Gamma-secretase subunit APH-1A

UniProt Q96BI3 Organism Homo sapiens Gene APH1A, PSF

Also known as: APH1A, PSF

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). 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).

Classification

Family (Pfam): PF06105 Aph-1
InterPro: Aph-1
Functional cluster: Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 25

5A63 EM 3.40A
5FN2 EM 4.20A
5FN3 EM 4.10A
5FN4 EM 4.00A
5FN5 EM 4.30A
6IDF EM 2.70A
6IYC EM 2.60A
6LQG EM 3.10A
6LR4 EM 3.00A
7C9I EM 3.10A
7D8X EM 2.60A
7Y5T EM 2.90A
… and 13 more

A predicted model is available from AlphaFold.

Gene Ontology · 23

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-1A 1.00
Gamma-secretase subunit Aph-1b 0.95
Gamma-secretase subunit APH-1B 0.93
Gamma-secretase subunit APH-1B 0.93
Gamma-secretase subunit APH1-like 0.93
Putative gamma-secretase subunit APH-1C 0.92
Gamma-secretase subunit APH-1B 0.92
Gamma-secretase subunit Aph-1 0.89
Gamma-secretase subunit aph-1 0.81
Insulin-induced gene 2 protein 0.58
Insulin-induced gene 2 protein 0.57
Insulin-induced gene 1 protein 0.55

Co-cited proteins · studied together in the literature

Gamma-secretase subunit PEN-2 10 shared papers
Gamma-secretase subunit APH-1A 1 shared papers
Gamma-secretase subunit APH-1B 2 shared papers
Nicastrin 7 shared papers
Presenilin-1 7 shared papers
Gamma-secretase subunit PEN-2 1 shared papers
Gamma-secretase subunit PEN-2 1 shared papers
Gamma-secretase subunit pen-2 1 shared papers
Gamma-secretase subunit Aph-1b 1 shared papers
Gamma-secretase subunit aph-1 1 shared papers
Gamma-secretase subunit pen-2 1 shared papers
Gamma-secretase subunit Aph-1 1 shared papers

Literature · 19 cited papers

Recognition of the amyloid precursor protein by human gamma-secretase. Science · 2019
Structural basis of Notch recognition by human gamma-secretase. Nature · 2019
Sampling the conformational space of the catalytic subunit of human gamma-secretase. Elife · 2015
An atomic structure of human gamma-secretase. Nature · 2015
Three-dimensional structure of human gamma-secretase. Nature · 2014
APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes. J. Biol. Chem. · 2009
The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
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
Membrane topology and nicastrin-enhanced endoproteolysis of APH-1, a component of the gamma-secretase complex. J. Biol. Chem. · 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
APH1, PEN2, and nicastrin increase Abeta levels and gamma-secretase activity. Biochem. Biophys. Res. Commun. · 2003
… and 7 more in the literature graph

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