ADAM10 (ADAM metallopeptidase domain 10)

	Figure 1. Representation of the ADAM10 gene organization.
Description	The gene spans a region of 15.36 kb and the coding part is divided into 16 exons.
Transcription	Only one type of transcript has been described. The 2247-nucleotide transcript encodes a protein of 748 amino acid residues. The first and last exons are partially untranslated.
Pseudogene	None described so far.

	Figure 2. Crystal structure of ADAM10 Disintegrin and cysteine-rich domain at 2.9 A resolution. Adapted from PDB (access number: 2AO7).
Description	ADAM10 is a metalloproteinase composed of 748 residues.
	Figure 3. ADAM10 tissue expression profile. Adapted from GeneAtlas U113A.
Expression	ADAM10 RNA has been reported to be present in wide range of human tissue (Yanai et al., 2005). Data obtained from GeneAtlas have shown that ADAM10 transcript is the most highly expressed in myeloid, NK cells and monocytes as well as cardiomyocytes and smooth muscle cells (figure 3). At the protein level, ADAM10 has been reported in epithelials tissue of the heart, liver and kidney (Hall and Erickson, 2003).
Localisation	ADAM10 is localized at the plasma membrane. However, nuclear localization of ADAM10 has been reported in prostate cancer and in mantle cell lymphoma cells (Armanious et al., 2011).
	Figure 4. ADAM10 protein structure organization.
Function	ADAM10 belongs to the family of metalloproteinases (Chantry et al., 1989; Chantry and Glynn, 1990; Edwards et al., 2008). ADAM10 protein is composed of multiple functional domains that include: a prodomain, a catalytic domain, a cysteine-rich domain, a transmembraneous domain, a cytoplasmic domain and a SH3 domain (Seals and Courtneidge, 2003; Edwards et al., 2008) (see figure 4). ADAM10 is synthesized as a pro-protein and therefore needs to be cleaved to be activated (Anders et al., 2001). Two proteins, the convertase 7 and the furin, have been implicated in the activation of ADAM10 (Anders et al., 2001). To date the major function of ADAM10 appears to be attributed to its enzymatic activity as a metalloproteinase. In fact, ADAM10 is involved in the intra-membrane proteolysis process, whereby it mediates ectodomain shedding of various membrane bound receptors, adhesion molecules, growth factors and cytokines like TNF-alpha (Rosendahl et al., 1997; Lunn et al., 1997; Hikita et al., 2009; Mezyk-Kopec et al., 2009), Notch (Hartmann et al., 2002; Gibb et al., 2010), E-cadherin (Maretzky et al., 2005), Ephrin (Janes et al., 2005), HER-2 (Liu et al., 2006), CD30 (Eichenauer et al., 2007), CD44 (Anderegg et al., 2009) and IL-6 receptor to name a few. The functional role of the SH3 domains of ADAM10 has never been studied. Moreover, the recent observation that ADAM10 can be found in the nucleus of some cells raises the possibility of new and uncovers function of ADAM10 (Arima et al., 2007). ADAM10 seems to be detrimental for embryogenesis as the knockout mice for ADAM10 die at day 9.5 of embryogenesis (Hartmann et al., 2002). The mice present several developmental defects in the nervous central system as well in the cardiovascular system. This latest observation correlates well with the fact that ADAM10 transcript is highly expressed in cardiomyocyte. In human, ADAM10 was recently been demonstrated to be a regulator of the lymphocyte development (Gibb et al., 2011).

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