hiw highwire [Drosophila melanogaster (fruit fly)] - Gene

Summary

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 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, Dec 2024]
Orthologs: all
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Genomic context

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_004354.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Dm0478 (e-PCR)
- UniSTS:11834

Homology

NCBI Orthologs

Orthologs from OrthoDB

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

NC_004354.4 Reference assembly

Range

15010137..15063429 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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