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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 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]
Also Known As
agro, dNicastrin, nic
Key Links
Genomic Location
Cytogenetic map
Sequence location
3R:24,851,601..24,854,869 [+]
Recombination map
3-86
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the nicastrin family. (Q9VC27)
Molecular Function (GO)
[Detailed GO annotations]
Experimental Evidence
-
Predictions / Assertions
-
Summaries
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, Dl 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. (Adapted from FBrf0225731 and FBrf0192604). Core pathway components are required for signaling from the sending cell and response in the receiving cell.
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 GBrowse view of Dmel\Nct or 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
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
Sequence Ontology: Class of Gene
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
RefSeq ID
GenBank
FBpp0084083
78.0
695
5.94
FBpp0291079
78.0
695
5.94
FBpp0297224
77.7
692
5.94
FBpp0306637
78.4
699
6.06
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
Gene Ontology (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
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000473190
(assigned by GO_Central )
Cellular Component (5 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from high throughput direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000473190
(assigned by GO_Central )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from high throughput direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Nct in GBrowse 2
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
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
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, and Transgenic Constructs
Classical and Insertion Alleles ( 20 )
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
Deletions and Duplications ( 3 )
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 v7.1)
Homo sapiens (Human) (1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
Rattus norvegicus (Norway rat) (1)
13 of 13
Yes
Yes
Xenopus tropicalis (Western clawed frog) (1)
8 of 12
Yes
Yes
Danio rerio (Zebrafish) (1)
4 of 15
Yes
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
13 of 15
Yes
Yes
Arabidopsis thaliana (thale-cress) (1)
9 of 9
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (0)
No records found.
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091903FV )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091503QO )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W05FH )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Acyrthosiphon pisum
Pea aphid
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X05BI )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G03DV )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (0)
No records found.
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Model Summary Ribbon
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
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease Associations of Human Orthologs (via DIOPT v7.1 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
esyN Network Diagram
Show neighbor-neighbor interactions:
Select Layout:
Legend:
Protein
RNA
Selected Interactor(s)
Interactions Browser

Please see the Physical Interaction reports below for full details
protein-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
esyN Network Diagram
esyN Network Key:
Suppression
Enhancement

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.
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Gene Group - Pathway Membership (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, Dl 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. (Adapted from FBrf0225731 and FBrf0192604). Core pathway components are required for signaling from the sending cell and response in the receiving cell.
External Data
Genomic Location and Detailed Mapping Data
Chromosome (arm)
3R
Recombination map
3-86
Cytogenetic map
Sequence location
3R:24,851,601..24,854,869 [+]
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 (12)
Genomic Clones (15)
 

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

cDNA Clones (180)
 

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 GBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequences
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
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
Antibody Information
Laboratory Generated Antibodies
 
Commercially Available Antibodies
 
Other Information
Relationship to Other Genes
Source for database identify of
Source for identity of: nicastrin CG7012
Source for identity of: Nct nct
Source for database merge of
Source for merge of: nct agro
Additional 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).
Source for identity of nicastrin CG7012 was sequence comparison ( date:000915 ).
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.
Origin and Etymology
Discoverer
Etymology
Identification
External Crossreferences and Linkouts ( 58 )
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/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
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
InterPro - A database of protein families, domains and functional sites
KEGG Genes - Molecular building blocks of life in the genomic space.
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
modMine - A data warehouse for the modENCODE project
SignaLink - A signaling pathway resource with multi-layered regulatory networks.
Linkouts
BioGRID - A database of protein and genetic interactions.
DPiM - Drosophila Protein interaction map
DroID - A comprehensive database of gene and protein interactions.
DRSC - Results frm RNAi screens
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyMine - An integrated database for Drosophila genomics
Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
MIST (genetic) - An integrated Molecular Interaction Database
MIST (protein-protein) - An integrated Molecular Interaction Database
Synonyms and Secondary IDs (13)
Datasets (0)
Study focus (0)
Experimental Role
Project
Project Type
Title
References (75)