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

GPR1

Family: Class A Orphans

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Tissue Distribution
Expression Datasets
Gene Expression and Pathophysiology
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 355 2q33.3 GPR1 G protein-coupled receptor 1
Mouse 7 353 1 C2 Gpr1 G protein-coupled receptor 1
Rat 7 353 9q31 Gpr1 G protein-coupled receptor 1
Previous and Unofficial Names
GPR1
G-protein coupled receptor 1
probable G-protein coupled receptor 1
G protein-coupled receptor 1
Database Links
Ensembl ENSG00000183671 (Hs), ENSMUSG00000046856 (Mm)
Entrez Gene 2825 (Hs), 241070 (Mm), 25457 (Rn)
GeneCards GPR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Gpr1 (Mm)
HomoloGene 21094 (Hs)
Human Protein Reference Database 02585 (Hs)
InterPro P46091 (Hs), Q8K087 (Mm), P46090 (Rn)
KEGG Gene hsa:2825 (Hs), mmu:241070 (Mm), rno:25457 (Rn)
OMIM 600239 (Hs)
PharmGKB Gene PA28846 (Hs)
PhosphoSitePlus P46091 (Hs), Q8K087 (Mm), P46090 (Rn)
Protein Ontology (PRO) PRO:000001502 (Hs)
RefSeq Nucleotide NM_005279 (Hs), NM_146250 (Mm), NM_012961 (Rn)
RefSeq Protein NP_005270 (Hs), NP_666362 (Mm), NP_037093 (Rn)
TreeFam ENSG00000183671 (Hs), ENSMUSG00000046856 (Mm)
UniGene Hs. 184907 (Hs)
UniProt P46091 (Hs), Q8K087 (Mm), P46090 (Rn)
Wikipedia GPR1
Orphan and other 7TM receptors
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
chemerin {Sp: Human} Hs Full agonist 8.28 pKd 3
chemerin {Sp: Human} Hs Full agonist 9.62 pEC50 3
Agonist Comments
vMIP-I was found to be a strong inhibitor of HIV infection mediated by GPR1 [31]. A C-terminal fragment representing amino acids 145–157 of the mature chemerin protein activated GPR1 with an EC50 of 1 nM [3]. GPR1 has also been described as a receptor for chimerin, although its functional relevance is currently unknown [4].
Tissue Distribution
Fetal astrocytes
Species:  Human
Technique:  RT-PCR
References:  6
Hippocampus
Species:  Human
Technique:  Northern blot
References:  22
Trophoblastic cells from early placenta
Species:  Human
Technique:  RT-PCR
References:  25
Oral keratinocytes
Species:  Human
Technique:  RT-PCR
References:  15
CD4+ alveolar macrophages
Species:  Human
Technique:  RT-PCR
References:  9
Mesangial cells
Species:  Human
Technique:  RT-PCR, Western blot
References:  36
Diencephalon, dorsal root ganglion, tongue, fetal liver, spongiotrophoblast layer of the placenta
Species:  Mouse
Technique:  In situ hybridisation
References:  12
Hippocampus
Species:  Rat
Technique:  Northern blot
References:  23
Tissue Distribution Comments
Rhesus macaque brain capillary endothelial cells express GPR1 [8], as do simian astrocytes [6]. GPR1 is upregulated in normal human oral keratinocytes in cell senescence (microarray analysis) [15]. GPR1 has been identified in simian brain progenitor cells by RT-PCR [14].

In addition to the tissue distribution studies outlined above, GPR1 has also been shown to be expressed in the following cells lines:

CEMss, U87, HeLa and 293T mouse cell lines using RT-PCR [7]

BT-3,U87/CD4 (high); BT-20/Nm (medium); C8166 (low) human cells lines using RT-PCR [29]
Expression Datasets

