Nedd4l NEDD4 like E3 ubiquitin protein ligase [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Nedd4lprovided by RGD
Official Full Name: NEDD4 like E3 ubiquitin protein ligaseprovided by RGD
Primary source: RGD:735047
See related: EnsemblRapid:ENSRNOG00000017610 AllianceGenome:RGD:735047
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: Nedd4-2
Summary: Enables potassium channel inhibitor activity and ubiquitin-protein transferase activity. Involved in several processes, including positive regulation of caveolin-mediated endocytosis; protein monoubiquitination; and ventricular cardiac muscle cell action potential. Predicted to be located in plasma membrane. Predicted to be active in cytoplasm and glutamatergic synapse. Human ortholog(s) of this gene implicated in periventricular nodular heterotopia. Orthologous to human NEDD4L (NEDD4 like E3 ubiquitin protein ligase). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Kidney (RPKM 172.1), Brain (RPKM 135.9) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 18q12.1

Exon count:: 37

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	18	NC_086036.1 (60663918..60996824)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	18	NC_051353.1 (58393759..58726709)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	18	NC_005117.4 (60392376..60719720)

Chromosome 18 - NC_086036.1 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?

NEDD4L Promotes IkappaBalpha Ubiquitination and Degradation in the Pathogenesis of Diabetic Retinopathy.
Title: NEDD4L Promotes IκBα Ubiquitination and Degradation in the Pathogenesis of Diabetic Retinopathy.
NGF-Induced Nav1.7 Upregulation Contributes to Chronic Post-surgical Pain by Activating SGK1-Dependent Nedd4-2 Phosphorylation.
Title: NGF-Induced Nav1.7 Upregulation Contributes to Chronic Post-surgical Pain by Activating SGK1-Dependent Nedd4-2 Phosphorylation.
USP36 actions extend beyond TrkA because the presence of USP36 interferes with Nedd4-2-dependent Kv7.2/3 channel regulation.
Title: Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 (Kv7.2/3).
Nedd4-2 plays an important role in the regulation of HCN1 trafficking and may compete with TRIP8b(1a-4) in this process
Title: Nedd4-2 regulates surface expression and may affect N-glycosylation of hyperpolarization-activated cyclic nucleotide-gated (HCN)-1 channels.
Nedd4-2-mediated ubiquitination of beta-ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport.
Title: Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway.
SGK1,3 enhances the expression level of mature hERG channels by inhibiting Nedd4-2 as well as by promoting Rab11-mediated hERG recycling.
Title: The serum- and glucocorticoid-inducible kinases SGK1 and SGK3 regulate hERG channel expression via ubiquitin ligase Nedd4-2 and GTPase Rab11.
The results of this study indicated that Nedd4-2 is present in nociceptive neurons, is downregulated after peripheral nerve injury.
Title: Neuronal expression of the ubiquitin ligase Nedd4-2 in rat dorsal root ganglia: modulation in the spared nerve injury model of neuropathic pain.
hERG expression in the plasma membrane is regulated by Cav3 via Nedd4-2
Title: Cell surface expression of human ether-a-go-go-related gene (hERG) channels is regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2.
ENaC and Nedd4-2 are involved in the transition from lung fluid secretion to fluid absorption near term and at birth.
Title: Involvement of {alpha}ENaC and Nedd4-2 in the conversion from lung fluid secretion to fluid absorption at birth in the rat as assayed by RNA interference analysis.
both Akt and Sgk are components of an insulin signaling pathway that increases Na(+) absorption by up-regulating membrane expression of ENaC via a regulatory system that involves inhibition of Nedd4-2
Title: Akt mediates the effect of insulin on epithelial sodium channels by inhibiting Nedd4-2.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AU048729 (e-PCR)
- UniSTS:145179

AU046785 (e-PCR)
- UniSTS:111135

RH140712 (e-PCR)
- UniSTS:222778

BF411259 (e-PCR)
- UniSTS:247617

D18Rat52 (e-PCR), detects polymorphism
- UniSTS:226947

D18Rat91 (e-PCR), detects polymorphism
- UniSTS:226956

RH132932 (e-PCR)
- UniSTS:216215

D18Chm95 (e-PCR)
- UniSTS:518397

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables potassium channel inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables potassium channel inhibitor activity	ISO Inferred from Sequence Orthology more info
enables potassium channel regulator activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium channel inhibitor activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium channel inhibitor activity	ISO Inferred from Sequence Orthology more info
enables sodium channel regulator activity	ISO Inferred from Sequence Orthology more info
enables transmembrane transporter 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	ISO Inferred from Sequence Orthology more info
enables ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of establishment of localization in cell	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of potassium ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of potassium ion transmembrane transporter activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein localization to cell surface	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of sodium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of sodium ion transmembrane 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
acts_upstream_of_or_within negative regulation of sodium ion transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of systemic arterial blood pressure	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of cation channel activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of caveolin-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of dendrite extension	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in protein K48-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein monoubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein ubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of bicellular tight junction assembly	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 membrane depolarization	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane repolarization	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 stability	ISO Inferred from Sequence Orthology more info
involved_in regulation of sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of sodium ion transport	ISO Inferred from Sequence Orthology more info
involved_in regulation protein catabolic process at postsynapse	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to salt stress	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in postsynapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: E3 ubiquitin-protein ligase NEDD4-like

