Smurf SMAD specific E3 ubiquitin protein ligase [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Smurfprovided by FlyBase
Official Full Name: SMAD specific E3 ubiquitin protein ligaseprovided by FlyBase
Primary source: FLYBASE:FBgn0029006
Locus tag: Dmel_CG4943
See related: AllianceGenome:FB:FBgn0029006
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: CG4943; d-smurf; D-smurf; Dmel\CG4943; dSmurf; Dsmurf; DSmurf; dSmurf1; lack; Lack; LACK; smurf; SMURF; Smurf ubiquitin ligase
Summary: Enables ubiquitin protein ligase activity. Involved in several processes, including cellular protein metabolic process; gamete generation; and regulation of signal transduction. Located in cytosol. Is expressed in adult head; germarium; spermatozoon; wing hinge primordium; and wing pouch. Orthologous to several human genes including SMURF2 (SMAD specific E3 ubiquitin protein ligase 2). [provided by Alliance of Genome Resources, Apr 2022]
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Genomic context

Location:: 54C12-54D1; 2-83 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	2R	NT_033778.4 (17592791..17604461)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	2R	NT_033778.3 (13480296..13491966)

Chromosome 2R - NT_033778.4 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 hedgehog (Hh)-induced phosphorylation of signal transducer Smoothened (Smo) inhibits smurf E3 ligase (Smurf) recruitment to Smo.
Title: Hedgehog reciprocally controls trafficking of Smo and Ptc through the Smurf family of E3 ubiquitin ligases.
dSmurf is required for synapse remodeling and axon pruning by glia
Title: Drosophila ubiquitin E3 ligase dSmurf is required for synapse remodeling and axon pruning by glia.
Together, our results demonstrate that transcriptional repression of Ed followed by Smurf-mediated downregulation of pretranslated Ed in amnioserosa regulates the establishment of a taut leading edge during dorsal closure
Title: Smurf Downregulates Echinoid in the Amnioserosa To Regulate Drosophila Dorsal Closure.
Interaction with Slimb leads to the ubiquitination and degradation of dSmurf, resulting in negative regulation of dSmurf-mediated Yki phosphorylation and activity in the Hippo pathway. Thus our study revealed a new regulatory mechanism of the Hippo pathway which may provide implications for developing tumor treatment.
Title: The Drosophila F-box protein Slimb controls dSmurf protein turnover to regulate the Hippo pathway.
Sufficient knock-down of dSmurf increases the protein abundance of Wts and thus increases phosphorylation level at S168 of Yki, the key downstream target of Wts in the Hippo pathway.
Title: Ubiquitin E3 ligase dSmurf is essential for Wts protein turnover and Hippo signaling.
Smo interacts with Smurf and promotes it to mediate Patched ubiquitination by targeting the K1261 site in Ptc.
Title: Activation of Smurf E3 ligase promoted by smoothened regulates hedgehog signaling through targeting patched turnover.
Smurf-mediated differential proteolysis generates dynamic BMP signaling in germline stem cells during Drosophila testis development.
Title: Smurf-mediated differential proteolysis generates dynamic BMP signaling in germline stem cells during Drosophila testis development.
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.
dSmurf specifically targets phosphorylated MAD to proteasome-dependent degradation and regulates DPP signaling during development.
Title: dSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development.

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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

Orthologs from OrthoDB

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 transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin-protein transferase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in embryonic development via the syncytial blastoderm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in embryonic hindgut morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in germarium-derived egg chamber formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in male gamete generation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of BMP signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of BMP signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of BMP signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hippo signaling	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 receptor-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of smoothened signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of growth	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
part_of ubiquitin ligase complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: SMAD specific E3 ubiquitin protein ligase

Names: CG4943-PA; CG4943-PB; Smurf-PA; Smurf-PB; Smurf1; lethal with a checkpoint kinase; smad ubiquitination regulatory factor; smurf; smurf E3 ligase

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

NT_033778.4 Reference assembly

Range

17592791..17604461

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001274132.1 → NP_001261061.1 SMAD specific E3 ubiquitin protein ligase, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001261061.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9U3W2, Q9V853

UniProtKB/TrEMBL

A0A0B4KFU5

Conserved Domains (5) summary

cd08382
Location:14 → 135

C2_Smurf-like; C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins

smart00456
Location:562 → 594

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:726 → 1058

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:702 → 1058

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

pfam00397
Location:169 → 198

WW; WW domain
NM_079055.3 → NP_523779.1 SMAD specific E3 ubiquitin protein ligase, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_523779.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9U3W2, Q9V853

UniProtKB/TrEMBL

A0A0B4KFU5

Related

FBpp0086011

Conserved Domains (5) summary

cd08382
Location:14 → 135

C2_Smurf-like; C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins

smart00456
Location:562 → 594

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:726 → 1058

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:702 → 1058

HECTc; HECT domain; C-terminal catalytic domain of a subclass of Ubiquitin-protein ligase (E3). It binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ...

pfam00397
Location:169 → 198

WW; WW domain