PSEN2

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Presenilin 2
Identifiers
Symbols PSEN2 ; AD3L; AD4; CMD1V; PS2; STM2
External IDs OMIM600759 MGI109284 HomoloGene386 IUPHAR: 2403 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:

References[edit]

  1. ^ Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH et al. (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, Widmer DS, Praetorius C, Einarsson SO 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. ^ Passer BJ, Pellegrini L, Vito P, Ganjei JK, 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. 274 (34): 24007–13. doi:10.1074/jbc.274.34.24007. PMID 10446169. 
  5. ^ Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T et al. (May 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. 1 (5): 797–9. doi:10.3892/ijmm.1.5.797. PMID 9852298. 
  6. ^ Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ (June 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. 145 (6): 1277–92. doi:10.1083/jcb.145.6.1277. PMC 2133148. PMID 10366599. 
  7. ^ Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE et al. (October 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. 4 (10): 1177–81. doi:10.1038/2673. PMID 9771752. 
  8. ^ Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C et al. (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. 276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID 11278424. 
  9. ^ Tanahashi H, Tabira T (September 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. 9 (15): 2281–9. doi:10.1093/oxfordjournals.hmg.a018919. PMID 11001931. 
  10. ^ Zhang W, Han SW, McKeel DW, Goate A, Wu JY (February 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. 18 (3): 914–22. PMC 2042137. PMID 9437013. 
  11. ^ Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N et al. (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. 277 (17): 14965–75. doi:10.1074/jbc.M200897200. PMID 11847232. 
  12. ^ Lee SF, Shah S, Li H, Yu C, Han W, Yu G (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. 277 (47): 45013–9. doi:10.1074/jbc.M208164200. PMID 12297508. 
  13. ^ Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A et al. (September 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature 407 (6800): 48–54. doi:10.1038/35024009. PMID 10993067. 
  14. ^ Mah AL, Perry G, Smith MA, Monteiro MJ (November 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. 151 (4): 847–62. doi:10.1083/jcb.151.4.847. PMC 2169435. PMID 11076969. 

Further reading[edit]

External links[edit]