ETDEESEEPGRRGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHIPNIFSLQLCGAGFPLNQTEALASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVEDVATSQDDCYKFAVSQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTAAVEGPFVTADMEDCGYNIPQTDESTLMTIAYVMAAICALFMLPLCLMVCQWRCLRCLRHQHDDFADDISLLK
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sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is
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Protein Length
Full Length of Mature Protein
Tag Info
N-terminal 10xHis-tagged
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Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves CHL1.
Gene References into Functions
network analysis supports an intimate connection between immune response via NF-kappaB and BACE1 signaling through the NRG1/Akt1 pathway.PMID:28004339
BACE1 regulates the expression of insulin receptor in the liverPMID:29610518
Beta-site APP cleaving enzyme 1 knockout (Bace1-/-) mice and rats differed in body weight, spontaneous locomotor activity, and prepulse inhibition of startle.PMID:28281673
These results provide evidence for an emerging role of BAG-1M in the regulation of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-kappaB complex may provide a mechanism for inhibiting Abeta production and plaque formation.PMID:28502705
we have demonstrated that raised hypothalamic Abeta1-42, in conjunction with HFD, is sufficient to induce leptin resistance in the absence of increased inflammation, ER stress, SOCS3 and PTP1B. Thus, counteracting raised Bace1 activity associated with chronic HFD will play a critical protective role against metabolic diseasePMID:29311632
BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone.PMID:28669600
We aimed to explore the potential therapeutic effect of PGC-1alpha by generating a lentiviral vector to express human PGC-1alpha and target it by stereotaxic delivery to hippocampus and cortex of APP23 transgenic mice . Four months after hPGC-1alpha injection, mice showed improved spatial and recognition memory concomitant with a significant reduction in Abeta deposition, associated with a decrease in BACE1 expressionPMID:27791018
that BACE1 deficiency enhances proliferation of Schwann cell due to the elevated Jag1/Delta1-Notch signalingPMID:28191691
the synaptic localization of APP, ADAM10, and BACE1 in the mouse cerebral cortex, was examined.PMID:26497029
Chronic variable stress led to increased Bace1 expression in the hippocampus of young adult mice and the hippocampus, prefrontal cortex and amygdala of aged mice. The increased expression of Bace1 was associated with decreased methylation of several CpGs in the Bace1 promoter region.PMID:27404286
Results indicate that SNX4-mediated regulation of the steady-state levels and trafficking of BACE1, as well as the subsequent increase in BACE1-mediated cleavage, may be relevant to Alzheimer's disease progression.PMID:28109317
In conclusion, glucocorticoid couples mGR with Galphas and triggers cAMP-PKA-CREB axis dependent on the lipid raft to stimulate BACE1 upregulation and Abeta generation.SIGNIFICANCE STATEMENT Patients with Alzheimer's disease (AD) have been growing sharply and stress is considered as the major environment factor of AD.PMID:28855330
study supports the hypothesis that Abeta induces microtubule disruption in presynaptic dystrophic neurites that surround plaques, thus impairing axonal transport and leading to accumulation of BACE1 and exacerbation of amyloid pathology in Alzheimer's diseasePMID:26993139
Here, we demonstrate that Snapin-mediated retrograde transport plays a critical role in removing BACE1 from presynaptic terminals toward the soma, thus reducing synaptic Abeta production. Adeno-associated virus-mediated Snapin overexpression in the hippocampus of mutant hAPP mice significantly decreases synaptic Abeta levels, attenuates synapse loss, and thus rescues cognitive deficits. Our study uncovers a new pathway...PMID:28159908
beta-site APP cleaving enzyme 1 (BACE1) is essential for amyloid beta protein production. We discovered that A673V mutation shifted the BACE1 cleavage site from the Glu(11) to the Asp(1) site, resulting in much higher C99 level and C99/C89 ratio.PMID:28626014
the depletion of BIN1 increases cellular BACE1 levels through impaired endosomal trafficking and reduces BACE1 lysosomal degradation, resulting in increased Ab production. Our findings provide a mechanistic role of BIN1 in the pathogenesis of Alzheimer disease (AD), as a novel genetic regulator of BACE1 levels and Ab productionPMID:27179792
In an Alzheimer's disease mouse model we show that BACE-1 is upregulated at the blood-brain barrier compared to healthy controls.PMID:26661166
study provides new insights into autophagy-mediated regulation of BACE1 turnover and APP processing, thus building a foundation for future development of potential Alzheimer's disease therapeutic strategies.PMID:28028177
analysis suggests that some familial Alzheimer's disease mutations in APP are amyloidogenic and/or amyloidolytic via selection of alternative BACE1 cleavage sitesPMID:27687728
