y, Kato HE, Nakada-Nakura Y et al.. (2017) Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA6. Nature, 548 (7667): 356-360. [PMID:28792932]
18. Tariq M, Ayub M, Jelani M, Basit S, Naz G, Wasif N, Raza SI, Naveed AK, ullah Khan S, Azeem Z et al.. (2009) Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families. Br J Dermatol, 160 (5): 1006-10. [PMID:19292720]
19. von Kügelgen I. (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Ther, 110 (3): 415-32. [PMID:16257449]
20. Webb TE, Kaplan MG, Barnard EA. (1996) Identification of 6H1 as a P2Y purinoceptor: P2Y5. Biochem Biophys Res Commun, 219 (1): 105-10. [PMID:8619790]
21. Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, Taguchi R, Shimizu T, Ishii S. (2009) Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J Biol Chem, 284 (26): 17731-41. [PMID:19386608]
22. Yukiura H, Kano K, Kise R, Inoue A, Aoki J. (2015) LPP3 localizes LPA6 signalling to non-contact sites in endothelial cells. J Cell Sci, 128 (21): 3871-7. [PMID:26345369]
