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APP beta-secretase or beta-site APP-cleaving enzyme (BACE)

Function: 1) cleaves APP between Met671 & Asp672 (APP-770 designation), generating the free NH2 terminus of beta-amyloid (A4), or 2) preferentially cuts APP at positions 1 or 11 of A4 sequence [5] 3) APP beta-secretase may cleave APP (in part) during late secretory trafficking [8] 4) activity may be enhanced by cholesterol or cholesterol esters [7] 5) trafficking may be regulated by retromer complex [9] Compartment: - found mostly in endosomes Expression: - high levels are expressed in brain & exocrine pancreas Pathology: - in concert with APP gamma-secretase, generates Abeta

Related

A4 amyloid peptide; beta-peptide amyloid precursor protein (APP) or A4/beta amyloid precursor protein APP secretase

Specific

APP beta-secretase 1, beta-site APP-cleaving enzyme 1 (BACE 1), memapsin-2 or Asp2 protein beta-secretase 2, beta-site APP-cleaving enzyme 2 (BACE 2) or Asp1 protein

General

aspartic proteinase; carboxyl acid protease membrane protein

Properties

COMPARTMENT: cellular membrane MOTIF: membrane region active site MOTIF: aspartate residue (2)

References

  1. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999 Oct 22;286(5440):735-41. PMID: 10531052
  2. Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999 Dec 2;402(6761):533-7. PMID: 10591213
  3. Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari SM, Wang S, Walker D, Zhao J, McConlogue L, John V. Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature. 1999 Dec 2;402(6761):537-40. PMID: 10591214
  4. Ashall F, Goate AM. Role of the beta-amyloid precursor protein in Alzheimer's disease. Trends Biochem Sci. 1994 Jan;19(1):42-6. Review. PMID: 8140621
  5. Russo C, Schettini G, Saido TC, Hulette C, Lippa C, Lannfelt L, Ghetti B, Gambetti P, Tabaton M, Teller JK. Presenilin-1 mutations in Alzheimer's disease. Nature. 2000 Jun 1;405(6786):531-2. No abstract available. PMID: 10850703
  6. Hong L, Koelsch G, Lin X, Wu S, Terzyan S, Ghosh AK, Zhang XC, Tang J. Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor. Science. 2000 Oct 6;290(5489):150-3. PMID: 11021803
  7. Marx J. Science 294:508, 2001
  8. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: 11274343
  9. Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H, Honig L, Vonsattel JP, Kim TW. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann Neurol. 2005 Dec;58(6):909-19. PMID: 16315276