G protein-coupled receptor 1 (GPR1)

G protein-coupled receptor 1 (GPR1) is an orphan class A (rhodopsin-like) G protein-coupled receptor that primarily couples to Gi proteins in response to its natural ligand, chemerin, and possibly other ligands. It is a canonical member of the rhodopsin-like (class A) GPCR family, often studied in parallel with CMKLR1 due to high sequence and functional similarity. Cryo-EM studies indicate GPR1 shares high homology with CMKLR1 and utilizes a chemokine-type "two-site" activation model for ligand recognition. Upon activation, GPR1 inhibits adenylyl cyclase via Gi, leading to decreased cellular cAMP. Its biological roles include signal transduction downstream of chemerin, dampening of cAMP signaling, involvement in immune cell migration, and potentially in metabolic and tumor-related pathways. GPR1 is implicated in multiple physiological and pathophysiological processes including metabolic regulation, inflammation, and cancer. Although no approved drugs interact directly with GPR1 as of 2024, and its orphan status previously hampered clinical translation, it is considered a molecular target for conditions with aberrant chemerin signaling. Its structure and signaling features are being elucidated for potential drug development. Ligand binding stabilizes an active conformation that allows Gi protein association and downstream inhibition of adenylyl cyclase, a classic signal transduction mechanism for many GPCRs. No evidence suggests that GPR1 is an incorrect or ambiguous molecular target designation in the context of human biology. Chemerin is recognized as the natural agonist mediating GPR1 activation.

Other names

GPR-1G protein-coupled receptor 1Orphan receptor GPR1

Ligand (chemerin or peptide fragment) binding induces Gi protein coupling, resulting in inhibition of adenylyl cyclase and reduced cAMP production[1][3]