Click here to show/hide data

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!
Gene Expression and Pathophysiology Comments
GPR1 serves as a coreceptor for SIV and HIV [9,11,26,38], although use of receptors other than CCR5 by HIV has been shown to be rare in vitro [41]. Only one SIV Env protein, BK28, can mediate infection via GPR1 in a CD4-dependent manner [7,20,36]. Utilisation of orphan receptors as coreceptors is variable and heterogenous [32], although one paper demonstrates GPR1's action as a coreceptor allowing replication of HIV type 1 and 2 in brain derived cell lines [29]. Inhibition of HIV-1 infection can be achieved with synthetic peptide analogues derived from the NH2 terminal extracellular region of GPR1 [13]. A small domain of a few amino acids containing a tyrosine is critical for the co-receptor activity of GPR1 [30].
Biologically Significant Variants
V256L
SNP accession:  rs79246498 
Type:  Naturally occurring SNPs.
Species:  Human
References: 
I307V
SNP accession:  rs3732083 
Type:  Naturally occurring SNPs.
Species:  Human
References: 
General Comments
Results from yeast Saccharomyces cerevisiae suggest that Gpr1p is a G-protein coupled receptor which localized at plasma membrane. It is likely that a Gpr1p monitors the extracellular signal such as nutrition and transduce it via Gpa2p a possible positive regulator of cAMP level [10,21,39,41]. The GPR1/GPA2 pathway activates the Sch9p kinase to generate a response that acts in parallel with that generated by the Ras/cAMP pathway [40], and mediates the response of cells to the toxic action of dicarbon compounds like acetic acid and ethanol [37], and pseudohyphal differentiation via PKA and PLC [1,16,24,27,33-34]. Gpr1 is specifically required for glucose activation of the cAMP pathway [18,28]. Glucose-stimulated calcium influx is inhibited in GPR1 depleted cells [35], and receptor delection slows adaptation to acetic acid [2]. The receptor may also have a role in the activation cascade of yeast plasma membrane proton pump [17]. Glucose and sucrose agonise the Saccharomyces cerevisiae GPCR, whilst mannose antagonises it [5,19].
Available Assays
DiscoveRx PathHunter® CHO-K1 GPR1 (Orphan) High Expression β-Arrestin Cell Line Human Cat No. 93-0335C2
DiscoveRx PathHunter® eXpress GPR1 CHO-K1 β-Arrestin (Orphan) GPCR Assay Human Cat No. 93-0335E2C2

REFERENCES

Show »

1. Ansari, K; Martin, S; Farkasovsky, M; Ehbrecht, IM; Küntzel, H. (1999) Phospholipase C binds to the receptor-like GPR1 protein and controls pseudohyphal differentiation in Saccharomyces cerevisiae. J. Biol. Chem., 274 (42): 30052-8. [PMID:10514491]

2. Augstein, A; Barth, K; Gentsch, M; Kohlwein, SD; Barth, G. (2003) Characterization, localization and functional analysis of Gpr1p, a protein affecting sensitivity to acetic acid in the yeast Yarrowia lipolytica. Microbiology (Reading, Engl.), 149 (Pt 3): 589-600. [PMID:12634328]

3. Barnea, G; Strapps, W; Herrada, G; Berman, Y; Ong, J; Kloss, B; Axel, R; Lee, KJ. (2008) The genetic design of signaling cascades to record receptor activation. Proc. Natl. Acad. Sci. U.S.A., 105 (1): 64-9. [PMID:18165312]

4. Bondue, B; Wittamer, V; Parmentier, M. (2011) Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev., 22 (5-6): 331-8. [PMID:22119008]

5. Colombo, S; Ronchetti, D; Thevelein, JM; Winderickx, J; Martegani, E. (2004) Activation state of the Ras2 protein and glucose-induced signaling in Saccharomyces cerevisiae. J. Biol. Chem., 279 (45): 46715-22. [PMID:15339905]

6. Croitoru-Lamoury, J; Guillemin, GJ; Boussin, FD; Mognetti, B; Gigout, LI; Chéret, A; Vaslin, B; Le Grand, R; Brew, BJ; Dormont, D. (2003) Expression of chemokines and their receptors in human and simian astrocytes: evidence for a central role of TNF alpha and IFN gamma in CXCR4 and CCR5 modulation. Glia, 41 (4): 354-70. [PMID:12555203]

7. Edinger, AL; Hoffman, TL; Sharron, M; Lee, B; O'Dowd, B; Doms, RW. (1998) Use of GPR1, GPR15, and STRL33 as coreceptors by diverse human immunodeficiency virus type 1 and simian immunodeficiency virus envelope proteins. Virology, 249 (2): 367-78. [PMID:9791028]

8. Edinger, AL; Mankowski, JL; Doranz, BJ; Margulies, BJ; Lee, B; Rucker, J; Sharron, M; Hoffman, TL; Berson, JF; Zink, MC; Hirsch, VM; Clements, JE; Doms, RW. (1997) CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc. Natl. Acad. Sci. U.S.A., 94 (26): 14742-7. [PMID:9405683]

9. Farzan, M; Choe, H; Martin, K; Marcon, L; Hofmann, W; Karlsson, G; Sun, Y; Barrett, P; Marchand, N; Sullivan, N; Gerard, N; Gerard, C; Sodroski, J. (1997) Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J. Exp. Med., 186 (3): 405-11. [PMID:9236192]

10. Forsberg, H; Ljungdahl, PO. (2001) Sensors of extracellular nutrients in Saccharomyces cerevisiae. Curr. Genet., 40 (2): 91-109. [PMID:11680826]

11. Gabuzda, D; Wang, J. (1999) Chemokine receptors and virus entry in the central nervous system. J. Neurovirol., 5 (6): 643-58. [PMID:10602405]

