3.4.23.46: memapsin 2

This is an abbreviated version!
For detailed information about memapsin 2, go to the full flat file.

Reaction

broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein =

Synonyms

alpha-secretase, amyloid precursor protein secretase, APP secretase, Asec-1A, aspartic protease BACE, aspartic protease BACE1, Aspartic proteinase, aspartic proteinase BACE1, BACE, BACE 1, BACE I, BACE-1, BACE-2, BACE1, BACE1/beta-secretase, BACE2, beta protein amyloidogenase, beta secretase, beta-amyloid cleaving enzyme, beta-amyloid cleaving enzyme 1, beta-amyloid cleaving enzyme-1, beta-amyloid precursor protein cleavage enzyme 1, beta-amyloid precursor protein cleaving enzyme, beta-amyloid protein precursor secretase, beta-amyloid-cleaving enzyme, beta-amyloid-converting enzyme-1, beta-APP cleaving enzyme 1, beta-secretase, beta-secretase enzyme 1, beta-secretase-1, beta-site Alzheimer's amyloid precursor protein cleaving enzyme 1 (BACE1), beta-site amyloid cleaving enzyme, beta-site amyloid precursor protein cleavage enzyme, beta-site amyloid precursor protein cleaving enzyme, beta-site amyloid precursor protein cleaving enzyme 1, beta-site amyloid precursor protein cleaving enzyme-1, beta-site amyloid precursor protein enzyme 1, beta-site amyloid precursor protein-cleaving enzyme, beta-site amyloid precursor protein-cleaving enzyme 1, beta-site APP (amyloid precursor protein) cleaving enzyme, beta-site APP cleaving enzyme, beta-site APP cleaving enzyme 1, beta-site APP cleaving enzyme-1, beta-site APP-cleaving enzyme 1, D-aspartyl-beta-amyloid secretase, gamma-secretase, memapsin 1, memapsin 2, memapsin2, membrane-bound aspartic protease, NACE1, presenilin 1, presenilin-1, presenilin-2, protease Asp2, proteinase BACE1

ECTree

     3 Hydrolases

         3.4 Acting on peptide bonds (peptidases)

             3.4.23 Aspartic endopeptidases

                3.4.23.46 memapsin 2

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Results	in table
21	Activating Compound
1083	AA Sequence
35	Application
1	CAS Registry Number
27	Cloned(Commentary)
27	Crystallization (Commentary)
7484	Disease/ Diagnostics
21	Expression
15	General Information
419	IC50 Value
715	Inhibitors
3	kcat/KM [mM/s]
76	Ki Value [mM]
12	KM Value [mM]
27	Localization
2	Metals/Ions
4	Molecular Weight [Da]
151	Natural Substrates/ Products (Substrates)
1	Organic Solvent Stability
196	Organism
696	PDB ID
5	pH Optimum
2	pH Range
1	Posttranslational Modification
19	Protein Variants
5	Purification (Commentary)
6	Reaction
193	Reference
1	Renatured (Commentary)
132	Source Tissue
21	Specific Activity [micromol/min/mg]
272	Substrates and Products (Substrate)
4	Subunits
266	Synonyms
3	Temperature Optimum [°C]
6	Turnover Number [1/s]

General Information

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General Information on EC 3.4.23.46 - memapsin 2

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GENERAL INFORMATION

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

malfunction

2 entries

metabolism

Homo sapiens

P56817

BACE1 is responsible for the first step in the production of the beta-amyloid protein of Alzheimer's disease

712812

physiological function

12 entries

malfunction

Mus musculus

-

BACE1 heterozygous deletion rescues conditioned taste aversion memory deficits in 5XFAD mice

711918

malfunction

Mus musculus

P56818

loss of enzyme in the dentate gyrus leads to increased granule cell excitability, indicated by enhanced efficiency of synaptic potentials to generate granule cell spikes. The increase in granule cell excitability is accompanied by prolonged paired-pulse inhibition, altered network gamma oscillations, and impaired synaptic plasticity at entorhinal-dentate synapses of the perforant path

