APH1A

APH1A is a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1

Full Name

Aph-1 Homolog A, Gamma-Secretase Subunit

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, PubMed:30598546, PubMed:30630874). 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).

Biological Process

Amyloid-beta formation Source: ARUK-UCL
Amyloid fibril formation Source: Reactome
Amyloid precursor protein catabolic process Source: ARUK-UCL
Amyloid precursor protein metabolic process Source: UniProtKB
Ephrin receptor signaling pathway Source: Reactome
Membrane protein ectodomain proteolysis Source: HGNC-UCL
Membrane protein intracellular domain proteolysis Source: UniProtKB
Metanephros development Source: Ensembl
Notch receptor processing Source: ARUK-UCL
Notch receptor processing, ligand-dependent Source: Reactome
Notch signaling pathway Source: GO_Central
Positive regulation of apoptotic process Source: Reactome
Positive regulation of catalytic activity Source: HGNC-UCL
Positive regulation of endopeptidase activity Source: ARUK-UCL
Protein processing Source: HGNC-UCL

Cellular Location

Golgi stack membrane; Endoplasmic reticulum membrane. Predominantly located in the endoplasmic reticulum and in the cis-Golgi.

Topology

Lumenal: 1-2 aa
Helical: 3-23 aa
Cytoplasmic: 24-31 aa
Helical: 32-52 aa
Lumenal: 53-68 aa
Helical: 69-89 aa
Cytoplasmic: 90-118 aa
Helical: 119-139 aa
Lumenal: 140-158 aa
Helical: 159-179 aa
Cytoplasmic: 180-186 aa
Helical: 187-207 aa
Lumenal: 208-213 aa
Helical: 214-234 aa
Cytoplasmic: 235-265 aa