Nicastrin

A nicastrin that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92542]

Synonyms

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 5 target(s):

Target	Category	Definition
protein binding	molecular function	Binding to a protein. [GOC:go_curators]
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]
aspartic endopeptidase activity, intramembrane cleaving	molecular function	Catalysis of the hydrolysis of nonterminal peptide bonds in a polypeptide chain, occurring within a membrane. [GOC:jl, ISBN:0198506732]
ATPase binding	molecular function	Binding to an ATPase, any enzyme that catalyzes the hydrolysis of ATP. [GOC:ai]
growth factor receptor binding	molecular function	Binding to a growth factor receptor. [GOC:mah, GOC:vw]

Located In

This protein is located in 16 target(s):

Target	Category	Definition
Golgi membrane	cellular component	The lipid bilayer surrounding any of the compartments of the Golgi apparatus. [GOC:mah]
lysosomal membrane	cellular component	The lipid bilayer surrounding the lysosome and separating its contents from the cell cytoplasm. [GOC:ai]
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]
focal adhesion	cellular component	A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ). [GOC:aruk, GOC:bc, ISBN:0124325653, ISBN:0815316208, PMID:10419689, PMID:12191915, PMID:15246682, PMID:1643657, PMID:16805308, PMID:19197329, PMID:23033047, PMID:26923917, PMID:28796323, PMID:8314002]
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]
azurophil granule membrane	cellular component	The lipid bilayer surrounding an azurophil granule, a primary lysosomal granule found in neutrophil granulocytes that contains a wide range of hydrolytic enzymes and is released into the extracellular fluid. [GOC:bf, PMID:17152095]
sarcolemma	cellular component	The outer membrane of a muscle cell, consisting of the plasma membrane, a covering basement membrane (about 100 nm thick and sometimes common to more than one fiber), and the associated loose network of collagen fibers. [ISBN:0198506732]
melanosome	cellular component	A tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored. Melanosomes are synthesized in melanocyte cells. [GOC:jl, PMID:11584301]
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]
extracellular exosome	cellular component	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm. [GOC:BHF, GOC:mah, GOC:vesicles, PMID:15908444, PMID:17641064, PMID:19442504, PMID:19498381, PMID:22418571, PMID:24009894]

Active In

This protein is active in 1 target(s):

Target	Category	Definition
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]

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 25 target(s):

Target	Category	Definition
myeloid cell homeostasis	biological process	The process of regulating the proliferation and elimination of myeloid cells such that the total number of myeloid cells within a whole or part of an organism is stable over time in the absence of an outside stimulus. [CL:0000763, GOC:add]
proteolysis	biological process	The hydrolysis of proteins into smaller polypeptides and/or amino acids by cleavage of their peptide bonds. [GOC:bf, GOC:mah]
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/]
dopamine receptor signaling pathway	biological process	The series of molecular signals generated as a consequence of a dopamine receptor binding to one of its physiological ligands. [GOC:mah, PMID:21711983]
glutamate receptor signaling pathway	biological process	The series of molecular signals initiated by the binding of glutamate to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:mah, GOC:signaling, PMID:9131252]
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]
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]
learning or memory	biological process	The acquisition and processing of information and/or the storage and retrieval of this information over time. [GOC:jid, PMID:8938125]
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]
cerebellum development	biological process	The process whose specific outcome is the progression of the cerebellum over time, from its formation to the mature structure. The cerebellum is the portion of the brain in the back of the head between the cerebrum and the pons. In mice, the cerebellum controls balance for walking and standing, modulates the force and range of movement and is involved in the learning of motor skills. [GO_REF:0000021, GOC:cls, GOC:dgh, GOC:dph, GOC:jid, ISBN:0838580343]
central nervous system myelination	biological process	The process in which neuronal axons and dendrites become coated with a segmented lipid-rich sheath (myelin) to enable faster and more energetically efficient conduction of electrical impulses. The sheath is formed by the cell membranes of oligodendrocytes in the central nervous system. Adjacent myelin segments are separated by a non-myelinated stretch of axon called a node of Ranvier. [GO_REF:0000021, GOC:cls, GOC:dgh, GOC:dph, GOC:jid]
adult behavior	biological process	Behavior in a fully developed and mature organism. [GOC:mah, ISBN:0877797099]
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]
T cell proliferation	biological process	The expansion of a T cell population by cell division. Follows T cell activation. [GOC:jl]
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 biosynthetic process	biological process	The chemical reactions and pathways resulting in the formation of amyloid precursor protein (APP), the precursor of amyloid-beta, a glycoprotein associated with Alzheimer's disease. [GOC:go_curators]
positive regulation of amyloid precursor protein biosynthetic process	biological process	Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of amyloid precursor protein (APP), the precursor of amyloid-beta. [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]
epithelial cell proliferation	biological process	The multiplication or reproduction of epithelial cells, resulting in the expansion of a cell population. Epithelial cells make up the epithelium, the covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. [ISBN:0721662544]
neuron apoptotic process	biological process	Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [CL:0000540, GOC:mtg_apoptosis]
cellular response to calcium ion	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a calcium ion stimulus. [GOC:mah]
regulation of long-term synaptic potentiation	biological process	Any process that modulates the frequency, rate or extent of long-term synaptic potentiation. [GOC:BHF, GOC:TermGenie]
short-term synaptic potentiation	biological process	The process by which synaptic transmission, induced by the arrival of a spike (action potential) at a synapse, acts to increase the amount of neurotransmitter released in response to the arrival of subsequent spikes. This effect is seen when a train of closely space spikes arrives at a synapse with a low initial release probability. It occurs in a timeframe of tens to hundreds of milliseconds. [GOC:dos, GOC:sp, ISBN:9780071120005, PMID:11826273, PMID:26738595]