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General Information
Symbol
Dmel\sisA
Species
D. melanogaster
Name
sisterless A
Annotation Symbol
CG1641
Feature Type
FlyBase ID
FBgn0003411
Gene Model Status
Stock Availability
Gene Snapshot
sisterless A (sisA) encodes a transcription factor that activates transcription of the master feminizing switch gene Sxl specifically in diplo-X somatic cells. It is also required for proper embryonic midgut development in both sexes. [Date last reviewed: 2019-03-14]
Also Known As
sis-a, sis a
Key Links
Genomic Location
Cytogenetic map
Sequence location
X:11,321,579..11,322,357 [-]
Recombination map
1-34
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
-
Protein Signatures (InterPro)
    -
    Summaries
    Gene Group (FlyBase)
    BASIC LEUCINE ZIPPER TRANSCRIPTION FACTORS -
    The basic leucine zipper (bZIP) transcription factors are sequence-specific DNA-binding proteins that regulate transcription. They are characterized by a 60-80 amino acid bZIP domain: a basic DNA binding domain followed by a leucine zipper dimerization domain. (Adapted from FBrf0152056).
    Protein Function (UniProtKB)
    Involved in sex determination and dosage compensation. Required for proper expression of Sxl in embryonic somatic cells. Also has an essential function in the yolk nuclei. Involved in endoderm migration and midgut formation.
    (UniProt, Q9VZ09)
    Phenotypic Description (Red Book; Lindsley and Zimm 1992)
    sis-a: sisterless a (T.W. Cline)
    Homozygous females die but hemizygous males and heterozygous females fully viable; females die as embryos and larvae; rare morphologically normal and fertile escapers observed at lower temperatures. Single extant allele hypomorphic; locus also defined by dominant behavior of deficiencies and duplications. Dominant lethal for females simultaneously heterozygous for sis-b- or Sxl- or whose mothers are heterozygous for da-. Magnitude of female-lethal dominant synergism sensitive to genetic background, but can be very high. Lethal interactions are generally less severe at lower culture temperatures. Constitutive allele, SxlM1, suppresses female lethality of sis-a homozygote or of any heterozygous combination of mutant alleles or deficiencies of these four genes. Duplication of Sxl+ also suppresses, but less effectively. Female-lethal interactions between sis-a and Sxl mutations display remarkably similar Sxl allele specificity to those between maternal da and zygotic Sxl mutations, indicating that da and sis-a disrupt the same aspect of Sxl regulation. Oogenesis normal for homozygous sis-a germ-line clones induced by mitotic recombination; no maternal effect. Sexual phenotype of 2X:3A animals extremely sensitive to sis-a+ dose (more male at lower temperatures), and like da and Sxl-, shows masculinizing interaction with autosomal male-specific lethal mutations but no increase in viability of escapers; nevertheless, sexual phenotype of homozygous sis-a clones generated by mitotic recombination normal. Female-lethal effects caused by decrease in sis-a function have their complement in male-lethal interactions caused by increase in sis-a function (duplications). Male lethality is increased as Sxl+ dose or sis-b+ dose is increased, and is suppressed by loss-of-function Sxl mutations. The dose-dependent interactions of this gene with Sxl+ identify it as part of the numerator of what has been called the X/A balance, the primary sex-determination signal--a character it shares with sis-b.
    Gene Model and Products
    Number of Transcripts
    1
    Number of Unique Polypeptides
    1

    Please see the GBrowse view of Dmel\sisA or the JBrowse view of Dmel\sisA 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 5.50
    Sequence Ontology: Class of Gene
    Transcript Data
    Annotated Transcripts
    Name
    FlyBase ID
    RefSeq ID
    Length (nt)
    Assoc. CDS (aa)
    FBtr0073461
    779
    189
    Additional Transcript Data and Comments
    Reported size (kB)
    0.8 (northern blot)
    Comments
    External Data
    Crossreferences
    Polypeptide Data
    Annotated Polypeptides
    Name
    FlyBase ID
    Predicted MW (kDa)
    Length (aa)
    Theoretical pI
    RefSeq ID
    GenBank
    FBpp0073317
    21.3
    189
    9.85
    Polypeptides with Identical Sequences

