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Gene Review

ADAM28  -  ADAM metallopeptidase domain 28

Homo sapiens

Synonyms: ADAM 28, ADAM23, Disintegrin and metalloproteinase domain-containing protein 28, Epididymal metalloproteinase-like, disintegrin-like, and cysteine-rich protein II, MDC-L, ...
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Disease relevance of ADAM28


High impact information on ADAM28

  • In addition, cleavage of IGFBP-3 in breast carcinoma tissues was correlated with ADAM28 expression levels and inhibited by treatment with ADAM inhibitor or anti-ADAM28 antibody [2].
  • The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin alpha4beta1 [5].
  • We report here the identification of MDC-L (ADAM 23), a novel member of the MDC protein family [6].
  • The results obtained from cDNA cloning and Northern blot analysis of mRNA isolated from various lymphoid tissues indicate that a 2.8-kilobase mRNA encoding a transmembrane form, MDC-Lm, and a 2.2-kilobase mRNA encoding a secreted form, MDC-Ls, are expressed in a tissue-specific manner [6].
  • MDC-Lm was found to be expressed on the surface of human peripheral blood lymphocytes and transformed B- and T-lymphocyte cell lines as an 87-kDa protein [6].

Biological context of ADAM28

  • A mutation converting the catalytic-site glutamate residue into alanine abolishes pro-domain removal, even though this mutant form of ADAM28 can be transported to the cell surface in a manner similar to the wild-type protein [7].
  • Northern blot analysis of selected mouse tissues revealed that ADAM28 is expressed highly and in alternatively spliced forms in the epididymis, suggesting a possible role in sperm maturation, and at lower levels in lung [7].
  • This approach identified ADAM 28 residues Lys(437), Lys(442), Lys(455), Lys(459), Lys(460), Lys(469), and Glu(476) as being essential for alpha4beta1-dependent cell adhesion [8].
  • To elucidate which residues comprise the alpha4beta1 binding site in the ADAM 28 disintegrin domain, a charge-to-alanine mutagenesis strategy was utilized [8].
  • Unlike many MDC proteins expressed in the reproductive tract, eMDC II possesses the extended 'catalytic centre' consensus sequence characteristic of a reprolysin-like metalloproteinase [9].

Anatomical context of ADAM28

  • Although ADAM28 is expressed and synthesized in a precursor form (proADAM28) by lymphocytes and some cancer cells, its activation mechanism and substrates remain unclear [10].
  • The intracellular maturation of ADAM28 expressed in COS-7 cells resembles that of other ADAMs, in that ADAM28 is made as a precursor and processed to a mature form in a late Golgi compartment of the secretory pathway [7].
  • Given its unique expression pattern and potential functions, murine ADAM28 may play a role in organogenesis and organ-specific functions such as thymic T cell development [11].
  • While human ADAM28 is expressed in lymphocytes (J. Biol. Chem. 274 (1999) 29251), we observe expression of murine ADAM28 in thymic epithelial cells and developmentally related tissues including the trachea, thyroid, stomach, and lung, but not in lymphocytes [11].
  • Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported alpha4beta1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not [12].

Associations of ADAM28 with chemical compounds

  • Promoter hypermethylation was strongly associated with reductions in both mRNA and protein expression, with a threshold of 40-60% of modified CpG dinucleotides being required for the complete silencing of ADAM23 mRNA expression [3].
  • However, there was no interference by these two drugs with the measurement of MDCL in the hypoxanthine/xanthine oxidase superoxide anion generation system [13].
  • Both KF and CF could suppress all opsonized zymosan-induced neutrophil MDCL in a dose-dependent fashion, but not all ADCL [13].
  • Similar inhibitory effects of KF and CF were observed on the phorbol myristate acetate-induced MDCL [13].

