Beta-secretase 2
Template:Short description Template:Cs1 config Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). Beta-secretase 2 (EC 3.4.23.45, also known as memapsin-1) is an enzyme[1][2][3][4] 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.
Gene
This gene is located in the "Down critical region" of chromosome 21, which has been implicated in the pathogenesis of Down syndrome. Three transcript variants encoding different isoforms have been described for this gene.[4]
Function
Script error: No such module "Labelled list hatnote". The protein encoded by this gene is a member of the peptidase A1 family, and functions as a type I integral membrane glycoprotein and aspartic protease. It is involved in the proteolytic cleavage of amyloid precursor protein (APP), a key step in the production of amyloid beta peptide. Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease and a common complication in Down syndrome.
BACE2 has also been identified as the primary protease responsible for the release of the amyloidogenic ectodomain of Pmel17 in melanocytes, a process essential for the formation of the melanosome amyloid matrix.[5]
Clinical significance
BACE2 has been implicated in the maintenance of pancreatic β cells and regulation of glucose homeostasis. In mouse models, higher BACE2 activity has been associated with improved pancreatic function, suggesting potential therapeutic relevance for Type 2 Diabetes research.[6] In a separate context, a homozygous 25-base pair deletion in the BACE2 gene has been linked to the unique brown-and-white coat coloration in some giant pandas, as opposed to the typical black-and-white phenotype observed in the wild type.[7]
Interactions
BACE2 has been shown to interact with GGA1[8] and GGA2.[8]
References
Page Template:Reflist/styles.css has no content.
- ^ Page Module:Citation/CS1/styles.css has no content.Turner RT, Loy JA, Nguyen C, Devasamudram T, Ghosh AK, Koelsch G, et al. (July 2002). "Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivity". Biochemistry. 41 (27): 8742–8746. doi:10.1021/bi025926t. PMID 12093293.
- ^ Page Module:Citation/CS1/styles.css has no content.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): 177–184. doi:10.1159/000015608. PMID 10965118. S2CID 39880508.
- ^ Page Module:Citation/CS1/styles.css has no content.Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, et al. (May 2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–319. Bibcode:2000Natur.405..311H. doi:10.1038/35012518. PMID 10830953.
- ^ a b Page Module:Citation/CS1/styles.css has no content."Entrez Gene: BACE2 beta-site APP-cleaving enzyme 2".
- ^ Page Module:Citation/CS1/styles.css has no content.Rochin L, Hurbain I, Serneels L, Fort C, Watt B, Leblanc P, et al. (Jun 2013). "BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells". Proceedings of the National Academy of Sciences of the United States of America. 110 (26): 10658–10663. Bibcode:2013PNAS..11010658R. doi:10.1073/pnas.1220748110. PMC 3696817. PMID 23754390.
- ^ Page Module:Citation/CS1/styles.css has no content.Esterházy D, Stützer I, Wang H, Rechsteiner MP, Beauchamp J, Döbeli H, et al. (2011-09-07). "Bace2 is a β cell-enriched protease that regulates pancreatic β cell function and mass". Cell Metabolism. 14 (3): 365–377. doi:10.1016/j.cmet.2011.06.018. ISSN 1932-7420. PMID 21907142.
- ^ *Page Module:Citation/CS1/styles.css has no content.Guan D, Sun S, Song L, Zhao P, Nie Y, Huang X, et al. (Mar 2024). "Taking a color photo: A homozygous 25-bp deletion in Bace2 may cause brown-and-white coat color in giant pandas". Proceedings of the National Academy of Sciences of the United States of America. 121 (11) e2317430121. Bibcode:2024PNAS..12117430G. doi:10.1073/pnas.2317430121. PMC 10945837. PMID 38437540.
- ^ a b Page Module:Citation/CS1/styles.css has no content.He 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): 183–187. Bibcode:2002FEBSL.524..183H. doi:10.1016/S0014-5793(02)03052-1. PMID 12135764. S2CID 42042430.
Further reading
Page Template:Refbegin/styles.css has no content.
- Page Module:Citation/CS1/styles.css has no content.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. PMID 8764598. S2CID 11133791.
- Page Module:Citation/CS1/styles.css has no content.Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, et al. (Dec 1999). "Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity". Nature. 402 (6761): 533–537. Bibcode:1999Natur.402..533Y. doi:10.1038/990107. PMID 10591213. S2CID 4320087.
- Page Module:Citation/CS1/styles.css has no content.Sadik G, Kaji H, Takeda K, Yamagata F, Kameoka Y, Hashimoto K, et al. (Nov 1999). "In vitro processing of amyloid precursor protein by cathepsin D". The International Journal of Biochemistry & Cell Biology. 31 (11): 1327–1337. doi:10.1016/S1357-2725(99)00053-9. PMID 10605825.
