Nicastrin

From Wikipedia, the free encyclopedia

Nicastrin

Identifiers

NCSTN; APH2; KIAA0253; RP11-517F10.1

External IDs

OMIM: 605254 MGI: 1891700 HomoloGene: 41029

Gene ontology
Molecular Function:	• protein binding
Cellular Component:	• membrane fraction • endoplasmic reticulum • Golgi apparatus • integral to plasma membrane • membrane
Biological Process:	• membrane protein ectodomain proteolysis • Notch receptor processing • protein processing • amyloid precursor protein catabolic process • positive regulation of enzyme activity

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_015331 (mRNA)
NP_056146 (protein)

NM_021607 (mRNA)
NP_067620 (protein)

Location

Chr 1: 158.58 - 158.6 Mb

Chr 1: 173.9 - 173.92 Mb

Pubmed search

[1]

[2]

Nicastrin, also known as NCSTN, is a human gene.^[1]

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).^[2] 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. ^[3] Nicastrin has also been identified as a regulator of neprilysin, an enzyme involved in the degradation of amyloid beta fragment.^[4]

[edit] References

^ Entrez Gene: NCSTN nicastrin.
^ Kaether C, Haass C, Steiner H. (2006). Assembly, trafficking and function of gamma-secretase. Neurodegener Dis 3(4-5):275-83. PMID 17047368
^ 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
^ 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

[edit] Further reading

Nagase T, Seki N, Ishikawa K, et al. (1997). "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. PMID 9039502.
Yu G, Nishimura M, Arawaka S, et al. (2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing.". Nature 407 (6800): 48–54. doi:10.1038/35024009. PMID 10993067.
Fagan R, Swindells M, Overington J, Weir M (2001). "Nicastrin, a presenilin-interacting protein, contains an aminopeptidase/transferrin receptor superfamily domain.". Trends Biochem. Sci. 26 (4): 213–4. PMID 11295540.
Satoh J, Kuroda Y (2001). "Nicastrin, a key regulator of presenilin function, is expressed constitutively in human neural cell lines.". Neuropathology : official journal of the Japanese Society of Neuropathology 21 (2): 115–22. PMID 11396676.
Chen F, Yu G, Arawaka S, et al. (2001). "Nicastrin binds to membrane-tethered Notch.". Nat. Cell Biol. 3 (8): 751–4. doi:10.1038/35087069. PMID 11483961.
Fergani A, Yu G, St George-Hyslop P, Checler F (2002). "Wild-type and mutated nicastrins do not display aminopeptidase M- and B-like activities.". Biochem. Biophys. Res. Commun. 289 (3): 678–80. doi:10.1006/bbrc.2001.6030. PMID 11726200.
Leem JY, Vijayan S, Han P, et al. (2002). "Presenilin 1 is required for maturation and cell surface accumulation of nicastrin.". J. Biol. Chem. 277 (21): 19236–40. doi:10.1074/jbc.C200148200. PMID 11943765.
Dermaut B, Theuns J, Sleegers K, et al. (2002). "The gene encoding nicastrin, a major gamma-secretase component, modifies risk for familial early-onset Alzheimer disease in a Dutch population-based sample.". Am. J. Hum. Genet. 70 (6): 1568–74. PMID 11992262.
Li B, Cong F, Tan CP, et al. (2002). "Aph2, a protein with a zf-DHHC motif, interacts with c-Abl and has pro-apoptotic activity.". J. Biol. Chem. 277 (32): 28870–6. doi:10.1074/jbc.M202388200. PMID 12021275.
Yang DS, Tandon A, Chen F, et al. (2002). "Mature glycosylation and trafficking of nicastrin modulate its binding to presenilins.". J. Biol. Chem. 277 (31): 28135–42. doi:10.1074/jbc.M110871200. PMID 12032140.
Tomita T, Katayama R, Takikawa R, Iwatsubo T (2002). "Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments.". FEBS Lett. 520 (1-3): 117–21. PMID 12044882.
Edbauer D, Winkler E, Haass C, Steiner H (2002). "Presenilin and nicastrin regulate each other and determine amyloid beta-peptide production via complex formation.". Proc. Natl. Acad. Sci. U.S.A. 99 (13): 8666–71. doi:10.1073/pnas.132277899. PMID 12048259.
Hattori C, Asai M, Oma Y, et al. (2002). "BACE1 interacts with nicastrin.". Biochem. Biophys. Res. Commun. 293 (4): 1228–32. doi:10.1016/S0006-291X(02)00351-0. PMID 12054507.
Kimberly WT, LaVoie MJ, Ostaszewski BL, et al. (2002). "Complex N-linked glycosylated nicastrin associates with active gamma-secretase and undergoes tight cellular regulation.". J. Biol. Chem. 277 (38): 35113–7. doi:10.1074/jbc.M204446200. PMID 12130643.
Steiner H, Winkler E, Edbauer D, et al. (2002). "PEN-2 is an integral component of the gamma-secretase complex required for coordinated expression of presenilin and nicastrin.". J. Biol. Chem. 277 (42): 39062–5. doi:10.1074/jbc.C200469200. PMID 12198112.
Lee SF, Shah S, Li H, et al. (2003). "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.
Gu Y, Chen F, Sanjo N, et al. (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. 278 (9): 7374–80. doi:10.1074/jbc.M209499200. PMID 12471034.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Siman R, Velji J (2003). "Localization of presenilin-nicastrin complexes and gamma-secretase activity to the trans-Golgi network.". J. Neurochem. 84 (5): 1143–53. PMID 12603837.
Basrur V, Yang F, Kushimoto T, et al. (2003). "Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.". J. Proteome Res. 2 (1): 69–79. PMID 12643545.