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Gene Review

Adam17  -  a disintegrin and metallopeptidase domain 17

Mus musculus

Synonyms: ADAM 17, CD156b, Disintegrin and metalloproteinase domain-containing protein 17, TNF-alpha convertase, TNF-alpha-converting enzyme, ...
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Disease relevance of Adam17

  • Matrix metalloproteinases, tissue inhibitors of MMPs and TACE in experimental cerebral malaria [1].

High impact information on Adam17

  • Unchecked TACE activity causes an increase in levels of soluble TNF-alpha, which subsequently promotes diabetes and vascular inflammation [2].
  • Several EGFR agonists also stimulated Adam17(-/-) mammary organoid growth in culture, but only AREG was expressed abundantly in the developing ductal system in vivo [3].
  • As the transmembrane metalloproteinase ADAM17 can process AREG in culture and Adam17(-/-) mice tend to phenocopy Egfr(-/-) mice, we examined the role of each of these molecules in mammary development [3].
  • TNF shedding is mediated by TNF-alpha converting enzyme, which is selectively inhibited by the tissue inhibitor of metalloproteinase 3 (TIMP3) [4].
  • Melphalan increased membrane-bound but not secreted TNF in Kupffer cells and inhibited recombinant TNF-alpha converting enzyme in vitro [5].

Biological context of Adam17

  • These results indicate that PKCepsilon signal transduction pathways to TPA-stimulated TNFalpha ectodomain shedding are mediated by TACE, a transmembrane metalloprotease [6].
  • We accounted for this by proposing that Glu(31), an acidic residue situated at the base of the AB-loop of N-TIMP-3, is drawn into contact with Lys(315), a prominent basic residue adjacent to the TACE catalytic site [7].
  • Herein, we have found that TAPI, a synthetic inhibitor of TACE, inhibits embryonic mouse lung branching morphogenesis in culture [8].
  • To further investigate the biological significance of TACE as a shedding enzyme during early lung organogenesis, we have devised an antisense oligonucleotide to specifically block endogenous TACE gene expression at both transcriptional and translational levels in embryonic mouse lung explant culture [8].
  • Our findings provide evidence that TACE-mediated membrane protein shedding is indispensable for normal lung branching morphogenesis and cytodifferentiation, probably through regulating the availability of positive cytokines/growth factors essential for lung organogenesis such as TGF-alpha [8].

Anatomical context of Adam17


Associations of Adam17 with chemical compounds

  • We hypothesized that Marimastat, a broad-spectrum MMP and TNF-alpha converting enzyme (TACE) inhibitor, might modulate this injury through interruption of inflammatory pathways [11].
  • Taken together, this study identifies a novel sheddase, ADAM17, for Kitl1 and Kitl2, and demonstrates that ADAM19 can reduce ADAM17-dependent phorbol-ester-stimulated Kitl1 ectodomain shedding [12].

Other interactions of Adam17

  • Consistent with the hypothesis that TACE regulates EGF receptor (EGFR) ligand availability in vivo, mice heterozygous for Tace and homozygous for an impaired EGFR allele (wa-2) were born with open eyes significantly more often than Tace(+/+)Egfr(wa-2)(/)(wa-2) counterparts [13].
  • This high resolution map rules out candidate genes encoding apolipoprotein B, syndecan 1, and Adam17 [14].
  • Reactive oxygen species-dependent TNF-alpha converting enzyme activation through stimulation of 5-HT2B and alpha1D autoreceptors in neuronal cells [15].
  • TACE is known to be involved in the proteolytic release of TGF-alpha, an EGF family stimuli critical for lung growth and maturation [8].


