FB2026_02 , released June 18, 2026
Gene: Dmel\Nct
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General Information
Symbol
Dmel\Nct
Species
D. melanogaster
Name
Nicastrin
Annotation Symbol
CG7012
Feature Type
FlyBase ID
FBgn0039234
Gene Model Status
Stock Availability
Gene Summary
Nicastrin (Nct) encodes a transmembrane protein that is a key component of the γ-secretase, the protease complex for proteolytic cleavage of the Notch signaling receptor. [Date last reviewed: 2018-11-08] (FlyBase Gene Snapshot)
Also Known As

agro, dNicastrin, nic

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-86
RefSeq locus
NT_033777 REGION:24851601..24854869
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (13 terms)
Molecular Function (0 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (0 terms)
Biological Process (8 terms)
Terms Based on Experimental Evidence (7 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000473192
involved_in protein processing
inferred from biological aspect of ancestor with PANTHER:PTN000473190
inferred from electronic annotation with InterPro:IPR008710
Cellular Component (5 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
located_in late endosome
inferred from direct assay
located_in plasma membrane
inferred from high throughput direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
located_in membrane
inferred from electronic annotation with InterPro:IPR008710
is_active_in plasma membrane
inferred from biological aspect of ancestor with PANTHER:PTN000473190
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the nicastrin family. (Q9VC27)
Summaries
Gene Snapshot
Nicastrin (Nct) encodes a transmembrane protein that is a key component of the γ-secretase, the protease complex for proteolytic cleavage of the Notch signaling receptor. [Date last reviewed: 2018-11-08]
Pathway (FlyBase)
NOTCH SIGNALING PATHWAY CORE COMPONENTS -
The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Delta or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Core pathway components are required for signaling from the sending cell and response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
Gene Group (FlyBase)
GAMMA SECRETASE COMPLEX -
The γ-secretase complex is an intramembrane aspartyl protease complex that cleaves transmembrane proteins. In particular, it is known for cleaving amyloid precursor protein (Appl) and Notch (N) receptor. It is essential for Notch signaling, performing the second ligand-simulated cleavage, which yields Notch intracellular domain. (Adapted from FBrf0211009).
Protein Function (UniProtKB)
Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch. It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex.
(UniProt, Q9VC27)
Summary (Interactive Fly)

component of a proteolytic complex, along with Presenilin, that targets Notch and ß amyloid protein - Zn-dependent exopeptidase - co-expression of the four core γ-secretase components, Presenilin, Nicastrin, Aph-1, and Pen-2 promotes the efficient assembly of mature, proteolytically active γ-secretase

Gene Model and Products
Number of Transcripts
4
Number of Unique Polypeptides
3

Please see the JBrowse view of Dmel\Nct for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry Q9VC27)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.39

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.47

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084705
2409
695
FBtr0301865
2768
695
FBtr0306087
2606
692
FBtr0334570
2631
699
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0084083
78.0
695
5.94
FBpp0291079
78.0
695
5.94
FBpp0297224
77.7
692
5.94
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

695 aa isoforms: Nct-PA, Nct-PC
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)

Component of the gamma-secretase complex, a complex composed of a presenilin (Psn) homodimer, nicastrin (Nct), Aph-1 and Pen-2.

(UniProt, Q9VC27)
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Nucleotide / Polypeptide Records
 
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Nct using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.57

Transcript Expression
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in late endosome
inferred from direct assay
located_in plasma membrane
inferred from high throughput direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Nct in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 1-3
  • Stages(s) 4-6
  • Stages(s) 7-8
  • Stages(s) 9-10
  • Stages(s) 13-16
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 21 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 18 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Nct
Transgenic constructs containing regulatory region of Nct
Aberrations (Deficiencies and Duplications) ( 3 )
Inferred from experimentation ( 3 )
Inferred from location ( 6 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
cytoskeleton & follicle cell | somatic clone
sensory mother cell & dorsal mesothoracic disc
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (3)
14 of 14
Yes
Yes
1  
1 of 14
No
No
1  
1 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (3)
14 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (3)
13 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (2)
11 of 13
Yes
Yes
1 of 13
No
No
Danio rerio (Zebrafish) (4)
2 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (2)
13 of 14
Yes
Yes
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (3)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (1)
12 of 13
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (1)
1 of 13
Yes
No
Schizosaccharomyces pombe (Fission yeast) (0)
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Nct. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (4)
1 of 13
1 of 13
1 of 13
1 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Allele
Disease
Evidence
References
Potential Models Based on Orthology ( 1 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Allele
Disease
Interaction
References
Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
Homo sapiens (Human)
Gene name
Score
OMIM
OMIM Phenotype
DO term
Complementation?
Transgene?
Functional Complementation Data
Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
Interactions
Summary of Physical Interactions
Summary of Genetic Interactions
Interaction Browsers