Names: neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase

NP_001388249.1

EC 6.3.2.-

XP_038952600.1

EC 6.3.2.-

XP_038952602.1

EC 6.3.2.-

XP_038952603.1

EC 6.3.2.-

XP_038952607.1

EC 6.3.2.-

XP_063133265.1

EC 6.3.2.-

XP_063133266.1

EC 6.3.2.-

XP_063133267.1

EC 6.3.2.-

XP_063133268.1

EC 6.3.2.-

XP_063133269.1

EC 6.3.2.-

XP_063133270.1

EC 6.3.2.-

XP_063133271.1

EC 6.3.2.-

XP_063133272.1

EC 6.3.2.-

XP_063133273.1

EC 6.3.2.-

XP_063133274.1

EC 6.3.2.-

XP_063133275.1

EC 6.3.2.-

XP_063133276.1

EC 6.3.2.-

XP_063133277.1

EC 6.3.2.-

XP_063133278.1

EC 6.3.2.-

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_001401320.1 → NP_001388249.1 E3 ubiquitin-protein ligase NEDD4-like

Status: VALIDATED

Source sequence(s)

JAXUCZ010000018

UniProtKB/TrEMBL

A0A8I6A4L5, A6IXP5

Related

ENSRNOP00000088199.1, ENSRNOT00000094594.2

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_086036.1 Reference GRCr8

Range

60663918..60996824

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063277199.1 → XP_063133269.1 E3 ubiquitin-protein ligase NEDD4-like isoform X8

UniProtKB/TrEMBL

A6IXP5
XM_063277200.1 → XP_063133270.1 E3 ubiquitin-protein ligase NEDD4-like isoform X9

UniProtKB/TrEMBL

A6IXP5
XM_063277201.1 → XP_063133271.1 E3 ubiquitin-protein ligase NEDD4-like isoform X10

UniProtKB/TrEMBL

A6IXP5
XM_039096679.2 → XP_038952607.1 E3 ubiquitin-protein ligase NEDD4-like isoform X11

UniProtKB/TrEMBL

A0A8I6GLU0, A6IXP5

Related

ENSRNOP00000095085.2, ENSRNOT00000095391.2

Conserved Domains (4) summary

cd04033
Location:21 → 153

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

pfam00397
Location:368 → 397

WW; WW domain
XM_063277206.1 → XP_063133276.1 E3 ubiquitin-protein ligase NEDD4-like isoform X14

UniProtKB/TrEMBL

A6IXP7, A6IXP8
XM_063277204.1 → XP_063133274.1 E3 ubiquitin-protein ligase NEDD4-like isoform X12

UniProtKB/TrEMBL

A6IXP7
XM_063277203.1 → XP_063133273.1 E3 ubiquitin-protein ligase NEDD4-like isoform X12

UniProtKB/TrEMBL

A6IXP7
XM_063277207.1 → XP_063133277.1 E3 ubiquitin-protein ligase NEDD4-like isoform X14

UniProtKB/TrEMBL

A6IXP7, A6IXP8
XM_063277202.1 → XP_063133272.1 E3 ubiquitin-protein ligase NEDD4-like isoform X12

UniProtKB/TrEMBL

A6IXP7
XM_063277208.1 → XP_063133278.1 E3 ubiquitin-protein ligase NEDD4-like isoform X14

UniProtKB/TrEMBL

A6IXP7, A6IXP8

Related

ENSRNOP00000086606.2, ENSRNOT00000111699.2
XM_063277205.1 → XP_063133275.1 E3 ubiquitin-protein ligase NEDD4-like isoform X13

UniProtKB/TrEMBL

A6IXP7
XM_063277197.1 → XP_063133267.1 E3 ubiquitin-protein ligase NEDD4-like isoform X6
XM_039096672.1 → XP_038952600.1 E3 ubiquitin-protein ligase NEDD4-like isoform X1

Conserved Domains (5) summary

smart00456
Location:815 → 865

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:926 → 1255

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00201
Location:766 → 796

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:653 → 682

WW; WW domain

cl14603
Location:365 → 418

C2; C2 domain
XM_063277196.1 → XP_063133266.1 E3 ubiquitin-protein ligase NEDD4-like isoform X5
XM_063277195.1 → XP_063133265.1 E3 ubiquitin-protein ligase NEDD4-like isoform X3
XM_063277198.1 → XP_063133268.1 E3 ubiquitin-protein ligase NEDD4-like isoform X7

UniProtKB/TrEMBL

A0A8I6AEH7

Related

ENSRNOP00000090808.1, ENSRNOT00000101899.2
XM_039096674.1 → XP_038952602.1 E3 ubiquitin-protein ligase NEDD4-like isoform X2

Conserved Domains (4) summary

smart00456
Location:815 → 847

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:908 → 1237

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

pfam00397
Location:653 → 682

WW; WW domain

cl14603
Location:365 → 418

C2; C2 domain
XM_039096675.1 → XP_038952603.1 E3 ubiquitin-protein ligase NEDD4-like isoform X4

Related

ENSRNOP00000069274.3, ENSRNOT00000083363.3

Conserved Domains (5) summary

smart00456
Location:795 → 827

WW; Domain with 2 conserved Trp (W) residues

smart00119
Location:888 → 1217

HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

cd00201
Location:746 → 776

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:633 → 662

WW; WW domain

cl14603
Location:365 → 418

C2; C2 domain

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001008300.2: Suppressed sequence

Description

NM_001008300.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.