Information on EC 3.4.23.45 - memapsin 1

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The expected taxonomic range for this enzyme is: Euarchontoglires

EC NUMBER
COMMENTARY
3.4.23.45
-
RECOMMENDED NAME
GeneOntology No.
memapsin 1
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
show the reaction diagram
-
-
-
-
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
show the reaction diagram
active site structure, substrate binding structure, tetrahedral transition state intermediate
-
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
show the reaction diagram
preferential cleavage of the amyloid precursor protein between Phe690 and Phe691 or Phe691 and Ala692
-
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
show the reaction diagram
preferential cleavage within the A-beta region at Phe19 or Phe20
-
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
show the reaction diagram
cleavage at the beta-site but more effectively at a different site within A-beta
-
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
show the reaction diagram
preferential cleavage of amyloid precursor protein downstream of the alpha-site of A-beta (after Phe19, theta-site), resulting N-terminal sequence of product is FAEDVGSN
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
-
-
-
-
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aspartic protease BACE2
-
-
-
-
BACE 2
-
-
BACE-1 homologue
-
-
BACE-2
-
-
BACE2
-
-
-
-
BACE2
-
homologue to BACE1
BACE2
-
homologue to BACE1, which cleaves amyloid precursor protein at the beta site but preferably after Phe690 or Phe691
beta site APP cleaving enzyme
-
-
beta-secretase
-
-
-
-
beta-secretase
-
-
beta-secretase
-
beta-secretase 2
-
-
-
-
beta-secretase 2
-
-
beta-secretase 2
-
beta-site Alzheimer's amyloid precurser protein cleaving enzyme 2
-
-
-
-
beta-site amyloid precursor protein cleaving enzyme 2
-
-
-
-
beta-site amyloid precursor protein-cleaving enzyme 2
-
beta-site APP cleaving enzyme
-
-
beta-site APP-cleaving enzyme 2
-
-
-
-
beta-site APP-cleaving enzyme 2
-
down region aspartic protease
-
-
-
-
DRAP
-
-
memapsin-1
-
-
memapsin1
-
protease ASP1
-
-
-
-
theta-secretase
-
preferential cleavage of the amyloid precursor protein downstream of the alpha-site of A-beta
membrane aspartic protease of the pepsin family
-
-
additional information
-
subgroup of the A1 aspartyl protease family
additional information
-
the enzyme belongs to the A1 peptidase family
CAS REGISTRY NUMBER
COMMENTARY
447457-31-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
3 different forms: A,B and C; healthy and trisomy 21 patients
-
-
Manually annotated by BRENDA team
enzyme level is decreased in Alzheimer’s disease patients
-
-
Manually annotated by BRENDA team
form A; form B; form C
SwissProt
Manually annotated by BRENDA team
healthy and trisomy 21 patients
-
-
Manually annotated by BRENDA team
healthy and trisomy 21 patients
SwissProt
Manually annotated by BRENDA team
patients with Alzheimer’s disease, BACE1 and BACE2 levels are found to be decreased in Alzheimer’s disease patients
-
-
Manually annotated by BRENDA team
patients with Down syndrome and control individuals, protein levels between the groups do not differ significantly
-
-
Manually annotated by BRENDA team
patients with Down syndrome, slightly increased mRNA levels but protein level is identical to normal individuals
-
-
Manually annotated by BRENDA team
patients with myopathies
-
-
Manually annotated by BRENDA team
precursor protein
SwissProt
Manually annotated by BRENDA team
C57/B16
-
-
Manually annotated by BRENDA team
Mus musculus C57/B16
C57/B16
-
-
Manually annotated by BRENDA team
Sprague Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the key step in the generation of Abeta is cleavage of APP by beta-secretase
physiological function
-
