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General Information
Symbol
Dmel\Nedd4
Species
D. melanogaster
Name
Nedd4
Annotation Symbol
CG42279
Feature Type
FlyBase ID
FBgn0259174
Gene Model Status
Stock Availability
Gene Snapshot
Nedd4 (Nedd4) encodes an E3 ubiquitin ligase that negatively regulates the Notch signaling pathway and the genes comm, Amph. It contributes to neuromuscular synaptogenesis, transverse tubule formation in muscles, and in muscle function. [Date last reviewed: 2019-03-14]
Also Known As
DNedd4
Key Links
Genomic Location
Cytogenetic map
Sequence location
3L:17,530,081..17,546,660 [+]
Recombination map
3-45
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)
-
Summaries
Gene Group (FlyBase)
HECT UBIQUITIN LIGASES -
E3 (ubiquitin) ligases interact with both ubiquitin-E2 (ubiquitin-conjugating) enzymes and the target protein, transferring the ubiquitin from the E2 to the substrate. Members of the HECT family of E3 ubiquitin ligases are characterized by a C-terminal HECT domain. This catalytic domain forms an intermediate thioester bond with ubiquitin via a conserved Cys when transferring ubiquitin from the E2 to the target protein. (Adapted from FBrf0225009).
Pathway (FlyBase)
Negative Regulators of Hedgehog Signaling Pathway -
Negative regulators of hedgehog signaling down-regulation the pathway, resulting in the repression of transcription of hh-responsive genes.
Negative Regulators of Notch Signaling Pathway -
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. Negative regulators of the pathway down-regulate the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
Protein Function (UniProtKB)
Essential E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Down-regulates Notch/N signaling pathway by promoting Notch ubiquitination, endocytosis and degradation.
(UniProt, Q9VVI3)
Summary (Interactive Fly)
E3 ubiquitin ligase - negatively regulates the Notch signaling pathway and the genes and - contributes to neuromuscular synaptogenesis, transverse tubule formation in muscles, and muscle function - formation and actin-dependent patterning of the heart
Gene Model and Products
Number of Transcripts
9
Number of Unique Polypeptides
9

Please see the GBrowse view of Dmel\Nedd4 or the JBrowse view of Dmel\Nedd4 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
Low-frequency RNA-Seq exon junction(s) not annotated.
Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.
Gene model reviewed during 5.45
Tissue-specific extension of 3' UTRs observed during later stages (FBrf0218523, FBrf0219848); all variants may not be annotated
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0299642
3384
793
FBtr0299645
3917
956
FBtr0299646
3942
931
FBtr0299648
4131
994
FBtr0299647
4098
983
FBtr0300519
4454
1007
FBtr0300520
3651
834
FBtr0331843
4164
1005
FBtr0331844
4146
999
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
FBpp0288917
91.2
793
5.33
FBpp0288920
109.5
956
5.93
FBpp0288921
106.2
931
5.02
FBpp0288923
113.4
994
6.47
FBpp0288922
111.9
983
6.40
FBpp0289746
114.9
1007
6.57
FBpp0289747
95.3
834
6.15
FBpp0304227
114.6
1005
6.57
FBpp0304228
113.6
999
6.44
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)
Interacts (via WW2 domain) with comm (via PY-motifs) (PubMed:12165468, PubMed:16531238). Interacts with N (PubMed:15620649).
