FB2026_02 , released June 18, 2026
Gene: Dmel\Psn
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General Information
Symbol
Dmel\Psn
Species
D. melanogaster
Name
Presenilin
Annotation Symbol
CG18803
Feature Type
FlyBase ID
FBgn0284421
Gene Model Status
Stock Availability
Gene Summary
Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptor. Required for S3 cleavage of Notch, which releases activated Notch protein from the cell membrane. Involved in the patterning of the optic lobes. (UniProt, O02194)
Contribute a Gene Snapshot for this gene.
Also Known As

PS, γ-secretase, dPsn, Dps, dPresenilin

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-47
RefSeq locus
NT_037436 REGION:20432468..20435156
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (25 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from mutant phenotype
inferred from physical interaction with FLYBASE:spdo; FB:FBgn0260440
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
Biological Process (15 terms)
Terms Based on Experimental Evidence (13 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from direct assay
involved_in apoptotic process
inferred from mutant phenotype
inferred from mutant phenotype
involved_in copper ion import
inferred from mutant phenotype
inferred from direct assay
involved_in proteolysis
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
involved_in short-term memory
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (5 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000024430
inferred from biological aspect of ancestor with PANTHER:PTN000024430
inferred from biological aspect of ancestor with PANTHER:PTN000024429
inferred from biological aspect of ancestor with PANTHER:PTN000024430
involved_in protein processing
inferred from electronic annotation with InterPro:IPR001108
inferred from biological aspect of ancestor with PANTHER:PTN000024430
Cellular Component (6 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from direct assay
located_in late endosome
inferred from direct assay
located_in plasma membrane
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000024429
located_in membrane
inferred from electronic annotation with InterPro:IPR001108, InterPro:IPR006639
Protein Family (UniProt)
Belongs to the peptidase A22A family. (O02194)
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, 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).
A22 ASPARTIC ENDOPEPTIDASES -
A22 aspartic endopeptidases belong to MEROPS family A22, which are membrane-inserted endopeptidases. They catalyse the hydrolysis of internal, alpha-peptide bonds in a polypeptide chain by a mechanism in which a water molecule bound by the side chains of aspartic residues at the active center acts as a nucleophile. The family includes presenilins and signal peptide peptidases. (Adapted from PMID:12966028.)
Protein Function (UniProtKB)
Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptor. Required for S3 cleavage of Notch, which releases activated Notch protein from the cell membrane. Involved in the patterning of the optic lobes.
(UniProt, O02194)
Summary (Interactive Fly)

transmembrane protein involved in proteolysis of Notch - also processes βAPP - Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins

Gene Model and Products
Number of Transcripts
5
Number of Unique Polypeptides
3

Please see the JBrowse view of Dmel\Psn 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 O02194)

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 5.41

Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.

Gene model reviewed during 5.46

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0078192
2048
541
FBtr0078193
1849
527
FBtr0114517
1778
508
FBtr0333478
1879
527
FBtr0333479
1891
541
Additional Transcript Data and Comments
Reported size (kB)

4.0, 2.0 (northern blot)

2.0 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0077850
59.3
541
7.07
FBpp0077851
57.8
527
6.51
FBpp0113009
55.7
508
6.67
FBpp0305665
57.8
527
6.51
FBpp0305666
59.3
541
7.07
Polypeptides with Identical Sequences

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

541 aa isoforms: Psn-PA, Psn-PE
527 aa isoforms: Psn-PB, Psn-PD
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)

Homodimer (By similarity). Component of the gamma-secretase complex, a complex composed of a presenilin (Psn) homodimer, nicastrin (Nct), Aph-1 and Pen-2. Interacts with Mettl2. Isoform 2 shows a better interaction with Mettl2 than isoform 1.

(UniProt, O02194)
Post Translational Modification

Cleaved. The cleavage, which probably takes place between the 6th and the 7th transmembrane regions, may be required for activation of the gamma-secretase activity.

(UniProt, O02194)
Domain

The PAL motif is required for normal active site conformation.

(UniProt, O02194)
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

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

External Data
Crossreferences
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).

