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Target id: 102
Nomenclature: GPR35
Family: Class A Orphans
This receptor has a proposed ligand; see the Latest Pairings page for more information.
Gene and Protein Information | ||||||
class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 309 | 2q37.3 | GPR35 | G protein-coupled receptor 35 | |
Mouse | 7 | 307 | 1 D | Gpr35 | G protein-coupled receptor 35 | |
Rat | 6 | 306 | 9q36 | Gpr35 | G protein-coupled receptor 35 |
Previous and Unofficial Names |
G-protein coupled receptor 3 | KYNA receptor | Kynurenic acid receptor |
Database Links | |
Specialist databases | |
GPCRdb | gpr35_human (Hs), gpr35_mouse (Mm), q33bm1_rat (Rn) |
Other databases | |
Alphafold | Q9HC97 (Hs), Q9ES90 (Mm), Q33BM1 (Rn) |
ChEMBL Target | CHEMBL1293267 (Hs), CHEMBL2390813 (Mm), CHEMBL2390812 (Rn) |
Ensembl Gene | ENSG00000178623 (Hs), ENSMUSG00000026271 (Mm), ENSRNOG00000062887 (Rn) |
Entrez Gene | 2859 (Hs), 64095 (Mm), 367315 (Rn) |
Human Protein Atlas | ENSG00000178623 (Hs) |
KEGG Gene | hsa:2859 (Hs), mmu:64095 (Mm), rno:367315 (Rn) |
OMIM | 602646 (Hs) |
Orphanet | ORPHA367100 (Hs) |
Pharos | Q9HC97 (Hs) |
RefSeq Nucleotide | NM_005301 (Hs), NM_022320 (Mm), NM_001037359 (Rn) |
RefSeq Protein | NP_005292 (Hs), NP_071715 (Mm), NP_001032436 (Rn) |
UniProtKB | Q9HC97 (Hs), Q9ES90 (Mm), Q33BM1 (Rn) |
Wikipedia | GPR35 (Hs) |
Natural/Endogenous Ligands |
kynurenic acid |
2-oleoyl-LPA |
Comments: Proposed ligands, single publications |
Download all structure-activity data for this target as a CSV file
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Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Wang et al. [17] first reported that kynurenic acid was an agonist of GPR35; this observation has since been replicated in functional assays releasing interleukin 4 [2] and in a β-arrestin assay [14], but controversy remains whether the endogenous ligand reaches sufficient tissue concentrations to activate the receptor [6]. 2-Acyl lysophosphatidic acid (2-oleoyl-LPA) has also been proposed as an endogenous ligand [10] but these results were not replicated in a recent β-arrestin assay [14]. Zaprinast, a cyclic GMP-selective phosphodiesterase (PDE5A/PDE6) inhibitor, has become widely used as a surrogate agonist to investigate GPR35 pharmacology and signalling [14-15]. GPR35 is also activated by the loop diuretic drugs bumetanide and furosemide and the pharmaceutical adjunct pamoic acid [8,19]. |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
GPR35 is expressed by dendritic cells, macrophages, and granulocytes, all of which show chemotactic response to CXCL17 [13]. It is unclear whether the migration stimulatory response to CXCL17 is mediated by direct interaction with GPR35, and work by Park et al. (2017) indicates that this response is in fact not GPR35-dependent, at least in THP-1 cells [12]. |
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Expression Datasets | |
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General Comments |
Proposed ligand (kynurenic acid), supported by one publication [17]. |
1. Ellinghaus D, Folseraas T, Holm K, Ellinghaus E, Melum E, Balschun T, Laerdahl JK, Shiryaev A, Gotthardt DN, Weismüller TJ et al.. (2013) Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4. Hepatology, 58 (3): 1074-83. [PMID:22821403]
2. Fallarini S, Magliulo L, Paoletti T, de Lalla C, Lombardi G. (2010) Expression of functional GPR35 in human iNKT cells. Biochem Biophys Res Commun, 398 (3): 420-5. [PMID:20599711]