BACE2 colocalizes with clathrin-coated vesicles of the plasma membrane in MIN6 cells. Pharmacological inhibition of BACE2 results in increased BACE2 content in clathrin-coated vesicles, reduced insulin internalization rate, decreased in insulin receptor beta-subunit at the plasma membrane and increase in the Golgi apparatus, and a significant reduction in insulin gene expression. Similar results are obtained after specific BACE2 silencing in MIN6 cells. Data point to a role for BACE2 in the insulin receptor-beta subunit trafficking and insulin signaling
physiological function
-
mice with functionally inactive Bace2 and insulin-resistant mice treated with a Bace2 inhibitor both display augmented beta cell mass and improved control of glucose homeostasis due to increased insulin levels
physiological function
-
in a mouse model of in vivo BACE2 overexpression, BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. Transgenic BACE2 animals show increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(MCA)Glu-Val-Lys-Met-Asp-Ala-Glu-Phe-Lys(DNP) + H2O
(MCA)Glu-Val-Lys-Met + Asp-Ala-Glu-Phe-Lys(DNP)
show the reaction diagram
-
synthetic peptide substrate based on the beta-secretase cleavage site of wild-type APP
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
able to cleave the beta-site but preferential cleavage of amyloid precursor protein (APP) downstream of the alpha-site of A-beta (after Phe19, theta-site), not involved in the Alzheimer’s disease pathogenesis in Down syndrome patients, able to reduce A-beta formation when expressed in primary neurons expressing the Swedish mutant of APP
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
can cleave the amyloid precursor protein (APP) at the N terminal Asp-1 position of A-beta, preferential cleavage within the A-beta region at Phe19 or Phe20, enzyme function is not consistent with a requirement and function of BACE1 as a beta-secretase in the brain, may act antagonistically to BACE1
soluble ectodomain (sAPPb),and a membrane-bound APP C-terminal fragment of 99 amino acids
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
cleavage at the beta site of amyloid precursor protein but preferably between Phe690 and Phe691 or Phe691 and Ala692
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
cleavage at the beta-site but more effectively at a different site within A-beta, non-amyloidogenic function suggested
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
cleavage after Phe19
resulting N-terminal sequence is FAEDVGSN
?
amyloid-alpha pecursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
-
-
-
-
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
-
-
-
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid-beta precursor protein + H2O
?
show the reaction diagram
results in increase of beta-secretase-derived soluble amyloid precursor protein and the corresponding carboxy-terminal fragment
-
-
?
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
cleaves after the Phe19 and Phe20
-
-
?
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
cleaves in the middle of the amyloid-beta protein domain between Phe19 and Phe20, resulting in increased secretion of amyloid precursor proteins-alpha- and p3-like products
-
-
?
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
results in 40-42 residue amyloid-beta peptide
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
cleavage at KLVF-/-FAED and at LVFF-/-AEDV, and with low activity at EVKM-/-DAEF
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
cleavage at the beta-site
-
?
DELTA322-IL-1R2 + H2O
fragments of DELTA322-IL-1R2
show the reaction diagram
-
truncated protein cotransfected with the enzyme in HEK 293
cleavage in the same manner as for the full length protein with cleavage between Phe329 and Gln330
?
gamma-secretase cleavage site of notch + H2O
?
show the reaction diagram
-
NCH-gamma
-
-
?
IL-1R2 + H2O
fragments of IL-1R2
show the reaction diagram
-
cleavage produces fragments which are almost identical to those produced by alpha-sectretase, enzyme might act in an alternative alpha-sectretase like cleavage
cleavage between Phe329 and Gln330
?
IL-1R2 + H2O
fragments of IL-1R2
show the reaction diagram
-
intact recombinant protein with a mass of 2219.7 Da
fragments with masses of 916.7 Da and 1321 Da indicating a cleavage between Phe329 and Gln330
?
