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juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins The substrates of gamma-secretase include amyloid precursor protein (APP) and the Notch receptor. APP, also called APPI, or Alzheimer disease amyloid protein (ABPP), or amyloid precursor protein, or amyloid-beta A4 protein, or cerebral vascular amyloid peptide (CVAP), or PreA4, or protease nexin-II (PN-II), functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Notch proteins are a family of type-1 transmembrane proteins that form a core component of the Notch signaling pathway. They operate in a variety of different tissues and play a role in a variety of developmental processes by controlling cell fate decisions. Successive cleavage of the APP carboxyl-terminal fragment generates amyloid-beta (Abeta) peptides of varying lengths. Accumulation of Abeta peptides such as Abeta42 and Abeta43 leads to formation of amyloid plaques in the brain, a hallmark of Alzheimer's disease. Notch cleavage is involved in cell-fate determination during development and neurogenesis. The model corresponds to the juxtamembrane and transmembrane (JMTM) domain found in Notch and APP family proteins. It comprises a transmembrane helix (TM) with adjacent juxtamembrane (JM) regions. The JMTM domain is likely to be recognized by gamma-secretase in a similar fashion to both Notch and APP family proteins. |
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Jiyao W et al.(2023). "The conserved domain database in 2023.",