data indicate that Egr-1 promotes Abeta synthesis via transcriptional activation of BACE-1 and suggest that Egr-1 plays role in activation of BACE-1 and acceleration of Abeta synthesis in AD brain.PMID:27576688
PD98059 had no influence on the expression of BACE1 and PS1.PMID:27372924
Three- and six-month-old female APP/PS1 double transgenic mice were used to study abnormal accumulation of BACE-1 protein in brains. We found a high immunoreactive density of BACE-1 protein on the outer layer of brain blood vessels, implicating BACE-1 protein as a central player in the pathogenesis of Alzheimer's disease.PMID:27294139
Partial BACE1 reduction in a Down syndrome mouse model blocks Alzheimer-related endosomal anomalies and cholinergic neurodegeneration.PMID:26923405
Review discussing the major discoveries of the past 3 years concerning BACE1 biology and to what extent these could limit the use of BACE1 inhibitors in the clinicPMID:26833257
The electrophysiological effects of BACE1 on KCNQ1 reported here were independent of its enzymatic activity.PMID:26454161
Results suggest that ubiquilin-1 may mechanistically participate in Alzheimer's disease molecular pathogenesis by affecting BACE1 and thereby APP processing and Abeta accumulationPMID:26563932
Results indicate that DISC1 attenuates Abeta generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1PMID:26062786
A single bout of exercise reduced BACE1 cortical content and activity in obese mice.PMID:26404616
reduction in miR-186 levels during aging may lead to the up-regulation of BACE1 in the brain, thereby increasing a risk for Alzheimer's diseasePMID:26710318
reveal Dicer1-miR-328-Bace1 signalling as a determinant of brown adipose tissue functionPMID:26900752
The present findings are consistent with our previous behavioral data showing that BACE1 haploinsufficiency rescues memory deficits in 5XFAD mice irrespective of sex but only in the younger age group.PMID:26314636
p38alpha MAPK plays a critical role in the regulation of BACE1 degradation and Abeta generation in Alzheimer Disease pathogenesisPMID:26663083
Swedish mutant APP-based BACE1 binding site peptide reduces APP beta-cleavage and cerebral Abeta levels in Alzheimer's mice.PMID:26091071
evidence that HFD, by regulation of subcellular trafficking of BACE1, promotes APP cleavage.PMID:26414661
Traumatic brain injury-induced BACE1 up-regulation is significantly suppressed in brain with deficient N-acetylyglucosaminyltransferase-III.PMID:26467158
results indicate that NFAT is a BACE1 transcription factor. Our study suggests that inhibition of NFAT-mediated BACE1 expression may be a valuable drug target for AD therapyPMID:25663301
The results of this study concluded that stimulus-dependent neuronal activity can control the expression of the RA catabolic enzyme Cyp26B1 and downstream genes such as BACE1.PMID:24797530
MicroRNA-29c targets BACE1 and has a neuroprotective role in vitro and in vivo.PMID:25955795
BACE1 and ADAM10 are in close proximity in hippocampal neuron synaptic vesicles.PMID:26296617
loss of Bace1 in mice leads to no alterations in the course of acute experimental caerulein-pancreatitis.PMID:25961820
Amyloid beta (Abeta)-degrading effects of overexpressed neprilysin can block deleterious BACE1-elevating mechanisms that accelerate Abeta production.PMID:25884928
The finding of this study indicated important functions to BACE1 in structural and functional synaptic plasticity in the mature brain, with implications for cognition.PMID:25599931
findings indicate that atRA represses BACE1 gene expression under inflammatory conditions via the modulation of NFkappaB signaling.PMID:26240147
This study demonstrates that p300 mediates histone acetylation of PS1 and BACE1 in a cellular model of Alzheimer's disease.PMID:25051175
greater than 50% BACE1 inhibition might be necessary to significantly lower beta-amyloid peptidePMID:25567526
Decrease in Ab deposition was associated with a reduction in the expression of BACE1, the main enzyme responsible for Ab generation.PMID:25457554
BACE1 is inhibited by triptolide in a transgenic mouse model of Alzheimer's diseasePMID:25481013
Knockout mice lacking the biosynthetic enzyme for bisecting GlcNAc, GnT-III (Mgat3), revealed that cleavage of Abeta-precursor protein by BACE1 is reduced in these mice.PMID:25592972
Data show that C-type lectin-like domain family 4, member g (Clec4g) suppresses beta-Site amyloid precursor protein cleaving enzyme-1 (BACE1)-mediated amyloid-beta (Abeta) peptides generation.PMID:25957769
this study is the first to demonstrate the equal importance of axonal and Schwann cell BACE1 for remyelination of injured nervesPMID:25740511
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Subcellular Location
Cell membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network. Endoplasmic reticulum. Endosome. Late endosome. Early endosome. Cell surface. Cytoplasmic vesicle membrane. Membrane raft. Lysosome. Recycling endosome. Cell projection, axon. Cell projection, dendrite.
Protein Families
Peptidase A1 family
Tissue Specificity
Expressed in the brain, specifically in neurons and astrocytes (at protein level).