Recombinant Human GPR161 protein

GPR161 is a class A G protein-coupled receptor (GPCR) predominantly recognized for its role in the Hedgehog (Hh) signaling pathway, a critical regulator of embryonic development and tissue homeostasis. Discovered in 2007. GPR161 is constitutively active and couples primarily to Gαs proteins, elevating intracellular cyclic AMP (cAMP) levels. This receptor is highly expressed in the developing nervous system, limbs, and cilia of mammalian cells. Its function is tightly linked to the suppression of Hh signaling under basal conditions; upon Hh pathway activation, GPR161 is internalized from primary cilia, reducing cAMP-dependent protein kinase A (PKA) activity and enabling downstream signaling. Mutations or dysregulation of GPR161 are associated with developmental disorders (e.g., neural tube defects) and cancers (e.g., medulloblastoma).

Recombinant GPR161 protein refers to the purified, engineered form of the receptor produced in heterologous expression systems (e.g., bacteria, insect, or mammalian cell lines) for experimental applications. Its production typically involves cloning the human GPR161 gene into expression vectors, followed by transfection, protein extraction, and affinity purification (often using tags like FLAG or His). Recombinant GPR161 enables structural studies (e.g., cryo-EM), ligand-binding assays, and functional characterization of its signaling mechanisms. Recent structural insights into GPR161 have revealed unique features, such as an extracellular loop critical for basal activity and a lack of canonical orthosteric binding pockets, classifying it as an "orphan" receptor with no confirmed endogenous ligands. Current research focuses on deciphering its regulation, interactions with ciliary proteins (e.g., SUFU), and potential therapeutic targeting for Hh-driven diseases. Recombinant GPR161 tools are vital for advancing drug discovery and understanding developmental GPCR biology.