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Information on EC 3.4.23.45 - memapsin 1
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3.4.23.45 memapsin 1Specify your search results
Word Map
The enzyme appears in viruses and cellular organisms
Reaction Schemes
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
Synonyms
bace2, beta-site app cleaving enzyme, bace-2, memapsin 1, beta-secretase 2, bace 2, beta site app cleaving enzyme, protease asp1, beta-site app-cleaving enzyme 2, aspartic protease bace2, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aspartic protease BACE2
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BACE-2
BACE2
beta-secretase
beta-secretase 2
beta-site Alzheimer's amyloid precurser protein cleaving enzyme 2
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beta-site amyloid precursor protein cleaving enzyme 2
beta-site APP-cleaving enzyme 2
down region aspartic protease
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protease ASP1
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theta-secretase
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preferential cleavage of the amyloid precursor protein downstream of the alpha-site of A-beta
additional information
BACE2
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BACE2
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homologue to BACE1, which cleaves amyloid precursor protein at the beta site but preferably after Phe690 or Phe691
beta-secretase
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beta-secretase 2
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beta-site amyloid precursor protein cleaving enzyme 2
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beta-site APP-cleaving enzyme 2
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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
broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
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broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
active site structure, substrate binding structure, tetrahedral transition state intermediate
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broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
cleavage at the beta-site but more effectively at a different site within A-beta
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broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
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
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broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
preferential cleavage of the amyloid precursor protein between Phe690 and Phe691 or Phe691 and Ala692
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broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-/-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein
preferential cleavage within the A-beta region at Phe19 or Phe20
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cleavage of C-N-linkage
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hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
447457-31-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
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)
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synthetic peptide substrate based on the beta-secretase cleavage site of wild-type APP
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?
amyloid precursor protein + H2O
?
the enzyme cleaves amyloid precursor protein within the Abeta domain, particularly at the zeta-site (Phe20) to produce fragment C80 and prevents Abeta generation
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?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
delta and notch-like epidermal growth factor-related receptor + H2O
?
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?
DELTA322-IL-1R2 + H2O
fragments of DELTA322-IL-1R2
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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
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?
pigment cell-specific melanocyte protein + H2O
?
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BACE2 processes pigment cell-specific melanocyte protein to generate functional amyloids. BACE2 cleaves the integral membrane form of pigment cell-specific melanocyte protein within the juxtamembrane domain, releasing the luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis
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?
Tmem27 + H2O
?
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proliferative plasma membrane protein
BACE2 inactivates Tmem27 by cleavage to release a 25000 Da N-terminal part and a 22000 Da C-terminal fragment
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?
vascular cell adhesion molecule 1 + H2O
?
proinflammatory tumor necrosis factor induces a drastic increase in enzyme-mediated shedding of vascular cell adhesion molecule 1 in cerebrospinal fluid
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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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 Alzheimers disease pathogenesis in Down syndrome patients, able to reduce A-beta formation when expressed in primary neurons expressing the Swedish mutant of APP
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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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
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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cleavage at the beta site of amyloid precursor protein but preferably between Phe690 and Phe691 or Phe691 and Ala692
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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cleavage at the beta-site but more effectively at a different site within A-beta, non-amyloidogenic function suggested
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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cleavage after Phe19
resulting N-terminal sequence is FAEDVGSN
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?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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?
amyloid-beta precursor protein + H2O
?
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?
amyloid-beta precursor protein + H2O
?
results in increase of beta-secretase-derived soluble amyloid precursor protein and the corresponding carboxy-terminal fragment
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?
amyloid-beta precursor protein + H2O
?
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cleaves after the Phe19 and Phe20
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?
amyloid-beta precursor protein + H2O
?
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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
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?
amyloid-beta precursor protein + H2O
?
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results in 40-42 residue amyloid-beta peptide
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?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
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?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
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?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
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cleavage at KLVF-/-FAED and at LVFF-/-AEDV, and with low activity at EVKM-/-DAEF
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?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
cleavage at the beta-site
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?
IL-1R2 + H2O
fragments of IL-1R2
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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
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?
IL-1R2 + H2O
fragments of IL-1R2
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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
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?
additional information
?
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BACE2 cleaves at the beta site and more efficiently at a different site within amyloid-beta precursor protein
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?
additional information
?
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the enzyme is involved in Alzheimer's disease
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?
additional information
?
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the enzyme might be involved in Alzheimer's disease
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-
?
additional information
?
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the enzyme might be involved in Alzheimer's disease
-
-
?
additional information
?
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the enzyme might be involved in Alzheimer's disease
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?
additional information
?
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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
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?
additional information
?
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autoactivation in an acidic solution with cleavage of the own propeptide within the sequence Gly-leu-Ala-Leu--/-Ala-Leu-Glu-Pro
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?
additional information
?
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P-selctin, TNF-alpha and CD14 are not cleaved
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?
additional information
?
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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
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?
additional information
?
