ADAM15

ADAM15
Identifiers
Aliases ADAM15, MDC15, ADAM metallopeptidase domain 15
External IDs MGI: 1333882 HomoloGene: 2829 GeneCards: ADAM15
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez

8751

11490

Ensembl

ENSG00000143537

ENSMUSG00000028041

UniProt

Q13444

O88839

RefSeq (mRNA)

NM_001037722
NM_009614

RefSeq (protein)

NP_001032811.2
NP_033744.1

Location (UCSC) Chr 1: 155.05 – 155.06 Mb Chr 3: 89.34 – 89.35 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.[3]

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.[4]

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.[5] ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.[6]

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[7] 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.[8] 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[7] and also through its modulation of epithelial cell- tumour cell interactions.[9]

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.[8][12]

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Zhang XP, Kamata T, Yokoyama K, Puzon-McLaughlin W, Takada Y (April 1998). "Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3". J Biol Chem. 273 (13): 7345–50. doi:10.1074/jbc.273.13.7345. PMID 9516430.
  4. ↑ "Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)".
  5. ↑ 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. PMID 23918525.
  6. ↑ 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. PMID 20213810.
  7. 1 2 Kuefer R, Day KC, Kleer CG, Sabel MS, Hofer MD, Varambally S, Zorn CS, Chinnaiyan AM, Rubin MA, Day ML (April 2006). "ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease". Neoplasia. 8 (4): 319–29. doi:10.1593/neo.05682. PMC 1600681Freely accessible. PMID 16756724.
  8. 1 2 Zhong JL, Poghosyan Z, Pennington CJ, Scott X, Handsley MM, Warn A, Gavrilovic J, Honert K, Krüger A, Span PN, Sweep FC, Edwards DR (March 2008). "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma". Mol. Cancer Res. 6 (3): 383–94. doi:10.1158/1541-7786.MCR-07-2028. PMID 18296648.
  9. ↑ Najy AJ, Day KC, Day ML (February 2008). "ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction". Cancer Res. 68 (4): 1092–9. doi:10.1158/0008-5472.CAN-07-2432. PMID 18281484.
  10. 1 2 3 Poghosyan 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. PMID 11741929.
  11. 1 2 Howard 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. PMID 10531379.
  12. ↑ 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. PMID 19718658.

Further reading

  • Primakoff P, Myles DG (2000). "The ADAM gene family: surface proteins with adhesion and protease activity.". Trends Genet. 16 (2): 83–7. 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. 
  • Krätzschmar J, Lum L, Blobel CP (1996). "Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence.". J. Biol. Chem. 271 (9): 4593–6. doi:10.1074/jbc.271.9.4593. PMID 8617717. 
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
  • McKie N, Edwards T, Dallas DJ, et al. (1997). "Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes.". Biochem. Biophys. Res. Commun. 230 (2): 335–9. doi:10.1006/bbrc.1996.5957. PMID 9016778. 
  • Herren B, Raines EW, Ross R (1997). "Expression of a disintegrin-like protein in cultured human vascular cells and in vivo.". FASEB J. 11 (2): 173–80. PMID 9039960. 
  • Nath D, Slocombe PM, Stephens PE, et al. (1999). "Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells.". J. Cell. Sci. 112 (4): 579–87. PMID 9914169. 
  • 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. PMID 10531379. 
  • 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. PMID 10828588. 
  • Seldin MF, Hirohata S, Apte SS (2000). "Chromosomal mapping of Adam9, Adam15 and Adam21". Matrix Biol. 19 (2): 185–7. doi:10.1016/S0945-053X(00)00062-7. PMID 10842103. 
  • 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. PMID 11741929. 
  • 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. PMID 11839628. 
  • 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. PMID 11882657. 
  • 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. PMID 12091380. 
  • 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. PMID 12243749. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241Freely accessible. PMID 12477932. 
  • 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. PMID 12615925. 

External links

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