IL-1R2 + H2O
?
show the reaction diagram
-
synthetic peptide from Val322 to Ser341
-
-
?
insulin B chain + H2O
?
show the reaction diagram
-
only pro-BACE2-T1
-
-
?
kinetensin + H2O
?
show the reaction diagram
-
-
-
-
?
neuropetide + H2O
?
show the reaction diagram
-
Met-Lys-Arg-Ser-Arg-Gly-Pro-Ser-Pro-Arg-Arg
-
-
?
preproenkephalin fragment 128-140 + H2O
?
show the reaction diagram
-
-
-
-
?
preproenkephalin fragment 129-138 + H2O
?
show the reaction diagram
-
ENK-1
-
-
?
rhodamine-EVNLDAEFK-quencher + H2O
?
show the reaction diagram
-
FRET-substrate
-
-
?
Swedish amyloid-beta pecursor protein + H2O
?
show the reaction diagram
-
-
-
-
?
Swedish amyloid-beta pecursor protein + H2O
?
show the reaction diagram
-
-
-
?
Tmem27 + H2O
?
show the reaction diagram
-
proliferative plasma membrane protein
BACE2 inactivates Tmem27 by cleavage to release a 25000 Da N-terminal part and a 22000 Da C-terminal fragment
-
?
Mastoparan + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
BACE2 cleaves at the beta site and more efficiently at a different site within amyloid-beta precursor protein
-
-
-
additional information
?
-
-
the enzyme is involved in Alzheimer's disease
-
-
-
additional information
?
-
-
the enzyme might be involved in Alzheimer's disease
-
-
-
additional information
?
-
the enzyme might be involved in Alzheimer's disease
-
-
-
additional information
?
-
-
the enzyme might be involved in early onset of dementia in patients with Down syndrome, and is highly expressed in breast cancers, the enzyme may also be involved in muscle functions
-
-
-
additional information
?
-
-
autoactivation in an acidic solution with cleavage of the own propeptide within the sequence Gly-leu-Ala-Leu--/-Ala-Leu-Glu-Pro
-
-
-
additional information
?
-
-
P-selctin, TNF-alpha and CD14 are not cleaved
-
-
-
additional information
?
-
-
BACE-2 exhibits secretase activity with cleavage in the middle of the amyloid peptide domain at amino acids 19 and 20 generating a carboxy-terminal fragment of 79 residues, and does not contribute to the process of amyloid peptide generation, BACE-2 can cleave at the beta-site, but consistent with its different substrate specificity, does not cleave a preferred peptide-based BACE-1 substrate
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
Q9Y5Z0
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
able to cleave the beta-site but preferential cleavage of amyloid precursor protein (APP) downstream of the alpha-site of A-beta (after Phe19, theta-site), not involved in the Alzheimer’s disease pathogenesis in Down syndrome patients, able to reduce A-beta formation when expressed in primary neurons expressing the Swedish mutant of APP
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
can cleave the amyloid precursor protein (APP) at the N terminal Asp-1 position of A-beta, preferential cleavage within the A-beta region at Phe19 or Phe20, enzyme function is not consistent with a requirement and function of BACE1 as a beta-secretase in the brain, may act antagonistically to BACE1
soluble ectodomain (sAPPb),and a membrane-bound APP C-terminal fragment of 99 amino acids
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
cleavage at the beta site of amyloid precursor protein but preferably between Phe690 and Phe691 or Phe691 and Ala692
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
show the reaction diagram
-
cleavage at the beta-site but more effectively at a different site within A-beta, non-amyloidogenic function suggested
-
?
amyloid-beta precursor protein + H2O
?
show the reaction diagram
-
-
-
-
-
amyloid-beta precursor protein + H2O
?
show the reaction diagram
Q9Y5Z0
-
-
-
-
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
Q9Y5Z0
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
show the reaction diagram
-
cleavage at KLVF-/-FAED and at LVFF-/-AEDV, and with low activity at EVKM-/-DAEF
-
?
IL-1R2 + H2O
fragments of IL-1R2
show the reaction diagram
-
cleavage produces fragments which are almost identical to those produced by alpha-sectretase, enzyme might act in an alternative alpha-sectretase like cleavage
cleavage between Phe329 and Gln330
?
additional information
?
