PSEN2

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Presenilin 2
Identifiers
Symbols PSEN2 ; AD3L; AD4; CMD1V; PS2; STM2
External IDs OMIM600759 MGI109284 HomoloGene386 ChEMBL: 3708 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 Q61144
RefSeq (mRNA) NM_000447 NM_001128605
RefSeq (protein) NP_000438 NP_001122077
Location (UCSC) Chr 1:
227.06 – 227.08 Mb
Chr 1:
180.23 – 180.26 Mb
PubMed search [1] [2]

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

Function[edit]

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 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[edit]

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[edit]

  1. ^ Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K, Crowley AC, Fu YH, Guenette SY, Galas D, Nemens E, Wijsman EM, Bird TD, Schellenberg GD, Tanzi RE (September 1995). "Candidate gene for the chromosome 1 familial Alzheimer's disease locus". Science 269 (5226): 973–977. doi:10.1126/science.7638622. PMID 7638622. 
  2. ^ "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)". 
  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): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  4. ^ Mah, A L; Perry G; Smith M A; Monteiro M J (November 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. (UNITED STATES) 151 (4): 847–862. doi:10.1083/jcb.151.4.847. ISSN 0021-9525. PMC 2169435. PMID 11076969. 
  5. ^ Tanahashi, H; Tabira T (September 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. (ENGLAND) 9 (15): 2281–9. doi:10.1093/oxfordjournals.hmg.a018919. ISSN 0964-6906. PMID 11001931. 
  6. ^ Zhang, W; Han S W; McKeel D W; Goate A; Wu J Y (February 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. (UNITED STATES) 18 (3): 914–22. ISSN 0270-6474. PMC 2042137. PMID 9437013. 
  7. ^ Passer, B J; Pellegrini L; Vito P; Ganjei J K; D'Adamio L (August 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): 24007–24013. doi:10.1074/jbc.274.34.24007. ISSN 0021-9258. PMID 10446169. 
  8. ^ Lee, Sheu-Fen; Shah Sanjiv; Li Hongqiao; Yu Cong; Han Weiping; Yu Gang (November 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): 45013–45019. 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 (September 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 10993067. 
  10. ^ Morohashi, Yuichi; Hatano Noriyuki; Ohya Susumu; Takikawa Rie; Watabiki Tomonari; Takasugi Nobumasa; Imaizumi Yuji; Tomita Taisuke; Iwatsubo Takeshi (April 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): 14965–14975. 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. doi:10.3892/ijmm.1.5.797. ISSN 1107-3756. PMID 9852298. 
  12. ^ Stabler, S M; Ostrowski L L; Janicki S M; Monteiro M J (June 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. (UNITED STATES) 145 (6): 1277–1292. doi:10.1083/jcb.145.6.1277. ISSN 0021-9525. PMC 2133148. PMID 10366599. 
  13. ^ Buxbaum, J D; Choi E K; Luo Y; Lilliehook C; Crowley A C; Merriam D E; Wasco W (October 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): 1177–1181. doi:10.1038/2673. ISSN 1078-8956. PMID 9771752. 
  14. ^ Choi, E K; Zaidi N F; Miller J S; Crowley A C; Merriam D E; Lilliehook C; Buxbaum J D; Wasco W (June 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): 19197–19204. doi:10.1074/jbc.M008597200. ISSN 0021-9258. PMID 11278424. 

Further reading[edit]

External links[edit]