Active 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 (By similarity). 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. Interactions with egg membrane could be mediated via binding between the disintegrin-like domain to one or more integrin receptors on the egg. Binds 1 zinc ion per subunit. Interacts specifically with Src family protein-tyrosine kinases (PTKs) (By similarity). Interacts with ITAGV-ITGB3 (vitronectin receptor). Interacts with SH3GL2 and SNX9; this interaction occurs preferentially with ADAM15 precursor, rather than the processed form, suggesting it occurs in a secretory pathway compartment prior to the medial Golgi. Interacts with ITAG9-ITGB1. Interacts with SH3PXD2A (By similarity). Interacts with ITAGV-ITGB1. Interacts with GRB2, HCK, ITSN1, ITSN2, LYN, MAPK1, MAPK3, NCF1, NCK1, nephrocystin, PTK6, SNX33, LCK and SRC (By similarity). 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. Expressed moderately in pericytes of retina. Expressed in testis and in spermatozoa from the caput, corpus, and cauda epididymis, as well as in non-capacitated and acrosome-reacted sperm (at protein level). Highly expressed in heart, brain, lung, and kidney. Expressed at lower levels in spleen, liver, testis and muscle. At 13.5 dpc, strongly expressed in the developing vasculature of the endocardium. At P17, expressed throughout the retina (at protein level). At 9.5 dpc and thereafter, prominently expressed in the vasculature, including in ventral and dorsal aorta and the caudal artery. In developing heart, detected in endocardium and blood vessels of the ventricle, bulbus arteriosus, and atrium. Also highly expressed in hypertrophic cells of the developing bone. In adult, expressed prominently in brain, including in hippocampus, cerebellum, pons, thalamus, cortex, and olfactory bulb. By hypoxic stimulus in retina (at protein level). Up-regulated by VEGF in retina. The cytoplasmic domain is required for SH3GL2- and SNX9-binding. 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. The precursor is cleaved by a furin endopeptidase. An additional membrane proximal site of cleavage affects a small percentage of the proteins and results in disulfide-linked fragments. The prodomain is apparently cleaved in several positions that are N-terminal of the furin cleavage site. May be partially sialylated. Phosphorylation increases association with PTKs. Mice targeted for deletion of the first 27 amino acids of the ADAM15 N-terminal sequence are viable and fertile, showing no major developmental defects and displaying normal mortality or morbidity. These mutant mice, however, exhibit significantly reduced ischemia-induced retinal neovascularization, choroidal neovascularization at rupture sites in Bruch's membrane, and VEGF-induced subretinal neovascularization, and develop significantly smaller tumors following implantation of B16F0 melanoma cells. Aging mutant mice exhibit accelerated development of osteoarthritic lesions in knee joints.