presenilin-1; PS-1; EC=3.4.23.-; protein S182; contains: presenilin-1 NTF subunit; contains: presenilin-1 CTF subunit; contains: presenilin-1 CTF12; PS1-CTF12 (PSEN1, AD3, PS1, PSNL1)

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Function

Kinetic parameters:

  • PS1 & PS2 have turnover times of ~15 min
  • proteolytically cleaved N & C terminal fragments form heterodimers within the APP-gamma-secretase complex with a turnover time apparently > 12 hours [13-16,20]

Structure

Compartment

Alternative splicing

named isoforms=6 some isoforms may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay

Pathology

Genetics

Laboratory

More general terms

Additional terms

Component of

References

  1. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 1995 Jun 29;375(6534):754-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7596406
  2. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Alzheimer's Disease Collaborative Group. Nat Genet. 1995 Oct;11(2):219-22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7550356
  3. Murphy GM Jr, Forno LS, Ellis WG, Nochlin D, Levy-Lahad E, Poorkaj P, Bird TD, Jiang Z, Cordell B. Antibodies to presenilin proteins detect neurofibrillary tangles in Alzheimer's disease. Am J Pathol. 1996 Dec;149(6):1839-46. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8952521
  4. Levitan D, Greenwald I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature. 1995 Sep 28;377(6547):351-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7566091
  5. 5.0 5.1 Roperch JP, Alvaro V, Prieur S, Tuynder M, Nemani M, Lethrosne F, Piouffre L, Gendron MC, Israeli D, Dausset J, Oren M, Amson R, Telerman A. Inhibition of presenilin 1 expression is promoted by p53 and p21WAF-1 and results in apoptosis and tumor suppression. Nat Med. 1998 Jul;4(7):835-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9662377
  6. 6.0 6.1 Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE. Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science. 1997 Jul 18;277(5324):373-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9219695
  7. 7.0 7.1 De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature. 1998 Jan 22;391(6665):387-90. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9450754
  8. 8.0 8.1 Haass C, De Strooper B. The presenilins in Alzheimer's disease-proteolysis holds the key. Science. 1999 Oct 29;286(5441):916-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10542139
  9. Selkoe DJ. Translating cell biology into therapeutic advances in Alzheimer's disease. Nature. 1999 Jun 24;399(6738 Suppl):A23-31. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10392577
  10. 10.0 10.1 Kimberly WT, Xia W, Rahmati T, Wolfe MS, Selkoe DJ. The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation. J Biol Chem. 2000 Feb 4;275(5):3173-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10652302
  11. 11.0 11.1 Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature. 1999 Apr 8;398(6727):513-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10206644
  12. 12.0 12.1 Li YM, Lai MT, Xu M, Huang Q, DiMuzio-Mower J, Sardana MK, Shi XP, Yin KC, Shafer JA, Gardell SJ. Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6138-43. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10801983
  13. Harman. J Am Aging Assoc (AGE) 23:147, 2000
  14. Yu G, Chen F, Levesque G, Nishimura M, Zhang DM, Levesque L, Rogaeva E, Xu D, Liang Y, Duthie M, St George-Hyslop PH, Fraser PE. The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. J Biol Chem. 1998 Jun 26;273(26):16470-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9632714
  15. Jacobsen H, Reinhardt D, Brockhaus M, Bur D, Kocyba C, Kurt H, Grim MG, Baumeister R, Loetscher H. The influence of endoproteolytic processing of familial Alzheimer's disease presenilin 2 on abeta42 amyloid peptide formation. J Biol Chem. 1999 Dec 3;274(49):35233-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10575009
  16. Capell A, Grunberg J, Pesold B, Diehlmann A, Citron M, Nixon R, Beyreuther K, Selkoe DJ, Haass C. The proteolytic fragments of the Alzheimer's disease- associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex. J Biol Chem. 1998 Feb 6;273(6):3205-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/9452432
  17. 17.0 17.1 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: https://www.ncbi.nlm.nih.gov/pubmed/10850703
  18. 18.0 18.1 Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature. 2000 Jun 8;405(6787):689-94. PMID: https://www.ncbi.nlm.nih.gov/pubmed/10864326
  19. 19.0 19.1 Kamal A, Almenar-Queralt A, LeBlanc JF, Roberts EA, Goldstein LS. Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP. Nature. 2001 Dec 6;414(6864):643-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11740561
  20. 20.0 20.1 Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274343
  21. De Strooper B, Annaert W. Where Notch and Wnt signaling meet. The presenilin hub. J Cell Biol. 2001 Feb 19;152(4):F17-20. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11266476
  22. 22.0 22.1 Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH. Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell. 2002 Sep 20;110(6):751-62. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12297048
  23. UniProt http://www.uniprot.org/uniprot/P49768.html
  24. Alzheimer research forum; Note: presenilins mutations http://www.alzforum.org/res/com/mut/pre/default.asp
  25. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/PSEN1

Database