G protein-coupled receptor 35, GPR55, and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors
This subfamily is composed of GPR35, GPR55, and similar proteins. GPR35 shares closest homology with GPR55, and they belong to the class A G protein-coupled receptor superfamily, which all have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A number of studies have suggested that GPR35 may play important physiological roles in hypertension, atherosclerosis, nociception, asthma, glucose homeostasis and diabetes, and inflammatory bowel disease. GPR35 is thought to be responsible for brachydactyly mental retardation syndrome, which is associated with a deletion comprising chromosome 2q37 in human, and is also implicated as a potential oncogene in stomach cancer. GPR35 couples to G(13) and G(i/o) proteins, whereas GPR55 has been reported to couple to G(13), G(12), or G(q) proteins. Activation of GPR55 leads to activation of phospholipase C, RhoA, ROCK, ERK, p38MAPK, and calcium release. Recently, lysophosphatidylinositol (LPI) has been identified as an endogenous ligand for GPR55, while several endogenous ligands for GPR35 have been identified including kynurenic acid, 2-oleoyl lysophosphatidic acid, and zaprinast.
Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
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