Gamma-secretase subunit APH-1A

A gamma-secretase subunit APH-1A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96BI3]

Synonyms

APH-1a;
Aph-1alpha;
Presenilin-stabilization factor

Research

Bioassay Publications (31)

Timeframe	Studies on this Protein(%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	8 (25.81)	29.6817
2010's	20 (64.52)	24.3611
2020's	3 (9.68)	2.80

Compounds (21)

Drugs with Inhibition Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
7-amino-4-chloro-3-methoxy-2-benzopyran-1-one	Homo sapiens (human)	IC50	30.0000	1	1
tarenflurbil	Homo sapiens (human)	IC50	203.5000	2	2
cholanic acid	Homo sapiens (human)	IC50	5.6800	1	1
t0901317	Homo sapiens (human)	IC50	22.2500	2	2
n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester	Homo sapiens (human)	IC50	25.1553	4	4
sulindac sulfide	Homo sapiens (human)	IC50	147.9200	5	5
l 685458	Homo sapiens (human)	IC50	0.0782	7	7
mk 0752	Homo sapiens (human)	IC50	0.0300	2	2
ly 450139	Homo sapiens (human)	IC50	0.0523	12	12
chf 5074	Homo sapiens (human)	IC50	40.0000	1	1
ly 411575	Homo sapiens (human)	IC50	0.2004	6	6
4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acid	Homo sapiens (human)	IC50	5.1276	5	5
begacestat	Homo sapiens (human)	IC50	0.0821	11	11
e 2012	Homo sapiens (human)	IC50	1.4671	12	12
mrk 560	Homo sapiens (human)	IC50	0.0200	5	5
1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone	Homo sapiens (human)	IC50	1.0344	2	2
pf 3084014	Homo sapiens (human)	IC50	0.0068	5	5
bms 708163	Homo sapiens (human)	IC50	0.0006	7	7
ro 4929097	Homo sapiens (human)	IC50	0.0040	1	1
jnj 40418677	Homo sapiens (human)	IC50	0.2000	1	1
(r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline	Homo sapiens (human)	IC50	0.0031	4	4

Drugs with Activation Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
cholanic acid	Homo sapiens (human)	EC50	5.7000	1	1
t0901317	Homo sapiens (human)	EC50	3.6000	1	1
ly 450139	Homo sapiens (human)	EC50	0.0769	2	2
ly 411575	Homo sapiens (human)	EC50	0.0001	1	1
begacestat	Homo sapiens (human)	EC50	0.0141	3	3
e 2012	Homo sapiens (human)	EC50	0.0830	1	1
mrk 560	Homo sapiens (human)	EC50	0.0006	1	1
ro 4929097	Homo sapiens (human)	EC50	0.0095	2	2

Drugs with Other Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
begacestat	Homo sapiens (human)	ED50	0.0078	1	1
bms 708163	Homo sapiens (human)	ED50	0.0012	1	1
(r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline	Homo sapiens (human)	ED50	0.0011	1	1

Enables

This protein enables 4 target(s):

Target	Category	Definition
protein binding	molecular function	Binding to a protein. [GOC:go_curators]
enzyme binding	molecular function	Binding to an enzyme, a protein with catalytic activity. [GOC:jl]
protein-macromolecule adaptor activity	molecular function	The binding activity of a protein that brings together two or more macromolecules in contact, permitting those molecules to function in a coordinated way. The adaptor can bring together two proteins, or a protein and another macromolecule such as a lipid or a nucleic acid. [GOC:bf, GOC:mah, GOC:vw]
endopeptidase activator activity	molecular function	Binds to and increases the activity of an endopeptidase. [GOC:dph, GOC:tb]

Located In

This protein is located in 11 target(s):

