FB2024_02 , released April 23, 2024
Gene: Dmel\CrebA
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General Information
Symbol
Dmel\CrebA
Species
D. melanogaster
Name
Cyclic-AMP response element binding protein A
Annotation Symbol
CG7450
Feature Type
FlyBase ID
FBgn0004396
Gene Model Status
Stock Availability
Gene Summary
Cyclic-AMP response element binding protein A (CrebA) encodes a leucine-zipper transcription factor that upregulates genes encoding protein components of the canonical secretory pathway and tissue-specific genes in the salivary gland and epidermis. [Date last reviewed: 2019-03-07] (FlyBase Gene Snapshot)
Also Known As

dCREB-A, CREB, BBF-2, dCREBA, Creb-A

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-43
RefSeq locus
NT_037436 REGION:15535395..15553214
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (20 terms)
Molecular Function (7 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from direct assay
enables DNA binding
inferred from direct assay
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
Biological Process (8 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
Cellular Component (5 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
part_of chromatin
inferred from direct assay
located_in mitochondrion
inferred from direct assay
located_in nucleolus
inferred from direct assay
located_in nucleus
inferred from direct assay
inferred from physical interaction with FLYBASE:Jig; FB:FBgn0038239
Terms Based on Predictions or Assertions (0 terms)
Protein Family (UniProt)
Belongs to the bZIP family. (P29747)
Summaries
Gene Snapshot
Cyclic-AMP response element binding protein A (CrebA) encodes a leucine-zipper transcription factor that upregulates genes encoding protein components of the canonical secretory pathway and tissue-specific genes in the salivary gland and epidermis. [Date last reviewed: 2019-03-07]
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)
Transcriptional activator. Binds to fat body-specific enhancers of alcohol dehydrogenase (ADH) and yolk protein genes. BBF-2 may play a role in fat body gene expression. It binds the consensus sequence 5'-T[AC]NACGTAN[TG]C-3'.
(UniProt, P29747)
Summary (Interactive Fly)

basic leucine zipper transcription factor - regulates secretory pathways and tissue-specific genes in the salivary gland and epidermis

Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\CrebA 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 P29747)

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

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)
FBtr0075557
3189
516
FBtr0075558
4498
516
Additional Transcript Data and Comments
Reported size (kB)

4.3 (northern blot)

4.4 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0075311
56.3
516
6.31
FBpp0089339
56.3
516
6.31
Polypeptides with Identical Sequences

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

516 aa isoforms: CrebA-PA, CrebA-PB
Additional Polypeptide Data and Comments
Reported size (kDa)

515 (aa); 56 (kD)

516 (aa); 56.3 (kD)

Comments
External Data
Subunit Structure (UniProtKB)

May bind DNA as heterodimers with other bZIP proteins.

(UniProt, P29747)
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\CrebA 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).

-0.42

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
RNase protection, primer extension, SI map
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

CrebA transcripts are observed throughout development on northern blots with the highest levels in embryos and adults males. RNAse protection experiments show equivalent levels of CrebA transcripts in third instar larval gut, fat body, and trachea.

In embryos, CrebA transcripts are expressed in the developing salivary gland. In the adult, transcripts are found in the brain and optic lobe cell bodies, in salivary gland, and in midgut epithelial cells of the cardia. In females CrebA transcripts are expressed in columnar follicle cells. In males, they are expressed in the seminal vesicle, ejaculatory duct, and ejaculatory bulb.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
enzyme assay or biochemical detection
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

CrebA protein is present in extracts from ovaries.

Marker for
Subcellular Localization
CV Term
Evidence
References
part_of chromatin
inferred from direct assay
located_in mitochondrion
inferred from direct assay
located_in nucleolus
inferred from direct assay
located_in nucleus
inferred from direct assay
inferred from physical interaction with FLYBASE:Jig; FB:FBgn0038239
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\CrebA 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) 4-6
  • Stages(s) 9-10
  • Stages(s) 11-12
  • Stages(s) 13-16
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 25 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 12 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of CrebA
Transgenic constructs containing regulatory region of CrebA
Aberrations (Deficiencies and Duplications) ( 10 )
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) (9)
10 of 14
Yes
Yes
2  
9 of 14
No
Yes
3  
4 of 14
No
Yes
2  
4 of 14
No
Yes
1  
3 of 14
No
Yes
1  
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
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) (9)
9 of 14
Yes
Yes
9 of 14
Yes
Yes
4 of 14
No
Yes
4 of 14
No
Yes
3 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (9)
10 of 14
Yes
Yes
9 of 14
No
Yes
4 of 14
No
Yes
3 of 14
No
Yes
3 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (11)
7 of 13
Yes
Yes
2 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
Danio rerio (Zebrafish) (12)
10 of 14
Yes
Yes
10 of 14
Yes
Yes
4 of 14
No
Yes
3 of 14
No
Yes
3 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (2)
6 of 14
Yes
Yes
1 of 14
No
Yes
Anopheles gambiae (African malaria mosquito) (2)
11 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (0)
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:CrebA. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (2)
1 of 13
1 of 13
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 ( 1 )
    Modifiers Based on Experimental Evidence ( 2 )
    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
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Other Interaction Browsers

