Nomenclature: P2RY8

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor, absent in rats and mice
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 359 Xp22.33 and Yp11.3 P2RY8 purinergic receptor P2Y, G-protein coupled, 8
Previous and Unofficial Names
purinergic receptor P2Y, G-protein coupled, 8
P2Y8
MGC50878
P2RY8
G-protein coupled purinergic receptor P2Y8
purinergic receptor P2Y
G-protein coupled, 8
P2Y purinoceptor 8
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Tissue Distribution
Lymphocytes, heart, kidney, lung. Not detected in brain.
Species:  Human
Technique:  Northern blot
References:  3
Undifferentiated HL60 cells (Human promyelocytic leukemia cells). Barely detected in blood leukocytes.
Species:  Human
Technique:  RT-PCR
References:  1
Leukemic cells
Species:  Human
Technique:  RT-PCR
References:  6
Tissue Distribution Comments
P2RY8 mRNA is expressed transciently in the neural plate and tailbud during Xenopus development [2].
Functional Assays
Increase in the trans-activation activities of CREB and Elk-1, and increase in the transcriptional activities of the serum response element and enhancer-promoter fragments of the c-Fos and c-Myc genes
Species:  Human
Tissue:  Kidney
Response measured: 
References:  6
Gene Expression and Pathophysiology Comments
P2RY8 is reported to have oncogenic potential [6,9]. P2RY8-CRLF2 gene fusion, which results from PAR1 deletion of Xp22.3 and Yp11.3, is found to be associated with B-progenitor acute lymphoblastic leukemia (ALL) and ALL associated with Down syndrome [4,7-8,11]. Acute lymphoblastic leukemias in children with Down syndrome is associated with recurrent deletion of P2RY8 gene, which causes CRLR2 gene deregulation [5,10]. Somatic mutations in P2RY8 gene are identified in patients with diffuse large B-cell lymphoma (DLBCL) [9]. Increased expression of P2RY8 is found to be associated with leukemia [6]. A promoter swapping event juxtaposing SOX5 coding region to the P2RY8 promoter, which lead to the formation of a novel fusion gene involving P2RY8 and SOX5, is found to be associated with primary splenic follicular lymphoma (PSFL)[12] (Based on a single PSFL case).
Available Assays
DiscoveRx PathHunter® CHO-K1 P2RY8 β-Arrestin Orphan GPCR Cell Line (Cat no. 93-0635C2)
PathHunter® eXpress P2RY8 CHO-K1 β-Arrestin Orphan GPCR Assay (Cat no. 93-0635E2CP1M)
more info

REFERENCES

1. Adrian K, Bernhard MK, Breitinger HG, Ogilvie A. (2000) Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells. Biochim. Biophys. Acta1492 (1): 127-38. [PMID:11004484]

2. Bogdanov YD, Dale L, King BF, Whittock N, Burnstock G. (1997) Early expression of a novel nucleotide receptor in the neural plate of Xenopus embryos. J. Biol. Chem.272: 12583-12590. [PMID:9139711]

3. Cantagrel V, Lossi AM, Boulanger S, Depetris D, Mattei MG, Gecz J, Schwartz CE, Van Maldergem L, Villard L. (2004) Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males. J. Med. Genet.41 (10): 736-42. [PMID:15466006]

4. Chen IM, Harvey RC, Mullighan CG, Gastier-Foster J, Wharton W, Kang H, Borowitz MJ, Camitta BM, Carroll AJ, Devidas M et al.. (2012) Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children's Oncology Group study. Blood119 (15): 3512-22. [PMID:22368272]

5. Ensor HM, Schwab C, Russell LJ, Richards SM, Morrison H, Masic D, Jones L, Kinsey SE, Vora AJ, Mitchell CD et al.. (2011) Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial. Blood117 (7): 2129-36. [PMID:21106984]

6. Fujiwara S, Yamashita Y, Choi YL, Watanabe H, Kurashina K, Soda M, Enomoto M, Hatanaka H, Takada S, Ozawa K, Mano H. (2007) Transforming activity of purinergic receptor P2Y, G protein coupled, 8 revealed by retroviral expression screening. Leuk. Lymphoma48 (5): 978-86. [PMID:17487742]

7. Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL. (2010) Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia. Blood115 (26): 5312-21. [PMID:20139093]

8. Hertzberg L, Vendramini E, Ganmore I, Cazzaniga G, Schmitz M, Chalker J, Shiloh R, Iacobucci I, Shochat C, Zeligson S, Cario G, Stanulla M, Strehl S, Russell LJ, Harrison CJ, Bornhauser B, Yoda A, Rechavi G, Bercovich D, Borkhardt A, Kempski H, te Kronnie G, Bourquin JP, Domany E, Izraeli S. (2010) Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood115 (5): 1006-17. [PMID:19965641]

9. Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, Cruz-Gordillo P, Knoechel B, Asmann YW, Slager SL et al.. (2012) Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. U.S.A.109 (10): 3879-84. [PMID:22343534]

10. Lundin C, Hjorth L, Behrendtz M, Nordgren A, Palmqvist L, Andersen MK, Biloglav A, Forestier E, Paulsson K, Johansson B. (2012) High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome. Genes Chromosomes Cancer51 (2): 196-206. [PMID:22072402]

11. Mullighan CG, Collins-Underwood JR, Phillips LA, Loudin MG, Liu W, Zhang J, Ma J, Coustan-Smith E, Harvey RC, Willman CL, Mikhail FM, Meyer J, Carroll AJ, Williams RT, Cheng J, Heerema NA, Basso G, Pession A, Pui CH, Raimondi SC, Hunger SP, Downing JR, Carroll WL, Rabin KR. (2009) Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat. Genet.41 (11): 1243-6. [PMID:19838194]

12. Storlazzi CT, Albano F, Lo Cunsolo C, Doglioni C, Guastadisegni MC, Impera L, Lonoce A, Funes S, Macrì E, Iuzzolino P, Panagopoulos I, Specchia G, Rocchi M. (2007) Upregulation of the SOX5 by promoter swapping with the P2RY8 gene in primary splenic follicular lymphoma. Leukemia21 (10): 2221-5. [PMID:17554380]

To cite this database page, please use the following:

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: P2RY8. Last modified on 09/07/2013. Accessed on 26/07/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=164.

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