Nicastrin


Nicastrin
Nicastrin
Identifiers
Symbols NCSTN; APH2; KIAA0253
External IDs OMIM605254 MGI1891700 HomoloGene41029 GeneCards: NCSTN Gene
RNA expression pattern
PBB GE NCSTN 208759 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 23385 59287
Ensembl ENSG00000162736 ENSMUSG00000003458
UniProt Q92542 Q3T9E5
RefSeq (mRNA) NM_015331.2 NM_021607.3
RefSeq (protein) NP_056146.1 NP_067620.3
Location (UCSC) Chr 1:
160.31 – 160.33 Mb
Chr 1:
174 – 174.01 Mb
PubMed search [1] [2]

Nicastrin, also known as NCSTN, is a protein which in humans is encoded by the NCSTN gene.[1][2][3]

Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing amyloid precursor protein (APP) to the short Alzheimer's disease-associated peptide amyloid beta. The other proteins in the complex are presenilin, which is the catalytically active component of the complex, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2).[4] Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell.[5] Nicastrin has also been identified as a regulator of neprilysin, an enzyme involved in the degradation of amyloid beta fragment.[6]

Contents

History

The protein was named after the Italian village Nicastro, reflecting the fact that Alzheimer's disease was described in 1963 after studying descendants of an extended family originating in the village of Nicastro that had Familial Alzheimer's Disease (FAD).[7]

Interactions

Nicastrin has been shown to interact with PSEN1[8][9][10][11][3] and PSEN2.[11][3]

References

  1. ^ "Entrez Gene: NCSTN nicastrin". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23385. 
  2. ^ Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (October 1996). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502. http://dnaresearch.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9039502. 
  3. ^ a b c Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, 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 407 (6800): 48–54. doi:10.1038/35024009. PMID 10993067. 
  4. ^ Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neurodegener Dis 3 (4–5): 275–83. doi:10.1159/000095267. PMID 17047368. 
  5. ^ Zhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H (April 2005). "Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components". J. Biol. Chem. 280 (17): 17020–6. doi:10.1074/jbc.M409467200. PMC 1201533. PMID 15711015. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1201533. 
  6. ^ Pardossi-Piquard R, Dunys J, Yu G, St George-Hyslop P, Alves da Costa C, Checler F (May 2006). "Neprilysin activity and expression are controlled by nicastrin". J. Neurochem. 97 (4): 1052–6. doi:10.1111/j.1471-4159.2006.03822.x. PMID 16606360. 
  7. ^ Feldman RG, Chandler KA, Levy LL, Gaser GH (October 1963). "Familial Alzheimer's Disease". Neurology 13: 811–24. PMID 14066996. 
  8. ^ Haffner, Christof; Frauli Mélanie, Topp Stephanie, Irmler Martin, Hofmann Kay, Regula Jörg T, Bally-Cuif Laure, Haass Christian (Aug. 2004). "Nicalin and its binding partner Nomo are novel Nodal signaling antagonists". EMBO J. (England) 23 (15): 3041–50. doi:10.1038/sj.emboj.7600307. ISSN 0261-4189. PMC 514924. PMID 15257293. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514924. 
  9. ^ Baulac, Stephanie; LaVoie Matthew J, Kimberly W Taylor, Strahle Jennifer, Wolfe Michael S, Selkoe Dennis J, Xia Weiming (Nov. 2003). "Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase substrates". Neurobiol. Dis. (United States) 14 (2): 194–204. doi:10.1016/S0969-9961(03)00123-2. ISSN 0969-9961. PMID 14572442. 
  10. ^ Gu, Yongjun; Chen Fusheng, Sanjo Nobuo, Kawarai Toshitaka, Hasegawa Hiroshi, Duthie Monica, Li Wenping, Ruan Xueying, Luthra Anchla, Mount Howard T J, Tandon Anurag, Fraser Paul E, St George-Hyslop Peter (Feb. 2003). "APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes". J. Biol. Chem. (United States) 278 (9): 7374–80. doi:10.1074/jbc.M209499200. ISSN 0021-9258. PMID 12471034. 
  11. ^ a b 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. 

Further reading

External links


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