The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ADAM10  -  ADAM metallopeptidase domain 10

Homo sapiens

Synonyms: AD10, AD18, ADAM 10, CD156c, CDw156, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ADAM10


Psychiatry related information on ADAM10


High impact information on ADAM10

  • Cleavage of ephrin-A2 by the ADAM10 membrane metalloprotease enables contact repulsion between Eph- and ephrin-expressing cells [7].
  • Surprisingly, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells [7].
  • This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin-binding epidermal growth factor and activation of the epidermal growth factor receptor [3].
  • Structural comparisons with other disintegrin-containing enzymes indicate that TACE is unique, with noteable sequence identity to MADM, an enzyme implicated in myelin degradation, and to KUZ, a Drosophila homologue of MADM important for neuronal development [8].
  • ADAM 10 was implicated in the Notch signaling pathway [9].

Chemical compound and disease context of ADAM10


Biological context of ADAM10


Anatomical context of ADAM10


Associations of ADAM10 with chemical compounds


Physical interactions of ADAM10

  • Accordingly, ADAM9 is unable to cleave a fluorimetric substrate of membrane-bound alpha-secretase activity in ADAM10(-/-) fibroblasts [13].

Enzymatic interactions of ADAM10

  • In this study, we show that Pcdh gamma C3 and Pcdh gamma B4 are specifically cleaved within their ectodomains by the disintegrin and metalloprotease ADAM10 [25].
  • ADAM 10 correctly cleaves peptides and a soluble form of precursor TGF-alpha (proTGFecto) at the N-terminal site but not the C-terminal site [26].
  • This profile suggests the potential involvement of the ADAM-10 protease which was subsequently shown to cleave membrane CD40L to generate sCD40L [27].

Regulatory relationships of ADAM10

  • Furthermore, constitutive N1 secretion is drastically reduced in fibroblasts deficient for ADAM10 whereas phorbol 12,13-dibutyrate-regulated N1 production is fully abolished in TACE-deficient cells [28].
  • These results demonstrate, for the first time, activated pro-BTC shedding in response to extracellular calcium influx and APMA and provide evidence that ADAM10 mediates constitutive and activated pro-BTC shedding [21].
  • Furthermore, RNAi studies showed that EGF induced ADAM10 (a disintegrin and metalloproteinase 10)-dependent CD44 cleavage and cell migration [29].
  • The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3 [30].
  • ADAM-10 was found to be expressed by astrocytes in all MS and control sections studied; however, in some MS sections, perivascular macrophages were determined as an additional cellular source as well [31].

Other interactions of ADAM10

  • Transgenic mice with neuron-specific overexpression of ADAM10 showed significantly increased levels of soluble APLP2 and its C-terminal fragments [2].
  • Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1-ECV-304 cells but also prevented de-adhesion of bound THP-1 cells [32].
  • Indeed we found that alpha(9)beta(1) bound avidly to the disintegrin domains of ADAM1, 2, 3, and 9 but not to the disintegrin domains of ADAM10 and 17 [33].
  • CONCLUSIONS: AF is associated with an increase in the expression of ADAM10 and ADAM15 [34].
  • The lack of TIMP inhibition of ADAM8 and 9 contrasts with other membrane-associated metalloproteinases characterised to date in this respect (ADAM10, 12, 17, and the membrane-type metalloproteinases) which have been implicated in protein processing at the cell surface [35].