Please look at the allele data for full details of the genetic interactions
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
External Data
Subunit Structure (UniProtKB)
Component of the gamma-secretase complex, a complex composed of a presenilin (Psn) homodimer, nicastrin (Nct), Aph-1 and Pen-2.
(UniProt, Q9VC27 )
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Signaling Pathways (FlyBase)
Metabolic Pathways
FlyBase
External Links
External Data
Linkouts
KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
SignaLink - A signaling pathway resource with multi-layered regulatory networks.
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
3R
Recombination map
3-86
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
96B1-96B1
Limits computationally determined from genome sequence between P{PZ}crb07207&P{PZ}BRWD305842 and P{EP}CycB3EP3127
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
96A13-96B15
Experimentally Determined Recombination Data
Location
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (14)
Genomic Clones (15)
 

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (179)
 

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced
BDGP DGC clones
Other clones
Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

cDNA Clones, End Sequenced (ESTs)
RNAi and Array Information
Linkouts
DRSC - Results frm RNAi screens
Antibody Information
Laboratory Generated Antibodies
Commercially Available Antibodies
 
Cell Line Information
Publicly Available Cell Lines
 
    Other Stable Cell Lines
     
      Other Comments

      dsRNA made from a cDNA library with primers directed against this gene (+674-1448) is used in S2 cells to assess the effect on Psn maturation.

      nct plays a role in the γ-secretase step of N processing, and is required for signaling from membrane-anchored activated N. nct also plays a role in stabilising the Psn gene product.

      nct mutants and clones show N-like characteristics with defective cell fate specifications.

      nct is required for the long term stability of Psn in the follicle cells of egg chambers.

      nct is a novel neurogenic gene required cell autonomously for the transduction of the N signal in responding cells. The nct gene product is required for N signalling and acts specifically at the S3 cleavage step. nct and Psn have a novel function, independent of their role in N signaling, that relates to the organization of the spectrin cytoskeleton.

      Partially processed N accumulates apically in nct and Psn mutant follicle cells, which also show a disrupted spectrin cytoskeleton.

      The nct gene product is required for Psn-mediated transmembrane cleavage.

      Loss of nct activity blocks the accumulation of Psn gene product associated with the apical plasma membrane, abolishes Psn-dependent cleavage of the transmembrane domain of N and abrogates N signal transduction.

      Mutants block N signaling by affecting the processing of the receptor.

      Relationship to Other Genes
      Source for database merge of

      Source for merge of: nct agro

      Additional comments

      Source for identity of nicastrin CG7012 was sequence comparison ( date:000915 ).

      Nomenclature History
      Source for database identify of

      Source for identity of: nicastrin CG7012

      Source for identity of: Nct nct

      Nomenclature comments

      Changed symbol and name to have an initial uppercase letter in order to follow FlyBase nomenclature guidelines for genes named after an ortholog (FBrf0131223, FBrf0141674).

      Etymology
      Synonyms and Secondary IDs (15)
      Reported As
      Secondary FlyBase IDs
      • FBgn0043964
      Datasets (0)
      Study focus (0)
      Experimental Role
      Project
      Project Type
      Title
      Study result (0)
      Result
      Result Type
      Title
      External Crossreferences and Linkouts ( 54 )
      Sequence Crossreferences
      NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
      GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
      GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
      RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
      UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
      UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
      UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
      Other crossreferences
      AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
      BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
      DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
      EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
      FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
      FlyMine - An integrated database for Drosophila genomics
      InterPro - A database of protein families, domains and functional sites
      KEGG Genes - Molecular building blocks of life in the genomic space.
      MARRVEL_MODEL - MARRVEL (model organism gene)
      Linkouts
      BioGRID - A database of protein and genetic interactions.
      Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
      DroID - A comprehensive database of gene and protein interactions.
      DRSC - Results frm RNAi screens
      Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
      FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
      FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
      Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
      Flygut - An atlas of the Drosophila adult midgut
      FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
      iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
      Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
      KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
      MIST (genetic) - An integrated Molecular Interaction Database
      MIST (protein-protein) - An integrated Molecular Interaction Database
      Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
      SignaLink - A signaling pathway resource with multi-layered regulatory networks.
      References (90)