Beta-secretase 2 (EC3.4.23.45, also known as Memapsin-1) is an enzyme[5][6][7][8] that cleaves Glu-Val-Asn-Leu!Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein. BACE2 is a close homolog of BACE1.
Function
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]
^"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.
^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.
^BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells Pubmed
^ abHe X, Chang WP, Koelsch G, Tang J (Jul 2002). "Memapsin 2 (beta-secretase) cytosolic domain binds to the VHS domains of GGA1 and GGA2: implications on the endocytosis mechanism of memapsin 2". FEBS Letters. 524 (1–3): 183–7. doi:10.1016/S0014-5793(02)03052-1. PMID12135764.
Further reading
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.
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.
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.
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.
Turner RT, Loy JA, Nguyen C, Devasamudram T, Ghosh AK, Koelsch G, Tang J (Jul 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. PMID12093293.
Kim YT, Downs D, Wu S, Dashti A, Pan Y, Zhai P, Wang X, Zhang XC, Lin X (Nov 2002). "Enzymic properties of recombinant BACE2". European Journal of Biochemistry / FEBS. 269 (22): 5668–77. doi:10.1046/j.1432-1033.2002.03277.x. PMID12423367.
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.