12. Hiura, H; Sugawara, A; Ogawa, H; John, RM; Miyauchi, N; Miyanari, Y; Horiike, T; Li, Y; Yaegashi, N; Sasaki, H; Kono, T; Arima, T. (2010) A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip. Nucleic Acids Res., 38 (15): 4929-45. [PMID:20385583]

13. Ikeda, K; Konishi, K; Sato, M; Hoshino, H; Tanaka, K. (2001) Inhibition of HIV-1 infection by synthetic peptide analogues derived from the NH(2)-Terminal extracellular region of GPR1. Bioorg. Med. Chem. Lett., 11 (19): 2607-9. [PMID:11551760]

14. Iwata, N; Yoshida, H; Tobiume, M; Ono, F; Shimazaki, T; Sata, T; Nakajima, N. (2007) Simian fetal brain progenitor cells for studying viral neuropathogenesis. J. Neurovirol., 13 (1): 11-22. [PMID:17454444]

15. Kang, MK; Kameta, A; Shin, KH; Baluda, MA; Kim, HR; Park, NH. (2003) Senescence-associated genes in normal human oral keratinocytes. Exp. Cell Res., 287 (2): 272-81. [PMID:12837283]

16. Kim, JH; Johnston, M. (2006) Two glucose-sensing pathways converge on Rgt1 to regulate expression of glucose transporter genes in Saccharomyces cerevisiae. J. Biol. Chem., 281 (36): 26144-9. [PMID:16844691]

17. Kotyk, A; Lapathitis, G; Horák, J. (2003) Critical findings on the activation cascade of yeast plasma membrane H+-ATPase. FEMS Microbiol. Lett., 226 (1): 175-80. [PMID:13129624]

18. Kraakman, L; Lemaire, K; Ma, P; Teunissen, AW; Donaton, MC; Van Dijck, P; Winderickx, J; de Winde, JH; Thevelein, JM. (1999) A Saccharomyces cerevisiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose. Mol. Microbiol., 32 (5): 1002-12. [PMID:10361302]

19. Lemaire, K; Van de Velde, S; Van Dijck, P; Thevelein, JM. (2004) Glucose and sucrose act as agonist and mannose as antagonist ligands of the G protein-coupled receptor Gpr1 in the yeast Saccharomyces cerevisiae. Mol. Cell, 16 (2): 293-9. [PMID:15494315]

20. Liu, HY; Soda, Y; Shimizu, N; Haraguchi, Y; Jinno, A; Takeuchi, Y; Hoshino, H. (2000) CD4-Dependent and CD4-independent utilization of coreceptors by human immunodeficiency viruses type 2 and simian immunodeficiency viruses. Virology, 278 (1): 276-88. [PMID:11112502]

21. Lorenz, MC; Pan, X; Harashima, T; Cardenas, ME; Xue, Y; Hirsch, JP; Heitman, J. (2000) The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics, 154 (2): 609-22. [PMID:10655215]

22. Marchese, A., Docherty, J. M., Nguyen, T., Heiber, M., Cheng, R., Heng, H. H., Tsui, L. C., Shi, X., George, S. R. and O'Dowd, B. F. (1994) Cloning of human genes encoding novel G protein-coupled receptors. Genomics, 23: 609-618. [PMID:7851889]

23. Marchese, A; Cheng, R; Lee, MC; Porter, CA; Heiber, M; Goodman, M; George, SR; O'Dowd, BF. (1994) Mapping studies of two G protein-coupled receptor genes: an amino acid difference may confer a functional variation between a human and rodent receptor. Biochem. Biophys. Res. Commun., 205 (3): 1952-8. [PMID:7811287]

24. Miwa, T; Takagi, Y; Shinozaki, M; Yun, CW; Schell, WA; Perfect, JR; Kumagai, H; Tamaki, H. (2004) Gpr1, a putative G-protein-coupled receptor, regulates morphogenesis and hypha formation in the pathogenic fungus Candida albicans. Eukaryotic Cell, 3 (4): 919-31. [PMID:15302825]

25. Mognetti, B; Moussa, M; Croitoru, J; Menu, E; Dormont, D; Roques, P; Chaouat, G. (2000) HIV-1 co-receptor expression on trophoblastic cells from early placentas and permissivity to infection by several HIV-1 primary isolates. Clin. Exp. Immunol., 119 (3): 486-92. [PMID:10691921]

26. Ohagen, A; Devitt, A; Kunstman, KJ; Gorry, PR; Rose, PP; Korber, B; Taylor, J; Levy, R; Murphy, RL; Wolinsky, SM; Gabuzda, D. (2003) Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS. J. Virol., 77 (22): 12336-45. [PMID:14581570]

