Biology:ADAM15
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Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.[1]
Function
The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins 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.[2]
Clinical significance
Arthritis
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.[3] ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.[4]
Cancer
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[5] 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.[6] 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[5] and also through its modulation of epithelial cell- tumour cell interactions.[7]
Interactions
ADAM15 has been shown to interact with:
The alternatively spliced isoforms have also been shown to exhibit different preferential interactions with proteins containing SH3 domains.[6][10]
References
- ↑ "Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3". J Biol Chem 273 (13): 7345–50. April 1998. doi:10.1074/jbc.273.13.7345. PMID 9516430.
- ↑ "Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8751.
- ↑ "ADAM15 adds to apoptosis resistance of synovial fibroblasts by modulating focal adhesion kinase signaling". Arthritis Rheum. 65 (11): 2826–34. November 2013. doi:10.1002/art.38109. PMID 23918525.
- ↑ "ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis". Arthritis Rheum. 62 (5): 1372–82. May 2010. doi:10.1002/art.27387. PMID 20213810.
- ↑ 5.0 5.1 "ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease". Neoplasia 8 (4): 319–29. April 2006. doi:10.1593/neo.05682. PMID 16756724.
- ↑ 6.0 6.1 "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma". Mol. Cancer Res. 6 (3): 383–94. March 2008. doi:10.1158/1541-7786.MCR-07-2028. PMID 18296648.
- ↑ "ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction". Cancer Res. 68 (4): 1092–9. February 2008. doi:10.1158/0008-5472.CAN-07-2432. PMID 18281484.
- ↑ 8.0 8.1 8.2 "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. February 2002. doi:10.1074/jbc.M107430200. PMID 11741929.
- ↑ 9.0 9.1 "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. October 1999. doi:10.1074/jbc.274.44.31693. PMID 10531379.
- ↑ "Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins". J. Cell. Biochem. 108 (4): 877–85. November 2009. doi:10.1002/jcb.22317. PMID 19718658.
Further reading
- "The ADAM gene family: surface proteins with adhesion and protease activity.". Trends Genet. 16 (2): 83–7. 2000. doi:10.1016/S0168-9525(99)01926-5. PMID 10652535.
- Takagi J (2002). "[First atomic view of alpha V beta 3 integrin extracellular domain]". Tanpakushitsu Kakusan Koso 47 (2): 153–9. PMID 11840679.
- "Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence.". J. Biol. Chem. 271 (9): 4593–6. 1996. doi:10.1074/jbc.271.9.4593. PMID 8617717.
- "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. 1997. doi:10.1101/gr.6.9.791. PMID 8889548.
- "Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes.". Biochem. Biophys. Res. Commun. 230 (2): 335–9. 1997. doi:10.1006/bbrc.1996.5957. PMID 9016778.
- "Expression of a disintegrin-like protein in cultured human vascular cells and in vivo.". FASEB J. 11 (2): 173–80. 1997. doi:10.1096/fasebj.11.2.9039960. PMID 9039960.
- "Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells.". J. Cell Sci. 112 (4): 579–87. 1999. doi:10.1242/jcs.112.4.579. PMID 9914169.
- "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. 1999. doi:10.1074/jbc.274.44.31693. PMID 10531379.
- "Assignment of the ADAM15 gene to human chromosome band 1q21.3 by in situ hybridization.". Cytogenet. Cell Genet. 88 (3–4): 206–7. 2000. doi:10.1159/000015549. PMID 10828588.
- "Chromosomal mapping of Adam9, Adam15 and Adam21". Matrix Biol. 19 (2): 185–7. 2000. doi:10.1016/S0945-053X(00)00062-7. PMID 10842103.
- "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases". J. Biol. Chem. 277 (7): 4999–5007. 2002. doi:10.1074/jbc.M107430200. PMID 11741929.
- "Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating human atria". Circulation 105 (6): 720–5. 2002. doi:10.1161/hc0602.103639. PMID 11839628.
- "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. 2002. doi:10.1074/jbc.M200086200. PMID 11882657.
- "The role of ADAM 15 in glomerular mesangial cell migration". J. Biol. Chem. 277 (37): 33683–9. 2002. doi:10.1074/jbc.M200988200. PMID 12091380.
- "ADAM15 is an adherens junction molecule whose surface expression can be driven by VE-cadherin". Exp. Cell Res. 279 (2): 239–47. 2002. doi:10.1006/excr.2002.5606. PMID 12243749.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "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. 2003. doi:10.1074/jbc.M300267200. PMID 12615925.
External links
- The MEROPS online database for peptidases and their inhibitors: M12.215
- Human ADAM15 genome location and ADAM15 gene details page in the UCSC Genome Browser.
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