ADAM9

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene interacts with SH3 domain-containing proteins, binds mitotic arrest deficient 2 beta protein, and is also involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. Two alternative splice variants have been identified, encoding distinct isoforms. [provided by RefSeq]

Full Name

ADAM metallopeptidase domain 9 (meltrin gamma)

Function

Cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins.
Isoform 2: May act as alpha-secretase for amyloid precursor protein (APP).

Biological Process

Activation of MAPKK activity
Amyloid precursor protein catabolic process
Cell adhesion
Cell adhesion mediated by integrin
Cell-cell adhesion mediated by integrin
Cell-matrix adhesion
Cell migration
Cellular response to lipopolysaccharide
Integrin-mediated signaling pathway
Keratinocyte differentiation
Membrane protein ectodomain proteolysis
Membrane protein intracellular domain proteolysis
Monocyte activation
Positive regulation of cell adhesion mediated by integrin
Positive regulation of cell migration
Positive regulation of keratinocyte migration
Positive regulation of macrophage fusion
Positive regulation of membrane protein ectodomain proteolysis
Positive regulation of protein secretion
Protein processing
Response to calcium ion
Response to glucocorticoid
Response to hydrogen peroxide
Response to manganese ion
Response to tumor necrosis factor
Transforming growth factor beta receptor signaling pathway

Cellular Location

Isoform 1: Cell membrane
Isoform 2: Secreted

Involvement in disease

Cone-rod dystrophy 9 (CORD9): An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa, due to cone photoreceptors degenerating at a higher rate than rod photoreceptors.

Topology

Extracellular: 29-697 aa
Helical: 698-718 aa
Cytoplasmic: 719-819 aa

PTM

Proteolytically cleaved in the trans-Golgi network before it reaches the plasma membrane to generate a mature protein. The removal of the pro-domain occurs via cleavage at two different sites. Processed most likely by a pro-protein convertase such as furin, at the boundary between the pro-domain and the catalytic domain. An additional upstream cleavage pro-protein convertase site (Arg-56/Glu-57) has an important role in the activation of ADAM9.
Phosphorylation is induced in vitro by phorbol-12-myristate-13-acetate (PMA).