Nedd4 neural precursor cell expressed, developmentally down-regulated 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Nedd4provided by MGI
Official Full Name: neural precursor cell expressed, developmentally down-regulated 4provided by MGI
Primary source: MGI:MGI:97297
See related: Ensembl:ENSMUSG00000032216 AllianceGenome:MGI:97297
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gm7265; Nedd4a; Nedd4-1; EG639396; KIAA0093; E430025J12Rik
Summary: Enables several functions, including ionotropic glutamate receptor binding activity; protein phosphorylated amino acid binding activity; and sodium channel inhibitor activity. Involved in negative regulation of vascular endothelial growth factor receptor signaling pathway and regulation of dendrite morphogenesis. Acts upstream of or within several processes, including cellular protein metabolic process; circulatory system development; and neuromuscular junction development. Located in several cellular components, including cytosol; dendritic spine; and glutamatergic synapse. Part of ubiquitin ligase complex. Is active in postsynaptic cytosol. Is expressed in several structures, including alimentary system; eye; genitourinary system; limb; and nervous system. Orthologous to human NEDD4 (NEDD4 E3 ubiquitin protein ligase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in limb E14.5 (RPKM 241.1), CNS E11.5 (RPKM 217.5) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 D; 9 40.08 cM

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (72569613..72657133)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (72662331..72749851)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing.
Title: High glucose environment induces NEDD4 deficiency that impairs angiogenesis and diabetic wound healing.
NEDD4 Regulated Pyroptosis Occurred from Co-infection between Influenza A Virus and Streptococcus pneumoniae.
Title: NEDD4 Regulated Pyroptosis Occurred from Co-infection between Influenza A Virus and Streptococcus pneumoniae.
Nedd4-1 regulates human sodium-dependent vitamin C transporter-2 functional expression in neuronal and epithelial cells.
Title: Nedd4-1 regulates human sodium-dependent vitamin C transporter-2 functional expression in neuronal and epithelial cells.
MicroRNA-155-5p in serum derived-exosomes promotes ischaemia-reperfusion injury by reducing CypD ubiquitination by NEDD4.
Title: MicroRNA-155-5p in serum derived-exosomes promotes ischaemia-reperfusion injury by reducing CypD ubiquitination by NEDD4.
Phosphorylation by IKKbeta Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer.
Title: Phosphorylation by IKKβ Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer.
NEDD4 ameliorates myocardial reperfusion injury by preventing macrophages pyroptosis.
Title: NEDD4 ameliorates myocardial reperfusion injury by preventing macrophages pyroptosis.
p21-activated kinase 4 controls the aggregation of alpha-synuclein by reducing the monomeric and aggregated forms of alpha-synuclein: involvement of the E3 ubiquitin ligase NEDD4-1.
Title: p21-activated kinase 4 controls the aggregation of α-synuclein by reducing the monomeric and aggregated forms of α-synuclein: involvement of the E3 ubiquitin ligase NEDD4-1.
NEDD4-1 Is a Key Regulator of Epidermal Homeostasis and Wound Repair.
Title: NEDD4-1 Is a Key Regulator of Epidermal Homeostasis and Wound Repair.
Loss of NEDD4 causes complete XY gonadal sex reversal in mice.
Title: Loss of NEDD4 causes complete XY gonadal sex reversal in mice.
Dietary sodium modulates nephropathy in Nedd4-2-deficient mice.
Title: Dietary sodium modulates nephropathy in Nedd4-2-deficient mice.

Submit: New GeneRIF Correction See all GeneRIFs (60)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Gene trapped (5) 1 citation
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Nedd4 (e-PCR), detects polymorphism
- UniSTS:526089

