FB2024_04 , released June 25, 2024
Gene: Dmel\Dark
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General Information
Symbol
Dmel\Dark
Species
D. melanogaster
Name
Death-associated APAF1-related killer
Annotation Symbol
CG6829
Feature Type
FlyBase ID
FBgn0263864
Gene Model Status
Stock Availability
Gene Summary
Death-associated APAF1-related killer (Dark) encodes an essential component of the apoptosome. The products of Dark and Dronc form a pivotal holoenzyme required for apoptotic cell death with the products of Dark acting as an adaptor of the multimeric complex. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)
Also Known As

ark, hac-1, dapaf-1, Apaf-1, Apaf-1-related killer

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
2-81
RefSeq locus
NT_033778 REGION:17020027..17026703
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (23 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
enables ADP binding
inferred from electronic annotation with InterPro:IPR002182
inferred from sequence model
Biological Process (18 terms)
Terms Based on Experimental Evidence (18 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
involved_in chaeta development
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:Ank2; FB:FBgn0261788
inferred from direct assay
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (0 terms)
Cellular Component (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
part_of apoptosome
inferred from direct assay
Terms Based on Predictions or Assertions (0 terms)
Gene Group (FlyBase)
Protein Family (UniProt)
-
Summaries
Gene Snapshot
Death-associated APAF1-related killer (Dark) encodes an essential component of the apoptosome. The products of Dark and Dronc form a pivotal holoenzyme required for apoptotic cell death with the products of Dark acting as an adaptor of the multimeric complex. [Date last reviewed: 2019-03-07]
Gene Group (FlyBase)
APOPTOSOME -
The apoptosome is a ring-like multisubunit complex assembled upon receiving a pro-apoptotic signal. In Drosophila, Dark assembles into two stacked rings of eight subunits each. This scaffold binds ADP and an initiator caspase (Dronc in D.mel) which cleaves effector caspase(s). (Adapted from FBrf0212736).
Summary (Interactive Fly)

CED-4 domain protein that links mitochondrial events to activation of caspases during programd cell death

Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
2

Please see the JBrowse view of Dmel\Dark 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 Q7KLI1)

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
PDB - An information portal to biological macromolecular structures
Comments on Gene Model

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

Gene model reviewed during 5.50

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0086967
4883
531
FBtr0086968
4824
1440
Additional Transcript Data and Comments
Reported size (kB)

7.0 (northern blot)

5 (northern blot)

5.5 (unknown)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0086121
62.3
531
8.15
FBpp0086122
165.6
1440
6.08
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
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\Dark 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).

-0.81

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

The longer form of Dark transcript appears to be the predominantly expressed form. It is detected in embyros, larvae, pupae, and S2 cells on northern blots. It is expressed ubiquitously in embryos and in larval eye and wing discs.

The short form of Dark transcript appears to be the minor form which is detected in embryos.

Dark transcripts are detected at all stages assayed on northern blots. Levels are elevated in times associated with histolysis of larval tissues (third instar larvae and early pupae). Levels are lowest in embryos and adults.

Dark transcripts are broadly distributed in preblastoderm embryos. By stage 7, transcripts are predominantly located in the ventral neurogenic region and around several invagination furrows. In stages 10-11, the highest Dark transcript levels are found in the ectoderm and mesoderm of the procephalic region. Later, expression is observed in a segmentally repeated pattern. Dark expression is induced by X-ray or UV irradiation.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
part_of apoptosome
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Dark 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
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 46 )
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 Dark
Transgenic constructs containing regulatory region of Dark
Aberrations (Deficiencies and Duplications) ( 4 )
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
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (1)
4 of 14
Yes
Yes
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (1)
4 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
2 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (1)
2 of 13
Yes
Yes
Danio rerio (Zebrafish) (1)
4 of 14
Yes
Yes
Caenorhabditis elegans (Nematode, roundworm) (0)
Anopheles gambiae (African malaria mosquito) (1)
6 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (49)
1 of 13
Yes
Yes
1 of 13
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Yes
1 of 13
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Yes
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1 of 13
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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:Dark. 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 ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 4 )
    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
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement
    Other 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
    Linkouts
    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
    External Data
    Linkouts
    KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2R
    Recombination map
    2-81
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    53E4-53E4
    Limits computationally determined from genome sequence between P{lacW}l(2)k09837k09837 and P{lacW}l(2)k11405k11405&P{EP}EP641
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    54A2-54A2
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (13)
    Genomic Clones (22)
    cDNA Clones (20)
     

    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)
    BDGP DGC clones
      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

          Gene expression is increased in response to the presence of two copies of Scer\GAL4hs.PB.

          Ark mutant hemocytes are completely resistant to a Smac mimetic (which antagonises inhibitor of apoptosis proteins) or cycloheximide.