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enzyme additionally degrades amyloid beta-protein, with a catalytic efficiency similar to insulin-degrading enzyme IDE, EC 3.4.23.56
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?
additional information
?
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screen for substrate proteins in pancreatic beta cells by proteomic approach reveals non-redundant roles of BACE1 and BACE2 in ectodomain shedding, with BACE1 regulating a broader and BACE2 a more distinct set of beta-cell-enriched substrates including two proteins of the seizure 6 protein family, SEZ6L and SEZ6L2
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
amyloid precursor protein + H2O
?
the enzyme cleaves amyloid precursor protein within the Abeta domain, particularly at the zeta-site (Phe20) to produce fragment C80 and prevents Abeta generation
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
delta and notch-like epidermal growth factor-related receptor + H2O
?
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-
-
?
IL-1R2 + H2O
fragments of IL-1R2
-
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
-
?
pigment cell-specific melanocyte protein + H2O
?
-
BACE2 processes pigment cell-specific melanocyte protein to generate functional amyloids. BACE2 cleaves the integral membrane form of pigment cell-specific melanocyte protein within the juxtamembrane domain, releasing the luminal domain into endosomal precursors for the formation of amyloid fibrils and downstream melanosome morphogenesis
-
?
vascular cell adhesion molecule 1 + H2O
?
proinflammatory tumor necrosis factor induces a drastic increase in enzyme-mediated shedding of vascular cell adhesion molecule 1 in cerebrospinal fluid
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
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-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
-
-
-
?
amyloid precursor protein + H2O
fragments of amyloid precursor protein
-
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 Alzheimers 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
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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
-
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
-
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
-
-
-
-
?
amyloid-beta precursor protein + H2O
?
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-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
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-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
-
-
-
?
beta-amyloid precursor protein APP + H2O
beta-amyloid protein + beta-amyloid precursor protein pre-peptide
-
cleavage at KLVF-/-FAED and at LVFF-/-AEDV, and with low activity at EVKM-/-DAEF
-
-
?
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 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
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-N-(3-(3-amino-1-methyl-9-oxa-4-thia-2-azaspiro[5.5]undec-2-en-1-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
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(R)-N-(3-(3-amino-5-methyl-9,9-dioxido-2,9-dithia-4-azaspiro[5.5]undec-3-en-5-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
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(R)-N-(3-(3-amino-9,9-difluoro-5-methyl-2-thia-4-azaspiro[5.5]undec-3-en-5-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
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(R)-N-(3-(7-amino-2,2-difluoro-9-methyl-6-thia-8-azaspiro[3.5]non-7-en-9-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-fluoropicolinamide
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(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide
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2-(3-(imidazo[1,2-a]pyridin-2-yl)phenyl)-6-methoxy-1Hbenzo[d]imidazole
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inhibitor of BACE1, EC 3.4.23.46. 150fold more effective on BACE1 than BACE2
4-[2-(2,6-diethylpyridin-4-yl)-5-(pyrimidin-5-yl)phenyl]-1-methyl-4,5-dihydro-1H-imidazol-2-amine
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6-fluoro-2-(3-(7-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl)-1H-benzo[d]imidazole
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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
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inhibitor of BACE1, EC 3.4.23.46. 100fold more effective on BACE1 than BACE2
Glu-Val-Asn-Leu-CONH-Ala-Ala-Glu-Phe
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inhibitors based on this structure, molecular size is substantially reduced while maintaining comparable enzyme inhibitory potencies
Lys-Thr-Glu-Glu-Ile-Ser-Glu-Val-Asn-Stat-Val-Ala-Glu-Phe
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P10-P40 StatVal, beta-secretase inhibitor
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-N,5-dimethyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-N-methyl-5-[methyl(methylsulfonyl)amino]-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxohexan-2-yl]amino)-1-phenylbutan-2-yl]-N,5-dimethyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxohexan-2-yl]amino)-1-phenylbutan-2-yl]-N-methyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N'-[(2S,3R)-3-hydroxy-4-[(3-methoxybenzyl)amino]-1-phenylbutan-2-yl]-N,5-dimethyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N-(3-((4R,5R)-2-amino-5-methoxy-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
-
N-(3-((4S,5R)-2-amino-4-methyl-5-(tetrahydro-2H-pyran-4-yl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
-
N-(3-((4S,5R)-2-amino-4-methyl-5-phenyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
-
N-(3-((4S,5S)-2-amino-4-methyl-5-phenyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
-
N-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-5-methyl-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N-[(2S,3R)-3-hydroxy-4-[(3-methoxybenzyl)amino]-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
-
N-[2-[(4aR,6S,8aR)-2-amino-6-methyl-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-1,3-thiazol-4-yl]-5-(difluoromethoxy)pyridine-2-carboxamide
-
N-[3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl]-5-chloropyridine-2-carboxamide
-
N-[3-[(4aS,5S,7aS)-2-amino-5-(trifluoromethyl)-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]-4-fluorophenyl]-5-(1H-1,2,4-triazol-1-yl)pyrazine-2-carboxamide
-
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
N1-((2S,3R)-3-hydroxy-1-phenyl-4-((3-(trifluoromethyl)benzyl)amino)butan-2-yl)-N3,5-dimethyl-N3-((R)-1-phenylethyl)isophthalamide
-
N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)pentyl]amino]propyl]-N1-methyl-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide
-
N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)propyl]amino]propyl]-5-[methyl(methylsulfonyl)amino]-N1-[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide
-
[(1S,5S,6S)-3-amino-5-(2-fluoro-5-[(Z)-2-fluoro-2-[5-(prop-2-yn-1-yloxy)pyrazin-2-yl]ethenyl]phenyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-1-yl][(3R)-3-methylmorpholin-4-yl]methanone
-
additional information
-
M617V mutation in amyloid-beta precursor protein inhibits BACE2 beta-site cleavage
-
additional information
the juxtamembrane helix of amyloid precursor protein is crucial to inhibit the beta-secretase activity of the enzyme
-
additional information
-
the juxtamembrane helix of amyloid precursor protein is crucial to inhibit the beta-secretase activity of the enzyme
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Alzheimer Disease
1,3-Oxazines as BACE1 and/or BACE2 inhibitors: a patent evaluation (WO2012156284).
