GPR35
GPR35 (G protein-coupled receptor 35) is a class A orphan-group G protein-coupled receptor that binds metabolites including kynurenic acid, lysophosphatidic acid and 5-hydroxyindoleacetic acid. It links these ligands to G protein signalling in immune, cardiac and adipose contexts. Browse Assay Genie's current range of GPR35 research reagents below, or read on for the biology behind the target.
GPR35 is a G protein-coupled receptor that binds several ligands with high affinity, including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) and 5-hydroxyindoleacetic acid (5-HIAA). Ligand binding causes a conformational change that triggers rapid, transient activation of intracellular signalling pathways through G proteins, modulating downstream effectors such as adenylate cyclase. Depending on context, GPR35 couples to G(i)/G(o) proteins, inhibiting adenylate cyclase, or to G(12)/G(13) proteins, activating Rho small GTPases.
The receptor has distinct roles in different cell types. KYNA binding promotes monocyte adhesion to vascular endothelium under flow, via G(i)/GNAI1 activation. During ischaemia, KYNA-bound GPR35 is internalised to the outer mitochondrial membrane, where it inhibits mitochondrial adenylate cyclase (ADCY10), allowing ATPIF1 to repress ATP synthase activity; this contributes to cardioprotection through mitochondrial remodelling. In adipose tissue, KYNA activation stimulates lipid metabolism and thermogenic and anti-inflammatory gene expression. 5-HIAA, a major serotonin metabolite, acts as a physiological ligand that supports neutrophil recruitment to inflammatory sites and bacterial clearance. In macrophages, LPA activation drives a distinct transcriptional profile with TNF production linked to ERK and NF-kappa-B activation, and induces macrophage chemotaxis.
GPR35 belongs to the G protein-coupled receptor 1 family and is classed by HGNC among the class A orphan receptors. NCBI Gene annotation associates the gene with C-X-C chemokine receptor activity, leukocyte chemotaxis, negative regulation of cardiac muscle cell apoptosis and response to ischaemia. The protein is active at the plasma membrane and, as described above, at the outer mitochondrial membrane. The mouse ortholog is Gpr35.
GPR35 supports neutrophil recruitment, bacterial clearance and macrophage chemotaxis, making it relevant to studies of inflammatory signalling.
KYNA-activated GPR35 moves to the outer mitochondrial membrane and inhibits ADCY10, linking the receptor to mitochondrial remodelling during ischaemia.
Activation by KYNA stimulates lipid metabolism and thermogenic and anti-inflammatory gene expression in adipose tissue.
GPR35 responds to KYNA, LPA and 5-HIAA and couples to Gi/Go or G12/G13 proteins, offering a model for context-dependent GPCR signalling.
GPR35 is a G protein-coupled receptor activated by ligands such as kynurenic acid, lysophosphatidic acid and 5-hydroxyindoleacetic acid. It signals through G(i)/G(o) to inhibit adenylate cyclase or through G(12)/G(13) to activate Rho GTPases, with roles in inflammation, ischaemia and adipose tissue.
UniProt lists kynurenic acid (KYNA), lysophosphatidic acid (LPA) and 5-HIAA as high-affinity ligands. GPR35 couples to G(i)/G(o) or G(12)/G(13) classes of G alpha proteins depending on context. HGNC places it in the class A orphan receptor group.
A mouse ortholog, Gpr35, is recorded, so rodent models can be used to study the receptor. Human GPR35 is linked to response to ischaemia and leukocyte chemotaxis in NCBI Gene annotation. Check the datasheet of any product for its validated reactivity.
Other G protein-coupled receptors and orphan receptors with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9HC97; product specifications from Assay Genie datasheets.