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Validated All-in-One™ qPCR Primer for BACE1(NM_012104.4) Search again
Product ID:
HQP006277
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ASP2, BACE, HSPC104
Gene Description:
beta-secretase 1
Target Gene Accession:
NM_012104.4(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease. Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein (APP) by two proteases, one of which is the protein encoded by this gene. The encoded protein, a member of the peptidase A1 protein family, is a type I integral membrane glycoprotein and aspartic protease that is found mainly in the Golgi. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq].
Gene References into function
- BACE1 is in the distal Golgi membrane with a minor presence in the endoplasmic reticulum, endosomes, and plasma membrane in human neuroblastoma SHEP cells and in mouse Neuro-2a cell lines
- BACE has a loose substrate specificity and the substrate recognition site in BACE extends over several amino acids
- beta-Secretase cleavage of the amyloid precursor protein mediates neuronal apoptosis caused by familial ALzheimer's disease mutations.
- Intracellular localization of BACE affects sleavage site specificity; processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain
- Our data are consistent with a role for the cytoplasmic domain in regulating BACE trafficking and localization.
- A model of the three-dimensional structure of the beta-secretase zymogen has been constructed.
- BACE1 interacts with nicastrin
- Splice variants of the beta-site APP-cleaving enzyme BACE1 are found in human brain and pancreas (BACE1)
- Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity
- Results show an increase in protein expression of BACE in the cortex of Alzheimer's disease patients compared to age-matched controls
- endocytosis and intracellular transport of memapsin 2, mediated by its cytosolic domain, may involve the binding of GGA1 and GGA2
- Crystal structure analysis of memapsin-2 catalytic unit complexed with its inhibitor OM00-3 defines locations and functions of new binding pockets S3' and S4'.
- Activity levels are increased in brain regions affected by amyloid deposition and remain increased despite significant neuronal and synaptic loss in Alzheimer disease
- Oxidative stress induces increased BACE protein levels and activity in NT2 neurons accompanied by an increase in amyloid beta protein precursor.
- BACE mRNA amounts were similar in the hippocampus and cerebellum of Alzheimer's patients and controls.
- Results describe a decrease in alpha-secretase (81% of normal) and a large increase in beta-secretase activity (185%) in sporadic Alzheimer's disease temporal cortex.
- An isoenzyme specifically truncates amyloid beta-peptide after its presenilin-dependent generation.
- elevated expression and enzymatic activity in the brain of sporadic Alzheimer disease patients
- The association of beta-site APP cleaving enzyme (BACE) C786G polymorphism with Alzheimer's disease. No significant association of this polymorphism with the occurrence of AD can be established.
- Identification of domains for PLSCR1 and BACE binding and their colocalization in the Golgi area and endosomal compartments suggest involvement of PLSCR1 in the intracellular distribution and/or recruitment of BACE into the lipid raft.
- BACE1 and BACE2 (a) are expressed in normal adult muscle at the postsynaptic domain of neuromuscular junctions, and in cultured human muscle; (b) accumulate in the form of plaque-like inclusions in myositis vacuolated and necrotic muscle fibers
- stabilization by ceramide and role in amyloid beta-pepetide biogenesis
- gamma-secretase cleavage of CT99 is a prerequisite for BACE-mediated processing at Abeta-34 site and therefore, BACE and gamma-secretase activity can be mutually dependent.
- sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; but, a combination of a specific BACE1 allele and APOE epsilon 4 may increase the risk for Alzheimer disease over and above that attributed to APOE epsilon 4 alone.
- antagonistic effect with beta-site amyloid precursor protein-cleaving enzyme 2 on beta-amyloid peptide production in cells
- BACE exon 5 polymorphism plays an important role in the development of Alzheimer's disease, possibly by influencing Abeta(42) protein levels.
- BACE1 sheddase is distinct from alpha-secretase and, inhibition of BACE1 shedding does not influence amyloid precursor protein processing at the beta-site
- These data suggest a possible genetic relation between BACE1 and AD.
- acts on the P-selectin glycoprotein ligand 1, which mediates leukocyte adhesion in inflammatory reactions
- BACE 1 cleavage regulates a common function of APP and APLPs in neurons
- BACE1 gene expression is tightly regulated at the transcriptional level, and transcription factor Sp1 plays an important role in regulation of BACE1 to process APP generating Abeta in Alzheimer's disease.
- Homology models of alternatively spliced isoforms B (BACEI-476), C (BACEI-457) and D(BACEI-432) suggest that these should have diminished enzyme activity due to the the loss of key complexing residues
- beta-Secretase activity is enhanced by cellular targeting into intracellular cholesterol-rich microdomains
- BACE elevation may lead to increased amyloid beta peptide production and enhanced deposition of amyloid plaques in sporadic Alzheimer disease patients.
- BACE overexpression is not sufficient to produce beta-amyloid plaques, but simultaneous expression of BACE and its substrate (SwAPP) leads to an accelerated amyloid plaque formation.