Alzheimer Disease
A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase.
Alzheimer Disease
Altered beta-secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimer's disease brain.
Alzheimer Disease
BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.
Alzheimer Disease
BACE2 degradation is mediated by both the proteasome and lysosome pathways.
Alzheimer Disease
BACE2 distribution in major brain cell types and identification of novel substrates.
Alzheimer Disease
BACE2 is stored in secretory granules of mouse and rat pancreatic beta cells.
Alzheimer Disease
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.
Alzheimer Disease
BACE2, a conditional ?-secretase, contributes to Alzheimer's disease pathogenesis.
Alzheimer Disease
BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome.
Alzheimer Disease
Cellular prion protein regulates beta-secretase cleavage of the Alzheimer's amyloid precursor protein.
Alzheimer Disease
Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2.
Alzheimer Disease
Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: a two-stage study.
Alzheimer Disease
Common BACE2 Polymorphisms are Associated with Altered Risk for Alzheimer's Disease and CSF Amyloid Biomarkers in APOE ?4 Non-Carriers.
Alzheimer Disease
Coordinated expression of beta-amyloid precursor protein and the putative beta-secretase BACE and alpha-secretase ADAM10 in mouse and human brain.
Alzheimer Disease
Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor.
Alzheimer Disease
Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, ?-site amyloid precursor protein cleaving enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation.
Alzheimer Disease
Glycosaminoglycan-induced activation of the beta-secretase (BACE1) of Alzheimer's disease.
Alzheimer Disease
Inhibition of BACE2 counteracts hIAPP-induced insulin secretory defects in pancreatic ?-cells.
Alzheimer Disease
Lack of association between the polymorphisms of beta-site APP-cleaving enzyme 2 (BACE2) 5'-flanking region and sporadic Alzheimer's disease.
Alzheimer Disease
Large scale refolding and purification of the catalytic domain of human BACE-2 produced in E. coli.
Alzheimer Disease
Mapping the conformational space accessible to BACE2 using surface mutants and cocrystals with Fab fragments, Fynomers and Xaperones.
Alzheimer Disease
Mutations in the open reading frame of the beta-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease.
Alzheimer Disease
Reversible and Species-Specific Depigmentation Effects of AZD3293, a BACE Inhibitor for the Treatment of Alzheimer's Disease, Are Related to BACE2 Inhibition and Confined to Epidermis and Hair.
Alzheimer Disease
Salidroside attenuates hypoxia-induced abnormal processing of amyloid precursor protein by decreasing BACE1 expression in SH-SY5Y cells.
Alzheimer Disease
Specific BACE1 genotypes provide additional risk for late-onset Alzheimer disease in APOE epsilon 4 carriers.
Alzheimer Disease
Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity.
Alzheimer Disease
The association of beta-site APP cleaving enzyme (BACE) C786G polymorphism with Alzheimer's disease.
Alzheimer Disease
The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimer's disease brain.
Asthma
Genes Involved in Interleukin-1 Receptor Type II Activities Are Associated With Asthmatic Phenotypes.
Carcinogenesis
Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.
Carcinogenesis
m6A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.
Carcinogenesis
TGF?1-induced beta-site APP-cleaving enzyme 2 upregulation promotes tumorigenesis through the NF-?B signalling pathway in human gliomas.
Dementia
Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor.
Dementia
Erratum to "Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome" [Neurobiol. Aging 35 (2014) 1513.e1-1513.e5].
Dementia
Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.
Dementia
Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome.
Diabetes Mellitus, Type 2
Automated assessment of ?-cell area and density per islet and patient using TMEM27 and BACE2 immunofluorescence staining in human pancreatic ?-cells.
