Nedd4 NEDD4 E3 ubiquitin protein ligase [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Nedd4provided by RGD
Official Full Name: NEDD4 E3 ubiquitin protein ligaseprovided by RGD
Primary source: RGD:3157
See related: EnsemblRapid:ENSRNOG00000058898 AllianceGenome:RGD:3157
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Nedd4a
Summary: Enables ubiquitin-protein transferase activity. Involved in several processes, including protein K63-linked ubiquitination; regulation of postsynaptic neurotransmitter receptor internalization; and regulation of protein catabolic process at postsynapse, modulating synaptic transmission. Located in microvillus. Is active in glutamatergic synapse. Biomarker of muscular atrophy. Orthologous to human NEDD4 (NEDD4 E3 ubiquitin protein ligase). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Heart (RPKM 851.9), Muscle (RPKM 815.1) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 8q24

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	8	NC_086026.1 (82264751..82349642)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	8	NC_051343.1 (73384095..73468951)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	8	NC_005107.4 (79323408..79408842)

Chromosome 8 - NC_086026.1 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

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Gstp1 negatively regulates blood pressure in hypertensive rat via promoting APLNR ubiquitination degradation mediated by Nedd4.
Title: Gstp1 negatively regulates blood pressure in hypertensive rat via promoting APLNR ubiquitination degradation mediated by Nedd4.
NEDD4-2 and the CLC-2 channel regulate neuronal excitability in the pathogenesis of mesial temporal lobe epilepsy.
Title: NEDD4-2 and the CLC-2 channel regulate neuronal excitability in the pathogenesis of mesial temporal lobe epilepsy.
Serum and glucocorticoid inducible kinase 1 modulates mitochondrial dysfunction and oxidative stress in doxorubicin-induced cardiomyocytes by regulating Hippo pathway via Neural precursor cell-expressed developmentally down-regulated 4 type 2.
Title: Serum and glucocorticoid inducible kinase 1 modulates mitochondrial dysfunction and oxidative stress in doxorubicin-induced cardiomyocytes by regulating Hippo pathway via Neural precursor cell-expressed developmentally down-regulated 4 type 2.
NEDD4 attenuates phosgene-induced acute lung injury through the inhibition of Notch1 activation.
Title: NEDD4 attenuates phosgene-induced acute lung injury through the inhibition of Notch1 activation.
The data revealed that maternal immune activation impedes offspring's dendrite development and causes depressive like behaviors by upregulating ISG15 and suppressing NEDD4/Rap2A signaling.
Title: Inflammation-dependent ISG15 upregulation mediates MIA-induced dendrite damages and depression by disrupting NEDD4/Rap2A signaling.
NEDD4, the top focus hub gene, showed a clear time-dependent increased expression pattern in cardiomyocytes during angiotensin II treatment.
Title: Microarray analysis and functional characterization revealed NEDD4-mediated cardiomyocyte autophagy induced by angiotensin II.
NEDD4-1 levels were decreased after ischemia-reperfusion (I/R) and increased after ischemic preconditioning in rat heart tissue and in H9c2 cardiomyocytes. Overexpression activated the Akt pathway and regulated apoptosis-related proteins in H9c2 cardiomyocytes, attenuating SI/R-induced cell apoptosis and caspase 3/7 activities. Overexpression attenuated myocardial apoptosis after I/R.
Title: NEDD4-1 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis via the PI3K/Akt pathway.
Data suggest that dietary factors can regulate cardiac Scnn1g, Nedd4-2, and Sgk1 activity; here, proanthocyanidin dietary supplement PRO80 blocks aldosterone-dependent up-regulation of Scnn1g, Nedd4-2, and Sgk1 content in cardiac dysfunction. (Scnn1g = epithelial sodium channel 1, gamma subunit; Nedd4-2 = ubiquitin-protein ligase Nedd4-2; Sgk1 = serum-glucocorticoid regulated kinase 1)
Title: Proanthocyanidins block aldosterone-dependent up-regulation of cardiac gamma ENaC and Nedd4-2 inactivation via SGK1.
CRTC2 and Nedd4 ligase involvement in FSH and TGFbeta1 upregulation of connexin43 gap junction
Title: CRTC2 and Nedd4 ligase involvement in FSH and TGFβ1 upregulation of connexin43 gap junction.
Structural Studies of the Nedd4 WW Domains and Their Selectivity for the Connexin43 (Cx43) Carboxyl Terminus.
Title: Structural Studies of the Nedd4 WW Domains and Their Selectivity for the Connexin43 (Cx43) Carboxyl Terminus.

Submit: New GeneRIF Correction See all GeneRIFs (30)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH128183 (e-PCR)
- UniSTS:211491

RH139229 (e-PCR)
- UniSTS:221315

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables RNA polymerase binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase binding	ISO Inferred from Sequence Orthology more info
enables beta-2 adrenergic receptor binding	IEA Inferred from Electronic Annotation 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	ISO Inferred from Sequence Orthology more info
enables phosphoserine residue binding	ISO Inferred from Sequence Orthology more info
enables phosphothreonine residue binding	ISO Inferred from Sequence Orthology more info
enables proline-rich region binding	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation more info
enables sodium channel inhibitor activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin binding	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	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase activity	ISS Inferred from Sequence or Structural Similarity more info
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin-protein transferase activity	IEA Inferred from Electronic Annotation more info

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

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in cell cortex	IEA Inferred from Electronic Annotation more info
located_in cell cortex	ISO Inferred from Sequence Orthology more info
located_in chromatin	IEA Inferred from Electronic Annotation more info
located_in chromatin	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
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	ISO Inferred from Sequence Orthology more info
located_in microvillus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic cytosol	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of ubiquitin ligase complex	ISO Inferred from Sequence Orthology more info

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 4, E3 ubiquitin protein ligase; neural precursor cell expressed, developmentally down-regulated gene 4; neural precursor cell expressed, developmentally down-regulated gene 4A

NP_037118.1

EC 2.3.2.26

XP_017450968.1

EC 2.3.2.26

XP_038936817.1

EC 2.3.2.26

XP_063121020.1

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_012986.1 → NP_037118.1 E3 ubiquitin-protein ligase NEDD4

See identical proteins and their annotated locations for NP_037118.1

Status: VALIDATED

Source sequence(s)

BQ191927, CB326200, CB568921, CB615796, CF110862, CK365888, DY312717, DY318090, EV775947, U50842

UniProtKB/Swiss-Prot

Q62940

UniProtKB/TrEMBL

A0A0G2K8P3, A6KEM7

Related

ENSRNOP00000074683.2, ENSRNOT00000088391.3

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:463 → 495

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:556 → 885

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00078
Location:532 → 886

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_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086026.1 Reference GRCr8

Range

82264751..82349642

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063264950.1 → XP_063121020.1 E3 ubiquitin-protein ligase NEDD4 isoform X2

UniProtKB/TrEMBL

A0A0G2K8P3, A6KEM7
XM_039080889.1 → XP_038936817.1 E3 ubiquitin-protein ligase NEDD4 isoform X3

UniProtKB/Swiss-Prot

Q62940

Conserved Domains (5) 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:463 → 495

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:556 → 885

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

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
XM_017595479.3 → XP_017450968.1 E3 ubiquitin-protein ligase NEDD4 isoform X1

UniProtKB/TrEMBL

A0A8I6AJU5, A0A8I6GFW6

Related

ENSRNOP00000093946.2, ENSRNOT00000118222.2