A disintegrin & metalloproteinase domain 10; Kuzbanian protein homolog; mammalian disintegrin-metalloprotease; CDw156; CD156c (ADAM10, KUZ, MADM)
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Function
- cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' to its mature soluble form
- responsible for the proteolytic release of several other cell-surface proteins, including:
- responsible for constitutive & regulated alpha-secretase cleavage of amyloid precursor protein (APP)
- contributes to the normal cleavage of the cellular prion protein
- involved in the cleavage of the adhesion molecule L1 at the cell surface & in released membrane vesicles, suggesting a vesicle-based protease activity
- controls also the proteolytic processing of Notch & mediates lateral inhibition during neurogenesis (putative)
- interacts with ephrin-A2 (putative)
- precursor is cleaved by a furin endopeptidase
- EPH receptor binding triggers cleavage
- inhibited by TIMP1 & TIMP3, but not TIMP2 & TIMP4
- activity may be enhanced by cholesterol or cholesterol esters[3]
- transcription enhanced by SIRT1 deacetylation of RARB
- activity induces notch pathway involved in repair of damaged neurons[5]
Cofactor: binds 1 Zn+2 (putative)
Structure
- conserved Cys present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme; dissociation of the Cys from the Zn+2 upon the activation-peptide release activates the enzyme
- contains 1 disintegrin domain
- contains 1 peptidase M12B domain
Compartment
- plasma membrane
- intracytoplasmic membrane
- predominantly localized in the Golgi & in released membrane vesicles derived from the Golgi
Expression
- expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes & fetal liver
Pathology
- expressed in osteoarthritis affected-cartilage
- low levels of ADAM10 in psoriasis may be attributable to its regulatory role in keratinocyte differentiation and proliferation[6]
More general terms
References
- ↑ OMIM https://mirror.omim.org/entry/602192
- ↑ Yong VW et al Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci. 2001 Jul;2(7):502-11. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11433375
- ↑ 3.0 3.1 Marx J. Science 294:508, 2001
- ↑ UniProt http://www.uniprot.org/uniprot/O14672.html
- ↑ 5.0 5.1 Donmez G et al. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 2010 Jul 23; 142:320 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20655472
Wolfe MS and Selkoe DJ. Giving Alzheimer's the old one-two. Cell 2010 Jul 23; 142:194 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20655461 - ↑ 6.0 6.1 Gul C, Kilic S, Sehitoglu MH. The importance of ADAM10 and ADAM17 metalloproteinases in the pathogenesis of psoriasis. Clin Exp Dermatol. 2022. April 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35474465