Diabetes Mellitus, Type 2
BACE2 plays a role in the insulin receptor trafficking in pancreatic beta-cells.
Diabetes Mellitus, Type 2
BACE2 suppression promotes ?-cell survival and function in a model of type 2 diabetes induced by human islet amyloid polypeptide overexpression.
Diabetes Mellitus, Type 2
Design of Potent and Highly Selective Inhibitors for Human ?-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes.
Diabetes, Gestational
Replication of previous genome-wide association studies of HKDC1, BACE2, SLC16A11 and TMEM163 SNPs in a gestational diabetes mellitus case-control sample from Han Chinese population.
Down Syndrome
A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase.
Down Syndrome
BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome.
Down Syndrome
Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2.
Down Syndrome
Correction: Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.
Down Syndrome
Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor.
Down Syndrome
Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome.
Down Syndrome
In vivo effects of APP are not exacerbated by BACE2 co-overexpression: behavioural characterization of a double transgenic mouse model.
Down Syndrome
Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.
Down Syndrome
Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome.
Glioblastoma
TGF?1-induced beta-site APP-cleaving enzyme 2 upregulation promotes tumorigenesis through the NF-?B signalling pathway in human gliomas.
Glioma
Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.
Glioma
TGF?1-induced beta-site APP-cleaving enzyme 2 upregulation promotes tumorigenesis through the NF-?B signalling pathway in human gliomas.
Hirschsprung Disease
Association Analysis of Variants of DSCAM and BACE2 With Hirschsprung Disease Susceptibility in Han Chinese and Functional Evaluation in Zebrafish.
Hirschsprung Disease
Identification of Genes Associated with Hirschsprung Disease, Based on Whole-genome Sequence Analysis, and Potential Effects on Enteric Nervous System Development.
Hyperinsulinism
BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet.
Hypopigmentation
Reversible and Species-Specific Depigmentation Effects of AZD3293, a BACE Inhibitor for the Treatment of Alzheimer's Disease, Are Related to BACE2 Inhibition and Confined to Epidermis and Hair.
Insulin Resistance
BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet.
Lymphoma, B-Cell
Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway.
Melanoma
m6A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.
memapsin 1 deficiency
BACE2 suppression promotes ?-cell survival and function in a model of type 2 diabetes induced by human islet amyloid polypeptide overexpression.
Muscular Diseases
BACE2 is stored in secretory granules of mouse and rat pancreatic beta cells.
Myositis
Presence of BACE1 and BACE2 in muscle fibres of patients with sporadic inclusion-body myositis.
Neoplasms
Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile.
Neoplasms
Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor.
Neoplasms
m6A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.
Neoplasms
TGF?1-induced beta-site APP-cleaving enzyme 2 upregulation promotes tumorigenesis through the NF-?B signalling pathway in human gliomas.
Neuroblastoma
Morphine via nitric oxide modulates beta-amyloid metabolism: a novel protective mechanism for Alzheimer's disease.
Neuroinflammatory Diseases
The modulatory role of prime identified compounds in Geophila repens in mitigating scopolamine-induced neurotoxicity in experimental rats of Alzheimer's disease via attenuation of cholinesterase, ?-secretase, MAPt levels and inhibition of oxidative stress imparts inflammation.
Obesity
BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet.
Osteosarcoma
Prognostic scoring system for osteosarcoma using network-regularized high-dimensional Cox-regression analysis and potential therapeutic targets.
Pancreatitis
Loss of Bace1 in mice does not alter the severity of caerulein induced pancreatitis.
Parkinson Disease
Cerebrospinal fluid A?42 levels and APP processing pathway genes in Parkinson's disease.
Pre-Eclampsia
Protein misfolding, congophilia, oligomerization, and defective amyloid processing in preeclampsia.
Prostatic Neoplasms
[Effects of long non-coding RNA RP1-90L14.1 on the biological behaviors of cancer prostate LNCaP cells and its regulating mechanisms].