27. Pan, X; Heitman, J. (1999) Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol. Cell. Biol., 19 (7): 4874-87. [PMID:10373537]

28. Rolland, F; De Winde, JH; Lemaire, K; Boles, E; Thevelein, JM; Winderickx, J. (2000) Glucose-induced cAMP signalling in yeast requires both a G-protein coupled receptor system for extracellular glucose detection and a separable hexose kinase-dependent sensing process. Mol. Microbiol., 38 (2): 348-58. [PMID:11069660]

29. Shimizu, N; Soda, Y; Kanbe, K; Liu, HY; Jinno, A; Kitamura, T; Hoshino, H. (1999) An orphan G protein-coupled receptor, GPR1, acts as a coreceptor to allow replication of human immunodeficiency virus types 1 and 2 in brain-derived cells. J. Virol., 73 (6): 5231-9. [PMID:10233994]

30. Shimizu, N; Tanaka, A; Oue, A; Mori, T; Apichartpiyakul, C; Hoshino, H. (2008) A short amino acid sequence containing tyrosine in the N-terminal region of G protein-coupled receptors is critical for their potential use as co-receptors for human and simian immunodeficiency viruses. J. Gen. Virol., 89 (Pt 12): 3126-36. [PMID:19008402]

31. Simmons, G; Reeves, JD; Hibbitts, S; Stine, JT; Gray, PW; Proudfoot, AE; Clapham, PR. (2000) Co-receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands. Immunol. Rev., 177: 112-26. [PMID:11138769]

32. Singh, A; Besson, G; Mobasher, A; Collman, RG. (1999) Patterns of chemokine receptor fusion cofactor utilization by human immunodeficiency virus type 1 variants from the lungs and blood. J. Virol., 73 (8): 6680-90. [PMID:10400765]

33. Tamaki, H; Miwa, T; Shinozaki, M; Saito, M; Yun, CW; Yamamoto, K; Kumagai, H. (2000) GPR1 regulates filamentous growth through FLO11 in yeast Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun., 267 (1): 164-8. [PMID:10623592]

34. Thevelein, JM; Cauwenberg, L; Colombo, S; De Winde JH; Donation, M; Dumortier, F; Kraakman, L; Lemaire, K; Ma, P; Nauwelaers, D; Rolland, F; Teunissen, A; Van Dijck P; Versele, M; Wera, S; Winderickx, J. (2000) Nutrient-induced signal transduction through the protein kinase A pathway and its role in the control of metabolism, stress resistance, and growth in yeast. Enzyme Microb. Technol., 26 (9-10): 819-825. [PMID:10862891]

35. Tisi, R; Baldassa, S; Belotti, F; Martegani, E. (2002) Phospholipase C is required for glucose-induced calcium influx in budding yeast. FEBS Lett., 520 (1-3): 133-8. [PMID:12044885]

36. Tokizawa, S; Shimizu, N; Hui-Yu, L; Deyu, F; Haraguchi, Y; Oite, T; Hoshino, H. (2000) Infection of mesangial cells with HIV and SIV: identification of GPR1 as a coreceptor. Kidney Int., 58 (2): 607-17. [PMID:10916084]

37. Tzschoppe, K; Augstein, A; Bauer, R; Kohlwein, SD; Barth, G. (1999) trans-dominant mutations in the GPR1 gene cause high sensitivity to acetic acid and ethanol in the yeast Yarrowia lipolytica. Yeast, 15 (15): 1645-56. [PMID:10572261]

38. Vödrös, D; Thorstensson, R; Doms, RW; Fenyö, EM; Reeves, JD. (2003) Evolution of coreceptor use and CD4-independence in envelope clones derived from SIVsm-infected macaques. Virology, 316 (1): 17-28. [PMID:14599787]

39. Yun, CW; Tamaki, H; Nakayama, R; Yamamoto, K; Kumagai, H. (1997) G-protein coupled receptor from yeast Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun., 240 (2): 287-92. [PMID:9388468]

40. Yun, CW; Tamaki, H; Nakayama, R; Yamamoto, K; Kumagai, H. (1998) Gpr1p, a putative G-protein coupled receptor, regulates glucose-dependent cellular cAMP level in yeast Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun., 252 (1): 29-33. [PMID:9813141]

41. Zhang, YJ; Dragic, T; Cao, Y; Kostrikis, L; Kwon, DS; Littman, DR; KewalRamani, VN; Moore, JP. (1998) Use of coreceptors other than CCR5 by non-syncytium-inducing adult and pediatric isolates of human immunodeficiency virus type 1 is rare in vitro. J. Virol., 72 (11): 9337-44. [PMID:9765485]

To cite this database page, please use the following:

Amy E. Monaghan.
Class A Orphans: GPR1. Last modified on 02/11/2012. Accessed on 24/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=82.


Contact us | Print | Back to top | Help