The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembraneglycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.
ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress. ADAM15 also has an antiapoptotic effect in osteoarthriticchondrocytes.
The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels. ADAM15 has also been shown to have a role in Prostate Cancer again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues and also through its modulation of epithelial cell- tumour cell interactions.
^Böhm BB, Freund I, Krause K, Kinne RW, Burkhardt H (November 2013). "ADAM15 adds to apoptosis resistance of synovial fibroblasts by modulating focal adhesion kinase signaling". Arthritis Rheum. 65 (11): 2826–34. doi:10.1002/art.38109. PMID23918525.
^Böhm B, Hess S, Krause K, Schirner A, Ewald W, Aigner T, Burkhardt H (May 2010). "ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis". Arthritis Rheum. 62 (5): 1372–82. doi:10.1002/art.27387. PMID20213810.
^ abcPoghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR (February 2002). "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID11741929.
^ abHoward L, Nelson KK, Maciewicz RA, Blobel CP (October 1999). "Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1". J. Biol. Chem. 274 (44): 31693–9. doi:10.1074/jbc.274.44.31693. PMID10531379.
^Kleino I, Ortiz RM, Yritys M, Huovila AP, Saksela K (November 2009). "Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins". J. Cell. Biochem. 108 (4): 877–85. doi:10.1002/jcb.22317. PMID19718658.
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Howard L, Nelson KK, Maciewicz RA, Blobel CP (1999). "Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1.". J. Biol. Chem. 274 (44): 31693–9. doi:10.1074/jbc.274.44.31693. PMID10531379.
Kärkkäinen I, Karhu R, Huovila AP (2000). "Assignment of the ADAM15 gene to human chromosome band 1q21.3 by in situ hybridization.". Cytogenet. Cell Genet. 88 (3–4): 206–7. doi:10.1159/000015549. PMID10828588.
Poghosyan Z, Robbins SM, Houslay MD, et al. (2002). "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. doi:10.1074/jbc.M107430200. PMID11741929.
Arndt M, Lendeckel U, Röcken C, et al. (2002). "Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating human atria". Circulation. 105 (6): 720–5. doi:10.1161/hc0602.103639. PMID11839628.
Eto K, Huet C, Tarui T, et al. (2002). "Functional classification of ADAMs based on a conserved motif for binding to integrin alpha 9beta 1: implications for sperm-egg binding and other cell interactions". J. Biol. Chem. 277 (20): 17804–10. doi:10.1074/jbc.M200086200. PMID11882657.
Martin J, Eynstone LV, Davies M, et al. (2002). "The role of ADAM 15 in glomerular mesangial cell migration". J. Biol. Chem. 277 (37): 33683–9. doi:10.1074/jbc.M200988200. PMID12091380.
Ham C, Levkau B, Raines EW, Herren B (2002). "ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin". Exp. Cell Res. 279 (2): 239–47. doi:10.1006/excr.2002.5606. PMID12243749.
Abram CL, Seals DF, Pass I, et al. (2003). "The adaptor protein fish associates with members of the ADAMs family and localizes to podosomes of Src-transformed cells". J. Biol. Chem. 278 (19): 16844–51. doi:10.1074/jbc.M300267200. PMID12615925.
The MEROPS online database for peptidases and their inhibitors: M12.215
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