-
-
BACE2 cleaves at the beta site and more efficiently at a different site within amyloid-beta precursor protein
-
-
-
additional information
?
-
-
the enzyme is involved in Alzheimer's disease
-
-
-
additional information
?
-
-
the enzyme might be involved in Alzheimer's disease
-
-
-
additional information
?
-
Q9Y5Z0
the enzyme might be involved in Alzheimer's disease
-
-
-
additional information
?
-
-
the enzyme might be involved in early onset of dementia in patients with Down syndrome, and is highly expressed in breast cancers, the enzyme may also be involved in muscle functions
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-6-methoxy-1Hbenzo[d]imidazole
-
inhibitor of BACE1, EC 3.4.23.46. 150fold more effective on BACE1 than BACE2
6-fluoro-2-(3-(7-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo[d]imidazole
-
inhibitor of BACE1, EC 3.4.23.46. 200fold more effective on BACE1 than BACE2
6-fluoro-2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo-[d]imidazole
-
inhibitor of BACE1, EC 3.4.23.46. 100fold more effective on BACE1 than BACE2
Asn-Val-Met-Leu-(S)-CH(OH)CH2-Ala-Ala-Ile-Phe
-
-
brefeldin A
-
strongly inhibits cleavage of amyloid-beta precursor protein
Cu2+
-
70% inhibition at 1 mM
Glu-Glu-Asn-Leu-CH(OH)CH2-Ala-Met-Glu-Phe
-
-
-
Glu-Val-Asn-Leu-(S)-CH(OH)CH2-Ala-Ala-Glu-Phe
-
-
-
Glu-Val-Asn-Leu-CONH-Ala-Ala-Glu-Phe
-
inhibitors based on this structure, molecular size is substantially reduced while maintaining comparable enzyme inhibitory potencies
-
N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methylbenzyl)amino]propyl}dibenzo[b,f]oxepine-10-carboxamide
-
hydroxyethylamine transition-state inhibitor, binding structure at the active site, interaction mode
Zn2+
-
70% inhibition at 1 mM
Lys-Thr-Glu-Glu-Ile-Ser-Glu-Val-Asn-Stat-Val-Ala-Glu-Phe
-
P10-P40 StatVal, beta-secretase inhibitor
additional information
-
M617V mutation in amyloid-beta precursor protein inhibits BACE2 beta-site cleavage
-
additional information
-
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
gamma-secretase cleavage site of notch
-
pH 6.5, 37°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003224
2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-6-methoxy-1Hbenzo[d]imidazole
-
pH 4.5, 25°C
0.003568
6-fluoro-2-(3-(7-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo[d]imidazole
-
pH 4.5, 25°C
0.003081
6-fluoro-2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo-[d]imidazole
-
pH 4.5, 25°C
0.0000016
Glu-Val-Asn-Leu-(S)-CH(OH)CH2-Ala-Ala-Glu-Phe
-
-
-
0.000036
Glu-Val-Asn-Leu-CONH-Ala-Ala-Glu-Phe
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00332
2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-6-methoxy-1Hbenzo[d]imidazole
Homo sapiens
-
pH 4.5, 25°C
0.00367
6-fluoro-2-(3-(7-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo[d]imidazole
Homo sapiens
-
pH 4.5, 25°C
0.00317
6-fluoro-2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo-[d]imidazole
Homo sapiens
-
pH 4.5, 25°C
0.000041
Lys-Thr-Glu-Glu-Ile-Ser-Glu-Val-Asn-Stat-Val-Ala-Glu-Phe
Homo sapiens
-
pH 4.5, 37°C, substrate concentration 0.015 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.015
-
pro-BACE2-T1
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 5.5
-
-
6
-
pro-BACE2-T1 with preproenkephalin fragment 129-138 as substrate
9 - 10
-
pro-BACE2-T2 with gamma-secretase cleavage site of notch as substrate
9.5
-
pro-BACE2-T1 with gamma-secretase cleavage site of notch as substrate
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
low mRNA level in the brain compared with other organs, 10fold lower mRNA level in the brain compared with BACE1
Manually annotated by BRENDA team
-
mid-temporal cortex, low mRNA level compared with BACE1
