A disintegrin and metalloproteinase domain 15 (metargidin)
ADAM metallopeptidase domain 15
and cysteine-rich protein 15
Disintegrin and metalloproteinase domain-containing protein 15
Metalloprotease RGD disintegrin protein
Metalloproteinase like disintegrin like and cysteine rich protein 15
FunctionActive metalloproteinase with gelatinolytic and collagenolytic activity. Plays a role in the wound healing process. Mediates both heterotypic intraepithelial cell/T-cell interactions and homotypic T-cell aggregation. Inhibits beta-1 integrin-mediated cell adhesion and migration of airway smooth muscle cells. Suppresses cell motility on or towards fibronectin possibly by driving alpha-v/beta-1 integrin (ITAGV-ITGB1) cell surface expression via ERK1/2 inactivation. Cleaves E-cadherin in response to growth factor deprivation. Plays a role in glomerular cell migration. Plays a role in pathological neovascularization. May play a role in cartilage remodeling. May be proteolytically processed, during sperm epididymal maturation and the acrosome reaction. May play a role in sperm-egg binding through its disintegrin domain.
Tissue specificityExpressed in colon and small intestine. Expressed in airway smooth muscle and glomerular mesangial cells (at protein level). Ubiquitously expressed. Overexpressed in atherosclerotic lesions. Constitutively expressed in cultured endothelium and smooth muscle. Expressed in chondrocytes. Expressed in airway smooth muscle and glomerular mesangial cells.
DomainThe cytoplasmic domain interacts with endophilin I and sorting nexin 9. Disintegrin domain binds to integrin alphaV-beta3. The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Post-translational modificationsThe precursor is cleaved by a furin endopeptidase. Phosphorylation increases association with PTKs.
Cellular localizationEndomembrane system. Cell junction > adherens junction. Cell projection > cilium > flagellum. Cytoplasmic vesicle > secretory vesicle > acrosome. The majority of the protein is localized in a perinuclear compartment which may correspond to the trans-Golgi network or the late endosome. The pro-protein is the major detectable form on the cell surface, whereas the majority of the protein in the cell is processed.