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{{protein
{{Infobox_gene}}
|Name=nicastrin
'''Nicastrin''', also known as '''NCSTN''', is a [[protein]] that in humans is encoded by the ''NCSTN'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NCSTN nicastrin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23385| accessdate = }}</ref><ref name="pmid9039502">{{cite journal | vauthors = Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N | title = 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 | journal = DNA Research | volume = 3 | issue = 5 | pages = 321–9, 341–54 | date = Oct 1996 | pmid = 9039502 | doi = 10.1093/dnares/3.5.321 | url = http://dnaresearch.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=9039502 }}</ref><ref name=PMI10993067>{{cite journal | vauthors = 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 | title = Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing | journal = Nature | volume = 407 | issue = 6800 | pages = 48–54 | date = Sep 2000 | pmid = 10993067 | doi = 10.1038/35024009 }}</ref>
|caption=
|image=
|width=
|HGNCid=17091
|Symbol=NCSTN
|AltSymbols=
|EntrezGene=23385
|OMIM=605254
|RefSeq=NM_015331
|UniProt=Q92542
|PDB=
|ECnumber=
|Chromosome=1
|Arm=q
|Band=22
|LocusSupplementaryData=-q23
}}
'''Nicastrin''' (abbreviated NCT) is a [[protein]] that is part of the [[gamma secretase]] [[protein complex]], which is one of the [[protease]]s 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 [[catalysis|catalytically]] active component of the complex, [[APH-1]] (anterior pharynx-defective 1), and [[PEN-2]] (presenilin enhancer 2).<ref name="Kaether">Kaether C, Haass C, Steiner H. (2006). Assembly, trafficking and function of gamma-secretase. ''Neurodegener Dis'' 3(4-5):275-83. PMID 17047368</ref> 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. <ref name="Zhang">Zhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H. (2005). Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components. ''J Biol Chem'' 280(17):17020-6. PMID 15711015</ref> Nicastrin has also been identified as a regulator of [[neprilysin]], an [[enzyme]] involved in the degradation of amyloid beta fragment.<ref name="Pardossi">Pardossi-Piquard R, Dunys J, Yu G, St George-Hyslop P, Alves da Costa C, Checler F. (2006). Neprilysin activity and expression are controlled by nicastrin. ''J Neurochem'' 97(4):1052-6. PMID 16606360 </ref>


==References==
==Function==
{{reflist|2}}
Nicastrin (abbreviated NCT) is a [[protein]] that is part of the [[gamma secretase]] [[protein complex]], which is one of the [[protease]]s involved in processing [[amyloid precursor protein]] (APP) to the short [[Alzheimer's disease]]-associated peptide [[amyloid beta]]. The other proteins in the complex are [[PSEN1]] (presenilin-1), which is the [[catalysis|catalytically]] active component of the complex, [[APH-1]] (anterior pharynx-defective 1), and [[PEN-2]] (presenilin enhancer 2).<ref name="pmid17047368">{{cite journal | vauthors = Kaether C, Haass C, Steiner H | title = Assembly, trafficking and function of gamma-secretase | journal = Neuro-Degenerative Diseases | volume = 3 | issue = 4–5 | pages = 275–83 | year = 2006 | pmid = 17047368 | doi = 10.1159/000095267 }}</ref> 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.<ref name="pmid15711015">{{cite journal | vauthors = Zhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H | title = Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components | journal = The Journal of Biological Chemistry | volume = 280 | issue = 17 | pages = 17020–6 | date = Apr 2005 | pmid = 15711015 | pmc = 1201533 | doi = 10.1074/jbc.M409467200 }}</ref> Nicastrin has also been identified as a regulator of [[neprilysin]], an [[enzyme]] involved in the degradation of amyloid beta fragment.<ref name="pmid16606360">{{cite journal | vauthors = Pardossi-Piquard R, Dunys J, Yu G, St George-Hyslop P, Alves da Costa C, Checler F | title = Neprilysin activity and expression are controlled by nicastrin | journal = Journal of Neurochemistry | volume = 97 | issue = 4 | pages = 1052–6 | date = May 2006 | pmid = 16606360 | doi = 10.1111/j.1471-4159.2006.03822.x }}</ref>


==External links==
==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).<ref name="pmid14066996">{{cite journal | vauthors = Feldman RG, Chandler KA, Levy LL, Glaser GH | title = FAMILIAL ALZHEIMER'S DISEASE | journal = Neurology | volume = 13 | issue =  10| pages = 811–24 | date = Oct 1963 | pmid = 14066996 | doi = 10.1212/wnl.13.10.811 }}</ref>
 