(UniProt, Q9VVI3)
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\Nedd4 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 (27 terms)
Molecular Function (6 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
inferred from physical interaction with FLYBASE:Myo10A; FB:FBgn0263705
inferred from physical interaction with FLYBASE:N; FB:FBgn0004647
inferred from physical interaction with UniProtKB:Q24139
(assigned by UniProt )
inferred from direct assay
inferred from physical interaction with FLYBASE:comm; FB:FBgn0010105
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000134256
(assigned by GO_Central )
non-traceable author statement
(assigned by UniProt )
Biological Process (19 terms)
Terms Based on Experimental Evidence (13 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
(assigned by BHF-UCL )
inferred from mutant phenotype
(assigned by BHF-UCL )
inferred from mutant phenotype
(assigned by BHF-UCL )
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
(assigned by UniProt )
inferred from physical interaction with UniProtKB:Q24139
(assigned by UniProt )
inferred from mutant phenotype
(assigned by UniProt )
Terms Based on Predictions or Assertions (7 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000882924
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000134745
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000134745
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000134745
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000134256
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000882924
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000134745
(assigned by GO_Central )
Cellular Component (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
(assigned by UniProt )
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000134256
(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
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
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 direct assay
(assigned by UniProt )
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Nedd4 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
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 37 )
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 Nedd4
Transgenic constructs containing regulatory region of Nedd4
Deletions and Duplications ( 2 )
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 v7.1)
Homo sapiens (Human) (12)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
12 of 15
Yes
No
4 of 15
No
No
4 of 15
No
No
3 of 15
No
No
3 of 15
No
No
3 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (12)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
13 of 15
Yes
No
4 of 15
No
No
4 of 15
No
No
3 of 15
No
No
3 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (12)
9 of 13
Yes
Yes
8 of 13
Yes
No
3 of 13
No
No
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (7)
9 of 12
Yes
Yes
5 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (15)
12 of 15
Yes
Yes
7 of 15
No
Yes
4 of 15
No
No
3 of 15
No
No
3 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (4)
14 of 15
Yes
Yes
4 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (2)
1 of 9
Yes
No
1 of 9
Yes
No
Saccharomyces cerevisiae (Brewer's yeast) (2)
11 of 15
Yes
Yes
1 of 15
No
No
Schizosaccharomyces pombe (Fission yeast) (3)
8 of 12
Yes
Yes
6 of 12
No
Yes
2 of 12
No
No
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190282 )
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) ( EOG0915019U )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Aedes aegypti
Yellow fever mosquito
Anopheles darlingi
American malaria mosquito
Anopheles darlingi
American malaria mosquito
Anopheles gambiae
Malaria mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W012O )
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
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X010Z )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
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) ( EOG091G0SS8 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (7)
6 of 10
5 of 10
3 of 10
1 of 10
1 of 10
1 of 10
1 of 10
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.
    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
    RNA-RNA
    Physical Interaction
    Assay
    References
    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)
    Interacts (via WW2 domain) with comm (via PY-motifs) (PubMed:12165468, PubMed:16531238). Interacts with N (PubMed:15620649).
    (UniProt, Q9VVI3 )
    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)
    Negative Regulators of Hedgehog Signaling Pathway -
    Negative regulators of hedgehog signaling down-regulation the pathway, resulting in the repression of transcription of hh-responsive genes.
    Negative Regulators of Notch Signaling Pathway -
    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. Negative regulators of the pathway down-regulate the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
    External Data
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3L
    Recombination map
    3-45
    Cytogenetic map
    Sequence location
    3L:17,530,081..17,546,660 [+]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    74D3-74D3
    Limits computationally determined from genome sequence between P{PZ}frc00073&P{PZ}frc02619 and P{lacW}l(3)j11B2j11B2
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (29)
    Genomic Clones (25)
    cDNA Clones (123)
     

    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: Nedd4 CG7555
    Source for database merge of
    Source for merge of: Nedd4 CG32184
    Additional comments
    Annotations CG7555 and CG32184 merged as CG42279 in release 5.8 of the genome annotation.
    Other Comments
    dsRNA made from templates generated with primers directed against this gene tested in RNAi screen for effects on Kc167 and S2R+ cell morphology.
    New annotation (CG32184) in release 3 of the genome annotation.
    Identification: in a yeast two hybrid assay for proteins that interacts with the intracellular domain of comm.
    comm is a specific binding partner and substrate of Nedd4. Nedd4 is recruited by comm protein to control cell surface levels of the robo receptor.
    Origin and Etymology
    Discoverer
    Etymology
    Identification
    External Crossreferences and Linkouts ( 101 )
    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 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
    FlyMine - An integrated database for Drosophila genomics
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
    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
    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 (10)
    Reported As
    Symbol Synonym
    ACN62428.1
    Secondary FlyBase IDs
    • FBgn0036736
    • FBgn0052184
    Datasets (0)
    Study focus (0)
    Experimental Role
    Project
    Project Type
    Title
    References (122)