Gamma-secretase subunit APH-1B

Function

Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A.

Classification

Family (Pfam)

PF06105 Aph-1

InterPro

Aph-1

Functional cluster

Photosystem Cytochrome b559 & Membrane Proteins

Experimental structures · PDB · 2

• 8OQY EM 3.30A
• 8OQZ EM 3.40A

A predicted model is available from AlphaFold.

Gene Ontology · 14

• GO:0005789 endoplasmic reticulum membrane
• GO:0010008 endosome membrane
• GO:0070765 gamma-secretase complex
• GO:0000139 Golgi membrane
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0030133 transport vesicle
• GO:0061133 endopeptidase activator activity
• GO:0030674 protein-macromolecule adaptor activity
• GO:0042987 amyloid precursor protein catabolic process
• GO:0034205 amyloid-beta formation
• GO:0007220 Notch receptor processing
• GO:0007219 Notch signaling pathway
• GO:0016485 protein processing

Drugs targeting this protein · 7

• AVAGACESTAT inhibitor
• NIROGACESTAT inhibitor
• TARENFLURBIL modulator
• RG-4733 inhibitor
• NIROGACESTAT HYDROBROMIDE inhibitor
• BEGACESTAT inhibitor
• SEMAGACESTAT inhibitor

Related proteins · sequence + function similarity

• Gamma-secretase subunit APH-1B 1.00
• Putative gamma-secretase subunit APH-1C 0.97
• Gamma-secretase subunit APH-1B 0.97
• Gamma-secretase subunit Aph-1b 0.95
• Gamma-secretase subunit APH-1A 0.92
• Gamma-secretase subunit Aph-1 0.92
• Gamma-secretase subunit APH-1A 0.92
• Gamma-secretase subunit APH1-like 0.92
• Gamma-secretase subunit aph-1 0.81
• BOS complex subunit TMEM147 0.59
• BOS complex subunit TMEM147 0.59
• BOS complex subunit TMEM147 0.59

Co-cited proteins · studied together in the literature

• Gamma-secretase subunit APH-1A 2 shared papers
• Nicastrin 1 shared papers
• Gamma-secretase subunit PEN-2 1 shared papers
• Presenilin-1 1 shared papers

Literature · 8 cited papers

• Analysis of the DNA sequence and duplication history of human chromosome 15. Nature · 2006
• Identification and characterization of a novel human APH-1b splice variant lacking exon 4. Biochem. Biophys. Res. Commun. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. · 2003
• Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc. Natl. Acad. Sci. U.S.A. · 2003
• 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
• Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. Genome Res. · 2001