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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
0.000001
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-N,5-dimethyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.0000805
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-N-methyl-5-[methyl(methylsulfonyl)amino]-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.000038
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxohexan-2-yl]amino)-1-phenylbutan-2-yl]-N,5-dimethyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.000031
N'-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxohexan-2-yl]amino)-1-phenylbutan-2-yl]-N-methyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.00001402
N'-[(2S,3R)-3-hydroxy-4-[(3-methoxybenzyl)amino]-1-phenylbutan-2-yl]-N,5-dimethyl-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.0001828
N-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-5-methyl-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.0000146
N-[(2S,3R)-3-hydroxy-4-([(2S,3S)-3-hydroxy-1-[(2-methylpropyl)amino]-1-oxobutan-2-yl]amino)-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
0.000137
N-[(2S,3R)-3-hydroxy-4-[(3-methoxybenzyl)amino]-1-phenylbutan-2-yl]-5-[methyl(methylsulfonyl)amino]-N'-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide
pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000631
(R)-N-(3-(3-amino-1-methyl-9-oxa-4-thia-2-azaspiro[5.5]undec-2-en-1-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00209
(R)-N-(3-(3-amino-5-methyl-9,9-dioxido-2,9-dithia-4-azaspiro[5.5]undec-3-en-5-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.00166
(R)-N-(3-(3-amino-9,9-difluoro-5-methyl-2-thia-4-azaspiro[5.5]undec-3-en-5-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000129
(R)-N-(3-(7-amino-2,2-difluoro-9-methyl-6-thia-8-azaspiro[3.5]non-7-en-9-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000316
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(2,2,2-trifluoroethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000102
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(difluoromethyl)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000078
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.0000087
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-chloropicolinamide
Homo sapiens
pH and temperature not specified in the publication
0.000021
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide
Homo sapiens
pH and temperature not specified in the publication
0.000014
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-fluoropicolinamide
Homo sapiens
pH and temperature not specified in the publication
0.000085
(S)-N-(3-(2-amino-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
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
0.000251
N-(3-((4R,5R)-2-amino-5-methoxy-4-methyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000074
N-(3-((4S,5R)-2-amino-4-methyl-5-(tetrahydro-2H-pyran-4-yl)-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.000028
N-(3-((4S,5R)-2-amino-4-methyl-5-phenyl-5,6-dihydro-4H-1,3-thiazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide
Homo sapiens
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
patients with Alzheimers disease, BACE1 and BACE2 levels are found to be decreased in Alzheimers disease patients
-
-
brenda
patients with Down syndrome and control individuals, protein levels between the groups do not differ significantly
-
-
brenda
patients with Down syndrome, slightly increased mRNA levels but protein level is identical to normal individuals
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
transcription control at two sites, tissue-specific expression, overview
brenda
-
BACE2 mRNA is expressed at much lower levels than in pancreas
brenda
additional information
-
low mRNA level in the brain compared with other organs, 10fold lower mRNA level in the brain compared with BACE1
brenda
-
postmortem samples of fetal brain at 18-19 weeks of gestational age and of frontal cortex of adult brains
brenda
-
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
brenda
-
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
brenda
additional information
-
tissue-type specific expression, BACE2 expression is high in peripheral tissues and in brain regions including the postcentral gyrus and temporal lobes
brenda
additional information
-
BACE2 expression is virtually absent from all the other tissues
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
transmembrane enzyme with a large extracellular domain
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
metabolism
the key step in the generation of Abeta is cleavage of APP by beta-secretase
metabolism
enzyme-mediated beta-cleavage of amyloid precursor protein is a mechanism underlying Alzheimer's disease pathogenesis
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
-
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
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
BACE2 is highly expressed in pigment cells and homozygous Bace2 mutant mice display coat color defects, implying a specific role for BACE2 during melanogenesis
physiological function
mutations in Bace2 reveal a distinct melanocyte migration phenotype, which is not observed in homozygous Bace1 mutants. 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
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). BACE2_HUMAN
518
1
56180
Swiss-Prot
Secretory Pathway (Reliability: 1)
BACE2_MOUSE
514
2
55800
Swiss-Prot
Secretory Pathway (Reliability: 1)
BACE2_RAT
514
1
55858
Swiss-Prot
Secretory Pathway (Reliability: 1)
Q6PB20_XENLA
499
1
54804
TrEMBL
Secretory Pathway (Reliability: 1)
A0A061IC94_CRIGR
387
1
43079
TrEMBL
other Location (Reliability: 2)
A0A061I5J9_CRIGR
430
1
47351
TrEMBL
other Location (Reliability: 2)
A0A2P6PAH5_ROSCH
89
0
9755
TrEMBL
other Location (Reliability: 3)
B7PWI2_IXOSC
280
0
30926
TrEMBL
other Location (Reliability: 4)
B3KNE8_HUMAN
355
1
39152
TrEMBL
other Location (Reliability: 5)
Q7T0Y2_XENLA
500
1
54723
TrEMBL
Secretory Pathway (Reliability: 1)
B4F734_XENTR
499
2
54547
TrEMBL
Secretory Pathway (Reliability: 1)
Q5XJ89_DANRE
372
0
40577
TrEMBL