- Page Module:Citation/CS1/styles.css has no content.Hussain I, Powell D, Howlett DR, Tew DG, Meek TD, Chapman C, et al. (Dec 1999). "Identification of a novel aspartic protease (Asp 2) as beta-secretase". Molecular and Cellular Neurosciences. 14 (6): 419–427. doi:10.1006/mcne.1999.0811. PMID 10656250. S2CID 54308213.
- Page Module:Citation/CS1/styles.css has no content.Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J (Feb 2000). "Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein". Proceedings of the National Academy of Sciences of the United States of America. 97 (4): 1456–1460. Bibcode:2000PNAS...97.1456L. doi:10.1073/pnas.97.4.1456. PMC 26455. PMID 10677483.
- Page Module:Citation/CS1/styles.css has no content.Acquati F, Accarino M, Nucci C, Fumagalli P, Jovine L, Ottolenghi S, et al. (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. Bibcode:2000FEBSL.468...59A. doi:10.1016/S0014-5793(00)01192-3. PMID 10683441. S2CID 30941017.
- Page Module:Citation/CS1/styles.css has no content.Bennett BD, Babu-Khan S, Loeloff R, Louis JC, Curran E, Citron M, et al. (Jul 2000). "Expression analysis of BACE2 in brain and peripheral tissues". The Journal of Biological Chemistry. 275 (27): 20647–20651. doi:10.1074/jbc.M002688200. PMID 10749877.
- Page Module:Citation/CS1/styles.css has no content.Xin H, Stephans JC, Duan X, Harrowe G, Kim E, Grieshammer U, et al. (Jun 2000). "Identification of a novel aspartic-like protease differentially expressed in human breast cancer cell lines". Biochimica et Biophysica Acta. 1501 (2–3): 125–137. doi:10.1016/s0925-4439(00)00014-4. PMID 10838186.
- Page Module:Citation/CS1/styles.css has no content.Farzan M, Schnitzler CE, Vasilieva N, Leung D, Choe H (Aug 2000). "BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9712–9717. Bibcode:2000PNAS...97.9712F. doi:10.1073/pnas.160115697. PMC 16930. PMID 10931940.
- Page Module:Citation/CS1/styles.css has no content.Iijima K, Ando K, Takeda S, Satoh Y, Seki T, Itohara S, et al. (Sep 2000). "Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5". Journal of Neurochemistry. 75 (3): 1085–1091. doi:10.1046/j.1471-4159.2000.0751085.x. PMID 10936190. S2CID 41050912.
- Page Module:Citation/CS1/styles.css has no content.Hussain I, Powell DJ, Howlett DR, Chapman GA, Gilmour L, Murdock PR, et al. (Nov 2000). "ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site". Molecular and Cellular Neurosciences. 16 (5): 609–619. doi:10.1006/mcne.2000.0884. PMID 11083922. S2CID 54379424.
- Page Module:Citation/CS1/styles.css has no content.Hussain I, Christie G, Schneider K, Moore S, Dingwall C (Jun 2001). "Prodomain processing of Asp1 (BACE2) is autocatalytic". The Journal of Biological Chemistry. 276 (26): 23322–23328. doi:10.1074/jbc.M101069200. PMID 11316808.
- Page Module:Citation/CS1/styles.css has no content.Yan R, Munzner JB, Shuck ME, Bienkowski MJ (Sep 2001). "BACE2 functions as an alternative alpha-secretase in cells". The Journal of Biological Chemistry. 276 (36): 34019–34027. doi:10.1074/jbc.M105583200. PMID 11423558.
- Page Module:Citation/CS1/styles.css has no content.Grüninger-Leitch F, Schlatter D, Küng E, Nelböck P, Döbeli H (Feb 2002). "Substrate and inhibitor profile of BACE (beta-secretase) and comparison with other mammalian aspartic proteases". The Journal of Biological Chemistry. 277 (7): 4687–4693. doi:10.1074/jbc.M109266200. PMID 11741910.
- Page Module:Citation/CS1/styles.css has no content.Kim YT, Downs D, Wu S, Dashti A, Pan Y, Zhai P, et al. (Nov 2002). "Enzymic properties of recombinant BACE2". European Journal of Biochemistry. 269 (22): 5668–5677. doi:10.1046/j.1432-1033.2002.03277.x. PMID 12423367.
- Page Module:Citation/CS1/styles.css has no content.Kondoh K, Tsuji N, Kamagata C, Sasaki M, Kobayashi D, Yagihashi A, et al. (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. PMID 12611455. S2CID 2195115.
External links
- https://web.archive.org/web/20070318110931/http://www.ihop-net.org/UniPub/iHOP/gs/129262.html
- Online Mendelian Inheritance in Man (OMIM): 605668
- Template:UCSC gene info
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