Other interactions of ADAM28


Analytical, diagnostic and therapeutic context of ADAM28


  1. ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis. Ohtsuka, T., Shiomi, T., Shimoda, M., Kodama, T., Amour, A., Murphy, G., Ohuchi, E., Kobayashi, K., Okada, Y. Int. J. Cancer (2006) [Pubmed]
  2. ADAM28 Is Overexpressed in Human Breast Carcinomas: Implications for Carcinoma Cell Proliferation through Cleavage of Insulin-like Growth Factor Binding Protein-3. Mitsui, Y., Mochizuki, S., Kodama, T., Shimoda, M., Ohtsuka, T., Shiomi, T., Chijiiwa, M., Ikeda, T., Kitajima, M., Okada, Y. Cancer Res. (2006) [Pubmed]
  3. Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors. Costa, F.F., Verbisck, N.V., Salim, A.C., Ierardi, D.F., Pires, L.C., Sasahara, R.M., Sogayar, M.C., Zanata, S.M., Mackay, A., O'Hare, M., Soares, F., Simpson, A.J., Camargo, A.A. Oncogene (2004) [Pubmed]
  4. Novel modifications in the alkenyldiarylmethane (ADAM) series of non-nucleoside reverse transcriptase inhibitors. Casimiro-Garcia, A., Micklatcher, M., Turpin, J.A., Stup, T.L., Watson, K., Buckheit, R.W., Cushman, M. J. Med. Chem. (1999) [Pubmed]
  5. The lymphocyte metalloprotease MDC-L (ADAM 28) is a ligand for the integrin alpha4beta1. Bridges, L.C., Tani, P.H., Hanson, K.R., Roberts, C.M., Judkins, M.B., Bowditch, R.D. J. Biol. Chem. (2002) [Pubmed]
  6. MDC-L, a novel metalloprotease disintegrin cysteine-rich protein family member expressed by human lymphocytes. Roberts, C.M., Tani, P.H., Bridges, L.C., Laszik, Z., Bowditch, R.D. J. Biol. Chem. (1999) [Pubmed]
  7. Cloning and characterization of ADAM28: evidence for autocatalytic pro-domain removal and for cell surface localization of mature ADAM28. Howard, L., Maciewicz, R.A., Blobel, C.P. Biochem. J. (2000) [Pubmed]
  8. Integrin alpha4beta1-dependent adhesion to ADAM 28 (MDC-L) requires an extended surface of the disintegrin domain. Bridges, L.C., Hanson, K.R., Tani, P.H., Mather, T., Bowditch, R.D. Biochemistry (2003) [Pubmed]
  9. Identification, sequence analysis and expression of transcripts encoding a putative metalloproteinase, eMDC II, in human and macaque epididymis. Jury, J.A., Perry, A.C., Hall, L. Mol. Hum. Reprod. (1999) [Pubmed]
  10. ADAM28 is activated by MMP-7 (matrilysin-1) and cleaves insulin-like growth factor binding protein-3. Mochizuki, S., Shimoda, M., Shiomi, T., Fujii, Y., Okada, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  11. An ADAM family member with expression in thymic epithelial cells and related tissues. Haidl, I.D., Huber, G., Eichmann, K. Gene (2002) [Pubmed]
  12. ADAM disintegrin-like domain recognition by the lymphocyte integrins alpha4beta1 and alpha4beta7. Bridges, L.C., Sheppard, D., Bowditch, R.D. Biochem. J. (2005) [Pubmed]
  13. Inhibition of Fc gamma R- and CR-mediated human neutrophil chemiluminescent responses by anti-allergic and anti-histaminergic drugs. Shirouzu, K. The Kurume medical journal. (1995) [Pubmed]
  14. ADAM gene expression and regulation during human osteoclast formation. Verrier, S., Hogan, A., McKie, N., Horton, M. Bone (2004) [Pubmed]
  15. The ADAMDEC1 (decysin) gene structure: evolution by duplication in a metalloprotease gene cluster on chromosome 8p12. Bates, E.E., Fridman, W.H., Mueller, C.G. Immunogenetics (2002) [Pubmed]
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