GPR35

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. 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. 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. KYNA-binding promotes monocyte adhesion to vascular endothelium under flow conditions, leading to G(i)/GNAI1 activation and inhibition of adenylate cyclase. 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. 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. 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)..

Function from UniProtKB (Q9HC97), read 2026-09-23. CC BY 4.0.