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    RNA-RNA
    Physical Interaction
    Assay
    References
    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
    Subunit Structure (UniProtKB)
    May bind DNA as heterodimers with other bZIP proteins.
    (UniProt, P29747 )
    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
    External Data
    Linkouts
    SignaLink - A signaling pathway resource with multi-layered regulatory networks.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3L
    Recombination map
    3-43
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    71E1-71E1
    Limits computationally determined from genome sequence between P{lacW}cp309s2172&P{lacW}l(3)j2A2j2A2 and P{EP}Tfb2EP572
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    71D1-71D2
    (determined by in situ hybridisation)
    25C-25D
    (determined by in situ hybridisation)
    Placed in 71C--71D by deficiency mapping.
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (16)
    Genomic Clones (21)
    cDNA Clones (138)
     

    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
    DRSC - Results frm RNAi screens
    Antibody Information
    Laboratory Generated Antibodies
     
    Commercially Available Antibodies
     
    Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
    Cell Line Information
    Publicly Available Cell Lines
     
      Other Stable Cell Lines
       
        Other Comments

        CrebA protein binds to the copia ULR (untranslated leader region).

        In the epidermis CrebA is required for patterning cuticular structures on both the dorsal and ventral surfaces of larvae, mutant larvae have only lateral structures around the entire circumference of each segment. Epistasis tests with known dorsal/ventral patterning genes suggests that CrebA encodes a transcription factor near the end of both the dpp and spi signalling cascades to translate the corresponding extracellular signals into changes in gene expression. Double mutants with segment polarity genes confirm that CrebA is not involved in segment polarity.

        The genomic organisation of the CrebA locus has been characterised, and its expression pattern has been analysed.

        CrebA mutants display lateralisation of the larval cuticle and the cuticle is significantly weaker than wild type larval cuticle. The salivary gland and tracheae display a 'crooked' phenotype.

        CrebA protein binds to the fat body specific enhancers of Dmul\Adh1, Adh, Yp1 and Yp2 and may be an important component of tissue specific regulation.

        Isolation and characterization of Creb reveals that the protein binds to the CRE sequence and belongs to the leucine zipper family of transcription factors.

        Relationship to Other Genes
        Source for database merge of

        Source for merge of: CrebA Bbbf2

        Source for merge of: CrebA BcDNA:SD05937

        Additional comments

        Source for merge of CrebA Bbbf2 was sequence comparison ( date:000202 ).

        Source for merge of CrebA BcDNA:SD05937 was a shared cDNA ( date:030728 ).

        Nomenclature History
        Source for database identify of
        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (31)
        Reported As
        Symbol Synonym
        BOX B Binding Factor-2
        Bbbf2
        BcDNA:SD05937
        CrebA
        (Matthew et al., 2024, Delbare et al., 2023, Floc'hlay et al., 2023, Noyes and Davis, 2023, Tsarouhas et al., 2023, Wang et al., 2023, Zhang et al., 2023, Hurtado et al., 2022, Loganathan et al., 2022, Bilder et al., 2021, Cattenoz et al., 2021, Lindsey et al., 2021, Loganathan et al., 2021, Ma et al., 2021, Martin et al., 2021, Aboukilila et al., 2020, Cho et al., 2020, Johnson et al., 2020, Kent and Agrawal, 2020, Makhnovskii et al., 2020, Mishra et al., 2020, Park et al., 2020, Rust et al., 2020, Brunet Avalos et al., 2019, He et al., 2019, Shokri et al., 2019, Su et al., 2019, Xu et al., 2019, Gene Disruption Project members, 2018-, Lee et al., 2018, Troha et al., 2018, Chung et al., 2017, Karaiskos et al., 2017, Ragheb et al., 2017, Sharma et al., 2017, Song et al., 2017, Transgenic RNAi Project members, 2017-, Schwartz et al., 2016, Copf, 2015, Fox and Andrew, 2015, Gene Disruption Project members, 2015-, Graves et al., 2015, Nagarkar-Jaiswal et al., 2015, Schertel et al., 2015, Sîrbu et al., 2015, Ugrankar et al., 2015, Chandran et al., 2014, Fox et al., 2013, Ghezzi et al., 2013, Iyer et al., 2013, Short and Lazzaro, 2013, Mizrak et al., 2012, Chung et al., 2011, Maruyama et al., 2011, Obbard et al., 2011, Shaik et al., 2011, Fox et al., 2010, Skora and Spradling, 2010, Tang et al., 2010, Tsurudome et al., 2010, Chung et al., 2009, Christensen et al., 2008.4.15, Fox et al., 2008, Kheradpour et al., 2007, Quinones-Coello, 2007, Stark et al., 2007, Wang and Lin, 2007, Abrams et al., 2006, Meyer et al., 2006, Burgler and Macdonald, 2005, Greene et al., 2005, Stark et al., 2005, Gim et al., 2001)
        l(3)03576
        Name Synonyms
        Box B-binding factor 2
        CREB-binding protein
        Cyclic-AMP response element binding protein A
        cAMP response element binding protein
        cAMP response element binding protein A
        cyclic AMP response element binding protein
        Secondary FlyBase IDs
        • FBgn0004848
        • FBgn0010804
        • FBgn0041115
        • FBgn0062892
        Datasets (0)
        Study focus (0)
        Experimental Role
        Project
        Project Type
        Title
        Study result (0)
        Result
        Result Type
        Title
        External Crossreferences and Linkouts ( 55 )
        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
        Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
        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
        iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
        Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
        MIST (genetic) - An integrated Molecular Interaction Database
        MIST (protein-protein) - An integrated Molecular Interaction Database
        SignaLink - A signaling pathway resource with multi-layered regulatory networks.
        References (246)