ADAM10:Zn2+:TSPANs cleaves APP(18-770)

Stable Identifier
Reaction [transition]
Homo sapiens
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ADAM10 (A Disintegrin and Metalloproteinase 10) has been identified as the major physiological alpha-secretase in neurons (Lammich et al. 1999, Kuhn et al. 2010), responsible for cleaving amyloid precursor protein (APP(18-770)) in a non-amyloidogenic manner and producing APPs-alpha (APP(18-687), a neuroprotective APP-derived peptide (Mockett et al. 2017, Endres & Deller 2017). This cleavage also produces a cellular fragment, C83/CTF-alpha (APP(688-770). Cleavage by alpha-secretase at the cell surface is the major pathway in APP processing, accounting for 80–90% of APP turnover.

Literature References
PubMed ID Title Journal Year
20676056 ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons

Colombo, A, Ellwart, JW, Zeitschel, U, Wang, H, Rossner, S, Lichtenthaler, SF, Dislich, B, Kremmer, E, Kuhn, PH

EMBO J. 2010
10097139 Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease

Haass, C, Kojro, E, Pfeiffer, R, Lammich, S, Postina, R, Jasionowski, M, Fahrenholz, F, Gilbert, S

Proc. Natl. Acad. Sci. U.S.A. 1999
Catalyst Activity

metalloendopeptidase activity involved in amyloid precursor protein catabolic process of ADAM10:Zn2+:TSPANs [plasma membrane]

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