BACE2

From Wikipedia, the free encyclopedia

Beta-site APP-cleaving enzyme 2

PDB rendering based on 2ewy.

Available structures: 2ewy

Identifiers

Symbol(s)

BACE2; AEPLC; ALP56; ASP1; ASP21; BAE2; CDA13; CEAP1; DRAP

External IDs

OMIM: 605668 MGI: 1860440 HomoloGene: 22696

Gene ontology
Molecular Function:	• pepsin A activity • peptidase activity • aspartic-type signal peptidase activity
Cellular Component:	• membrane fraction • membrane • integral to membrane
Biological Process:	• protein modification process • membrane protein ectodomain proteolysis • protein secretion • peptide hormone processing • negative regulation of amyloid precursor protein biosynthetic process

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

n/a

Refseq

NM_012105 (mRNA)
NP_036237 (protein)

NM_019517 (mRNA)
NP_062390 (protein)

Location

Chr 21: 41.46 - 41.57 Mb

Chr 16: 97.46 - 97.54 Mb

Pubmed search

[1]

[2]

Beta-site APP-cleaving enzyme 2, also known as BACE2, is a human gene.^[1]

BACE2 is a close homolog of BACE1, a protease known to be an important enzyme involved in the cellular pathways that some believe lead to Alzheimer's disease. The physiological function and role of BACE2 in Alzheimer's disease is unknown.

Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease and a frequent complication of Down syndrome. Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein by 2 proteases, one of which is the protein encoded by this gene. This gene localizes to the 'Down critical region' of chromosome 21. The encoded protein, a member of the peptidase A1 protein family, is a type I integral membrane glycoprotein and aspartic protease. Three transcript variants encoding different isoforms have been described for this gene.^[1]

[edit] References

^ ^a ^b Entrez Gene: BACE2 beta-site APP-cleaving enzyme 2.

[edit] Further reading

Aplin AE, Gibb GM, Jacobsen JS, et al. (1996). "In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3beta.". J. Neurochem. 67 (2): 699-707. PMID 8764598.
Yan R, Bienkowski MJ, Shuck ME, et al. (1999). "Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity.". Nature 402 (6761): 533-7. doi:10.1038/990107. PMID 10591213.
Sadik G, Kaji H, Takeda K, et al. (2000). "In vitro processing of amyloid precursor protein by cathepsin D.". Int. J. Biochem. Cell Biol. 31 (11): 1327-37. doi:10.1016/S1357-2725(99)00053-9. PMID 10605825.
Hussain I, Powell D, Howlett DR, et al. (2000). "Identification of a novel aspartic protease (Asp 2) as beta-secretase.". Mol. Cell. Neurosci. 14 (6): 419-27. doi:10.1006/mcne.1999.0811. PMID 10656250.
Lin X, Koelsch G, Wu S, et al. (2000). "Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein.". Proc. Natl. Acad. Sci. U.S.A. 97 (4): 1456-60. doi:10.1073/pnas.97.4.1456. PMID 10677483.
Acquati F, Accarino M, Nucci C, et al. (2000). "The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region.". FEBS Lett. 468 (1): 59-64. doi:10.1016/S0014-5793(00)01192-3. PMID 10683441.
Bennett BD, Babu-Khan S, Loeloff R, et al. (2000). "Expression analysis of BACE2 in brain and peripheral tissues.". J. Biol. Chem. 275 (27): 20647-51. doi:10.1074/jbc.M002688200. PMID 10749877.
Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21.". Nature 405 (6784): 311-9. doi:10.1038/35012518. PMID 10830953.
Xin H, Stephans JC, Duan X, et al. (2000). "Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines.". Biochim. Biophys. Acta 1501 (2-3): 125-37. PMID 10838186.
Farzan M, Schnitzler CE, Vasilieva N, et al. (2000). "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. U.S.A. 97 (17): 9712-7. doi:10.1073/pnas.160115697. PMID 10931940.
Iijima K, Ando K, Takeda S, et al. (2000). "Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5.". J. Neurochem. 75 (3): 1085-91. doi:10.1046/j.1471-4159.2000.0751085.x. PMID 10936190.
Solans A, Estivill X, de La Luna S (2000). "A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase.". Cytogenet. Cell Genet. 89 (3-4): 177-84. doi:10.1159/000015608. PMID 10965118.
Hussain I, Powell DJ, Howlett DR, et al. (2001). "ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site.". Mol. Cell. Neurosci. 16 (5): 609-19. doi:10.1006/mcne.2000.0884. PMID 11083922.
Hussain I, Christie G, Schneider K, et al. (2001). "Prodomain processing of Asp1 (BACE2) is autocatalytic.". J. Biol. Chem. 276 (26): 23322-8. doi:10.1074/jbc.M101069200. PMID 11316808.
Yan R, Munzner JB, Shuck ME, Bienkowski MJ (2001). "BACE2 functions as an alternative alpha-secretase in cells.". J. Biol. Chem. 276 (36): 34019-27. doi:10.1074/jbc.M105583200. PMID 11423558.
Grüninger-Leitch F, Schlatter D, Küng E, et al. (2002). "Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases.". J. Biol. Chem. 277 (7): 4687-93. doi:10.1074/jbc.M109266200. PMID 11741910.
Turner RT, Loy JA, Nguyen C, et al. (2002). "Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity.". Biochemistry 41 (27): 8742-6. doi:10.1021/bi025926t. PMID 12093293.
Kim YT, Downs D, Wu S, et al. (2003). "Enzymic properties of recombinant BACE2.". Eur. J. Biochem. 269 (22): 5668-77. doi:10.1046/j.1432-1033.2002.03277.x. PMID 12423367.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899-903. doi:10.1073/pnas.242603899. PMID 12477932.
Kondoh K, Tsuji N, Kamagata C, et al. (2003). "A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer independently from the cathepsin D gene.". Breast Cancer Res. Treat. 78 (1): 37-44. doi:10.1023/A:1022149226430. PMID 12611455.