Target	Category	Definition
Golgi membrane	cellular component	The lipid bilayer surrounding any of the compartments of the Golgi apparatus. [GOC:mah]
early endosome	cellular component	A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways. [GOC:mah, NIF_Subcellular:nlx_subcell_20090701, PMID:19696797]
endoplasmic reticulum	cellular component	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). [ISBN:0198506732]
endoplasmic reticulum membrane	cellular component	The lipid bilayer surrounding the endoplasmic reticulum. [GOC:mah]
Golgi apparatus	cellular component	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. [ISBN:0198506732]
plasma membrane	cellular component	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363]
synaptic vesicle	cellular component	A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the 'active zone' of the presynaptic plasma membrane. [PMID:10099709, PMID:12563290]
endosome membrane	cellular component	The lipid bilayer surrounding an endosome. [GOC:mah]
membrane	cellular component	A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. [GOC:dos, GOC:mah, ISBN:0815316194]
Golgi cisterna membrane	cellular component	The lipid bilayer surrounding any of the thin, flattened compartments that form the central portion of the Golgi complex. [GOC:ecd, GOC:mah]
presynaptic membrane	cellular component	A specialized area of membrane of the axon terminal that faces the plasma membrane of the neuron or muscle fiber with which the axon terminal establishes a synaptic junction; many synaptic junctions exhibit structural presynaptic characteristics, such as conical, electron-dense internal protrusions, that distinguish it from the remainder of the axon plasma membrane. [GOC:jl, ISBN:0815316194]

Active In

This protein is active in 1 target(s):

Target	Category	Definition
endoplasmic reticulum	cellular component	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). [ISBN:0198506732]

Part Of

This protein is part of 1 target(s):

Target	Category	Definition
gamma-secretase complex	cellular component	A protein complex that has aspartic-type endopeptidase activity and contains a presenilin catalytic subunit (either PSEN1 or PSEN2), an APH1 subunit (multiple genes and splice variants exist), nicastrin (NCT), and presenilin enhancer (aka PEN-2 or Psenen), as the core complex. Variants of the complex with different subunit compositions differ in localization and specific substrates. Additionally, variants of the complex exist that contain a additional regulatory subunit as well as the four core subunits; known regulatory subunits include gamma-secretase-activating protein (aka gSAP), TMP1 (aka TMED10), and CD147 antigen (aka basigin). Gamma-secretase cleaves type I transmembrane protein substrates, including the cell surface receptor Notch and the amyloid-beta precursor protein. [GOC:krc, PMID:15286082, PMID:15890777, PMID:17047368, PMID:22122073, PMID:25565961, PMID:28320827, PMID:32616437]

Involved In

This protein is involved in 10 target(s):

Target	Category	Definition
metanephros development	biological process	The process whose specific outcome is the progression of the metanephros over time, from its formation to the mature structure. In mammals, the metanephros is the excretory organ of the fetus, which develops into the mature kidney and is formed from the rear portion of the nephrogenic cord. The metanephros is an endocrine and metabolic organ that filters the blood and excretes the end products of body metabolism in the form of urine. [GOC:bf, ISBN:0192800752]
membrane protein ectodomain proteolysis	biological process	The proteolytic cleavage of transmembrane proteins and release of their ectodomain (extracellular domain). [GOC:jl, http://www.copewithcytokines.de/]
Notch receptor processing	biological process	The series of successive proteolytic cleavages of the Notch protein, which result in an active form of the receptor. [PMID:12651094, PMID:14986688]
positive regulation of endopeptidase activity	biological process	Any process that increases the frequency, rate or extent of endopeptidase activity, the endohydrolysis of peptide bonds within proteins. [GOC:dph, GOC:tb]
protein processing	biological process	Any protein maturation process achieved by the cleavage of a peptide bond or bonds within a protein. Protein maturation is the process leading to the attainment of the full functional capacity of a protein. [GOC:curators, GOC:jl, GOC:jsg]
membrane protein intracellular domain proteolysis	biological process	The proteolytic cleavage of a transmembrane protein leading to the release of an intracellular domain. [PMID:12808018]
amyloid-beta formation	biological process	The generation of amyloid-beta by cleavage of the amyloid precursor protein (APP). [GOC:mah]
amyloid precursor protein metabolic process	biological process	The chemical reactions and pathways involving amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease. [GOC:go_curators]
amyloid precursor protein catabolic process	biological process	The chemical reactions and pathways resulting in the breakdown of amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease. [GOC:go_curators]
Notch signaling pathway	biological process	The series of molecular signals initiated by an extracellular ligand binding to the receptor Notch on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:go_curators, GOC:signaling]