BACE Antibody Cat. No.: 2253

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psi-iconSpecifications
HOST SPECIES:Rabbit
SPECIES REACTIVITY: Human, Mouse
HOMOLOGY: Predicted species reactivity based on immunogen sequence: Guinea pig: (94%), Rat: (94%), Bovine: (94%)
IMMUNOGEN: Anti-BACE antibody (2253) was raised against a peptide corresponding to 17 amino acids near the carboxy terminus of human BACE.

The immunogen is located within the last 50 amino acids of BACE.
TESTED APPLICATIONS: ELISA, ICC, IF, IHC-P, WB
APPLICATIONS: BACE can be used for detection of BACE by Western blot at 1 μg/mL. Antibody can also be used for immunocytochemistry starting at 10 μg/mL and immunohistochemistry starting at 2.5 μg/mL. For immunofluorescence start at 20 μg/mL.

Antibody validated: Western Blot in human and mouse samples; Immunohistochemistry in mouse samples; Immunocytochemistry in mouse samples and Immunofluorescence in mouse samples. All other applications and species not yet tested.
POSITIVE CONTROL:1) Cat. No. 1303 - Human Brain Tissue Lysate
 2) Cat. No. 1212 - 3T3 Cell Lysate
 3) Cat. No. 1224 - Daudi Cell Lysate
 4) Cat. No. 1201 - HeLa Cell Lysate
PREDICTED MOLECULAR WEIGHT: Predicted: 55kD

Observed: 65kD (Post-modification: 4 N-linked glycosylation)
psi-iconAdvanced Validation
VALIDATION:

Independent Antibody Validation in Cell lines (Figure 2) shows similar BACE expression profile in human cell lines detected by two independent anti-BACE antibodies that recognize different epitopes, 2253 against C-terminus domain and  32-238 against recombinant fragment protein.  BACE proteins are detected in all the tested cell lines except K562 at different expression levels by the two independent antibodies.  

KO validation (Figure 6,9): Anti-BACE antibody (2253) specificity was further verified by BACE KO mice (figure6) and KO cell line (figure9). BACE signal was not detected in BACE KO mice and KO cell line.

KD validation (Figure 7,8,10): Anti-BACE antibody (2253) specificity was verified by BACE BACE specific siRNA knockdown. BACE signal in mouse brain injected with BACE siRNAs and DRG transfected with BACE siRNAs was disrupted in comparison with control.

Overexpression validation (Figure 6): Anti-BACE antibody (2253) detected high expression levels of BACE in 293 cells transfected with hBACE or mBACE (figure6) as compared to eGFP transfected cells.

ISOFORMS: Human BACE has 6 isoforms, including isoform A (501aa, 55.8kD), isoform B (476aa, 52.9kD), isoform C (457aa, 51.1kD), isoform D (432aa, 48.2kD), isoform 5 (401aa, 45kD) and isoform 6 (376aa, 42.2kD). This antibody detects all human isoforms. Mouse BACE has only 1 isoform (501aa, 55.7kD). Rat BACE has only one isoform identified so far (501aa, 55.8kD).

psi-iconProperties
PURIFICATION:BACE Antibody is Ion exchange chromatography purified.
CLONALITY:Polyclonal
ISOTYPE:IgG
CONJUGATE:Unconjugated
PHYSICAL STATE:Liquid
BUFFER:BACE Antibody is supplied in PBS containing 0.02% sodium azide.
CONCENTRATION:1 mg/mL
STORAGE CONDITIONS:BACE antibody can be stored at 4˚C for three months and -20˚C, stable for up to one year. As with all antibodies care should be taken to avoid repeated freeze thaw cycles. Antibodies should not be exposed to prolonged high temperatures.