    There is only one protein coding transcript and one polypeptide associated with this gene

    Additional Polypeptide Data and Comments
    Reported size (kDa)
    189 (aa); 21 (kD predicted)
    Comments
    External Data
    Subunit Structure (UniProtKB)
    Homodimer. Interacts with dpn (via bHLH motif). Interacts with da (via bHLH motif). Interacts with Bap60.
    (UniProt, Q9VZ09)
    Crossreferences
    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\sisA 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 (11 terms)
    Molecular Function (3 terms)
    Terms Based on Experimental Evidence (1 term)
    CV Term
    Evidence
    References
    inferred from physical interaction with FLYBASE:Bap60; FB:FBgn0025463
    Terms Based on Predictions or Assertions (2 terms)
    CV Term
    Evidence
    References
    Biological Process (7 terms)
    Terms Based on Experimental Evidence (6 terms)
    CV Term
    Evidence
    References
    Terms Based on Predictions or Assertions (2 terms)
    CV Term
    Evidence
    References
    Cellular Component (1 term)
    Terms Based on Experimental Evidence (0 terms)
    Terms Based on Predictions or Assertions (1 term)
    CV Term
    Evidence
    References
    inferred by curator from GO:0045944
    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
    in situ
    Stage
    Tissue/Position (including subcellular localization)
    Reference
    organism

    Comment: maternally deposited

    Additional Descriptive Data
    sisA transcripts are detected in embryos from 0-12 hours but not at later stages of development. Transcripts are not detected in adult females indicating that the transcripts present in 0-2hr embryos are of zygotic origin. sisA transcripts are first detected at the end of the eighth nuclear cycle. Initially all nuclei express sisA but expression is extinguished in the prepole cell nuclei. Transcripts are closely associated with the somatic and yolk nuclei through cycle 10 after which they are distributed fairly uniformly in the somatic portion of the embryo and are no longer associated with nuclei. Transcript levels peak in late cycle 12 and cycle 13 and decay rapidly thereafter. In contrast to the somatic nuclei, the yolk nuclei accumulate high levels of sisA transcripts from cycle 8 until they degenerate ~10-11 hours after fertilization.
    Marker for
     
    Subcellular Localization
    CV Term
    Polypeptide Expression
    Additional Descriptive Data
    Marker for
     
    Subcellular Localization
    CV Term
    Evidence
    References
    Expression Deduced from Reporters
    High-Throughput Expression Data
    Associated Tools

    GBrowse - Visual display of RNA-Seq signals

    View Dmel\sisA 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
    Flygut - An atlas of the Drosophila adult midgut
    Images
    Alleles, Insertions, and Transgenic Constructs
    Classical and Insertion Alleles ( 6 )
    For All Classical and Insertion Alleles Show
     
    Other relevant insertions
    Transgenic Constructs ( 13 )
    For All Alleles Carried on Transgenic Constructs Show
    Transgenic constructs containing/affecting coding region of sisA
    Transgenic constructs containing regulatory region of sisA
    Deletions and Duplications ( 3 )
    Phenotypes
    Orthologs
    Human Orthologs (via DIOPT v7.1)
    Homo sapiens (Human) (0)
    No records found.
    Model Organism Orthologs (via DIOPT v7.1)
    Mus musculus (laboratory mouse) (0)
    No records found.
    Rattus norvegicus (Norway rat) (0)
    No records found.
    Xenopus tropicalis (Western clawed frog) (0)
    No records found.
    Danio rerio (Zebrafish) (0)
    No records found.
    Caenorhabditis elegans (Nematode, roundworm) (0)
    No records found.
    Arabidopsis thaliana (thale-cress) (0)
    No records found.
    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) ( EOG09190H8Y )
    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) ( EOG09150CZW )
    Organism
    Common Name
    Gene
    Multiple Dmel Genes in this Orthologous Group
    Musca domestica
    House fly
    Musca domestica
    House fly
    Musca domestica
    House fly
    Lucilia cuprina
    Australian sheep blowfly
    Lucilia cuprina
    Australian sheep blowfly
    Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( None identified )
    No non-Dipteran orthologies identified
    Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( None identified )
    No non-Insect Arthropod orthologies identified
    Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( None identified )
    No non-Arthropod Metazoa orthologies identified
    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 ( 0 )
      Allele
      Disease
      Evidence
      References
      Potential Models Based on Orthology ( 0 )
      Human Ortholog
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 0 )
      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
      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)
      Homodimer. Interacts with dpn (via bHLH motif). Interacts with da (via bHLH motif). Interacts with Bap60.
      (UniProt, Q9VZ09 )
      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)
      External Data
      Linkouts
      Genomic Location and Detailed Mapping Data
      Chromosome (arm)
      X
      Recombination map
      1-34
      Cytogenetic map
      Sequence location
      X:11,321,579..11,322,357 [-]
      FlyBase Computed Cytological Location
      Cytogenetic map
      Evidence for location
      10B2-10B2
      Limits computationally determined from genome sequence between P{EP}EP1321EP1321&P{EP}CG2061EP1537 and P{EP}CG11756EP1610
      Experimentally Determined Cytological Location
      Cytogenetic map
      Notes
      References
      Experimentally Determined Recombination Data
      Location
      1-34.3
      Left of (cM)
      Right of (cM)
      Notes
      Mapping based on 4496 v-m recombinants.
      Stocks and Reagents
      Stocks (5)
      Genomic Clones (12)
       

