Anti-APH1A

APH1A also known as Anterior pharynx-defective 1, is a multi-spanning membrane protein and an integral component of the high molecular weight gamma-secretase complex that also contains presenilin, nicastrin, and Pen-2. The gamma-secretase complex is required for the intramembrane proteolysis of APP (amyloid-beta precursor protein) and Notch. APH1A is essential for gamma-cleavage of APP to enable the intracellular domain to travel to the nucleus. APH1A satisfies three major criteria for a subunit of the gamma-secretase complex in mammalian cells. First, endogenous APH1A, nicastrin, and the presenilin NTF:CTF heterodimers physically interact with each other in vivo and under the conditions that are compatible with gamma-secretase activity. Second, like presenilin and nicastrin, APH1A is required for the intramembrane proteolysis of both APP and Notch. Third, the down-regulation of APH1A like presenilin or nicastrin leads to concurrent reduction of the mature nicastrin or the steady-state levels of the presenilin endoproteolytic fragments, the mature presenilin species within the gamma-secretase complex. Protein function: 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) (PubMed:12297508, PubMed:12522139, PubMed:12763021, PubMed:12679784, PubMed:25043039, PubMed:26280335). Required for normal gamma- secretase assembly (PubMed:12522139, PubMed:12471034, PubMed:12763021, PubMed:19369254). 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). [The UniProt Consortium]