          Expression of Ark in the post-embryonic central nervous system is necessary to reverse organismal lethality and to produce a viable adult.

          Ark is required for programmed cell death.

          Removal of Ark results in profound developmental defects and lethality.

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

          1 allele of l(2)SH0173 recovered in a P-insertion screen.

          Loss of Ark function results in pronounced inhibition of stress-induced apoptosis, but not rpr or grim induced apoptosis.

          Loss of function mutations of Ark show reduced cell death and caspase activities in embryos.

          Loss of function mutations in Ark attenuate programmed cell deaths during development, resulting in hyperplasia of the central nervous system and other abnormalities including melanotic tumours and defective wings.

          Ark is required for normal cell death during embryonic development.

          Loss of Ark function causes reduced cell death.

          Transcription unit identified during molecular analysis of the RhoGEF2 region.

          Relationship to Other Genes
          Source for database merge of

          Source for merge of: Ark anon-53Fa

          Source for merge of: Ark Hac1

          Source for merge of: l(2)SH0173 Ark

          Additional comments

          Source for merge of Ark Hac1 was sequence comparison ( date:991227 ).

          Nomenclature History
          Source for database identify of

          Source for identity of: Dark Ark

          Nomenclature comments

          Changed from 'Ark' to 'Dark' to reflect common usage in the literature.

          Etymology
          Synonyms and Secondary IDs (52)
          Reported As
          Symbol Synonym
          Dapaf-1/HAC-1
          Dark
          (Sulekh et al., 2024, Tian et al., 2024, Umargamwala et al., 2024, Cordes et al., 2023, Heigwer et al., 2023, Huang et al., 2023, Nakano et al., 2023, Nowaskie et al., 2023, Ciesielski et al., 2022, Dziedziech and Theopold, 2022, Mast et al., 2022, Moore et al., 2022, Tarikere et al., 2022, Xu et al., 2022, Buhlman et al., 2021, Hounsell and Fan, 2021, Vrailas-Mortimer et al., 2021, Fujisawa et al., 2020, Kosakamoto et al., 2020, Nakajima et al., 2020, Xu et al., 2020, Bieser et al., 2019, Meltzer et al., 2019, Stamm et al., 2019, Tettamanti and Casartelli, 2019, Diwanji and Bergmann, 2018, Dorstyn et al., 2018, Xu et al., 2018, Kamber Kaya et al., 2017, Kawamoto et al., 2016, Melzer and Broemer, 2016, Nicolson et al., 2015, Sakamaki et al., 2015, Griciuc et al., 2014, Steller et al., 2014.7.9, D'Brot et al., 2013, Denton et al., 2013, Dick and Megeney, 2013, Lee et al., 2013, Yuan and Akey, 2013, Chen et al., 2012, Darding and Meier, 2012, Domingues and Ryoo, 2012, Fabian and Brill, 2012, Vecchio et al., 2012, Verghese et al., 2012, Kuranaga, 2011, Miura, 2011, Yuan et al., 2011, Kim et al., 2010, Yang et al., 2010, Chew et al., 2009, Li and Cadigan, 2008, Pret et al., 2008, Chew et al., 2007, Lannan et al., 2007, Link et al., 2007, Akdemir et al., 2006, Arama et al., 2006, Leulier et al., 2006, Mendes et al., 2006, Kanuka et al., 2005, Kornbluth and White, 2005, Purves et al., 2005, Danial and Korsmeyer, 2004, McCall, 2004, Muro et al., 2004, Baehrecke, 2003, Cagan, 2003, Claveria and Torres, 2003, Lawen, 2003, Meier and Silke, 2003, Van Hoof and Goris, 2003, Adams and Cory, 2002, Igaki et al., 2002, Adams and Cory, 2001, Kimbrell and Beutler, 2001, Chen and Abrams, 2000, Gaumer et al., 2000, Kumar, 2000, Abrams, 1999, White, 1999)
          Dark/Dapaf-1/HAC1
          Dark/Hac-1/dApaf-1
          Dark/Hac-1/dApaf1
          Hac-1/Dark
          anon-53Fa
          dApaf-1/DARK/HAC-1
          dark/dapaf-1/hac-1
          dark/hac-1/dapaf-1
          l(2)SH0173
          Name Synonyms
          Secondary FlyBase IDs
          • FBgn0065914
          • FBgn0024252
          • FBgn0028733
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          External Crossreferences and Linkouts ( 59 )
          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/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
          KEGG Genes - Molecular building blocks of life in the genomic space.
          MARRVEL_MODEL - MARRVEL (model organism gene)
          PDB - An information portal to biological macromolecular structures
          Linkouts
          Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
          DroID - A comprehensive database of gene and protein interactions.
          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
          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
          References (299)