psi-iconAdditional Info
OFFICIAL SYMBOL:BACE1
ALTERNATE NAMES:BACE Antibody: ASP2, BACE, HSPC104, KIAA1149, Beta-secretase 1, Aspartyl protease 2, ASP2
ACCESSION NO.:AF190725
PROTEIN GI NO.:6118538
GENE ID:23621
USER NOTE:Optimal dilutions for each application to be determined by the researcher.
psi-iconBackground and References
BACKGROUND:BACE Antibody: Accumulation of the amyloid-beta (Abeta) plaque in the cerebral cortex is a critical event in the pathogenesis of Alzheimer's disease. Abeta peptide is generated by proteolytic cleavage of the beta-amyloid protein precursor (APP) at beta- and gamma-sites by two proteases. APP is first cleaved by beta-secretase, producing a soluble derivative of the protein and a membrane anchored 99-amino acid carboxy-terminal fragment (C99). The C99 fragment serves as substrate for gamma-secretase to generate the 4 kDa amyloid-beta peptide, which is deposited in the brains of all suffers of Alzheimer's disease. The long-sought beta-secretase was recently identified by several groups independently and designated beta-site APP cleaving enzyme (BACE) and aspartyl protease 2 (Asp2). BACE/Asp2 is a novel transmembrane aspartic protease and colocalizes with APP.
REFERENCES:1) Vassar R, Bennett BD, Babu-Khan S, et al. β-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999;286:735-41
2) Hussain I, Powell D, Howlett DR , et al. Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol Cell Neurosci 1999;14:419-27
3) Yan R, Bienkowski MJ, Shuck ME, et al. Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity. Nature 1999;402:533-7
4) Sinha S, Anderson JP, Barbour R, et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 1999;402:537-40 (WD0500)
psi-iconCITATIONS
CITATIONS: 1)Singer et al. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nat Neurosci. 2005;8(10):1343-9. PMID: 16136043
2)Jo et al.Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease. Neurobiol Aging. 2010;31(6):917-25. PMID: 18687504
3)Hyun. RNA Interference Against BACE1 Suppresses BACE1 and Aβ Expression in PC12 Cells and DRG Neurons. Stanford Journal of Neuroscience. 2007; 1(1):2-8.PMID:
4)Okada et al. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010;24(8):2783-94PMID: 20354142
5)Liu et al. Glu11 site cleavage and N-terminally truncated A beta production upon BACE overexpression. Biochemistry. 2002;41(9):3128-36PMID: 11863452
6)Colombo et al. JNK regulates APP cleavage and degradation in a model of Alzheimer's disease. Neurobiol Dis. 2009;33(3):518-25PMID: 19166938
7)Bettegazzi et al. β-Secretase activity in rat astrocytes:translational block of BACE1 and modulation of BACE2 expression. Eur J Neurosci. 2011;33(2):236-43.PMID: 21073551
8)Lichtenthaler et al. The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1. J Biol Chem. 2003;278(49):48713-9PMID: 14507929
9)Lee et al. Secretion and intracellular generation of truncated Abeta in beta site amyloid-beta precursor protein-cleaving enzyme expressing human neurons. J Biol Chem. 2003;278(7):4458-66PMID: 12480937
10)Rockenstein et al. High beta-secretase activity elicits neurodegeneration in transgenic mice despite reductions in amyloid-beta levels: implications for the treatment of Alzheimer disease. J Biol Chem. 2005;280(38):32957-67. PMID: 16027115
11)Catania et al. The amyloidogenic potential and behavioral correlates of stress. Mol Psychiatry. 2009;14(1):95-105PMID: 17912249
12)Parisiadou et al.Homer2 and Homer3 interact with amyloid precursor protein and inhibit Abeta production. Neurobiol Dis. 2008;30(3):353-64PMID: 18387811
13)Knock et al. SUMO1 impact on Alzheimer disease pathology in an amyloid depositing mouse model. Neurobiol Dis. 2018;110:154-165PMID: 29217476
14)Debatin et al. Association between deposition of beta-amyloid and pathological prion protein in sporadic Creutzfeldt-Jakob disease. Neurodegener Dis. 2008;5(6):347-54.PMID: 18349519
15)Gwon etal. Selenium attenuates A beta production and A beta-induced neuronal death. Neurosci Lett. 2010;469(3):391-5. PMID: 20026385
16)Kuhn et al. Regulated intramembrane proteolysis of the interleukin-1 receptor II by alpha-, beta, and gamma-secretase. J Biol Chem. 2007;282(16):11982-95. PMID: 17307738
17)Succol et al. A role for 12/15 lipoxygenase in the amyloid beta precursor protein metabolism. J Neurochem. 2007;103(1):380-7.PMID: 17877641
18)Zhuo et al. Severe In vivo hyper-homocysteinemia is not associatedwith elevation of amyloid-beta peptides in the Tg2576 mice. J Alzheimers Dis. 2010;21(1):133-40. PMID: 20555139
19)Zhuo et al. Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet. Exp Gerontol.2010;45(3):195-201. PMID: 20005283
20)Malnar et al. Cholesterol-depletion corrects APP and BACE1 misstrafficking in NPC1-deficient cells. Biochim Biophys Acta. 2012;1822(8):1270-83. PMID: 22551668

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