fu fused [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: fuprovided by FlyBase
Official Full Name: fusedprovided by FlyBase
Primary source: FLYBASE:FBgn0001079
Locus tag: Dmel_CG6551
See related: AllianceGenome:FB:FBgn0001079
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: CG6551; d Fu; dFu; Dm fu; Dmel\CG6551; Fu; FU; fu[mel]; l(1)fu
Summary: Enables protein homodimerization activity; protein serine/threonine kinase activity; and smoothened binding activity. Involved in several processes, including intraciliary transport; negative regulation of signal transduction; and regionalization. Located in cytosol. Part of Hedgehog signaling complex. Colocalizes with extrinsic component of cytoplasmic side of plasma membrane. Is expressed in several structures, including cystoblast; egg chamber; germarium region 2; imaginal disc; and wing disc anterior compartment. Human ortholog(s) of this gene implicated in primary ciliary dyskinesia. Orthologous to human STK36 (serine/threonine kinase 36). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 17D1-17D1; 1-60 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	X	NC_004354.4 (18657755..18661204)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	X	NC_004354.3 (18551788..18555237)

Chromosome X - NC_004354.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Data show that normal Ci-155 activation by Hh requires Cos2 binding to Fu, supporting the hypothesis that Cos2 mediates the apposition of Fu molecules suitable for cross-phosphorylation and consequent full activation of Fu kinase.
Title: Contributions of Costal 2-Fused interactions to Hedgehog signaling in Drosophila.
Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus.
Title: Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus.
Hh-induced Smo conformational change facilitates the assembly of active Smo-Cos2-Fu signaling complexes that promote Fu kinase domain dimerization, phosphorylation and activation; Fu regulates both the activator and repressor forms of Ci
Title: The Hedgehog-induced Smoothened conformational switch assembles a signaling complex that activates Fused by promoting its dimerization and phosphorylation.
Study shows that Fused (Fu), a serine/threonine kinase that regulates Hedgehog, functions in concert with the E3 ligase Smurf to regulate ubiquitination and proteolysis of the BMP receptor Thickveins in germline stem cells daughter cystoblasts.
Title: The Fused/Smurf complex controls the fate of Drosophila germline stem cells by generating a gradient BMP response.
Data suggest that, after activation of Smoothened, the Fused kinase induces a conformational change in Costal2 that allows the disassembly of the Smo-Fu-Cos2-Cubitus interruptus complex and consequent activation of Hedgehog target genes.
Title: Phosphorylation of the atypical kinesin Costal2 by the kinase Fused induces the partial disassembly of the Smoothened-Fused-Costal2-Cubitus interruptus complex in Hedgehog signalling.
Findings reveal a novel positive-feedback loop in Hedgehog transduction and support a model in which Fused and SMO enhance each other's activities & sustain high levels of signaling and render the pathway robust to Patched level fluctuations.
Title: Evidence for a novel feedback loop in the Hedgehog pathway involving Smoothened and Fused.
positive role for Fused in the transduction of somatic Hedgehog signaling instructing ovariole morphogenesis
Title: Hedgehog signaling controls Soma-Germen interactions during Drosophila ovarian morphogenesis.
Data show that the Costal2-Fused-Cubitus interruptus (Cos2-Fu-Ci) protein complex is associated with Smoothened (Smo) in membrane fractions, and that Cos2 binding on Smo is necessary for the Hedgehog-dependent dissociation of Ci from this complex.
Title: Stability and association of Smoothened, Costal2 and Fused with Cubitus interruptus are regulated by Hedgehog.
Hedgehog signaling requires an intramolecular association between two domains of the protein kinase Fused
Title: An intramolecular association between two domains of the protein kinase Fused is necessary for Hedgehog signaling.
we provide evidence that fused regulates these cystocyte divisions cell autonomously, while the tumorous phenotype probably reflects both a somatic and germline requirement for fused for cyst and follicle development.
Title: fused regulates germline cyst mitosis and differentiation during Drosophila oogenesis.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables smoothened binding	IDA Inferred from Direct Assay more info	PubMed
enables smoothened binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in germarium-derived egg chamber formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intraciliary transport	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 smoothened signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nucleocytoplasmic transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in segment polarity determination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smoothened signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in smoothened signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in smoothened signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in wing disc pattern formation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of Hedgehog signaling complex	IPI Inferred from Physical Interaction more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with extrinsic component of cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: fused

Names: CG6551-PA; fu-PA

NP_477499.1

EC 2.7.11.1

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

18657755..18661204

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_058151.5 → NP_477499.1 fused [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_477499.1

Status: REVIEWED

UniProtKB/Swiss-Prot

P23647, Q26346, Q26347, Q27412, Q9VWR7

Related

FBpp0074373

Conserved Domains (2) summary

cd14002
Location:2 → 254

STKc_STK36; Catalytic domain of Serine/Threonine Kinase 36

pfam00069
Location:4 → 254

Pkinase; Protein kinase domain