Analytical, diagnostic and therapeutic context of ADAM10


  1. Effects of anoxia and hypoxia on amyloid precursor protein processing in cerebral microvascular smooth muscle cells. Auerbach, I.D., Vinters, H.V. J. Neuropathol. Exp. Neurol. (2006) [Pubmed]
  2. Shedding of the amyloid precursor protein-like protein APLP2 by disintegrin-metalloproteinases. Endres, K., Postina, R., Schroeder, A., Mueller, U., Fahrenholz, F. FEBS J. (2005) [Pubmed]
  3. Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells. Lemjabbar, H., Basbaum, C. Nat. Med. (2002) [Pubmed]
  4. ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein. Obregon, D.F., Rezai-Zadeh, K., Bai, Y., Sun, N., Hou, H., Ehrhart, J., Zeng, J., Mori, T., Arendash, G.W., Shytle, D., Town, T., Tan, J. J. Biol. Chem. (2006) [Pubmed]
  5. Janus kinase 2 influences growth hormone receptor metalloproteolysis. Loesch, K., Deng, L., Cowan, J.W., Wang, X., He, K., Jiang, J., Black, R.A., Frank, S.J. Endocrinology (2006) [Pubmed]
  6. Variation at the ADAM10 gene locus is not associated with Creutzfeldt-Jakob disease. Plamont, M.A., Chasseigneaux, S., Delasnerie-Lauprêtre, N., Beaudry, P., Peoc'h, K., Laplanche, J.L. Neurosci. Lett. (2003) [Pubmed]
  7. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Janes, P.W., Saha, N., Barton, W.A., Kolev, M.V., Wimmer-Kleikamp, S.H., Nievergall, E., Blobel, C.P., Himanen, J.P., Lackmann, M., Nikolov, D.B. Cell (2005) [Pubmed]
  8. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Moss, M.L., Jin, S.L., Milla, M.E., Bickett, D.M., Burkhart, W., Carter, H.L., Chen, W.J., Clay, W.C., Didsbury, J.R., Hassler, D., Hoffman, C.R., Kost, T.A., Lambert, M.H., Leesnitzer, M.A., McCauley, P., McGeehan, G., Mitchell, J., Moyer, M., Pahel, G., Rocque, W., Overton, L.K., Schoenen, F., Seaton, T., Su, J.L., Becherer, J.D. Nature (1997) [Pubmed]
  9. ADAMs: focus on the protease domain. Black, R.A., White, J.M. Curr. Opin. Cell Biol. (1998) [Pubmed]
  10. ADAM17 Mediates Epidermal Growth Factor Receptor Transactivation and Vascular Smooth Muscle Cell Hypertrophy Induced by Angiotensin II. Ohtsu, H., Dempsey, P.J., Frank, G.D., Brailoiu, E., Higuchi, S., Suzuki, H., Nakashima, H., Eguchi, K., Eguchi, S. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  11. Acetylcholinesterase inhibitors increase ADAM10 activity by promoting its trafficking in neuroblastoma cell lines. Zimmermann, M., Gardoni, F., Marcello, E., Colciaghi, F., Borroni, B., Padovani, A., Cattabeni, F., Di Luca, M. J. Neurochem. (2004) [Pubmed]
  12. Expression of the disintegrin metalloprotease, ADAM-10, in prostate cancer and its regulation by dihydrotestosterone, insulin-like growth factor I, and epidermal growth factor in the prostate cancer cell model LNCaP. McCulloch, D.R., Akl, P., Samaratunga, H., Herington, A.C., Odorico, D.M. Clin. Cancer Res. (2004) [Pubmed]
  13. The disintegrin ADAM9 indirectly contributes to the physiological processing of cellular prion by modulating ADAM10 activity. Cissé, M.A., Sunyach, C., Lefranc-Jullien, S., Postina, R., Vincent, B., Checler, F. J. Biol. Chem. (2005) [Pubmed]
  14. ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. Maretzky, T., Reiss, K., Ludwig, A., Buchholz, J., Scholz, F., Proksch, E., de Strooper, B., Hartmann, D., Saftig, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  15. Engagement of CD44 promotes Rac activation and CD44 cleavage during tumor cell migration. Murai, T., Miyazaki, Y., Nishinakamura, H., Sugahara, K.N., Miyauchi, T., Sako, Y., Yanagida, T., Miyasaka, M. J. Biol. Chem. (2004) [Pubmed]
  16. Radiation hybrid mapping of human ADAM10 gene to chromosome 15. Yamazaki, K., Mizui, Y., Tanaka, I. Genomics (1997) [Pubmed]
  17. Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Asai, M., Hattori, C., Szabó, B., Sasagawa, N., Maruyama, K., Tanuma, S., Ishiura, S. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  18. Levels of beta-secretase BACE and alpha-secretase ADAM10 mRNAs in Alzheimer hippocampus. Gatta, L.B., Albertini, A., Ravid, R., Finazzi, D. Neuroreport (2002) [Pubmed]
  19. Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes. Namba, K., Nishio, M., Mori, K., Miyamoto, N., Tsurudome, M., Ito, M., Kawano, M., Uchida, A., Ito, Y. Cell. Immunol. (2001) [Pubmed]
