ADGRA2

ADGRA2 is an endothelial receptor which plays a role as a WNT7-specific coactivator of canonical Wnt signaling (By similarity). It is required for normal endothelial cell sprouting and migration in the forebrain and neural tube (By similarity). ADGRA2 has a major role in establishing the blood-brain barrier (By similarity). It binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate (PubMed:16982628).

adhesion G protein-coupled receptor A2

Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B). Plays a key role in Wnt7-specific responses, such as endothelial cell sprouting and migration in the forebrain and neural tube, and establishment of the blood-brain barrier (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling: required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. ADGRA2-tethering function does not rely on its G-protein coupled receptor (GPCR) structure but instead on its combined capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly. Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate.

Cell surface receptor signaling pathway
Central nervous system development
Endothelial cell migration
G protein-coupled receptor signaling pathway
Negative regulation of vascular endothelial growth factor signaling pathway
Positive regulation of canonical Wnt signaling pathway
Positive regulation of endothelial cell migration
Regulation of angiogenesis
Regulation of chemotaxis
Regulation of establishment of blood-brain barrier
Sprouting angiogenesis
Wnt signaling pathway

Cell membrane; Filopodium. Enriched at lateral cell borders and also at sites of cell-ECM (extracellular matrix) contact.

Extracellular: 34-771 aa
Helical: 772-792 aa
Cytoplasmic: 793-807 aa
Helical: 808-828 aa
Extracellular: 829-832 aa
Helical: 833-853 aa
Cytoplasmic: 854-886 aa
Helical: 887-907 aa
Extracellular: 908-924 aa
Helical: 925-945 aa
Cytoplasmic: 946-1019 aa
Helical: 1020-1040 aa
Extracellular: 1041-1047 aa
Helical: 1048-1068 aa
Cytoplasmic: 1069-1338 aa

Glycosylated.
Proteolytically cleaved into two subunits, an extracellular subunit and a seven-transmembrane subunit. Cleaved by thrombin (F2) and MMP1. Also cleaved by MMP9, with lower efficiency. Presence of the protein disulfide-isomerase P4HB at the cell surface is additionally required for shedding of the extracellular subunit, suggesting that the subunits are linked by disulfide bonds. Shedding is enhanced by the growth factor FGF2 and may promote cell survival during angiogenesis.