- Alternative splicing in the BACE-1 5'UTR affects the efficiency of translation initiation
- promotor and 5' UTR sequence analysis
- transcription response element analysis of 5' flanking region
- The major structural difference in the bound and unbound memapsin 2 is a large movement of the flap of about 4.5 angstroms at the tip; the flap in the unbound memapsin 2 appears in a novel "open" position permitting access to the active-site cleft.
- memapsin 2 and APP, immunoprecipitated together from cell lysates, suggested that the interaction of these two proteins is part of the native cellular processes [memapsin-2]
- Stimulation of cells with muscarinic agonists increased BACE1 expression up to twofold over basal levels. Similar effects of BACE1 up-regulation were observed when protein kinase C was directly activated by phorbol esters.
- NMR structure of the 45.3 kDa catalytic domain of human BACE1
- processing of APP by BACE1 is dependent on a mutual structural compatibility in addition to the sequence feature
- homodimerization of BACE may help the enzyme to acquire specific mechanisms to associate with its substrates to exert catalytic activity.
- Results describe the apo structure of BACE (beta-secretase) to 1.75 A, and the structure of a hydroxyethylamine inhibitor complex derived by soaking.
- transgenic mice overexpressing both human BACE1 and APP show specific alterations in APP processing and age-dependent Abeta deposition suggesting that modulation of BACE1 activity may play a significant role in Alzheimer disease pathogenesis
- serine phosphorylation of BACE is a physiologically relevant post-translational modification that regulates trafficking in the juxtanuclear compartment by interaction with GGA1
- Dimerization of BACE might facilitate binding and cleavage of physiological substrates
- Recombinant BACE1 can recognize and cleave APP peptide substrates at the postulated beta'-cleavage site. It does not appear to be a significant species specificity to this cleavage.
- review of the structural features of the catalytic/specificity apparatus, transmembrane domain, cytosolic domain and the implications of these features in the physiological and pathological roles of this protease
- GGA proteins funstion with the phosphorylated ACDL in the memasin 2-recycling pathway from endosomes to trans Golgi on the way back to the cell surface.
- Data show that the C-terminal domain of PAR-4 is necessary for forming a complex with the cytosolic tail of BACE1.
- BACE1 gene polymorphism C786G might act as an APOE epsilon4 allele-dependent risk factor for developing late onset Alzheimer's disease in Chinese
- BACE1 and gamma-secretase use beta subunits of voltage-gated sodium channels as substrates
- data indicate that despite being homologous in amino acid sequence, beta-site beta amyloid precursor protein cleaving enzyme 2(BACE2) and BACE1 have distinct functions and transcriptional regulation
- the mechanism of IL-1beta-induced-sAPP(alpha) release is dependent on MEK1/2- and JNK-activated alpha-secretase cleavage in neuroglioma U251 cells
- GGA1 regulates the retrograde transport of internalized BACE1 from endosomal compartments to the TGN by direct interaction in a phosphorylation-dependent manner.
- BACE1-G allele appeared to increase risk of developing Alzheimer's disease
- high levels of BACE1 activity are sufficient to elicit neurodegeneration and neurological decline in vivo
- BACE is transported to the late endosomal/lysosomal compartments where it is degraded via the lysosomal pathway and that the di-leucine motif plays a role in sorting BACE to lysosomes
- M2 acetylcholine receptor down-regulation in brains with Alzheimer's disease(AD) affects expression of several genes and proteins with major functions in the pathology of AD, including beta-secretase BACE1 and several modulators of tau protein.
- These findings suggest that the release of BACE1 holoproteins may be a physiologically relevant cellular process.
- Evidence for alterations in beta-secretase activity, and/or alterations in BACE expression, in post-mortem brain tissue and platelets from individuals with Alzheimer disease. (review)
- X-ray crystallographic analysis of BACE1 with macrocyclic peptidomimetics
- Overexpression of secretase in HEK293 cells increased the release of neurotrophic soluble APLP2 severalfold.
- fully processed BACE1 represents a high quality well-folded protein which is highly stable over a long period of time, and is suitable for evaluation of inhibitor binding by NMR for drug intervention
- BACE1 processing pathways are critical for cognitive, emotional, and synaptic functions
- Lower BACE transcription is responsible for the minority of APP undergoing the amyloidogenic pathway and relatively lower Abeta production in the normal conditions, and that a slight increase in BACE1 can induce a dramatic elevation in Abeta production.
- These results suggest that the precision of cleavage by the PS/gamma-secretase complex may be physiologically regulated by the subcellular location and conditions.
- Alterations of the leaky scanning and reinitiation in BACE1 gene expression could play an important role in AD pathogenesis.
- Results suggest that BACE1 gene promoter activity is differentially regulated, and the 91-bp fragment represents a novel promoter region for cell type-specific regulation.
