PEN-2

From Wikipedia, the free encyclopedia

PEN-2 (presenilin enhancer 2) is a protein that is a regulatory component of the gamma secretase complex, a protease complex responsible for proteolysis of transmembrane proteins such as the Notch protein and amyloid precursor protein (APP). The gamma secretase complex consists of PEN-1, APH-1, nicastrin, and the catalytic subunit presenilin.[1] PEN-2 is a 101-amino acid integral membrane protein likely with a topology such that both the N-terminus and the C-terminus face first the lumen of the endoplasmic reticulum and later the extracellular environment.[2] Biochemical studies have shown that a conserved sequence motif D-Y-L-S-F at the C-terminus, as well as the overall length of the C-terminal tail, is required for the formation of an active gamma secretase complex.[3]

  1. ^ Kaether C, Haass C, Steiner H. (2006). Assembly, trafficking and function of gamma-secretase. Neurodegener Dis 3(4-5):275-83. PMID 17047368
  2. ^ Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D. (2002). aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3(1):85-97. PMID 12110170
  3. ^ Hasegawa H, Sanjo N, Chen F, Gu YJ, Shier C, Petit A, Kawarai T, Katayama T, Schmidt S, Mathews P, Schmitt-Ulms G, Fraser PE, St George-Hyslop P. (2004). Both the Sequence and Length of the C Terminus of PEN-2 Are Critical for Intermolecular Interactions and Function of Presenilin Complexes. J Biol Chem 279(45): 46455-46463
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