Secretory Pathway (Reliability: 2)
X4Z0F5_DANRE
462
0
50041
TrEMBL
other Location (Reliability: 2)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60000
62000
60000
-
glycosylated, SDS-PAGE, present in muscle biopsies, but not in cultured fibers
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
amino acid sequence and domain structure, comparison to BACE1
additional information
modeling the tertiary structure, domain structure, overview
additional information
-
modeling the tertiary structure, domain structure, overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
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
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
evolutionary trace analysis identifies group-specific residues in the ligand binding sites of BACE1, EC 3.4.23.46, and BACE2.The residues are Pro70, Ile110, Ile126, andAsn233 of BACE1 substituting Lys86, Leu126, Leu142, and Leu246 of BACE2, respectively.These group-specific residues would be the reason for cleavage site selectivity in BACE1 and BACE2 biological function
in complex with inhibitor N3-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(1S,2S)-2-hydroxy-1-(isobutylcarbamoyl)propyl]amino]propyl]-5-[methyl(methylsulfonyl)amino]-N1 -[(1R)-1-phenylpropyl]benzene-1,3-dicarboxamide
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
-
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PROTEIN VARIANTS
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
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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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 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
-
the encoding gene is located on chromosome 21 in the Down syndrome critical region
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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
BACE2 mRNA levels are significantly increased after 1 and 3 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
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RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding of recombinant zymogen from Escherichia coli strain BL21(DE3) inclusion bodies followed by autoactivation
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
therapeutic interventions that potentiate BACE2 may prevent Alzheimers disease
medicine
pharmacology
the enzyme is a potential target for development of inhibitors in Alzheimer's disease therapy and treatment of Down syndrome
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
medicine
in patients with preclinical to late-stage Alzheimer's disease, including amnestic mild cognitive impairment, and age-matched controls, cases of frontotemporal dementia, and Down's syndrome, BACE2 protein and enzymatic activity increase as early as preclinical Alzheimer's disease and are found in neurons and astrocytes. Although the levels of total BACE2 mRNA are unchanged, the mRNA for BACE2 splice form C (missing exon 7) increases in parallel with BACE2 protein and activity. BACE1 and BACE2 are strongly correlated with each other at all levels. BACE2 is also elevated in frontotemporal dementia but not in Down's syndrome, even in patients with substantial amyloid beta deposition
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Farzan, M.; Schnitzler, C.E.; Vasilieva, N.; Leung, D.; Choe, H.
BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein
Proc. Natl. Acad. Sci. USA
97
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2000
Homo sapiens
brenda
Fluhrer, R.; Capell, A.; Westmeyer, G.; Willem, M.; Hartung, B.; Condron, M.M.; Teplow, D.B.; Haass, C.; Walter, J.
A non-amyloidogenic function of BACE-2 in the secretory pathway
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Homo sapiens
brenda
Ghosh, A.K.; Bilcer, G.; Harwood, C.; Kawahama, R.; Shin, D.; Hussain, K.A.; Hong, L.; Loy, J.A.; Nguyen, C.; Koelsch, G.; Ermolieff, J.; Tang, J.
Structure-based design: potent inhibitors of human brain memapsin 2 (beta-secretase)
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44
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2001
Homo sapiens
brenda
Kim, Y.T.; Downs, D.; Wu, S.; Dashti, A.; Pan, Y.; Zhai, P.; Wang, X.; Zhang, X.C.; Lin, X.
Enzymic properties of recombinant BACE2
Eur. J. Biochem.
269
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2002
Homo sapiens
brenda
Li, G.; Percontino, L.; Sun, Q.; Qazi, A.S.; Frederikse, P.H.
beta-Amyloid secretases and beta-amyloid degrading enzyme expression in lens
Mol. Vis.
9
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2003
Mus musculus, Rattus norvegicus, Mus musculus C57B16/J
brenda
Motonaga, K.; Itoh, M.; Becker, L.E.; Goto, Y.I.; Takashima, S.
Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome
Neurosci. Lett.
326
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2002
Homo sapiens
brenda
Solans, A.; Estivill, X.; de La Luna, S.
A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase
Cytogenet. Cell Genet.
89
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Homo sapiens, Homo sapiens (Q9Y5Z0)
brenda
Turner, R.T.3rd.; Loy, J.A.; Nguyen, C.; Devasamudram, T.; Ghosh, A.K.; Koelsch, G.; Tang, J.
Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity
Biochemistry
41
8742-8746
2002
Homo sapiens
brenda
Vattemi, G.; Engel, W.K.; McFerrin, J.; Pastorino, L.; Buxbaum, J.D.; Askanas, V.
BACE1 and BACE2 in pathologic and normal human muscle
Exp. Neurol.
179
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2003
Homo sapiens
brenda
Hussain, I.; Powell, D.J.; Howlett, D.R.; Chapman, G.A.; Gilmour, L.; Murdock, P.R.; Tew, D.G.; Meek, T.D.; Chapman, C.; Schneider, K.; Ratcliffe, S.J.; Tattersall, D.; Testa, T.T.; Southan, C.; Ryan, D.M.; Simmons, D.L.; Walsh, F.S.; Dingwall, C.; Christie, G.
ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site
Mol. Cell. Neurosci.
16
609-619
2000
Homo sapiens (Q9Y5Z0)
brenda
Tang, J.; Koelsch, G.
Memapsin 1
Handbook of Proteolytic Enzymes (Barrett, J. ; Rawlings, N. D. ; Woessner, J. F. , eds. )
1
64-66
2004
Homo sapiens
-
brenda
Ostermann, N.; Eder, J.; Eidhoff, U.; Zink, F.; Hassiepen, U.; Worpenberg, S.; Maibaum, J.; Simic, O.; Hommel, U.; Gerhartz, B.
Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor
J. Mol. Biol.
355
249-261
2006
Homo sapiens
brenda
Lahiri, D.K.; Maloney, B.; Ge, Y.W.
Functional domains of the BACE1 and BACE2 promoters and mechanisms of transcriptional suppression of the BACE2 promoter in normal neuronal cells
J. Mol. Neurosci.
29
65-80
2006
Homo sapiens
brenda
Maloney, B.; Ge, Y.W.; Greig, N.H.; Lahiri, D.K.
Characterization of the human beta-secretase 2 (BACE2) 5-flanking region: identification of a 268-bp region as the basal BACE2 promoter
J. Mol. Neurosci.
29
81-99
2006
Homo sapiens
brenda
Chou, K.C.
Insights from modeling the tertiary structure of human BACE2
J. Proteome Res.
3
1069-1072
2004
Homo sapiens (Q9Y5Z0), Homo sapiens
brenda
Stockley, J.H.; O'Neill, C.
The proteins BACE1 and BACE2 and beta-secretase activity in normal and Alzheimers disease brain
Biochem. Soc. Trans.
35
574-576
2007
Homo sapiens
brenda
Stockley, J.H.; Ravid, R.; ONeill, C.
Altered beta-secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimers disease brain
FEBS Lett.
580
6550-6560
2006
Homo sapiens, Rattus norvegicus
brenda
Cheon, M.S.; Dierssen, M.; Kim, S.H.; Lubec, G.
Protein expression of BACE1, BACE2 and APP in Down syndrome brains
Amino Acids
35
339-343
2007
Homo sapiens
brenda
Sun, X.; He, G.; Song, W.
BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimers disease in Down syndrome
FASEB J.
20
1369-1376
2006
Homo sapiens
brenda
Kuhn, P.H.; Marjaux, E.; Imhof, A.; De Strooper, B.; Haass, C.; Lichtenthaler, S.F.
Regulated intramembrane proteolysis of the interleukin-1 receptor II by alpha-, beta-, and gamma-secretase
J. Biol. Chem.
282
11982-11995
2007
Homo sapiens
brenda
Venugopal, C.; Demos, C.M.; Rao, K.S.; Pappolla, M.A.; Sambamurti, K.
beta-Secretase: structure, function, and evolution
CNS Neurol. Disord. Drug Targets
7
278-294
2008
Homo sapiens
brenda
Castorina, A.; Tiralongo, A.; Giunta, S.; Carnazza, M.L.; Scapagnini, G.; DAgata, V.
Early effects of aluminum chloride on beta-secretase mRNA expression in a neuronal model of ss-amyloid toxicity
Cell Biol. Toxicol.
26
367-377
2010
Homo sapiens (Q9Y5Z0)
brenda
Ahmed, R.R.; Holler, C.J.; Webb, R.L.; Li, F.; Beckett, T.L.; Murphy, M.P.
BACE1 and BACE2 enzymatic activities in Alzheimers disease
J. Neurochem.
112
1045-1053
2010
Homo sapiens
brenda
Vassar, R.; Kovacs, D.M.; Yan, R.; Wong, P.C.
The beta-secretase enzyme BACE in health and Alzheimers disease: regulation, cell biology, function, and therapeutic potential
J. Neurosci.
29
12787-12794
2009
Homo sapiens
brenda
Casas, S.; Casini, P.; Piquer, S.; Altirriba, J.; Soty, M.; Cadavez, L.; Gomis, R.; Novials, A.
BACE2 plays a role in the insulin receptor trafficking in pancreatic beta-cells
Am. J. Physiol. Endocrinol. Metab.
299
E1087-E1095
2010
Homo sapiens
brenda
Esterhazy, D.; Stuetzer, I.; Wang, H.; Rechsteiner, M.P.; Beauchamp, J.; Doebeli, H.; Hilpert, H.; Matile, H.; Prummer, M.; Schmidt, A.; Lieske, N.; Boehm, B.; Marselli, L.; Bosco, D.; Kerr-Conte, J.; Aebersold, R.; Spinas, G.A.; Moch, H.; Migliorini, C.; Stoffel, M.
Bace2 is a beta cell-enriched protease that regulates pancreatic beta cell function and mass
Cell Metab.
14
365-377
2011
Mus musculus
brenda
Azkona, G.; Amador-Arjona, A.; Obradors-Tarrago, C.; Varea, E.; Arque, G.; Pinacho, R.; Fillat, C.; De La Luna, S.; Estivill, X.; Dierssen, M.
Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2
Genes Brain Behav.
9
160-172
2010
Homo sapiens
brenda
Al-Tel, T.; Semreen, M.; Al-Qawasmeh, R.; Schmidt, M.; El-Awadi, R.; Ardah, M.; Zaarour, R.; Rao, S.; El-Agnaf, O.
