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FLASH GENE
Symbol NCSTN contributors: mct - updated : 27-01-2015
HGNC name nicastrin
HGNC id 17091
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivemouthtongue  highly
Reproductivefemale systemuteruscervix highly
 female systembreastmammary gland highly
 female systemplacenta  highly
 male systemprostate  highly
 male systemtestis  highly
Respiratorylung   highly
 respiratory tractlarynx  highly
Skin/Tegumentskin   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow   
Connectivebone   
Muscular    
cell lineage
cell lines
fluid/secretion blood
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • a N terminal signal peptide, a region with four conserved cysteine residues, followed by the DYIGS
  • two highly conserved domains
  • a transmembrane segment (TM1)
  • a short hydrophilic cytoplasmic tail of 20 AA with 16 extracellular potential glycosylation sites
  • one aminopeptidase I transferrin receptor superfamily domain (binding domain for beta-amyloid precursor protein)
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to rattus Ncstn
    ortholog to murine Ncstn
    Homologene
    FAMILY
  • gamma secretase family
  • nicastrin family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,lysosome
    text colocalizing with presenilin
    basic FUNCTION
  • modulating presenilin mediated notch/glp-1 signal transduction in C elegans
  • potential modulator of APP beta cleavage by secretase gamma
  • involved in the degradation of amyloid precursor protein to produce beta-amyloid peptides
  • member of the gamma-secretase complex, playing a role, with PSEN1, APH1A, PSENEN, necessary and sufficient to reconstitute gamma-secretase activity
  • essential component of the gamma secretase (GS) enzyme complex, required for its synthesis and recognition of substrates for proteolytic cleavage
  • can function to maintain epithelial to mesenchymal transition during breast cancer progression
  • part of the gamma-secretase complex and potentially involved in substrate recognition and selection
  • regulates EMT and breast cancer stem cells through NOTCH and AKT1 pathways
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    text
  • amyloid precursor protein catabolism
  • membrane protein ectodomain proteolysis
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
  • component of PSEN1 and PSEN2 complexes
  • may be part of a complex involved in the intramembrane processing of transmembrane protein
  • part of gamma-secretase complex, composed of four non-covalently bound transmembrane proteins Presenilin, Nicastrin APH1A, APH1B, PSENEN, that is responsible for the intramembranous cleavage of amyloid precursor protein (APP) and NOTCH
  • PSEN1 or PSEN2, nicastrin (NCSTN), anterior pharynx-defective 1 (APH1A), and PSENEN have been considered the minimal essential subunits required to form an active gamma-secretase complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PSEN1
  • PSEN2
  • interacted with LMAN1 prior to its association with the active gamma-secretase complex
  • SYVN1 interacts with NCSTN (SYVN1-mediated ubiquitination is involved in the degradation of immature nicastrin, and probably regulates amyloid beta-protein generation)
  • HERPUD1 is likely involved in degradation of immature nicastrin by facilitating VCP-dependent nicastrin retranslocation and ubiquitination)
  • may have an important mechanistic role underlying the increased risk of dissemination of Breast cancer cells through regulation of vimentin, SNAI1, and MMPs
  • extracellular domain of NCSTN directly binds PSENEN at the thin end
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AIF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer (
    Susceptibility to Alzheimer disease
    Variant & Polymorphism SNP
  • HAPB increased the risk of early-onset Alzheimer disease
  • rare SNP (N417Y) with a statistically higher frequency in Alzheimer disease compared to controls
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    nicastrin blocking antibody could be used to limit metastatic dissemination in invasive breast cancer
    ANIMAL & CELL MODELS