The printable version is no longer supported and may have rendering errors. Please update your browser bookmarks and please use the default browser print function instead.
anterior pharynx defective 1 homolog A (C. elegans)
APH-1 (anterior pharynx-defective 1) is a proteingene product originally identified in the Notch signaling pathway in Caenorhabditis elegans as a regulator of the cell-surface localization of nicastrin.[1] APH-1 homologs in other organisms, including humans, have since been identified as components of the gamma secretase complex along with the catalytic subunit presenilin and the regulatory subunits nicastrin and PEN-2. The gamma-secretase complex is a multimeric protease responsible for the intramembrane proteolysis of transmembrane proteins such as the Notch protein and amyloid precursor protein (APP). Gamma-secretase cleavage of APP is one of two proteolytic steps required to generate the peptide known as amyloid beta, whose misfolded form is implicated in the causation of Alzheimer's disease.[2]</ref> All of the components of the gamma-secretase complex undergo extensive post-translational modification, especially proteolytic activation; APH-1 and PEN-2 are regarded as regulators of the maturation process of the catalytic component presenilin.[3]</ref> APH-1 contains a conserved alpha helix interaction motifglycine-X-X-X-glycine (GXXXG) that is essential to both assembly of the gamma secretase complex and to the maturation of the components.[4]</ref>
↑Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases. 3 (4–5): 275–83. doi:10.1159/000095267. PMID17047368.
↑Luo WJ, Wang H, Li H, Kim BS, Shah S, Lee HJ, Thinakaran G, Kim TW, Yu G, Xu H (March 2003). "PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1". The Journal of Biological Chemistry. 278 (10): 7850–4. doi:10.1074/jbc.C200648200. PMID12522139.
↑Lee SF, Shah S, Yu C, Wigley WC, Li H, Lim M, Pedersen K, Han W, Thomas P, Lundkvist J, Hao YH, Yu G (February 2004). "A conserved GXXXG motif in APH-1 is critical for assembly and activity of the gamma-secretase complex". The Journal of Biological Chemistry. 279 (6): 4144–52. doi:10.1074/jbc.M309745200. PMID14627705.
