Gamma-secretase subunit APH-1A

Definition

Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Required for normal gamma-secretase assembly. The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable).

References:

[1]. Dieter Edbauer, et al. Reconstitution of gamma-secretase activity. Nat Cell Biol. 2003 May;5(5):486-8. [Content Brief]

[2]. Xiao-Chen Bai, et al. An atomic structure of human γ-secretase. Nature. 2015 Sep 10;525(7568):212-217. [Content Brief]

[3]. Peilong Lu, et al. Three-dimensional structure of human γ-secretase. Nature. 2014 Aug 14;512(7513):166-170. [Content Brief]

[4]. Guanghui Yang, et al. Structural basis of Notch recognition by human γ-secretase. Nature. 2019 Jan;565(7738):192-197. [Content Brief]

[5]. Rui Zhou, et al. Recognition of the amyloid precursor protein by human γ-secretase. Science. 2019 Feb 15;363(6428):eaaw0930. [Content Brief]

[6]. Wen-jie Luo, et al. PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1. J Biol Chem. 2003 Mar 7;278(10):7850-4. [Content Brief]

[7]. Laura Marlow, et al. APH1, PEN2, and Nicastrin increase Abeta levels and gamma-secretase activity. Biochem Biophys Res Commun. 2003 Jun 6;305(3):502-9. [Content Brief]

[8]. Raphaëlle Pardossi-Piquard, et al. APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes. J Biol Chem. 2009 Jun 12;284(24):16298-16307. [Content Brief]

[9]. Yongjun Gu, et al. APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes. J Biol Chem. 2003 Feb 28;278(9):7374-80. [Content Brief]

[10]. Sheu-Fen Lee, et al. Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch. J Biol Chem. 2002 Nov 22;277(47):45013-9. [Content Brief]

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