Design, synthesis, and qualitative structure-activity evaluations of novel beta-secretase inhibitors as potential Alzheimers drug leads
J. Med. Chem.
54
8373-8385
2011
Homo sapiens
brenda
Holler, C.; Webb, R.; Laux, A.; Beckett, T.; Niedowicz, D.; Ahmed, R.; Liu, Y.; Simmons, C.; Dowling, A.; Spinelli, A.; Khurgel, M.; Estus, S.; Head, E.; Hersh, L.; Murphy, M.
BACE2 expression increases in human neurodegenerative disease
Am. J. Pathol.
180
337-350
2012
Homo sapiens (Q9Y5Z0), Homo sapiens
brenda
Stuetzer, I.; Selevsek, N.; Esterhazy, D.; Schmidt, A.; Aebersold, R.; Stoffel, M.
Systematic proteomic analysis identifies beta-site amyloid precursor protein cleaving enzyme 2 and 1 (BACE2 and BACE1) substrates in pancreatic beta-cells
J. Biol. Chem.
288
10536-10547
2013
Mus musculus (Q9JL18)
brenda
van Bebber, F.; Hruscha, A.; Willem, M.; Schmid, B.; Haass, C.
Loss of Bace2 in zebrafish affects melanocyte migration and is distinct from Bace1 knock out phenotypes
J. Neurochem.
127
471-481
2013
Danio rerio (X4Z0F5), Danio rerio
brenda
Abdul-Hay, S.O.; Sahara, T.; McBride, M.; Kang, D.; Leissring, M.A.
Identification of BACE2 as an avid beta-amyloid-degrading protease
Mol. Neurodegener.
7
46
2012
Homo sapiens (Q9Y5Z0)
brenda
Rochin, L.; Hurbain, I.; Serneels, L.; Fort, C.; Watt, B.; Leblanc, P.; Marks, M.S.; De Strooper, B.; Raposo, G.; van Niel, G.
BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells
Proc. Natl. Acad. Sci. USA
110
10658-10663
2013
Mus musculus (Q9JL18)
brenda
Mirsafian, H.; Mat Ripen, A.; Merican, A.F.; Bin Mohamad, S.
Amino acid sequence and structural comparison of BACE1 and BACE2 using evolutionary trace method
ScientificWorldJournal
2014
482463
2014
Homo sapiens (Q9Y5Z0)
brenda
Ghosh, A.K.; Reddy, B.S.; Yen, Y.C.; Cardenas, E.; Rao, K.V.; Downs, D.; Huang, X.; Tang, J.; Mesecar, A.D.
Design of potent and highly selective inhibitors for human beta-secretase 2 (memapsin 1), a target for type 2 diabetes
Chem. Sci.
7
3117-3122
2016
Homo sapiens (Q9Y5Z0), Homo sapiens
brenda
Ghosh, A.K.; Brindisi, M.; Yen, Y.C.; Lendy, E.K.; Kovela, S.; Cardenas, E.L.; Reddy, B.S.; Rao, K.V.; Downs, D.; Huang, X.; Tang, J.; Mesecar, A.D.
Highly selective and potent human beta-secretase 2 (BACE2) inhibitors against type 2 diabetes design, synthesis, X-ray structure and structure-activity relationship studies
ChemMedChem
14
545-560
2019
Homo sapiens (Q9Y5Z0), Homo sapiens
brenda
Fujimoto, K.; Matsuoka, E.; Asada, N.; Tadano, G.; Yamamoto, T.; Nakahara, K.; Fuchino, K.; Ito, H.; Kanegawa, N.; Moechars, D.; Gijsen, H.J.M.; Kusakabe, K.I.
Structure-based design of selective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors targeting the flap to gain selectivity over BACE2
J. Med. Chem.
62
5080-5095
2019
Homo sapiens (Q9Y5Z0)
brenda
Kumalo, H.M.; Soliman, M.E.
A comparative molecular dynamics study on BACE1 and BACE2 flap flexibility
J. Recept. Signal Transduct. Res.
36
505-514
2016
Homo sapiens (Q9Y5Z0)
brenda
Wang, Z.; Xu, Q.; Cai, F.; Liu, X.; Wu, Y.; Song, W.
BACE2, a conditional beta-secretase, contributes to Alzheimer's disease pathogenesis
JCI Insight
4
e123431
2019
Mus musculus (Q9JL18), Mus musculus
brenda
Voytyuk, I.; Mueller, S.A.; Herber, J.; Snellinx, A.; Moechars, D.; van Loo, G.; Lichtenthaler, S.F.; De Strooper, B.
BACE2 distribution in major brain cell types and identification of novel substrates
Life Sci. Alliance
1
e201800026
2018
Mus musculus (Q9JL18), Mus musculus
brenda
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EXTERNAL LINKS (specific for EC-Number 3.4.23.45)
Transporter Classification Database (TCDB): 8.A.32.1.2, 8.A.32.1.3
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