3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P et al.. (2004) The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res, 14 (10B): 2121-7. [PMID:15489334]
4. Horikawa Y, Oda N, Cox NJ, Li X, Orho-Melander M, Hara M, Hinokio Y, Lindner TH, Mashima H, Schwarz PE et al.. (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet, 26 (2): 163-75. [PMID:11017071]
5. Jenkins L, Brea J, Smith NJ, Hudson BD, Reilly G, Bryant NJ, Castro M, Loza MI, Milligan G. (2010) Identification of novel species-selective agonists of the G-protein-coupled receptor GPR35 that promote recruitment of β-arrestin-2 and activate Gα13. Biochem J, 432 (3): 451-9. [PMID:20919992]
6. Kuc D, Zgrajka W, Parada-Turska J, Urbanik-Sypniewska T, Turski WA. (2008) Micromolar concentration of kynurenic acid in rat small intestine. Amino Acids, 35 (2): 503-5. [PMID:18235993]
7. Maravillas-Montero JL, Burkhardt AM, Hevezi PA, Carnevale CD, Smit MJ, Zlotnik A. (2015) Cutting edge: GPR35/CXCR8 is the receptor of the mucosal chemokine CXCL17. J Immunol, 194 (1): 29-33. [PMID:25411203]
8. Neubig RR. (2010) Mind your salts: when the inactive constituent isn't. Mol Pharmacol, 78 (4): 558-9. [PMID:20651116]
9. O'Dowd BF, Nguyen T, Marchese A, Cheng R, Lynch KR, Heng HH, Kolakowski Jr LF, George SR. (1998) Discovery of three novel G-protein-coupled receptor genes. Genomics, 47 (2): 310-3. [PMID:9479505]
10. Oka S, Ota R, Shima M, Yamashita A, Sugiura T. (2010) GPR35 is a novel lysophosphatidic acid receptor. Biochem Biophys Res Commun, 395 (2): 232-7. [PMID:20361937]
11. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K et al.. (2004) Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet, 36 (1): 40-5. [PMID:14702039]
12. Park SJ, Lee SJ, Nam SY, Im DS. (2018) GPR35 mediates lodoxamide-induced migration inhibitory response but not CXCL17-induced migration stimulatory response in THP-1 cells; is GPR35 a receptor for CXCL17?. Br J Pharmacol, 175 (1): 154-161. [PMID:29068046]
13. Pisabarro MT, Leung B, Kwong M, Corpuz R, Frantz GD, Chiang N, Vandlen R, Diehl LJ, Skelton N, Kim HS et al.. (2006) Cutting edge: novel human dendritic cell- and monocyte-attracting chemokine-like protein identified by fold recognition methods. J Immunol, 176 (4): 2069-73. [PMID:16455961]
14. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]
15. Taniguchi Y, Tonai-Kachi H, Shinjo K. (2006) Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35. FEBS Lett, 580 (21): 5003-8. [PMID:16934253]
16. Thimm D, Funke M, Meyer A, Müller CE. (2013) 6-Bromo-8-(4-[(3)H]methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic Acid: a powerful tool for studying orphan G protein-coupled receptor GPR35. J Med Chem, 56 (17): 7084-99. [PMID:23888932]
17. Wang J, Simonavicius N, Wu X, Swaminath G, Reagan J, Tian H, Ling L. (2006) Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem, 281 (31): 22021-8. [PMID:16754668]
18. Yang Y, Fu A, Wu X, Reagan JD. (2012) GPR35 is a target of the loop diuretic drugs bumetanide and furosemide. Pharmacology, 89 (1-2): 13-7. [PMID:22236570]
19. Zhao P, Sharir H, Kapur A, Cowan A, Geller EB, Adler MW, Seltzman HH, Reggio PH, Heynen-Genel S, Sauer M, Chung TD, Bai Y, Chen W, Caron MG, Barak LS, Abood ME. (2010) Targeting of the orphan receptor GPR35 by pamoic acid: a potent activator of extracellular signal-regulated kinase and β-arrestin2 with antinociceptive activity. Mol Pharmacol, 78 (4): 560-8. [PMID:20826425]