ADAM15
Identifiers
AliasesADAM15, MDC15, ADAM metallopeptidase domain 15
External IDsOMIM: 605548 MGI: 1333882 HomoloGene: 2829 GeneCards: ADAM15
Orthologs
SpeciesHumanMouse
Entrez

8751

11490

Ensembl

ENSG00000143537

ENSMUSG00000028041

UniProt

Q13444

O88839

RefSeq (mRNA)

NM_001037722
NM_009614

RefSeq (protein)

NP_001032811
NP_033744

Location (UCSC)Chr 1: 155.05 – 155.06 MbChr 3: 89.25 – 89.26 Mb
PubMed search[3][4]
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.[5]

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.[6]

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.[7] ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.[8]

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[9] 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.[10] 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[9] and also through its modulation of epithelial cell- tumour cell interactions.[11]

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.[10][14]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000143537 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028041 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ "Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)".
  7. ^ 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.
  8. ^ 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.
  9. ^ a b 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 1600681. PMID 16756724.
  10. ^ a b 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.
  11. ^ 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.
  12. ^ a b c 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.
  13. ^ a b 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.
  14. ^ 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. S2CID 25997734.

Further reading

External links

Proteases: metalloendopeptidases (EC 3.4.24)
Enzymes
More
Categories