== Interactions ==
 
Nicastrin has been shown to [[Protein-protein interaction|interact]] with [[PSEN1]]<ref name=pmid10993067>{{cite journal | vauthors = 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 | title = Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing | journal = Nature | volume = 407 | issue = 6800 | pages = 48–54 | date = Sep 2000 | pmid = 10993067 | doi = 10.1038/35024009 }}</ref><ref name=pmid15257293>{{cite journal | vauthors = Haffner C, Frauli M, Topp S, Irmler M, Hofmann K, Regula JT, Bally-Cuif L, Haass C | title = Nicalin and its binding partner Nomo are novel Nodal signaling antagonists | journal = The EMBO Journal | volume = 23 | issue = 15 | pages = 3041–50 | date = Aug 2004 | pmid = 15257293 | pmc = 514924 | doi = 10.1038/sj.emboj.7600307 }}</ref><ref name=pmid14572442>{{cite journal | vauthors = Baulac S, LaVoie MJ, Kimberly WT, Strahle J, Wolfe MS, Selkoe DJ, Xia W | title = Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase substrates | journal = Neurobiology of Disease | volume = 14 | issue = 2 | pages = 194–204 | date = Nov 2003 | pmid = 14572442 | doi = 10.1016/S0969-9961(03)00123-2 }}</ref><ref name=pmid12471034>{{cite journal | vauthors = Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, Luthra A, Mount HT, Tandon A, Fraser PE, St George-Hyslop P | title = APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 9 | pages = 7374–80 | date = Feb 2003 | pmid = 12471034 | doi = 10.1074/jbc.M209499200 }}</ref><ref name=pmid12297508>{{cite journal | vauthors = Lee SF, Shah S, Li H, Yu C, Han W, Yu G | title = Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 45013–9 | date = Nov 2002 | pmid = 12297508 | doi = 10.1074/jbc.M208164200 }}</ref> and [[PSEN2]].<ref name=pmid10993067/><ref name=pmid12297508/>
{{clear}}
== References ==
{{reflist|30em}}
 
== External links ==
* {{MeshName|nicastrin+protein}}
* {{MeshName|nicastrin+protein}}


[[Category:Alzheimer's disease]]
[[Category:Alzheimer's disease]]
[[Category:Proteins]]
[[Category:Proteins]]
{{protein-stub}}
{{WikiDoc Sources}}

Latest revision as of 18:02, 6 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

Function

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 PSEN1 (presenilin-1), 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]

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][12] and PSEN2.[8][12]

References

  1. ↑ "Entrez Gene: NCSTN nicastrin".
  2. ↑ Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N (Oct 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 Research. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
  3. ↑ 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 (Sep 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". Neuro-Degenerative Diseases. 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 (Apr 2005). "Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components". The Journal of Biological Chemistry. 280 (17): 17020–6. doi:10.1074/jbc.M409467200. PMC 1201533. PMID 15711015.
  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". Journal of Neurochemistry. 97 (4): 1052–6. doi:10.1111/j.1471-4159.2006.03822.x. PMID 16606360.
  7. ↑ Feldman RG, Chandler KA, Levy LL, Glaser GH (Oct 1963). "FAMILIAL ALZHEIMER'S DISEASE". Neurology. 13 (10): 811–24. doi:10.1212/wnl.13.10.811. PMID 14066996.
  8. ↑ 8.0 8.1 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 (Sep 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature. 407 (6800): 48–54. doi:10.1038/35024009. PMID 10993067.
  9. ↑ Haffner C, Frauli M, Topp S, Irmler M, Hofmann K, Regula JT, Bally-Cuif L, Haass C (Aug 2004). "Nicalin and its binding partner Nomo are novel Nodal signaling antagonists". The EMBO Journal. 23 (15): 3041–50. doi:10.1038/sj.emboj.7600307. PMC 514924. PMID 15257293.
  10. ↑ Baulac S, LaVoie MJ, Kimberly WT, Strahle J, Wolfe MS, Selkoe DJ, Xia W (Nov 2003). "Functional gamma-secretase complex assembly in Golgi/trans-Golgi network: interactions among presenilin, nicastrin, Aph1, Pen-2, and gamma-secretase substrates". Neurobiology of Disease. 14 (2): 194–204. doi:10.1016/S0969-9961(03)00123-2. PMID 14572442.
  11. ↑ Gu Y, Chen F, Sanjo N, Kawarai T, Hasegawa H, Duthie M, Li W, Ruan X, Luthra A, Mount HT, Tandon A, Fraser PE, St George-Hyslop P (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". The Journal of Biological Chemistry. 278 (9): 7374–80. doi:10.1074/jbc.M209499200. PMID 12471034.
  12. ↑ 12.0 12.1 Lee SF, Shah S, Li H, Yu C, Han W, Yu G (Nov 2002). "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch". The Journal of Biological Chemistry. 277 (47): 45013–9. doi:10.1074/jbc.M208164200. PMID 12297508.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Nicastrin&oldid=1410754"