- results strongly suggest that heparin stimulates the partially active BACE1 zymogen, and we propose that the activation is mediated by high-affinity binding of heparin to the pro domain
- Results describe the functional domains of the BACE1 and BACE2 promoters and mechanisms of transcriptional suppression of the BACE2 promoter in normal neuronal cells.
- Novel molecular mechanism by which Alzheimer's disease(AD) develops in Down syndrome(DS) and support the therapeutic potential of inhibiting BACE1 in AD and DS.
- Affects glycosylation not only by directly cleaving glycosyltransferases but also by modifying the secretion of glycosyltransferases via some other mechanisms.
- two enzymatic activities are required to generate the pathogenic beta-amyloid; both activities are carried out by two unusual aspartyl proteases known as beta- and gamma-secretase--{review}
- Results describe the mapping of interaction domains mediating binding between BACE1 and RTN3/Nogo proteins.
- These results indicate that increased V(max) for beta-secretase is a feature of AD pathogenesis and this increase does not correlate directly with levels of BACE1, the principal beta-secretase in brain.
- Platelet membrane beta-secretase activity (expressed as initial rate) varied over fourfold between individuals.
- altered cholesterol metabolism and amyloid precursor protein trafficking mediated by ABC transporter 8 may contribute to the accelerated onset of Alzheimer's disease neuropathology in Down syndrome
- BACE1 and BACE2 may act as alternative alpha-secretase-like proteases in proteolytic processing of IL-1R2 and APP
- These results suggest that while excess Abeta is functionally pathological, BACE1-mediated processing of APP and other substrates play a role in "normal" learning, memory and sensorimotor processes.
- Transgenic BACE1 elevation is triggered by an accumulation of amyloid plaques and may drive a positive-feedback loop in an Alzheimer's disease model.
- Lysine acetylation is necessary for nascent BACE1 to leave the endoplasmic reticulum and move ahead in the secretory pathway, and for the molecular stabilization of the protein.
- SOD1 activity, cytosolic copper and ectodomain cleavage of APP are linked through BACE1.
- Endogenous beta2 processing and Na(v)1.1 protein levels are elevated in brains of BACE1-transgenic mice and Alzheimer's disease patients with high BACE1 levels.
- BACE1 expression and activity is relevance in Alzheimer's disease.
- the membrane topology of RTN3 has an effect on binding of RTN3 to BACE1
- soluble ST6Gal I produced by BACE1 plays, at least in part, a role in the sialylation of soluble glycoproteins
- The I-127 isoform of BACE is regulated by both nonsense-mediated mRNA decay (NMD) and proteasome-dependent degradation.(I-127)
- Taken together, our results not only suggest that bis(7)-tacrine may reduce the biosynthesis of Abeta mainly by directly inhibiting BACE-1 activity, but also provide new insights into the rational design of novel anti-Alzheimer's dimers.
- The expression levels of BACE1 was increased, but did not reach statistical significance. But BACE1 was comparable between DS and controls in adult brain.
- The kinetic constants (kcat, Km, kcat/Km) for cleaving peptides with beta-sites of the WT or the mutated Swedish families (SW) APP by human BACE 1 and cathepsin D were determined and found to be similar.
- amyloid precursor protein (APP) ectodomain are regulated by the loop region and affect beta-secretase cleavage of APP
- Data suggest that BACE1 polymorphism in exon 5 influences risk for late-onset Alzheimer's disease in those carrying the ApoE epsilon4 allele.
- wild-type or Swedish mutated betaAPP overexpression modulates BACE1 promoter transactivation and activity via an NFkappaB-dependent pathway.
- BACE and APP come into close proximity within the cell, but probably not on the cell surface.
- The crystal structure of the catalytically active form of BACE1 was reported.
- we review the basic biology of BACE1, focusing on the regulation, structure and function of this enzyme--REVIEW
- Loss of specific miRNAs can contribute to increased BACE1 and Abeta levels in sporadic Alzheimer's disease.
- Expression of a noncoding RNA is elevated in Alzheimer disease and drives feed-forward regulation of BACE1.
- analysis of the consequences of individual N-glycan deletions and of proteasomal inhibition on secretion of active BACE
- Proteolytic shedding of ST6Gal-I by BACE1 regulates the glycosylation and function of alpha4beta1 integrins
- Data show that the serine protease PCSK9 (proprotein convertase subtilisin kexin type 9) contributes to the disposal of non-acetylated BACE1.
- Elevated BACE1 activity may contribute to the amyloidogenic process in sporadic Alzheimer's disease and is associated with the intensity of axonal degeneration.
- that the activated conformation of BACE1 is important for protein transport and localization to lipid rafts.
- study demonstrated that caspase-3 inhibition attenuated ischemia-induced beta-amyloid formation by reducing BACE1 production and activity
- Both ATase1 and ATase2 regulate the steady-state levels of BACE1
- findings show that BACE1 alters sodium channel gating not only through the cleavage of beta subunits, but also through a direct, non-proteolytic interaction with the alpha subunit