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    hiw highwire [ Drosophila melanogaster (fruit fly) ]

    Gene ID: 32429, updated on 18-Sep-2024

    Summary

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    Official Symbol
    hiwprovided by FlyBase
    Official Full Name
    highwireprovided by FlyBase
    Primary source
    FLYBASE:FBgn0030600
    Locus tag
    Dmel_CG32592
    See related
    AllianceGenome:FB:FBgn0030600
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Drosophila melanogaster
    Lineage
    Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
    Also known as
    CG32592; CG9041; CG9049; Dmel\CG32592; Hiw; HIW
    Summary
    Predicted to enable ubiquitin protein ligase activity and zinc ion binding activity. Involved in several processes, including long-term memory; positive regulation of neuromuscular synaptic transmission; and regulation of synapse organization. Located in cytoplasmic vesicle and plasma membrane. Is expressed in embryonic/larval central nervous system and spermatozoon. Used to study brain disease. Orthologous to human MYCBP2 (MYC binding protein 2). [provided by Alliance of Genome Resources, Apr 2022]
    Orthologs
    all
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    Genomic context

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    See hiw in Genome Data Viewer
    Location:
    13A5-13A8; 1-49 cM
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    Release 6.54 current Release 6 plus ISO1 MT (GCF_000001215.4) X NC_004354.4 (15010137..15063429, complement)
    Release 5.57 previous assembly Release 5 (GCF_000001215.2) X NC_004354.3 (14904170..14957462, complement)

    Chromosome X - NC_004354.4Genomic Context describing neighboring genes Neighboring gene uncharacterized protein Neighboring gene ether a go-go Neighboring gene ben Neighboring gene uncharacterized protein Neighboring gene NADH dehydrogenase (ubiquinone) B18 subunit Neighboring gene opossum Neighboring gene doppelganger von brummer

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Distinct homeostatic modulations stabilize reduced postsynaptic receptivity in response to presynaptic DLK signaling. Goel P, et al. Nat Commun, 2018 May 10. PMID 29748610, Free PMC Article
    2. Human Senataxin Modulates Structural Plasticity of the Neuromuscular Junction in Drosophila through a Neuronally Conserved TGFβ Signalling Pathway. Mushtaq Z, et al. Neurodegener Dis, 2016. PMID 27197982
    3. PHRs: bridging axon guidance, outgrowth and synapse development. Po MD, et al. Curr Opin Neurobiol, 2010 Feb. PMID 20079626
    4. Programmed axon degeneration: from mouse to mechanism to medicine. Coleman MP, et al. Nat Rev Neurosci, 2020 Apr. PMID 32152523, Free PMC Article
    5. HSP90 is a chaperone for DLK and is required for axon injury signaling. Karney-Grobe S, et al. Proc Natl Acad Sci U S A, 2018 Oct 16. PMID 30275300, Free PMC Article

