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proteins. Page last changed on 19 Dec 2016.
Nicastrin
Nicastrin, APH-2, NCSTN
This gene encodes a Type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Alternatively spliced transcript variants have been described, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008] (from
NCBI)
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Top mentioned proteins:
Presenilin-1, APH, APP, APH-1, PEN-2
Papers on
Nicastrin
Gene expression profiling of skin and blood in hidradenitis suppurativa.
New
Groningen, Netherlands. In Br J Dermatol, Jan 2016
Mutations in genes encoding for essential compounds of the transmembrane protease ү-secretase, including NCSTN, PSEN1 and PSENEN, have been identified in familial HS.((1,2))
Quinomycin A targets Notch signaling pathway in pancreatic cancer stem cells.
New
Kansas City, United States. In Oncotarget, Jan 2016
The γ-secretase complex proteins, Presenilin 1, Nicastrin, Pen2, and APH-1, required for Notch activation also exhibited decreased expression.
Phenotype of 53 Chinese individuals with nicastrin gene mutations in association with familial hidradenitis suppurativa (acne inversa).
New
Nanjing, China. In Br J Dermatol, Dec 2015
In 2010, Wang et al firstly reported that familial HS was related to γ-secretase mutation (2) , which consists of presenilin, nicastrin (NCSTN), presenilin enhancer 2, and anterior pharynx defective 1. Subsequently, other studies provided further evidence to support this finding.
Characterization of a Novel Mutation in the NCSTN Gene in a Large Chinese Family with Acne Inversa.
New
Fuding, China. In Acta Derm Venereol, Nov 2015
UNASSIGNED: is missing (Short communication).
Preclinical Evaluation of miR-15/107 Family Members as Multifactorial Drug Targets for Alzheimer's Disease.
Québec, Canada. In Mol Ther Nucleic Acids, 2014
We further identified Nicastrin, a γ-secretase component involved in Aβ generation, as a target of miR-16.
The FDA-approved natural product dihydroergocristine reduces the production of the Alzheimer's disease amyloid-β peptides.
Shanghai, China. In Sci Rep, 2014
A Surface Plasmon Resonance assay showed that DHEC binds directly to γ-secretase and Nicastrin, with equilibrium dissociation constants (Kd) of 25.7 nM and 9.8 μM, respectively.
Development and mechanism of γ-secretase modulators for Alzheimer's disease.
Review
New York City, United States. In Biochemistry, 2013
γ-Secretase is an aspartyl intramembranal protease composed of presenilin, Nicastrin, Aph1, and Pen2 with 19 transmembrane domains.
γ-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis.
Review
London, United Kingdom. In J Invest Dermatol, 2013
It may segregate as an autosomal dominant trait, and heterozygous mutations in the γ-secretase genes NCSTN, PSENEN, and PSEN1 have recently been reported in a small number of multiplex kindreds and sporadic cases.
Oxidative lipid modification of nicastrin enhances amyloidogenic γ-secretase activity in Alzheimer's disease.
GeneRIF
Suwŏn, South Korea. In Aging Cell, 2012
The gamma-secretase substrate receptor, nicastrin, was found to be modified by 4-hydroxynonenal in cultured neurons and in brain specimens from patients with Alzheimer's disease.
Functional and genetic analysis of haplotypic sequence variation at the nicastrin genomic locus.
GeneRIF
Oxford, United Kingdom. In Neurobiol Aging, 2012
We therefore conclude that it is unlikely that common variation at the NCSTN locus is a risk factor for Alzheimer's disease.
Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of γ-secretase using synthetic antibodies.
GeneRIF
Chicago, United States. In Proc Natl Acad Sci U S A, 2012
Data suggest that nicastrin functions as a "substrate receptor" within the gamma-secretase complex.
Phosphorylation of nicastrin by SGK1 leads to its degradation through lysosomal and proteasomal pathways.
GeneRIF
Kwangju, South Korea. In Plos One, 2011
SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT.
[Nicastrin].
GeneRIF
Japan. In Nihon Rinsho, 2011
Nicastrin is an essential component in the activation of gama-selectase complex. Its physical function and molecular genetic studies have been reveiwed.
Gamma-secretase gene mutations in familial acne inversa.
Impact
GeneRIF
Beijing, China. In Science, 2010
study found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN in 6 Chinese acne inversa (AI) families; results identify the gamma-secretase component genes as culprits for a subset of familial AI
Signal peptide peptidases: a family of intramembrane-cleaving proteases that cleave type 2 transmembrane proteins.
Review
Jacksonville, United States. In Semin Cell Dev Biol, 2009
At least two of the human SPPs (SPP and SPPL3) appear to function without additional cofactors, but PSENs function as a protease, called gamma-secretase, only when complexed with Nicastrin, APH-1 and Pen-2.
Interactions between the products of the Herpes simplex genome and Alzheimer's disease susceptibility genes: relevance to pathological-signalling cascades.
Review
In Neurochem Int, 2008
For example, HSV-1 binds to heparan sulphate proteoglycans (HSPG2), or alpha-2-macroglobulin (A2M), and enters cells via nectin receptors, which are cleaved by gamma-secretase (APH1B, PSEN1, PSEN2, PEN2, NCSTN).
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database.
Impact
United States. In Nat Genet, 2007
In addition to identifying the epsilon4 allele of APOE and related effects, we pinpointed over a dozen potential Alzheimer disease susceptibility genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM and TNF) with statistically significant allelic summary odds ratios (ranging from 1.11-1.38 for risk alleles and 0.92-0.67 for protective alleles).
Convergence of genes implicated in Alzheimer's disease on the cerebral cholesterol shuttle: APP, cholesterol, lipoproteins, and atherosclerosis.
Review
In Neurochem Int, 2007
Gamma-secretase (PSEN1, PSEN2, NCSTN) cleaves LRP1 and LRP8 as well as APP and their degradation products control transcription factor TFCP2, which regulates thymidylate synthase (TS) and GSK3B expression.
Nicastrin is required for Presenilin-mediated transmembrane cleavage in Drosophila.
Impact
New York City, United States. In Nat Cell Biol, 2001
The transmembrane glycoprotein Nicastrin was identified in a complex with the multipass membrane protein Presenilin.
Nicastrin binds to membrane-tethered Notch.
Impact
Toronto, Canada. In Nat Cell Biol, 2001
Although absence of the Caenorhabditis elegans nicastrin homologue (aph-2) is known to cause an embryonic-lethal glp-1 phenotype, the role of nicastrin in this process has not been explored.