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

      cDNA Clones (7)
       

      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)
        BDGP DGC clones
          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: sisA CG1641
          Source for database merge of
          Additional comments
          Other Comments
          In the absence of sisA function, endoderm migration and midgut formation are blocked in the embryo.
          sisA has an essential function in the yolk nuclei of both sexes.
          Expression of sisA and Sxl is as tightly coupled as Dvir\sisA and Dvir\Sxl, suggesting that the same primary sex determination mechanism exists throughout the genus Drosophila.
          In a sample of 79 genes with multiple introns, 33 showed significant heterogeneity in G+C content among introns of the same gene and significant positive correspondence between the intron and the third codon position G+C content within genes. These results are consistent with selection adding against preferred codons at the start of genes.
          An extensive genetic screen for dominant suppressors of the female specific lethal sisA mutation identified 10 alleles of dpn but no other loci.
          sisA is required and functions as a dose-dependent positive regulator for Sxl-Pe activity in female embryos.
          The yeast two hybrid system has been used to demonstrate specific interactions within the sisA, sc, dpn and da group of gene products, and to delimit their interaction domains. The results support and extend the model of the molecular basis of the X/A ratio signal.
          When daughters lack her function a duplication of sc can improve prospects but be made worse by a single mutation of sisA. Males with extra wild type sisA or sc genes have an increased chance of survival when maternal her function is defective.
          The wild type maternal function of her may be participating in the same process as sisA during female development and maternal her function is needed for the initiation of Sxl function.
          An increased sisA and sc dose equivalent to that in females causes male lethal effects and cannot activate the construct P{SxlPe-lacZ}, which carries the embryonic promoter of Sxl, to the female expression level in all tissues. Male lethality can be completely suppressed by a Sxl null mutation.
          sisA is required in all somatic nuclei for the proper activation of Sxl.
          sc, sisA and run are not required to activate Sxl in the female germline.
          sisA gene product acts in combination with maternally encoded products of signal transduction genes, da, which communicate the number of X chromosomes to Sxl and thereby determine sexual fate.
          Mutations in zygotic gene sisA interact with RpII140wimp.
          sisA/Df(1)HC244 females are fully fertile.
          Origin and Etymology
          Discoverer
          Etymology
          Identification
          External Crossreferences and Linkouts ( 23 )
          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
          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.
          Flygut - An atlas of the Drosophila adult midgut
          GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
          KEGG Genes - Molecular building blocks of life in the genomic space.
          modMine - A data warehouse for the modENCODE project
          Linkouts
          BioGRID - A database of protein and genetic interactions.
          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
          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
          Synonyms and Secondary IDs (11)
          Reported As
          Symbol Synonym
          Name Synonyms
          sisterless A
          sisterlessA
          Secondary FlyBase IDs
            Datasets (0)
            Study focus (0)
            Experimental Role
            Project
            Project Type
            Title
            References (129)