0.97

Transcript Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
RT-PCR
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

RT-PCR analysis of Psn transcript supports the expression of three isoforms at all developmental stages.

The Psn transcript is detected in nurse cells and the oocyte during oogenesis. In larvae the Psn transcript is detected in eye-antennal discs in regions that give rise to the occellar and interoccellar bristles, and in the posterior region of the leg disc which gives rise to the tibia and femur.

The Psn transcript is detected primarily in the central nervous system in stage 14 embryos, though low levels are detected throughout the embryo. In stage 16 embryos, the Psn transcript levels are increased in the central nervous system.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

PS protein appears to be membrane associated in most cells.

PS protein is expressed in most cells in the developing embryo and during oogenesis. Higher levels of expression are detected in the somatic cells during oogenesis, as well as in the ectoderm durning embryogenesis. During larval and pupal stages PS is expressed in most tissues. Expression in the wing disc and the eye disc is detacted associated with apical cell membranes and in the photoreceptors.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
located_in late endosome
inferred from direct assay
located_in plasma membrane
inferred from 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\Psn 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
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
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 32 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 87 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Psn
Transgenic constructs containing regulatory region of Psn
Aberrations (Deficiencies and Duplications) ( 8 )
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
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
adult thorax & macrochaeta, with Scer\GAL4c625
adult thorax & microchaeta, with Scer\GAL419A
cytoskeleton & follicle cell | somatic clone
eye disc & neuron
neuron & eye | supernumerary | somatic clone
scutum & macrochaeta, with Scer\GAL419A
scutum & macrochaeta, with Scer\GAL4c625
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (2)
13 of 14
Yes
Yes
7  
13 of 14
Yes
Yes
3  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (2)
13 of 14
Yes
Yes
13 of 14
Yes
Yes
Mus musculus (laboratory mouse) (2)
12 of 14
Yes
Yes
12 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (3)
10 of 13
Yes
Yes
6 of 13
No
Yes
1 of 13
No
Yes
Danio rerio (Zebrafish) (2)
13 of 14
Yes
Yes
12 of 14
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (3)
13 of 14
Yes
Yes
7 of 14
No
Yes
4 of 14
No
Yes
Anopheles gambiae (African malaria mosquito) (1)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (2)
11 of 13
Yes
Yes
11 of 13
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (0)
Schizosaccharomyces pombe (Fission yeast) (0)
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Psn. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 21 )
Allele
Disease
Evidence
References
Potential Models Based on Orthology ( 7 )
Modifiers Based on Experimental Evidence ( 15 )
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.
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
suppressible
External Data
Subunit Structure (UniProtKB)
Homodimer (By similarity). Component of the gamma-secretase complex, a complex composed of a presenilin (Psn) homodimer, nicastrin (Nct), Aph-1 and Pen-2. Interacts with Mettl2. Isoform 2 shows a better interaction with Mettl2 than isoform 1.
(UniProt, O02194 )
Linkouts
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.
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
3L
Recombination map
3-47
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
77C3-77C3
Limits computationally determined from genome sequence between P{EP}trblEP3519 and P{EP}fngEP3082&P{lacW}skdL7062
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
77B-77C
(determined by in situ hybridisation)
77A-77B
(determined by in situ hybridisation)
77B-77B
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (75)
Genomic Clones (10)
 

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

cDNA Clones (102)
 

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
      Antibody Information
      Laboratory Generated Antibodies
      Commercially Available Antibodies
       
      Cell Line Information
      Publicly Available Cell Lines
       
        Other Stable Cell Lines
         
          Other Comments

          Psn promotes dietary copper uptake.

          The high adhesion force between cells expressing N and Dl is lost within minutes, primarily due to the action of the Psn protein.

          dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.

          Psn and nct have a novel function, independent of their role in N signaling, that relates to the organization of the spectrin cytoskeleton.

          Psn is necessary for proper neuronal differentiation and may regulate the subcellular localization of N proteins within cells.

          Null mutations in Psn abolish N signal transduction and prevent its intracellular domain from entering the nucleus.

          Psn is required for the proteolytic release of the intracellular domain of N following activation of N by ligand.