D9Mit34.1 (e-PCR), detects polymorphism
- UniSTS:131903

Nedd4 (e-PCR), detects polymorphism
- UniSTS:546894

Nedd4 (e-PCR), detects polymorphism
- UniSTS:527445

Nedd4 (e-PCR), detects polymorphism
- UniSTS:526939

RH139229 (e-PCR)
- UniSTS:221315

RH136317 (e-PCR)
- UniSTS:210308

AA959633 (e-PCR)
- UniSTS:159896

RH125447 (e-PCR)
- UniSTS:162266

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables RNA polymerase binding	ISO Inferred from Sequence Orthology more info
enables beta-2 adrenergic receptor binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables ionotropic glutamate receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphoserine residue binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphothreonine residue binding	IDA Inferred from Direct Assay more info	PubMed
enables proline-rich region binding	IPI Inferred from Physical Interaction more info	PubMed
enables proline-rich region binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	ISO Inferred from Sequence Orthology more info
enables sodium channel inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium channel inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables sodium channel inhibitor activity	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin binding	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info
enables ubiquitin-protein transferase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in DNA damage response	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within T cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within adaptive immune response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within blood vessel morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to UV	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within endocardial cushion development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within endocardial cushion development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of establishment of localization in cell	IDA Inferred from Direct Assay more info	PubMed
involved_in formation of structure involved in a symbiotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_positive_effect innate immune response	ISO Inferred from Sequence Orthology more info
involved_in intracellular glucocorticoid receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in lysosomal transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of sodium ion transmembrane transporter activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of sodium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of sodium ion transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of vascular endothelial growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within nervous system development	IEA Inferred from Electronic Annotation more info
involved_in neuromuscular junction development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within neuromuscular junction development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron projection development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within outflow tract morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within outflow tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of nucleocytoplasmic transport	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in progesterone receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within protein monoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein targeting to lysosome	ISO Inferred from Sequence Orthology more info
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein ubiquitination	ISO Inferred from Sequence Orthology more info	PubMed
involved_in protein ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in receptor catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor catabolic process	ISO Inferred from Sequence Orthology more info
involved_in receptor internalization	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in regulation of dendrite morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of dendrite morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of monoatomic ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of postsynaptic neurotransmitter receptor internalization	ISO Inferred from Sequence Orthology more info
involved_in regulation of potassium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein catabolic process at postsynapse, modulating synaptic transmission	ISO Inferred from Sequence Orthology more info
involved_in regulation of synapse organization	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of synapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation protein catabolic process at postsynapse	ISO Inferred from Sequence Orthology more info
acts_upstream_of sodium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of viral budding	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in cell cortex	ISO Inferred from Sequence Orthology more info
part_of chromatin	ISO Inferred from Sequence Orthology more info
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 cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in microvillus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of ubiquitin ligase complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: E3 ubiquitin-protein ligase NEDD4

Names: HECT-type E3 ubiquitin transferase NEDD4; neural precursor cell expressed developmentally down-regulated protein 4; neural precursor cell expressed, developmentally down-regulated gene 4a

NP_001344927.1

EC 2.3.2.26

NP_035020.2

EC 2.3.2.26

XP_011240974.1

EC 2.3.2.26

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001357998.1 → NP_001344927.1 E3 ubiquitin-protein ligase NEDD4 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks multiple 5' exons and contains an alternate 5' UTR and 5' coding region compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is longer than isoform 1.

Source sequence(s)

AC123683, CT027588

UniProtKB/TrEMBL

A0A571BDN7

Related

ENSMUSP00000158796.2, ENSMUST00000238315.2

Conserved Domains (5) summary

smart00456
Location:781 → 813

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:874 → 1203

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00201
Location:574 → 602

WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

pfam00397
Location:727 → 756

WW; WW domain

cl14603
Location:477 → 530

C2; C2 domain
NM_010890.4 → NP_035020.2 E3 ubiquitin-protein ligase NEDD4 isoform 1

See identical proteins and their annotated locations for NP_035020.2

Status: VALIDATED

Source sequence(s)

AC123683, AK133838, CF736340, CO426280, CX565415, CX566785

Consensus CDS

CCDS72275.1

UniProtKB/Swiss-Prot

O08758, P46935, Q3UZI2, Q8BGB3

UniProtKB/TrEMBL

B2RSC8

Related

ENSMUSP00000034740.8, ENSMUST00000034740.15

Conserved Domains (6) summary

cd04033
Location:79 → 210

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:461 → 493

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:554 → 883

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:530 → 884

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 ...

cd00201
Location:254 → 282

WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

pfam00397
Location:407 → 436

WW; WW domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000075.7 Reference GRCm39 C57BL/6J

Range

72569613..72657133

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011242672.4 → XP_011240974.1 E3 ubiquitin-protein ligase NEDD4 isoform X1

Conserved Domains (5) summary

smart00456
Location:283 → 315

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:376 → 705

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00201
Location:76 → 104

WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

pfam00397
Location:229 → 258

WW; WW domain

cl14603
Location:1 → 32

C2; C2 domain

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001039251.2: Suppressed sequence

Description

NM_001039251.2: This RefSeq was temporarily suppressed because currently there is not sufficient data to support this transcript.