  20. Localization of ADAM10 and Notch receptors in bone. Dallas, D.J., Genever, P.G., Patton, A.J., Millichip, M.I., McKie, N., Skerry, T.M. Bone (1999) [Pubmed]
  21. ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p-aminophenylmercuric acetate and extracellular calcium influx. Sanderson, M.P., Erickson, S.N., Gough, P.J., Garton, K.J., Wille, P.T., Raines, E.W., Dunbar, A.J., Dempsey, P.J. J. Biol. Chem. (2005) [Pubmed]
  22. The search for alpha-secretase and its potential as a therapeutic approach to Alzheimer s disease. Hooper, N.M., Turner, A.J. Current medicinal chemistry. (2002) [Pubmed]
  23. Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain. Marcinkiewicz, M., Seidah, N.G. J. Neurochem. (2000) [Pubmed]
  24. Altered expression of disintegrin metalloproteinases and their inhibitor in human dilated cardiomyopathy. Fedak, P.W., Moravec, C.S., McCarthy, P.M., Altamentova, S.M., Wong, A.P., Skrtic, M., Verma, S., Weisel, R.D., Li, R.K. Circulation (2006) [Pubmed]
  25. Regulated ADAM10-dependent ectodomain shedding of gamma-protocadherin C3 modulates cell-cell adhesion. Reiss, K., Maretzky, T., Haas, I.G., Schulte, M., Ludwig, A., Frank, M., Saftig, P. J. Biol. Chem. (2006) [Pubmed]
  26. Multiple metalloproteinases process protransforming growth factor-alpha (proTGF-alpha). Hinkle, C.L., Mohan, M.J., Lin, P., Yeung, N., Rasmussen, F., Milla, M.E., Moss, M.L. Biochemistry (2003) [Pubmed]
  27. Differential regulation of soluble and membrane CD40L proteins in T cells. Matthies, K.M., Newman, J.L., Hodzic, A., Wingett, D.G. Cell. Immunol. (2006) [Pubmed]
  28. The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein. Vincent, B., Paitel, E., Saftig, P., Frobert, Y., Hartmann, D., De Strooper, B., Grassi, J., Lopez-Perez, E., Checler, F. J. Biol. Chem. (2001) [Pubmed]
  29. Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10. Murai, T., Miyauchi, T., Yanagida, T., Sako, Y. Biochem. J. (2006) [Pubmed]
  30. The in vitro activity of ADAM-10 is inhibited by TIMP-1 and TIMP-3. Amour, A., Knight, C.G., Webster, A., Slocombe, P.M., Stephens, P.E., Knäuper, V., Docherty, A.J., Murphy, G. FEBS Lett. (2000) [Pubmed]
  31. ADAM-10 and ADAM-17 in the inflamed human CNS. Kieseier, B.C., Pischel, H., Neuen-Jacob, E., Tourtellotte, W.W., Hartung, H.P. Glia (2003) [Pubmed]
  32. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Hundhausen, C., Misztela, D., Berkhout, T.A., Broadway, N., Saftig, P., Reiss, K., Hartmann, D., Fahrenholz, F., Postina, R., Matthews, V., Kallen, K.J., Rose-John, S., Ludwig, A. Blood (2003) [Pubmed]
  33. 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. Eto, K., Huet, C., Tarui, T., Kupriyanov, S., Liu, H.Z., Puzon-McLaughlin, W., Zhang, X.P., Sheppard, D., Engvall, E., Takada, Y. J. Biol. Chem. (2002) [Pubmed]
  34. Altered expression of ADAMs (A Disintegrin And Metalloproteinase) in fibrillating human atria. Arndt, M., Lendeckel, U., Röcken, C., Nepple, K., Wolke, C., Spiess, A., Huth, C., Ansorge, S., Klein, H.U., Goette, A. Circulation (2002) [Pubmed]
  35. The enzymatic activity of ADAM8 and ADAM9 is not regulated by TIMPs. Amour, A., Knight, C.G., English, W.R., Webster, A., Slocombe, P.M., Knäuper, V., Docherty, A.J., Becherer, J.D., Blobel, C.P., Murphy, G. FEBS Lett. (2002) [Pubmed]
  36. ADAM10 Inhibition of Human CD30 Shedding Increases Specificity of Targeted Immunotherapy In vitro. Eichenauer, D.A., Simhadri, V.L., von Strandmann, E.P., Ludwig, A., Matthews, V., Reiners, K.S., von Tresckow, B., Saftig, P., Rose-John, S., Engert, A., Hansen, H.P. Cancer Res. (2007) [Pubmed]
  37. [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients. Colciaghi, F., Borroni, B., Pastorino, L., Marcello, E., Zimmermann, M., Cattabeni, F., Padovani, A., Di Luca, M. Mol. Med. (2002) [Pubmed]
  38. The expression of the ADAMs proteases in prostate cancer cell lines and their regulation by dihydrotestosterone. McCulloch, D.R., Harvey, M., Herington, A.C. Mol. Cell. Endocrinol. (2000) [Pubmed]
  39. A basolateral sorting signal directs ADAM10 to adherens junctions and is required for its function in cell migration. Wild-Bode, C., Fellerer, K., Kugler, J., Haass, C., Capell, A. J. Biol. Chem. (2006) [Pubmed]
WikiGenes - Universities