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ADGRG6

Domain

A short peptide sequence (termed the Stachel sequence) in the C-terminal part of the extra-cellular domain (ECD) functions as a tethered agonist. Upon structural changes within the ECD, e.g. due to extracellular ligand binding or mechanical movements, this intramolecular agonist is exposed to the 7TM domain, triggering G-protein activation.

Function

G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane (By similarity). Couples to G(i)-proteins as well as G(s)-proteins (PubMed:24227709). Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:24227709). Regulates neural, cardiac and ear development via G-protein- and/or N-terminus-dependent signaling (By similarity). May act as a receptor for PRNP which may promote myelin homeostasis (By similarity).

Involvement in disease

Lethal congenital contracture syndrome 9

LCCS9

A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Proteolytically cleaved into 2 conserved sites: one in the GPS domain (S1 site) and the other in the middle of the extracellular domain (S2 site). The proteolytic cleavage at S1 site generates an extracellular subunit and a seven-transmembrane subunit. Furin is involved in the cleavage of the S2 site generating a soluble fragment. Processing at the GPS domain occurred independent of and probably prior to the cleavage at the S2 site. Proteolytic cleavage is required for activation of the receptor.

Highly glycosylated.

Sequence similarities

Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.

Tissue specificity

Expressed in placenta and to a lower extent in pancreas and liver. Detected in aortic endothelial cells but not in skin microvascular endothelial cells.

Cellular localization

  • Cell membrane
  • Multi-pass membrane protein
  • Detected on the cell surface of activated but not resting umbilical vein.

Alternative names

  • Adhesion G-protein coupled receptor G6
  • Developmentally regulated G-protein-coupled receptor
  • G-protein coupled receptor 126
  • Vascular inducible G protein-coupled receptor
  • ADGRG6
  • VIGR
  • GPR126
  • DREG

Target type

Proteins

Molecular weight

136695Da