The Full Wiki

PSEN2: Wikis

Advertisements

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

edit
Presenilin 2 (Alzheimer disease 4)
Identifiers
Symbols PSEN2; AD3L; AD4; PS2; STM2
External IDs OMIM600759 MGI109284 HomoloGene386 GeneCards: PSEN2 Gene
RNA expression pattern
PBB GE PSEN2 204261 s at tn.png
PBB GE PSEN2 204262 s at tn.png
PBB GE PSEN2 211373 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5664 19165
Ensembl ENSG00000143801 ENSMUSG00000010609
UniProt P49810 Q3U4P5
RefSeq (mRNA) NM_000447 NM_011183
RefSeq (protein) NP_000438 NP_035313
Location (UCSC) Chr 1:
225.12 - 225.15 Mb
Chr 1:
182.06 - 182.08 Mb
PubMed search [1] [2]

Presenilin-2 is a protein that in humans is encoded by the PSEN2 gene.[1]

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Two alternative transcripts of PSEN2 have been identified.[2]

In melanocytic cells PSEN2 gene expression may be regulated by MITF[3].

Interactions

PSEN2 has been shown to interact with UBQLN1,[4] FHL2,[5] FLNB,[6] BCL2-like 1,[7] Nicastrin,[8][9] KCNIP4,[10] CAPN1,[11] CIB1[12] and Calsenilin.[13][14]

References

  1. ^ Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KA, Weber JL, Bird TD, Schellenberg GD (Sep 1995). "A familial Alzheimer's disease locus on chromosome 1". Science 269 (5226): 970–3. PMID 7638621.  
  2. ^ "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5664.  
  3. ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.  
  4. ^ Mah, A L; Perry G, Smith M A, Monteiro M J (Nov. 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. (UNITED STATES) 151 (4): 847–62. ISSN 0021-9525. PMID 11076969.  
  5. ^ Tanahashi, H; Tabira T (Sep. 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. (ENGLAND) 9 (15): 2281–9. ISSN 0964-6906. PMID 11001931.  
  6. ^ Zhang, W; Han S W, McKeel D W, Goate A, Wu J Y (Feb. 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. (UNITED STATES) 18 (3): 914–22. ISSN 0270-6474. PMID 9437013.  
  7. ^ Passer, B J; Pellegrini L, Vito P, Ganjei J K, D'Adamio L (Aug. 1999). "Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death". J. Biol. Chem. (UNITED STATES) 274 (34): 24007–13. ISSN 0021-9258. PMID 10446169.  
  8. ^ Lee, Sheu-Fen; Shah Sanjiv, Li Hongqiao, Yu Cong, Han Weiping, Yu Gang (Nov. 2002). "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch". J. Biol. Chem. (United States) 277 (47): 45013–9. doi:10.1074/jbc.M208164200. ISSN 0021-9258. PMID 12297508.  
  9. ^ Yu, G; Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song Y Q, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang D S, Holmes E, Milman P, Liang Y, Zhang D M, Xu D H, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer L S, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (Sep. 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature (ENGLAND) 407 (6800): 48–54. doi:10.1038/35024009. ISSN 0028-0836. PMID 10993060.  
  10. ^ Morohashi, Yuichi; Hatano Noriyuki, Ohya Susumu, Takikawa Rie, Watabiki Tomonari, Takasugi Nobumasa, Imaizumi Yuji, Tomita Taisuke, Iwatsubo Takeshi (Apr. 2002). "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4". J. Biol. Chem. (United States) 277 (17): 14965–75. doi:10.1074/jbc.M200897200. ISSN 0021-9258. PMID 11847232.  
  11. ^ Shinozaki, K; Maruyama K, Kume H, Tomita T, Saido T C, Iwatsubo T, Obata K (May. 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. (GREECE) 1 (5): 797–9. ISSN 1107-3756. PMID 9852298.  
  12. ^ Stabler, S M; Ostrowski L L, Janicki S M, Monteiro M J (Jun. 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. (UNITED STATES) 145 (6): 1277–92. ISSN 0021-9525. PMID 10366599.  
  13. ^ Buxbaum, J D; Choi E K, Luo Y, Lilliehook C, Crowley A C, Merriam D E, Wasco W (Oct. 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. (UNITED STATES) 4 (10): 1177–81. doi:10.1038/2673. ISSN 1078-8956. PMID 9771743.  
  14. ^ Choi, E K; Zaidi N F, Miller J S, Crowley A C, Merriam D E, Lilliehook C, Buxbaum J D, Wasco W (Jun. 2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem. (United States) 276 (22): 19197–204. doi:10.1074/jbc.M008597200. ISSN 0021-9258. PMID 11278424.  

Further reading

  • Cruts M, Van Broeckhoven C (1998). "Presenilin mutations in Alzheimer's disease.". Hum. Mutat. 11 (3): 183–90. doi:10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J. PMID 9521418.  
  • McGeer PL, Kawamata T, McGeer EG (1998). "Localization and possible functions of presenilins in brain.". Reviews in the neurosciences 9 (1): 1–15. PMID 9683324.  
  • Nishimura M, Yu G, St George-Hyslop PH (1999). "Biology of presenilins as causative molecules for Alzheimer disease.". Clin. Genet. 55 (4): 219–25. PMID 10361981.  
  • da Costa CA (2006). "Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments.". Current Alzheimer research 2 (5): 507–14. PMID 16375654.  
  • Wolfe MS (2007). "When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease.". EMBO Rep. 8 (2): 136–40. doi:10.1038/sj.embor.7400896. PMID 17268504.  
  • De Strooper B (2007). "Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease.". EMBO Rep. 8 (2): 141–6. doi:10.1038/sj.embor.7400897. PMID 17268505.  
Advertisements

Advertisements






Got something to say? Make a comment.
Your name
Your email address
Message