Nedd4 Nedd4 [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Nedd4provided by FlyBase
Official Full Name: Nedd4provided by FlyBase
Primary source: FLYBASE:FBgn0259174
Locus tag: Dmel_CG42279
See related: AllianceGenome:FB:FBgn0259174
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: ACN62428.1; CG32184; CG42279; CG7555; Dmel\CG42279; dNedd4; DNedd4; dNedd4-1; nedd4; NEDD4
Old locus tag: Dmel_CG32184; Dmel_CG7555
Summary: Enables several functions, including Notch binding activity; myosin binding activity; and ubiquitin protein ligase activity. Involved in several processes, including imaginal disc-derived wing vein morphogenesis; negative regulation of signal transduction; and positive regulation of cellular component organization. Located in plasma membrane and subsynaptic reticulum. Is expressed in adult head and organism. Human ortholog(s) of this gene implicated in periventricular nodular heterotopia. Orthologous to several human genes including NEDD4L (NEDD4 like E3 ubiquitin protein ligase). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 74D2-74D3; 3-45 cM

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3L	NT_037436.4 (17530081..17546660)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3L	NT_037436.3 (17523181..17539760)

Chromosome 3L - NT_037436.4 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?

miR-1-mediated regulation of Nedd4/Nedd4L expression may serve to broadly modulate the trafficking or degradation of Nedd4/Nedd4L substrates in the heart
Title: The E3 ubiquitin ligase Nedd4/Nedd4L is directly regulated by microRNA 1.
Nedd4Lo destabilizes Amph in muscles, leading to impaired T-tubule formation and muscle function.
Title: Drosophila Nedd4-long reduces Amphiphysin levels in muscles and leads to impaired T-tubule formation.
NEDD4 controls the Hippo pathway leading to coordinated cell proliferation and apoptosis
Title: NEDD4 controls intestinal stem cell homeostasis by regulating the Hippo signalling pathway.
data in two evolutionarily distant model organisms strongly suggest that Nedd4 is a modifier of alpha-synuclein pathobiology and thus a potential target for neuroprotective therapies
Title: Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease.
Nedd4, another E3 ubiquitin ligase that may have a role in PD, is functionally related to Sep4 and could be involved in regulating Sep4 subcellular localization/trafficking.
Title: Septin 4, the drosophila ortholog of human CDCrel-1, accumulates in parkin mutant brains and is functionally related to the Nedd4 E3 ubiquitin ligase.
splice isoforms of the same dNedd4 gene can lead to opposite effects on neuromuscular synaptogenesis
Title: A splice isoform of DNedd4, DNedd4-long, negatively regulates neuromuscular synaptogenesis and viability in Drosophila.
dNedd4 and ubiquitination are required for Commissureless endocytosis and proper neuromuscular synaptogenesis.
Title: Regulation of Commissureless by the ubiquitin ligase DNedd4 is required for neuromuscular synaptogenesis in Drosophila melanogaster.
Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation.
Title: Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation.
These studies provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development.
Title: Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex.

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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

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables Notch binding	IPI Inferred from Physical Interaction more info	PubMed
enables myosin binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IDA Inferred from Direct Assay more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium channel inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin-protein transferase activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in axon midline choice point recognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in axon midline choice point recognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in imaginal disc-derived wing vein morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of Notch signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of smoothened signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in neuromuscular junction development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cardiac myofibril assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cardioblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endocytosis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synapse assembly	IMP Inferred from Mutant Phenotype more info	PubMed
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 receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor internalization	IPI Inferred from Physical Interaction more info	PubMed
involved_in regulation of dendrite morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in subsynaptic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: Nedd4

Names: CG42279-PE; CG42279-PF; CG42279-PG; CG42279-PH; CG42279-PI; CG42279-PJ; CG42279-PK; CG42279-PL; CG42279-PM; DNedd4; Nedd4-PE; Nedd4-PF; Nedd4-PG; Nedd4-PH; Nedd4-PI; Nedd4-PJ; Nedd4-PK; Nedd4-PL; Nedd4-PM

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_037436.4 Reference assembly

Range

17530081..17546660

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_140736.3 → NP_648993.1 Nedd4, isoform J [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_648993.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q7KUR2, Q8IQR6, Q95R64, Q95TQ0, Q95ZF9, Q9VVI3

Related

FBpp0289746

Conserved Domains (5) summary

cd04033
Location:71 → 204

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:581 → 613

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:674 → 1003

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:650 → 1003

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:248 → 277

WW; WW domain
NM_001275061.1 → NP_001261990.1 Nedd4, isoform L [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001261990.1

Status: REVIEWED

UniProtKB/TrEMBL

M9PFK2

Conserved Domains (5) summary

cd04033
Location:71 → 205

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:579 → 611

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:672 → 1001

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:648 → 1001

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:249 → 278

WW; WW domain
NM_168738.4 → NP_730284.2 Nedd4, isoform G [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_730284.2

Status: REVIEWED

UniProtKB/TrEMBL

Q8IQR5

Conserved Domains (5) summary

cd04033
Location:71 → 204

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:505 → 537

WW; Domain with 2 conserved Trp (W) residues

COG5021
Location:81 → 927

HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]

cd00078
Location:574 → 927

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:248 → 277

WW; WW domain
NM_001144492.2 → NP_001137964.1 Nedd4, isoform I [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001137964.1

Status: REVIEWED

UniProtKB/TrEMBL

B7Z067

Conserved Domains (5) summary

cd04033
Location:71 → 204

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:557 → 589

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:650 → 979

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:626 → 979

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:248 → 277

WW; WW domain
NM_001144493.3 → NP_001137965.1 Nedd4, isoform H [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001137965.1

Status: REVIEWED

UniProtKB/TrEMBL

B7Z068

Conserved Domains (5) summary

cd04033
Location:71 → 204

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:568 → 600

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:661 → 990

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:637 → 990

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:248 → 277

WW; WW domain
NM_168736.4 → NP_730282.1 Nedd4, isoform K [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_730282.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9VVI3

Related

FBpp0289747

Conserved Domains (5) summary

cd04033
Location:71 → 204

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:408 → 440

WW; Domain with 2 conserved Trp (W) residues

COG5021
Location:81 → 830

HUL4; Ubiquitin-protein ligase [Posttranslational modification, protein turnover, chaperones]

cd00078
Location:477 → 830

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:248 → 277

WW; WW domain
NM_001275062.1 → NP_001261991.1 Nedd4, isoform M [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001261991.1

Status: REVIEWED

UniProtKB/TrEMBL

M9PFY9

Conserved Domains (5) summary

cd04033
Location:71 → 201

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:573 → 605

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:666 → 995

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:642 → 995

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:245 → 274

WW; WW domain
NM_168737.2 → NP_730283.1 Nedd4, isoform F [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_730283.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9VVI3

Related

FBpp0288920

Conserved Domains (5) summary

cd04033
Location:33 → 166

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:530 → 562

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:623 → 952

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:599 → 952

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:210 → 239

WW; WW domain
NM_206394.2 → NP_996116.1 Nedd4, isoform E [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_996116.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q9VVI3

Conserved Domains (5) summary

cd04033
Location:33 → 163

C2_NEDD4_NEDD4L; C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42)

smart00456
Location:367 → 399

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:460 → 789

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:436 → 789

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:207 → 236

WW; WW domain