Adhesion G protein-coupled receptor G1 (ADGRG1)

Adhesion G protein-coupled receptor G1 (ADGRG1), commonly known as GPR56, is a member of the adhesion GPCR subfamily, distinguished by a large and modular extracellular domain mediating cell–cell and cell–matrix interactions[1][3]. The receptor undergoes autoproteolysis at a GPCR autoproteolysis-inducing (GAIN) domain, generating an N-terminal fragment (NTF) and a C-terminal fragment (CTF) that remain non-covalently associated until dissociation triggers signaling via a tethered agonist (the “Stachel” sequence)[1][2][4]. ADGRG1/GPR56 plays essential roles in neuronal migration, cortical and oligodendrocyte development, and is a critical modulator of platelet activation through G13 signaling in response to collagen and shear stress[1][2][4][5]. Mutations cause developmental brain malformations, and altered expression/function is implicated in tumor progression (notably melanoma) and hemostatic disorders[5]. The receptor interacts with several ligands (e.g., collagen III in the brain, collagen I in platelets), with therapeutic targeting subject to risks due to its diverse roles in the nervous system and the vasculature[1][2][4].

Other names

GPR56TM7LN4TM7XN1BFPPBPPRCDCBM14BCDCBM15Atesticular tissue protein Li 77UNQ540/PRO1083GPR56 N-terminal fragmentGPR56 C-terminal fragmentGPR56 extracellular subunitGPR56 subunit alphaGPR56 subunit beta

Activation through N-terminal fragment dissociation, exposing a tethered peptide agonist (“Stachel” sequence) that activates intracellular G protein (mainly Gα13) signaling[2][4]. Ligand-induced (e.g., collagen III, collagen I) activation and downstream RhoA pathway stimulation[2][3][4].