LPA6 receptor

Nomenclature: LPA6 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.  » Email us

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 344 13q14 LPAR6 lysophosphatidic acid receptor 6 9,13
Mouse 7 344 14 Lpar6 lysophosphatidic acid receptor 6
Rat 7 344 15p11 Lpar6 lysophosphatidic acid receptor 6
Previous and Unofficial Names
P2Y5
MGC120358
P2RY5
LPAR6
purinergic receptor P2Y, G-protein coupled, 5
MGC112684
LPA receptor 6
LPA-6
P2Y purinoceptor 5
lysophosphatidic acid receptor 6
oleoyl-L-alpha-lysophosphatidic acid receptor
purinergic receptor 5
similar to purinergic receptor P2Y, G-protein coupled, 5
2610302I02Rik
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
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 6.0 pEC50 9,17
pEC50 6.0 [9,17]
LPA Mm Partial agonist 6.0 pEC50 17
pEC50 6.0 (EC50 1x10-6 M) [17]
View species-specific agonist tables
Agonist Comments
LPA6 was originally reported to bind extracellular nucleotides as ligands [16], although this was not substantiated by additional experiments [5,15].

Alkyl OMPT had similar agonist activity as 1-oleoyl LPA [17].
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family
Gi/Go family
G12/G13 family
Adenylate 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 [17], and Gα12/13-Rho, PLC, PKC, ROCK, p38, PI3K pathway stimulation [4].
References:  4,9,17
Tissue Distribution
Hair cells (follicles: skin, scalp, eyebrow), leukocytes
Expression level:  High
Species:  Human
Technique:  Protein blot, PCR, immunofluorescence
References:  8-10
Leukocytes
Expression level:  High
Species:  Human
Technique:  Protein blot, PCR, immunofluorescence
References:  9
Spleen, thymus, leukocyte, prostate, ovary, testis, small intestine, colon, pancreas, placenta, liver, lung, heart, brain, skeletal muscle, kidney, keratinocytes
Species:  Human
Technique:  RT-PCR
References:  9
Duodenum mucosa, jejunum mucosa, ileum mucosa, colon mucosa
Expression level:  High
Species:  Mouse
Technique:  Semiquantitative RT-PCR, Western immunoblotting
References:  4
Kidney, uterus, spleen, ileum, liver, skin, brain, heart, adrenal, lung
Species:  Mouse
Technique:  Northern blot
References:  9
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]

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Functional Assays
Neurite retraction
Species:  Rat
Tissue:  Neuroblastoma
Response measured:  Increased neurite retraction in B103-p2y5 cells after LPA exposure
References:  17
Membrane blebbing
Species:  Rat
Tissue:  Liver
Response measured:  Increased membrane blebbing in RH7777-p2y5 hepatoma cells after LPA exposure
References:  17
Increased intracellular calcium when LPA6 was co-expressed with a promiscuous Gs protein, reduced forskolin-stimulated [cAMP]I, and ERK1/2 activation
Species:  Mouse
Tissue:  Liver
Response measured:  Increased intracellular calcium, reduced forskolin-stimulated [cAMP]I, and ERK1/2 activation
References:  17
Physiological Functions
LPA6 was identified as critical mediator for hair growth
Species:  Human
Tissue:  Hair follicles (skin, scalp, eyebrow)
References:  3,8-9,12
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
Disease:  Woolly hair
OMIM:  278150
Orphanet:  170
References: 
Mutations not determined
Disease:  Familial hair loss: hypotrichosis
OMIM:  278150
Orphanet:  55654
Role: 
Comments: 
References:  3,7-9,12
Click column headers to sort
Type Species Molecular location Description Reference
Deletion Human c.472delC One base pair deletion that leads to frameshift and premature stop 8
Deletion Human - Deletion of entire LPAR6 gene 6
Insertion Human p.I194FfsX11 Insertion in a stretch of T at position 577 to 583 lead to substitution of isoleucine to phenylalanine at amino acid position 194 and a frameshift leading to a premature stop 2
Insertion Human c.69insCATG; p.24insHfsX52 Insertion of 4-nucleotide base 1,13-14
Insertion Human 69insCATG 4-nucleotide insertion 13
Missense Human c.833G>A; p.C278Y Amino acid substitution of nonpolar cysteine to polar tyrosine 11
Missense Human p.G146R Missense mutation lead to substitution of glycine for arginine 1-2
Missense Human c.742A>T; p.N248Y Amino acid subsitution of a polar uncharged (neutral) asparagine with an aromatic hydrophobic nonpolar tyrosine 14
Missense Human c.830C>T; p.L277P Amino acid substitution of nonpolar hydrophobic leucine with cyclic proline 14
Missense Human c.188A>T; p.D63V Amino acid substitution of acidic polar aspartate to nonpolar valine 1,12,14
Missense Human c.436G>A; p.G146R Amino acid substitution of nonpolar glycine to polar arginine 1,14
Missense Human c.562A>T; p.I188F Amino acid substitution of nonpolar isoleucine to nonpolar phenylalanine 13-14
Other Human c.64_67dupTGCA 4 base pair duplication that leads to frameshift and premature stop 8
Clinically-Relevant Mutations and Pathophysiology Comments
Other distinct missense mutations include D63V, I188F, and E189K [13], as well as deletion (c.172-175delAACT; 177delG; p.N58-L59delinsCfsX88) [14].

References

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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 Dermatol22 (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 Venereol24 (7): 858-9. [PMID:20015179]

4. 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]

5. 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: 455-460. [PMID:9240460]

6. 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]

7. Nakamura M, Tokura Y. (2009) Congenital woolly hair without P2RY5 mutation. Dermatoendocrinol1 (1): 58-9. [PMID:20046591]

8. 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]

9. 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]

10. 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]

11. 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. Genomics92 (5): 273-8. [PMID:18692127]

12. 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]

13. 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]

14. 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]

15. von Kügelgen I. (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol. Ther.110 (3): 415-32. [PMID:16257449]

16. Webb TE, Kaplan MG, Barnard EA. (1996) Identification of 6H1 as a P2Y purinoceptor: P2Y5. Biochem. Biophys. Res. Commun.219: 105-110. [PMID:8619790]

17. 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]

How to cite this page

Yun C. Yung, Jerold Chun, Chido Mpamhanga.
Lysophospholipid (LPA) receptors: LPA6 receptor. Last modified on 17/03/2014. Accessed on 29/07/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=163.