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General Information
Symbol
Dmel\hiw
Species
D. melanogaster
Name
highwire
Annotation Symbol
CG32592
Feature Type
FlyBase ID
FBgn0030600
Gene Model Status
Stock Availability
Gene Summary
Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (By similarity). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (By similarity). Required in the presynaptic motoneuron to down-regulate the levels of wnd and restrain synaptic terminal growth at the neuromuscular junction (NMJ) together with Rae1 and Fsn (PubMed:10839352, PubMed:21874015, PubMed:17697379). (UniProt, Q9NB71)
Contribute a Gene Snapshot for this gene.
Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
1-49
RefSeq locus
NC_004354 REGION:15010137..15063429
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Ontology (GO) Annotations (20 terms)
Molecular Function (3 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from physical interaction with FLYBASE:Rae1; FB:FBgn0034646
inferred from physical interaction with FLYBASE:Fsn; FB:FBgn0043010
inferred from physical interaction with UniProtKB:O62609
(assigned by UniProt )
inferred from physical interaction with UniProtKB:Q9V6L9
(assigned by UniProt )
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001820464
(assigned by GO_Central )
inferred from sequence or structural similarity with UniProtKB:O75592
inferred from sequence model
Biological Process (14 terms)
Terms Based on Experimental Evidence (10 terms)
CV Term
Evidence
References
involved_in autophagy
inferred from direct assay
involved_in long-term memory
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from genetic interaction with UniProtKB:Q9W2E7
(assigned by UniProt )
inferred from genetic interaction with UniProtKB:Q9V6L9
(assigned by UniProt )
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
Terms Based on Predictions or Assertions (5 terms)
CV Term
Evidence
References
non-traceable author statement
involved_in axon guidance
inferred from biological aspect of ancestor with PANTHER:PTN002338293
(assigned by GO_Central )
involved_in locomotion
non-traceable author statement
inferred from sequence or structural similarity with UniProtKB:Q8WY64
(assigned by UniProt )
inferred from biological aspect of ancestor with PANTHER:PTN002338293
(assigned by GO_Central )
traceable author statement
Cellular Component (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
located_in plasma membrane
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
is_active_in nucleus
inferred from biological aspect of ancestor with PANTHER:PTN001820464
(assigned by GO_Central )
is_active_in plasma membrane
inferred from biological aspect of ancestor with PANTHER:PTN001820464
(assigned by GO_Central )
Protein Family (UniProt)
Belongs to the RING-Cys relay (RCR) family. (Q9NB71)
Summaries
Gene Group (FlyBase)
OTHER RING DOMAIN UBIQUITIN LIGASES -
The RING (Really Interesting New Gene) finger domain co-ordinates two Zn2+ ions via conserved Cys and His residues. Most proteins which contain a RING finger are assumed to be ubiquitin (E3) ligases. The RING finger binds ubiquitin-conjugating enzymes (E2) and promotes direct transfer of ubiquitin to the target protein. (Adapted from FBrf0215242 and PMID:19489725).
Pathway (FlyBase)
Negative Regulators of BMP Signaling Pathway -
Negative regulators of Bone Morphogenetic Protein (BMP) signaling down-regulate the pathway, ultimately resulting in the decreased nuclear activity of the Mad/Med transcription factor complex.
Protein Function (UniProtKB)
Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (By similarity). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (By similarity). Required in the presynaptic motoneuron to down-regulate the levels of wnd and restrain synaptic terminal growth at the neuromuscular junction (NMJ) together with Rae1 and Fsn (PubMed:10839352, PubMed:21874015, PubMed:17697379).
(UniProt, Q9NB71)
Summary (Interactive Fly)

synaptic protein - B-box zinc finger superfamily - a negative regular of synaptic growth - regulates guidance of sister axons in the mushroom body

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

Please see the JBrowse view of Dmel\hiw 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 New Section
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry Q9NB71)

If you don't see the viewer to the right, 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.

Comments on Gene Model

Gene model reviewed during 5.50

Gene model reviewed during 5.56

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0073970
16177
5233
FBtr0346087
16734
5233
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
UniProt
RefSeq ID
GenBank
FBpp0073787
565.6
5233
6.87
FBpp0311921
565.6
5233
6.87
Polypeptides with Identical Sequences

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

5233 aa isoforms: hiw-PA, hiw-PB
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)

Component of an E3 ubiquitin ligase complex composed of hiw, Rae1 and Fsn (PubMed:17697379, PubMed:21874015). Interacts with Rae1; the interaction with Rae1 may protect hiw from autophagy-mediated degradation (PubMed:21874015).