          Psn is required for activity and nuclear access of N.

          Loss of Psn function increases levels of apoptosis in developing tissues. Overexpression of Psn causes apoptotic and neurogenic phenotypes resembling those of Psn loss-of-function mutants, suggesting that Psn exerts a dominant negative effect when expressed at high levels. Psn-induced apoptosis is cell autonomous and can be blocked by constitutive N activation.

          Genetically, Psn acts upstream of both the membrane-bound form and the activated nuclear form of N.

          Psn is required for the normal proteolytic production of carboxy-terminal N fragments that are needed for receptor saturation and signalling.

          Symbol Psn adopted, rather than 'PS', to avoid confusion with Position Specific integrin genes.

          Cloning and characterisation of Psn.

          Isolation and characterisation of the homolog of the presenilin genes.

          Relationship to Other Genes
          Source for database merge of

          Source for merge of: Psn CG18803

          Source for merge of: Psn l(3)S049314a l(3)S048015a

          Additional comments

          Source for merge of Psn CG18803 was sequence comparison ( date:001104 ).

          Nomenclature History
          Source for database identify of
          Nomenclature comments
          Etymology
          Synonyms and Secondary IDs (33)
          Reported As
          Symbol Synonym
          Psn
          (Karmelic et al., 2026, Shi et al., 2026, He et al., 2025, Collins et al., 2024, Everman and Macdonald, 2024, Gao et al., 2024, Wang et al., 2024, Ghalayini and Boulianne, 2023, Li et al., 2023, Yu et al., 2023, Schnute et al., 2022, Salazar et al., 2021, Bolus et al., 2020, Salazar et al., 2020, Subaraja et al., 2020, Vajente et al., 2020, Katsube et al., 2019, Gene Disruption Project members, 2018-, Kannan et al., 2018, Li et al., 2018, Rieche et al., 2018, Salazar and Yamamoto, 2018, Troha et al., 2018, Yang and Deng, 2018, Kang et al., 2017, Lin et al., 2017, Transgenic RNAi Project members, 2017-, Trylinski et al., 2017, Morimoto et al., 2016, Nemetschke and Knust, 2016, Bouleau and Tricoire, 2015, Neuhaus-Follini and Bashaw, 2015, Ashwal-Fluss et al., 2014, Jia et al., 2014, Wang et al., 2014, Zacharioudaki and Bray, 2014, Almenar-Queralt et al., 2013, Müller et al., 2013, Sun and Spradling, 2013, van de Hoef et al., 2013, Japanese National Institute of Genetics, 2012.5.21, Rincon-Limas et al., 2012, Singh and Mlodzik, 2012, Troost and Klein, 2012, Yamakawa et al., 2012, Friedman et al., 2011, Li et al., 2011, Mukherjee et al., 2011, Nicholson et al., 2011, Toku et al., 2011, Wangler et al., 2011, Boyles et al., 2010, Saj et al., 2010, Stempfle et al., 2010, Ayroles et al., 2009, Barakat et al., 2009, Carmine-Simmen et al., 2009, Cuc et al., 2009, Michno et al., 2009, Parks, 2009.7.23, van de Hoef et al., 2009, Guo et al., 2008, Kaspar et al., 2008, Stokin et al., 2008, Wilkin et al., 2008, Yamada et al., 2008, Isoo et al., 2007, Lu et al., 2007, Giebel and Wodarz, 2006, Herranz and Milan, 2006, Jaekel and Klein, 2006, Koelzer and Klein, 2006, LeComte et al., 2006, Mahoney et al., 2006, Peel et al., 2005, Nowotny et al., 2000)
          l(3)S048015a
          l(3)S049314
          l(3)S049314a
          Name Synonyms
          Dpresenilin
          gamma-secretase
          lethal (3) S048015a
          lethal (3) S049314a
          γ-secretase component
          Secondary FlyBase IDs
          • FBgn0019947
          • FBgn0042202
          • FBgn0040112
          • FBgn0060856
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          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/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.
          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
          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
          FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
          FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
          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.
          Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
          References (303)