  1. Matrix metalloproteinases, tissue inhibitors of MMPs and TACE in experimental cerebral malaria. Van den Steen, P.E., Van Aelst, I., Starckx, S., Maskos, K., Opdenakker, G., Pagenstecher, A. Lab. Invest. (2006) [Pubmed]
  2. Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF-alpha. Federici, M., Hribal, M.L., Menghini, R., Kanno, H., Marchetti, V., Porzio, O., Sunnarborg, S.W., Rizza, S., Serino, M., Cunsolo, V., Lauro, D., Mauriello, A., Smookler, D.S., Sbraccia, P., Sesti, G., Lee, D.C., Khokha, R., Accili, D., Lauro, R. J. Clin. Invest. (2005) [Pubmed]
  3. Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Sternlicht, M.D., Sunnarborg, S.W., Kouros-Mehr, H., Yu, Y., Lee, D.C., Werb, Z. Development (2005) [Pubmed]
  4. Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation. Smookler, D.S., Mohammed, F.F., Kassiri, Z., Duncan, G.S., Mak, T.W., Khokha, R. J. Immunol. (2006) [Pubmed]
  5. Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors. Kresse, M., Latta, M., Künstle, G., Riehle, H.M., van Rooijen, N., Hentze, H., Tiegs, G., Biburger, M., Lucas, R., Wendel, A. J. Immunol. (2005) [Pubmed]
  6. Protein kinase Cepsilon is linked to 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor-alpha ectodomain shedding and the development of metastatic squamous cell carcinoma in protein kinase Cepsilon transgenic mice. Wheeler, D.L., Ness, K.J., Oberley, T.D., Verma, A.K. Cancer Res. (2003) [Pubmed]
  7. Tailoring tissue inhibitor of metalloproteinases-3 to overcome the weakening effects of the cysteine-rich domains of tumour necrosis factor-alpha converting enzyme. Lee, M.H., Dodds, P., Verma, V., Maskos, K., Knäuper, V., Murphy, G. Biochem. J. (2003) [Pubmed]
  8. Abrogation of tumor necrosis factor-alpha converting enzyme inhibits embryonic lung morphogenesis in culture. Zhao, J., Chen, H., Wang, Y.L., Warburton, D. Int. J. Dev. Biol. (2001) [Pubmed]
  9. Antibody-induced shedding of CD44 from adherent cells is linked to the assembly of the cytoskeleton. Shi, M., Dennis, K., Peschon, J.J., Chandrasekaran, R., Mikecz, K. J. Immunol. (2001) [Pubmed]
  10. Tumour necrosis factor-alpha stimulates expression of TNF-alpha converting enzyme in endothelial cells. Bzowska, M., Jura, N., Lassak, A., Black, R.A., Bereta, J. Eur. J. Biochem. (2004) [Pubmed]
  11. Inhibition of matrix metalloproteinases increases PPAR-{alpha} and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model. Alwayn, I.P., Andersson, C., Lee, S., Arsenault, D.A., Bistrian, B.R., Gura, K.M., Nose, V., Zauscher, B., Moses, M., Puder, M. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  12. Different ADAMs have distinct influences on Kit ligand processing: phorbol-ester-stimulated ectodomain shedding of Kitl1 by ADAM17 is reduced by ADAM19. Kawaguchi, N., Horiuchi, K., Becherer, J.D., Toyama, Y., Besmer, P., Blobel, C.P. J. Cell. Sci. (2007) [Pubmed]
  13. Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. Sunnarborg, S.W., Hinkle, C.L., Stevenson, M., Russell, W.E., Raska, C.S., Peschon, J.J., Castner, B.J., Gerhart, M.J., Paxton, R.J., Black, R.A., Lee, D.C. J. Biol. Chem. (2002) [Pubmed]
  14. Fine mapping of Ath6, a quantitative trait locus for atherosclerosis in mice. Purcell, M.K., Mu, J.L., Higgins, D.C., Elango, R., Whitmore, H., Harris, S., Paigen, B. Mamm. Genome (2001) [Pubmed]
  15. Reactive oxygen species-dependent TNF-alpha converting enzyme activation through stimulation of 5-HT2B and alpha1D autoreceptors in neuronal cells. Pietri, M., Schneider, B., Mouillet-Richard, S., Ermonval, M., Mutel, V., Launay, J.M., Kellermann, O. FASEB J. (2005) [Pubmed]
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