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Gene Review

Adam17  -  ADAM metallopeptidase domain 17

Rattus norvegicus

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

  • Amelioration of hepatic ischemia/reperfusion injury after inhibition of TACE activity by TIMP-3 suggests that TACE inhibition may play an important role in preventing liver ischemia/reperfusion injury warranting further experimental and clinical study [1].
  • Moreover, selective inhibition of TACE activity by specific inhibitor tissue inhibitor of metalloproteinase (TIMP)-3 at dosages of 100 or 1000 ng/kg body weight showed significant decrease of circulating TNF-alpha and serum alanine transferase (ALT) levels and histological improvement of hepatic ischemia/reperfusion injuries [1].
  • Here, we report that TNF-alpha converting enzyme (TACE) (a disintegrin and metalloproteinase 17, ADAM17) induces disinhibition of FGF2-stimulated neurite outgrowth of dorsal root ganglion neurons (DRGN) cultured in the presence of a predetermined concentration of inhibitory CNS myelin-derived ligands [2].
  • Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis [3].
  • Matrix metalloproteinases (MMPs) and tumour necrosis factor alpha (TNF-alpha) converting enzyme (TACE) contribute synergistically to the pathophysiology of bacterial meningitis [4].

Psychiatry related information on Adam17


High impact information on Adam17


Biological context of Adam17


Anatomical context of Adam17


Associations of Adam17 with chemical compounds

  • Stress-induced increase in both TACE activity and TNF-alpha levels seems to be mediated by excitatory amino acids since they can be blocked by MK-801 (dizocilpine) (0.2 mg/kg i.p.), an antagonist of the N-methyl-D-aspartate subtype of glutamate receptor [12].
  • CONCLUSIONS: Lack of a striking effect of the MMP and TACE antagonist GM 6001 on postoperative adhesions suggests that MMP activity and TNF-alpha might not be major adhesiogenic factors [13].
  • Inhibition of tumor necrosis factor-alpha (TNF-alpha) production and arthritis in the rat by GW3333, a dual inhibitor of TNF-alpha-converting enzyme and matrix metalloproteinases [14].
  • These findings indicate that TACE and TNF-alpha account for stress-induced short-term persistence of NOS-2 activity and MDA accumulation after 14 days of repeated exposure and support a possible neuroprotective role for specific blockers of TNF-alpha in this situation [15].
  • N-hydroxyformamide peptidomimetics as TACE/matrix metalloprotease inhibitors: oral activity via P1' isobutyl substitution [16].

Enzymatic interactions of Adam17

  • TNF-alpha converting enzyme (TACE) or disintegrin and metalloproteinase (ADAM)-17 is a metalloproteinase disintegrin that specifically cleaves precursor TNF-alpha to its mature form and is involved in the ectodomain shedding of TNF receptors [1].

