ADGRG1

This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants.

adhesion G protein-coupled receptor G1

Receptor involved in cell adhesion and probably in cell-cell interactions. Mediates cell matrix adhesion in developing neurons and hematopoietic stem cells. Receptor for collagen III/COL3A1 in the developing brain and involved in regulation of cortical development, specifically in maintenance of the pial basement membrane integrity and in cortical lamination (By similarity). Binding to the COL3A1 ligand inhibits neuronal migration and activates the RhoA pathway by coupling to GNA13 and possibly GNA12. Plays a role in the maintenance of hematopoietic stem cells and/or leukemia stem cells in bone marrow niche (By similarity). Plays a critical role in cancer progression by inhibiting VEGFA production threreby inhibiting angiogenesis through a signaling pathway mediated by PRKCA. Plays an essential role in testis development (By similarity).
ADGRG1 N-terminal fragment: Plays a critical role in cancer progression by activating VEGFA production and angiogenesis through a signaling pathway mediated by PRKCA.

Adenylate cyclase-activating G protein-coupled receptor signaling pathway
Angiogenesis
Brain development
Cell adhesion
Cell-cell signaling
Cell migration
Cell surface receptor signaling pathway
Cerebral cortex radial glia guided migration
Cerebral cortex regionalization
G protein-coupled receptor signaling pathway
Hematopoietic stem cell homeostasis
Layer formation in cerebral cortex
Negative regulation of cell population proliferation
Negative regulation of neuron migration
Positive regulation of cell adhesion
Positive regulation of neural precursor cell proliferation
Positive regulation of Rho protein signal transduction
Protein kinase C signaling
Rho protein signal transduction
Seminiferous tubule development
Vascular endothelial growth factor production

Cell membrane
ADGRG1 N-terminal fragment: Secreted
ADGRG1 C-terminal fragment: Membrane raft
Interaction with its ligand COL3A1 leads to the release of ADGRG1 NT from the membrane and triggers the association of ADGRG1 CT with lipid rafts.

Polymicrogyria, bilateral frontoparietal (BFPP): A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination, most severe in the frontoparietal regions. BFPP clinical manifestations include developmental and psychomotor delay, cerebellar and pyramidal signs, truncal ataxia, seizures, hyperreflexia. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization.
Polymicrogyria, bilateral perisylvian, autosomal recessive (BPPR): A form of polymicrogyria, a malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination. BPPR is characterized by strikingly restricted polymicrogyria limited to the cortex surrounding the Sylvian fissure. Affected individuals have intellectual and language difficulty and seizures, but no motor disability. Polymicrogyria is a heterogeneous disorder, considered to be the result of post-migratory abnormal cortical organization.

Extracellular: 26-402 aa
Helical: 403-423 aa
Cytoplasmic: 424-448 aa
Helical: 449-469 aa
Extracellular: 470-476 aa
Helical: 477-497 aa
Cytoplasmic: 498-518 aa
Helical: 519-539 aa
Extracellular: 540-576 aa
Helical: 577-597 aa
Cytoplasmic: 598-609 aa
Helical: 610-630 aa
Extracellular: 631-636 aa
Helical: 637-657 aa
Cytoplasmic: 658-693 aa

Autoproteolytically cleaved into 2 fragments; the large extracellular N-terminal fragment (ADGRG1 NT) and the membrane-bound C-terminal fragment (ADGRG1 CT) predominantly remain associated and non-covalently linked. Shedding to yield the secreted ADGRG1 N-terminal fragment seems to involve metalloprotease(s).
N-glycosylated. Contains sialic acid residues.
Ubiquitinated. Undergoes polyubiquitination upon activation.