Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol NCSTN contributors: mct - updated : 27-01-2015
HGNC name nicastrin
HGNC id 17091
Corresponding disease
AIF acne inversa, familial
Location 1q23.2      Physical location : 160.313.062 - 160.328.741
Synonym name anterior pharynx-defective 2
Synonym symbol(s) KIAA0253, APH2, NCT
DNA
TYPE functioning gene
STRUCTURE 15.68 kb     17 Exon(s)
Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
LOC171422 1q23.1 C-reactive protein pseudogene CRP 1q23.2 C-reactive protein, pentraxin-related FLJ20442 1q23.1 hypothetical protein FLJ20442 LOC343413 1q23.1 similar to Fc receptor homolog expressed in B cells; Fc receptor related protein X SLAMF8 1q23.1 SLAM family member 8 LOC391123 1 similar to hypothetical protein A030011M19 NESG1 1q22 similar to hypothetical protein A030011M19 TAGLN2 1q22 transgelin 2 IGSF9 1q22-q23 immunoglobulin superfamily, member 9 SLAMF9 1q23.1 SLAM family member 9 LOC391124 1 similar to ribosomal protein L27a; ribosomal protein L29 homolog (yeast) PIGM 1q22 phosphatidylinositol glycan, class M KCNJ10 1q22 potassium inwardly-rectifying channel, subfamily J, member 10 KCNJ9 1q22 potassium inwardly-rectifying channel, subfamily J, member 9 IGSF8 1q23.1 immunoglobulin superfamily, member 8 ATP1A2 1q22 ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide ATP1A4 1q22 ATPase, Na+/K+ transporting, alpha 4 polypeptide CASQ1 1q22 calsequestrin 1 (fast-twitch, skeletal muscle) PEA15 1q22 phosphoprotein enriched in astrocytes 15 H326 1q22-q23 H326 LOC388707 1 hypothetical gene supported by BC005391; NM_002295 COPA 1q22 coatomer protein complex, subunit alpha PXF 1q22 peroxisomal farnesylated protein NCSTN 1q22 peroxisomal farnesylated protein NHLH1 1q22 nescient helix loop helix 1 VANGL2 1q22 vang-like 2 (van gogh, Drosophila) SLAMF6 1q23.1 SLAM family member 6 CD84 1q22-q23 CD84 antigen (leukocyte antigen) SLAMF1 1q21.3-1q23.2 signaling lymphocytic activation molecule family member 1 CD48 1q23 CD48 antigen (B-cell membrane protein) SLAMF7 1q23.1-q24.1 SLAM family member 7 LY9 1q21.3-q22 lymphocyte antigen 9 CD244 1q23.1 CD244 natural killer cell receptor 2B4 ITLN1 1q21.3 intelectin 1 (galactofuranose binding) LOC284679 1q23.1 similar to spermine synthase; spermidine aminopropyltransferase ITLN2 1q22-q23.5 intelectin 2 F11R 1q21.2-q21.3 F11 receptor
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
17 - 2944 - 709 - 2006 16938437
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