Other interactions of Adam17


Analytical, diagnostic and therapeutic context of Adam17


  1. TIMP-3 Ameliorates Hepatic Ischemia/Reperfusion Injury Through Inhibition of Tumor Necrosis Factor-Alpha-Converting Enzyme Activity in Rats. Tang, Z.Y., Loss, G., Carmody, I., Cohen, A.J. Transplantation (2006) [Pubmed]
  2. TACE-induced cleavage of NgR and p75NTR in dorsal root ganglion cultures disinhibits outgrowth and promotes branching of neurites in the presence of inhibitory CNS myelin. Ahmed, Z., Mazibrada, G., Seabright, R.J., Dent, R.G., Berry, M., Logan, A. FASEB J. (2006) [Pubmed]
  3. Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis. Colón, A.L., Menchén, L.A., Hurtado, O., De Cristóbal, J., Lizasoain, I., Leza, J.C., Lorenzo, P., Moro, M.A. Cytokine (2001) [Pubmed]
  4. Inhibition of matrix metalloproteinases and tumour necrosis factor alpha converting enzyme as adjuvant therapy in pneumococcal meningitis. Leib, S.L., Clements, J.M., Lindberg, R.L., Heimgartner, C., Loeffler, J.M., Pfister, L.A., Täuber, M.G., Leppert, D. Brain (2001) [Pubmed]
  5. Hepatic integrity dependent on matrix metalloproteinase inhibition, not tumor necrosis factor alpha or different bleeding rates. Santibanez-Gallerani, A.S., Barber, A.E., Williams, S.J., Zhao, Y., Shires, G.T. J. Surg. Res. (2000) [Pubmed]
  6. Upregulation of TACE/ADAM17 after ischemic preconditioning is involved in brain tolerance. Cárdenas, A., Moro, M.A., Leza, J.C., O'Shea, E., Dávalos, A., Castillo, J., Lorenzo, P., Lizasoain, I. J. Cereb. Blood Flow Metab. (2002) [Pubmed]
  7. In pneumococcal meningitis a novel water-soluble inhibitor of matrix metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury of the cerebral cortex. Meli, D.N., Loeffler, J.M., Baumann, P., Neumann, U., Buhl, T., Leppert, D., Leib, S.L. J. Neuroimmunol. (2004) [Pubmed]
  8. In vitro ischemic tolerance involves upregulation of glutamate transport partly mediated by the TACE/ADAM17-tumor necrosis factor-alpha pathway. Romera, C., Hurtado, O., Botella, S.H., Lizasoain, I., Cárdenas, A., Fernández-Tomé, P., Leza, J.C., Lorenzo, P., Moro, M.A. J. Neurosci. (2004) [Pubmed]
  9. Endoneurial remodeling by TNFalph- and TNFalpha-releasing proteases. A spatial and temporal co-localization study in painful neuropathy. Shubayev, V.I., Myers, R.R. J. Peripher. Nerv. Syst. (2002) [Pubmed]
  10. Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. Suzuki, T., Hide, I., Ido, K., Kohsaka, S., Inoue, K., Nakata, Y. J. Neurosci. (2004) [Pubmed]
  11. Up-regulation of TNF-alpha convertase (TACE/ADAM17) after oxygen-glucose deprivation in rat forebrain slices. Hurtado, O., Cárdenas, A., Lizasoain, I., Boscá, L., Leza, J.C., Lorenzo, P., Moro, M.A. Neuropharmacology (2001) [Pubmed]
  12. The increase in TNF-alpha levels is implicated in NF-kappaB activation and inducible nitric oxide synthase expression in brain cortex after immobilization stress. Madrigal, J.L., Hurtado, O., Moro, M.A., Lizasoain, I., Lorenzo, P., Castrillo, A., Boscá, L., Leza, J.C. Neuropsychopharmacology (2002) [Pubmed]
  13. Effect of a matrix metalloproteinase activity and TNF-alpha converting enzyme inhibitor on intra-abdominal adhesions. Mirastschijski, U., Johannesson, K., Jeppsson, B., Agren, M.S. European surgical research. Europäische chirurgische Forschung. Recherches chirurgicales européennes. (2005) [Pubmed]
  14. Inhibition of tumor necrosis factor-alpha (TNF-alpha) production and arthritis in the rat by GW3333, a dual inhibitor of TNF-alpha-converting enzyme and matrix metalloproteinases. Conway, J.G., Andrews, R.C., Beaudet, B., Bickett, D.M., Boncek, V., Brodie, T.A., Clark, R.L., Crumrine, R.C., Leenitzer, M.A., McDougald, D.L., Han, B., Hedeen, K., Lin, P., Milla, M., Moss, M., Pink, H., Rabinowitz, M.H., Tippin, T., Scates, P.W., Selph, J., Stimpson, S.A., Warner, J., Becherer, J.D. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  15. TNF-alpha accounts for short-term persistence of oxidative status in rat brain after two weeks of repeated stress. Munhoz, C., Madrigal, J.L., García-Bueno, B., Pradillo, J.M., Moro, M.A., Lizasoain, I., Lorenzo, P., Scavone, C., Leza, J.C. Eur. J. Neurosci. (2004) [Pubmed]
  16. N-hydroxyformamide peptidomimetics as TACE/matrix metalloprotease inhibitors: oral activity via P1' isobutyl substitution. Musso, D.L., Andersen, M.W., Andrews, R.C., Austin, R., Beaudet, E.J., Becherer, J.D., Bubacz, D.G., Bickett, D.M., Chan, J.H., Conway, J.G., Cowan, D.J., Gaul, M.D., Glennon, K.C., Hedeen, K.M., Lambert, M.H., Leesnitzer, M.A., McDougald, D.L., Mitchell, J.L., Moss, M.L., Rabinowitz, M.H., Rizzolio, M.C., Schaller, L.T., Stanford, J.B., Tippin, T., Warner, J.R., Whitesell, L.G., Wiethe, R.W. Bioorg. Med. Chem. Lett. (2001) [Pubmed]
  17. Synthesis and biological activity of piperazine-based dual MMP-13 and TNF-alpha converting enzyme inhibitors. Letavic, M.A., Barberia, J.T., Carty, T.J., Hardink, J.R., Liras, J., Lopresti-Morrow, L.L., Mitchell, P.G., Noe, M.C., Reeves, L.M., Snow, S.L., Stam, E.J., Sweeney, F.J., Vaughn, M.L., Yu, C.H. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
  18. Importance of tumor necrosis factor-alpha cleavage process in post-transplantation lung injury in rats. Goto, T., Ishizaka, A., Kobayashi, F., Kohno, M., Sawafuji, M., Tasaka, S., Ikeda, E., Okada, Y., Maruyama, I., Kobayashi, K. Am. J. Respir. Crit. Care Med. (2004) [Pubmed]
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