Biology:Beta-secretase 2

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Short description: Enzyme found in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.

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.[4] It has been reported that BACE2 is the main protease that mediates the release of the amyloidogenic ectodomain of Pmel17 in melanocytes. [5] 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.[6]

Interactions

BACE2 has been shown to interact with GGA1[7] and GGA2.[7]

References

  1. ↑ 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. PMID 12093293. 
  2. ↑ "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. Sep 2000. doi:10.1159/000015608. PMID 10965118. 
  3. ↑ "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. May 2000. doi:10.1038/35012518. PMID 10830953. Bibcode: 2000Natur.405..311H. 
  4. ↑ 4.0 4.1 "Entrez Gene: BACE2 beta-site APP-cleaving enzyme 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=25825. 
  5. ↑ *Rochin, L.; Hurbain, I.; Serneels, L.; Fort, C.; Watt, B.; Leblanc, P.; Marks, M. S.; De Strooper, B. et al. (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. doi:10.1073/pnas.1220748110. PMID 23754390. Bibcode: 2013PNAS..11010658R. 
  6. ↑ Esterházy, Daria; Stützer, Ina; Wang, Haiyan; Rechsteiner, Markus P.; Beauchamp, Jeremy; Döbeli, Heinz; Hilpert, Hans; Matile, Hugues 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. 
  7. ↑ 7.0 7.1 "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. Jul 2002. doi:10.1016/S0014-5793(02)03052-1. PMID 12135764. 

Further reading

External links




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