    See all (151) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Highwire downregulates dNmnat to promote evoked synaptic release, suggesting that Highwire balances the axoprotective and synapse-inhibitory functions of dNmnat.
      Title: The E3 ligase Highwire promotes synaptic transmission by targeting the NAD-synthesizing enzyme dNmnat.
    2. Study provide specific evidence that in Drosophila melanogaster hiw plays an important role in the regulation of behavioral nociception and nociceptor sensitivity through the bone morphogenetic protein (BMP) pathway.
      Title: BMP signaling downstream of the Highwire E3 ligase sensitizes nociceptors.
    3. Results indicate that the ability of faf, hiw or Rdl to modulate sleep and protect against cognitive impairments during waking is circuit dependent. Decreasing hiw and Rdl within the Mushroom Bodies protects against the negative effects of sleep deprivation as indicated by the absence of a subsequent homeostatic response, or deficits in short-term memory.
      Title: Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss.
    4. Highwire promotes axon termination, pruning and synaptogenesis.
      Title: Axon Termination, Pruning, and Synaptogenesis in the Giant Fiber System of Drosophila melanogaster Is Promoted by Highwire.
    5. The dual leucine zipper kinase (DLK) signaling pathway in Drosophila, which consists of Highwire and Wallenda and controls axonal growth, regeneration, and degeneration, is also involved in dendritic growth in vivo.
      Title: Bimodal control of dendritic and axonal growth by the dual leucine zipper kinase pathway.
    6. An increased level of Nmnat protein in hiw mutants is both required and sufficient to inhibit axonal degeneration.
      Title: The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein.
    7. Genetic interaction studies suggest that Highwire and Plexin A signals may interact to regulate normal morphogenesis of alpha/beta axons.
      Title: Highwire regulates guidance of sister axons in the Drosophila mushroom body.
    8. The regulation of Wnd protein turnover by Hiw can function as a damage surveillance mechanism for responding to axonal injury.
      Title: Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury.
    9. BMP signaling mutants suppress the excessive synaptic growth in Highwire mutants. Activation of BMP signaling in Highwire mutants causes further synaptic expansion.
      Title: Highwire regulates presynaptic BMP signaling essential for synaptic growth.
    10. These results suggest that Highwire controls structural plasticity of the synapse by regulating gene expression through a MAP kinase signaling pathway.
      Title: Highwire restrains synaptic growth by attenuating a MAP kinase signal.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    mobile_element

    • Loc: c15018073-15017993 mobile_element_type = transposon:INE-1{}3058
    • Loc: c15048601-15047992 mobile_element_type = transposon:HB{}134

    Gene Ontology Provided by FlyBase

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables zinc ion binding ISM
    Inferred from Sequence Model
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in adult walking behavior NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in autophagy IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in axon guidance IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in locomotion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in long-term memory IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of BMP signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of synaptic assembly at neuromuscular junction IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in negative regulation of synaptic assembly at neuromuscular junction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of neuromuscular synaptic transmission IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein ubiquitination ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of synaptic assembly at neuromuscular junction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of synaptic assembly at neuromuscular junction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of synaptic assembly at neuromuscular junction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of terminal button organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in response to axon injury IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in synapse organization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    highwire
    Names
    CG32592-PA
    CG32592-PB
    hiw-PA
    hiw-PB

    NCBI Reference Sequences (RefSeq)

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    Genome Annotation

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference assembly

    Genomic

    1. NC_004354.4 Reference assembly

      Range
      15010137..15063429 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001298329.1 → NP_001285258.1  highwire, isoform B [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_001285258.1

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q8MZ36, Q9NB71, Q9VXZ5
      UniProtKB/TrEMBL
      X2JF19
      Conserved Domains (4) summary
      pfam00415
      Location:985 → 1031
      RCC1; Regulator of chromosome condensation (RCC1) repeat
      pfam08005
      Location:1437 → 1585
      PHR; PHR domain
      pfam13540
      Location:968 → 997
      RCC1_2; Regulator of chromosome condensation (RCC1) repeat
      pfam13639
      Location:4989 → 5042
      zf-RING_2; Ring finger domain

    2. NM_078604.4 → NP_511159.3  highwire, isoform A [Drosophila melanogaster]

      See identical proteins and their annotated locations for NP_511159.3

      Status: REVIEWED

      UniProtKB/Swiss-Prot
      Q8MZ36, Q9NB71, Q9VXZ5
      UniProtKB/TrEMBL
      X2JF19
      Conserved Domains (4) summary
      pfam00415
      Location:985 → 1031
      RCC1; Regulator of chromosome condensation (RCC1) repeat
      pfam08005
      Location:1437 → 1585
      PHR; PHR domain
      pfam13540
      Location:968 → 997
      RCC1_2; Regulator of chromosome condensation (RCC1) repeat
      pfam13639
      Location:4989 → 5042
      zf-RING_2; Ring finger domain
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NB71.2 Q9NB71
    X2JF19 X2JF19

    Gene LinkOut

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