Recombinant Human G-protein coupled receptor 35 (GPR35) Protein

Function

G protein-coupled receptor that binds to several ligands including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) or 5-hydroxyindoleacetic acid (5-HIAA) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways (PubMed:16754668, PubMed:19473985, PubMed:20361937, PubMed:24347166, PubMed:35148838, PubMed:35926043). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:19473985, PubMed:35926043). GPR35 can couple with G(i)/G(o)- or G(12)/G(13) classes of G alpha proteins depending on the context, mediating the inhibition of adenylate cyclase or activation Rho small GTPases, respectively (PubMed:19473985, PubMed:35926043, PubMed:36543774). KYNA-binding promotes monocyte adhesion to vascular endothelium under flow conditions, leading to G(i)/GNAI1 activation and inhibition of adenylate cyclase (PubMed:19473985). Involved in cardioprotection during ischemia by promoting mitochondrial remodeling: following KYNA-binding and G(i)/GNAI1 activation, GPR35 is internalized to the outer mitochondrial membrane, where it inhibits mitochondrial adenylate cyclase (ADCY10), allowing ATPIF1 to repress ATP synthase activity (PubMed:35926043). Stimulates lipid metabolism, thermogenic and anti-inflammatory gene expression in adipose tissue once activated by KYNA (By similarity). Plays a role in neutrophil recruitment to sites of inflammation and bacterial clearance through the major serotonin metabolite 5-HIAA that acts as a physiological ligand (PubMed:35148838). In macrophages, activation by lysophosphatidic acid promotes GPR35-induced signaling with a distinct transcriptional profile characterized by TNF production associated with ERK and NF-kappa-B activation (By similarity). In turn, induces chemotaxis of macrophages (By similarity)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Mitochondrion outer membrane (Multi-pass membrane protein)

Tissue Specificity

Predominantly expressed in immune and gastrointestinal tissues

Subunit

Interacts with ARRB2 (PubMed:35101446, PubMed:37660910)

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• Horikawa Y. et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. — Nat. Genet. (2000)
• Warren C.N. et al. Isolation of complete coding sequence for G-protein coupled receptor 35 (GPR35). (APR-)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Ebert L. et al. Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201). (JUN-)
• Hillier L.W. et al. Generation and annotation of the DNA sequences of human chromosomes 2 and 4. — Nature (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Wang J. et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. — J. Biol. Chem. (2006)