(UniProt, Q9NB71)
Domain

The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners (By similarity).

The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.

(UniProt, Q9NB71)
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\hiw 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
Expression Summary Ribbons
Colored tiles in ribbon indicate that the Fly Cell Atlas project found the gene expressed in that cell type. Darker colors mean that more cells of that cell type express the gene:
 low
high 
Colorless tiles indicate that there is no scRNAseq data for the gene in that cell type.
Colored tiles in ribbon indicate that expression data (RNA and/or protein) has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
Colored tiles in the ribbon indicate the average RNA expression level of the gene at the indicated stages:
 low
high 
as determined by RNA-seq (RPKM) using whole organism samples modENCODE, Brown et al., 2014. For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
located_in plasma membrane
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\hiw 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
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
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 67 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 17 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of hiw
Transgenic constructs containing regulatory region of hiw
Aberrations (Deficiencies and Duplications) ( 2 )
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
indirect flight muscle motor neuron MN4 & bouton | ectopic
Orthologs
Human Orthologs (via DIOPT v8.0)
Homo sapiens (Human) (1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
14 of 15
Yes
Yes
Model Organism Orthologs (via DIOPT v8.0)
Mus musculus (laboratory mouse) (1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
13 of 15
Yes
Yes
Rattus norvegicus (Norway rat) (2)
8 of 13
Yes
Yes
2 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (1)
3 of 12
Yes
Yes
Danio rerio (Zebrafish) (1)
10 of 15
Yes
Yes
Caenorhabditis elegans (Nematode, roundworm) (2)
15 of 15
Yes
Yes
13 of 15
No
Yes
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.
Other Organism Orthologs (via OrthoDB)
Paralogs
Paralogs (via DIOPT v8.0)
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 ( 1 )
Allele
Disease
Evidence
References
Potential Models Based on Orthology ( 0 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 6 )
Disease Associations of Human Orthologs (via DIOPT v8.0 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)
Component of an E3 ubiquitin ligase complex composed of hiw, Rae1 and Fsn (PubMed:17697379, PubMed:21874015). Interacts with Rae1; the interaction with Rae1 may protect hiw from autophagy-mediated degradation (PubMed:21874015).
(UniProt, Q9NB71 )
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)
Negative Regulators of BMP Signaling Pathway -
Negative regulators of Bone Morphogenetic Protein (BMP) signaling down-regulate the pathway, ultimately resulting in the decreased nuclear activity of the Mad/Med transcription factor complex.
Metabolic Pathways
External Data
Linkouts
Genomic Location and Detailed Mapping Data
Chromosome (arm)
X
Recombination map
1-49
Cytogenetic map
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
13A5-13A8
Limits computationally determined from genome sequence between P{EP}EP334&P{EP}EP977 and P{EP}hiwEP1305
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
13A5-13A8
13A5-13A6
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Location
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (24)
Genomic Clones (25)
cDNA Clones (24)
 

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 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
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    Antibody Information
    Laboratory Generated Antibodies
     
    Commercially Available Antibodies
     
    Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
    Other Information
    Relationship to Other Genes
    Source for database identify of

    Source for identity of: hiw CG9041 CG9049

    Source for database merge of
    Additional comments

    Annotations CG9041, CG9049 merged as CG32592 in release 3 of the genome annotation.

    Source for identity of hiw CG9041 CG9049 was sequence comparison ( date:000622 ).

    Other Comments

    hiw regulates synaptic physiology through a distinct molecular pathway that does not require wnd.

    hiw functions to control wnd primarily in larva.

    Synaptic overgrowth in hiw mutants requires JNK signalling.

    The RING domain of hiw plays an essential role in regulating synaptic function.

    hiw dependant ubiquitination has a role in controlling the level of activity of critical regulatory molecules at the synapse.

    hiw appears to function as a negative regulator of synaptic growth.

    Origin and Etymology
    Discoverer
    Etymology
    Identification
    External Crossreferences and Linkouts ( 62 )
    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.
    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
    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
    Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
    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
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    KEGG Genes - Molecular building blocks of life in the genomic space.
    MARRVEL_MODEL - MARRVEL (model organism gene)
    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
    Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
    FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
    FlyMine - An integrated database for Drosophila genomics
    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
    Synonyms and Secondary IDs (8)
    Reported As
    Symbol Synonym
    CG9041
    CG9049
    Secondary FlyBase IDs
    • FBgn0030604
    • FBgn0052592
    Datasets (0)
    Study focus (0)
    Experimental Role
    Project
    Project Type
    Title
    Study result (0)
    Result
    Result Type
    Title
    References (160)