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.[8]
It has been reported that BACE2 is the main protease that mediates the release of the amyloidogenic ectodomain of Pmel17 in melanocytes.
[9] BACE2 has also been observed in mice to be correlated with maintaining the pancreatic β cells and improving control of glucose homeostasis, which may prove to be useful for research on Type 2 Diabetes.[10] Deletion of BACE2 in Giant Panda may cause it to have brown and white color instead of the wild type's black and white color.[11]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Turner, R.T.; Loy, J.A.; Nguyen, C.; Devasamudram, T.; Ghosh, A.K.; Koelsch, G.; Tang, J. (2002). "Specificity of memapsin 1 and its implications on the design of memapsin 2 (β-secretase) inhibitor selectivity". Biochemistry. 41 (27): 8742–8746. doi:10.1021/bi025926t. PMID12093293.
^Solans A, Estivill X, de La Luna S (Sep 2000). "A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase". Cytogenetics and Cell Genetics. 89 (3–4): 177–84. doi:10.1159/000015608. PMID10965118. S2CID39880508.
^Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML (May 2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID10830953.
Aplin AE, Gibb GM, Jacobsen JS, Gallo JM, Anderton BH (Aug 1996). "In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3beta". Journal of Neurochemistry. 67 (2): 699–707. doi:10.1046/j.1471-4159.1996.67020699.x. PMID8764598. S2CID11133791.
Sadik G, Kaji H, Takeda K, Yamagata F, Kameoka Y, Hashimoto K, Miyanaga K, Shinoda T (Nov 1999). "In vitro processing of amyloid precursor protein by cathepsin D". The International Journal of Biochemistry & Cell Biology. 31 (11): 1327–37. doi:10.1016/S1357-2725(99)00053-9. PMID10605825.
Hussain I, Powell D, Howlett DR, Tew DG, Meek TD, Chapman C, Gloger IS, Murphy KE, Southan CD, Ryan DM, Smith TS, Simmons DL, Walsh FS, Dingwall C, Christie G (Dec 1999). "Identification of a novel aspartic protease (Asp 2) as beta-secretase". Molecular and Cellular Neurosciences. 14 (6): 419–27. doi:10.1006/mcne.1999.0811. PMID10656250. S2CID54308213.
Acquati F, Accarino M, Nucci C, Fumagalli P, Jovine L, Ottolenghi S, Taramelli R (Feb 2000). "The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region". FEBS Letters. 468 (1): 59–64. doi:10.1016/S0014-5793(00)01192-3. PMID10683441. S2CID30941017.
Xin H, Stephans JC, Duan X, Harrowe G, Kim E, Grieshammer U, Kingsley C, Giese K (Jun 2000). "Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines". Biochimica et Biophysica Acta. 1501 (2–3): 125–37. doi:10.1016/s0925-4439(00)00014-4. PMID10838186.
Kondoh K, Tsuji N, Kamagata C, Sasaki M, Kobayashi D, Yagihashi A, Watanabe N (Mar 2003). "A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer independently from the cathepsin D gene". Breast Cancer Research and Treatment. 78 (1): 37–44. doi:10.1023/A:1022149226430. PMID12611455. S2CID2195115.