753126

physiological function

Cricetulus griseus

-

BACE1 is a key protein in the pathogenesis of Alzheimer's disease

711091

physiological function

Homo sapiens

-

BACE1 is involved in regulating ectodomain shedding, maturation and trafficking of the amyloid precursor protein family of proteins. BACE1 expression regulates the levels and species of full-length amyloid precursor-like protein 1, amyloid precursor protein, and amyloid precursor-like protein 2, of their shed ectodomains, and of their membrane-bound C-terminal fragments

711981

physiological function

Homo sapiens

-

BACE1 is the principle beta-secretase responsible for the production of beta-amyloid in the brain

712811

physiological function

Homo sapiens

-

BACE1 is the rate-limiting enzyme for production of beta-amyloid peptides, which are proposed to drive the pathological changes found in Alzheimer's disease

713114

physiological function

Homo sapiens

-

beta-secretase plays a role in neurogenesis

711943

physiological function

Rattus norvegicus

-

gamma-secretase (regulated intramembrane proteolysis signaling) plays an important role in the restoration or collapse of axons in the white matter after hemisection of the spinal cord

713110

physiological function

Mus musculus

-

BACE1 knock-out and wild-type nerves degenerate at a similar rate after axotomy and to a similar extent in the experimental neuropathies produced by administration of paclitaxel and acrylamide. BACE1 knock-out mice have markedly enhanced clearance of axonal and myelin debris from degenerated fibers, accelerated axonal regeneration, and earlier reinnervation of neuromuscular junctions, compared with littermate controls

718021

physiological function

Mus musculus

P56818

BACE1-/- mice develop significant retinal pathology including retinal thinning, apoptosis, reduced retinal vascular density and an increase in the age pigment, lipofuscin. BACE1 expression is highest in the neural retina. Pigment epithelial-derived factor, a regulator of gamma-secretase, inhibits vascular endothelial growth factor-induced in vitro and in vivo angiogenesis and this is abolished by BACE1 inhibition. Intravitreal administration of BACE1 inhibitor or BACE1 small interfering RNA increases choroidal neovascularization in mice. BACE1 induces ectodomain shedding of vascular endothelial growth factor receptor VEGFR1 which is a prerequisite for gamma-secretase release of a 100 kDa intracellular domain. The increase in lipofuscin following BACE1 inhibition and RNAI knockdown is associated with lysosomal perturbations

733728

physiological function

Danio rerio

Q6NZT7

homozygous bace1 mutants are hypomyelinated in the peripheral nervous system while the central nervous system is not affected. The number of mechanosensory neuromasts is elevated. Double homozygous Bace1/Bace2 fish do not enhance the single mutant phenotypes indicating non-redundant distinct physiological functions. Single homozygous bace1 mutants as well as double homozygous bace1 and bace2 mutants are viable and fertile

734521

physiological function

Mus musculus

P56818

selective inhibition of peripheral BACE1 activity in wild-type mice or mice over-expressing amyloid precursor protein reduces amyloid beta levels in the periphery but not in the brain, not even after chronic treatment over several months. BACE1 inhibitor 4-fluoro-1-(pyridin-4-yl)-1-[3-(pyrimidin-5-yl)phenyl]-1H-isoindol-3-amine with improved brain disposition reduces amyloid beta levels in both brain and periphery already after acute dosing. Mice heterozygous for BACE1, display a 62% reduction in plasma amyloid beta40 levels, whereas brain amyloid beta40 is only lowered by 11%

734524

physiological function

Mus musculus

P56818

enzyme activity levels have an inverse effect on peripheral nerve repair after injury. Neuronal enzyme activity levels impact peripheral nerve regeneration. Enzyme overexpression impairs axonal regeneration as early as 3 days after injury and leads to impaired axonal regeneration 10 days after injury

754895

physiological function

Mus musculus

P56818

the enzyme is important for normal dentate gyrus network function

753126