Manually annotated by BRENDA team
-
postmortem samples of fetal brain at 18-19 weeks of gestational age and of frontal cortex of adult brains
Manually annotated by BRENDA team
-
very low mRNA level
Manually annotated by BRENDA team
-
of muscle cells
Manually annotated by BRENDA team
-
samples from frontal cortex of both Alzheimer's disease-affected individuals and age-matched controls. Samples show substantial total amounts of BACE2 protein and enzymatic activity. BACE2 activity does not change significantly in the brain of patients with Alzheimer's disease, and is not related to amyloid beta-peptide concentration
Manually annotated by BRENDA team
-
BACE2 mRNA is expressed at much lower levels than in pancreas
Manually annotated by BRENDA team
Mus musculus C57/B16
-
-
-
Manually annotated by BRENDA team
low expression; low expression
Manually annotated by BRENDA team
-
neurofibrillary tangle-bearing neurons
Manually annotated by BRENDA team
-
BACE2 is expressed at low levels in neurons of the brain
Manually annotated by BRENDA team
-
transcription control at two sites, tissue-specific expression, overview
Manually annotated by BRENDA team
-
BACE2 mRNA is expressed at much lower levels than in pancreas
Manually annotated by BRENDA team
-
in normal human pancreas, BACE2 expression is restricted to beta-cells. BACE2 colocalizes with clathrin-coated vesicles of the plasma membrane in MIN6 cells. Pharmacological inhibition of BACE2 results in increased BACE2 content in clathrin-coated vesicles, reduced insulin internalization rate, decreased in insulin receptor beta-subunit at the plasma membrane and increase in the Golgi apparatus, and a significant reduction in insulin gene expression. Similar results are obtained after specific BACE2 silencing in MIN6 cells. Data point to a role for BACE2 in the insulin receptor-beta subunit trafficking and insulin signaling
Manually annotated by BRENDA team
-
Bace2 mRNA expression is highest in pancreatic islets
Manually annotated by BRENDA team
-
BACE2 mRNA is expressed at much lower levels than in pancreas
Manually annotated by BRENDA team
low expression; low expression
Manually annotated by BRENDA team
-
at the postsynaptic domain of neuromuscular junctions
Manually annotated by BRENDA team
low expression; low expression
Manually annotated by BRENDA team
low expression; low expression
Manually annotated by BRENDA team
additional information
-
abundant expression
Manually annotated by BRENDA team
additional information
-
tissue-type specific expression
Manually annotated by BRENDA team
additional information
-
tissue-type specific expression, BACE2 expression is high in peripheral tissues and in brain regions including the postcentral gyrus and temporal lobes
Manually annotated by BRENDA team
additional information
-
BACE2 expression is virtually absent from all the other tissues
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
transmembrane enzyme with a large extracellular domain
Manually annotated by BRENDA team
-
transmembrane
Manually annotated by BRENDA team
-
transmembrane protein
Manually annotated by BRENDA team
-
enzyme is poorly reinternalized into membrane
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50000
-
non-glycosylated, SDS-PAGE
638902
55000
non-glycosylated, SDS-PAGE
638903
56000
-
SDS-PAGE
638898
60000
-
glycosylated, SDS-PAGE, present in muscle biopsies, but not in cultured fibers
638902
62000
-
non glycosylated, SDS-PAGE
638895
62000
glycosylated, SDS-PAGE
638903
65000
-
glycosylated, SDS-PAGE
638895
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
73000-75000 Da
?
-
x * 60000, SDS-PAGE, enzyme expressed in HEK 293; x * 73000-75000, SDS-PAGE, brain sample
?
-
x * 73000, SDS-PAGE, brain sample
additional information
-
structural comparison to distinct enzyme memapsin 2
additional information
-
amino acid sequence and domain structure, comparison to BACE1
additional information
modeling the tertiary structure, domain structure, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
N-glycosylation
glycoprotein
N-glycosylation; N-glycosylation
glycoprotein
-
glycoprotein
-
two potential glycosylation sites at Asn 170 at 366
proteolytic modification
-
autoactivation in an acidic solution with cleavage of the own propeptide within the sequence Gly-Leu-Ala-Leu--/-Ala-Leu-Glu-Pro
proteolytic modification
-
autoactivation of the inactive zymogen by cleavage of the propeptide
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified N- and C-terminally truncated BACE2, residues Ala13-Ala398, in complex with hydroxyethylamine transition-state inhibitor, 0.001 ml of 8.8 mg/ml protein in 10 mM Tris-HCl, pH 6.8, 350 mM NaCl, 2 mM inhibitor, and 2% v/v DMSO, 20°C, is mixed with 0.001 ml of reservoir solution containing 16% w/v PEG 8000, 100 mM CaCl2, and 5% v/v glycerol, equilibration against 0.6 ml reservoir solution, six to eight weeks, X-ray diffraction structure determination and analysis at 3.1 A resolution
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 12
-
stable, over 80% enzyme activity between pH 4 and pH 12
638897
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimethyl sulfoxide
-
assay in 3.3% final concentration
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
two variants of the pro-protease domain: pro-BACE2-T1 and pro-BACE2-T2
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
coexpressed with the Swedish mutant of APP in 20E2 cells, expressed as GFP-fusion protein using lentivirus
-
DNA and amino acid sequence analysis, 5'-flanking region analysis, BACE2 mapping to chromosome 21q22.3, expression analysis, sequence comparison to BACE1
-
DNA and amino acid sequence analysis, expression analysis, sequence comparison to BACE1, functional expression in primary rat cortical cell cultures
-
expressed as C-terminal Myc-His fusion protein in HEK 293 cells
-
expressed in HEK 293 cells
-
expressed together with full length IL-IR2 or truncated form DELTA322-IL-1R2 in HEK 293 cells
-
expression of the wild-type and mutated zymogens in Escherichia coli strain BL21(DE3) in inclusion bodies, followed by refolding and autoactivation
-
localization on chromosome 21
-
mouse model overexpresing BACE2
-
the encoding gene is located on chromosome 21 in the Down syndrome critical region
two variants of the pro-protease domain: pro-BACE2-T1 and pro-BACE2-T2
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
BACE2 mRNA levels are downregulated at 6, 12, and 24 h exposure to 0.01 mM AlCl3 and 0.002 mM amyloid beta peptide
neither treatment with 0.002 mM of the Abeta(25-35) fragment nor with 0.01 mM AlCl3 alone influences BACE2 gene mRNA after 24 h
BACE2 mRNA levels are significantly increased after 1 and 3 h exposure to 0.01 mM AlCl3 and 0.002 mM amyloid beta peptide
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R310Lys
-
mutation interferes with the ability of the enzyme to cleave at the beta site of amyloid-beta precursor protein, but not at their respective cleavage sites internal to amyloid-beta protein
additional information
-
construction of an N- and C-terminally truncated BACE2 lacking the transmembrane and the cytoplasmic domains
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
refolding of recombinant zymogen from Escherichia coli strain BL21(DE3) inclusion bodies followed by autoactivation
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
therapeutic interventions that potentiate BACE2 may prevent Alzheimer’s disease
medicine
-
samples from frontal cortex of both Alzheimer's disease-affected individuals and age-matched controls show substantial total amounts of BACE2 protein and enzymatic activity. BACE2 activity does not change significantly in the brain of patients with Alzheimer's disease, and is not related to amyloid beta-peptide concentration
pharmacology
the enzyme is a potential target for development of inhibitors in Alzheimer's disease therapy and treatment of Down syndrome