Tbio NEDD4L E3 ubiquitin-protein ligase NEDD4-like

Protein Summary

Description

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Uniprot Accession IDs

• Q96PU5
• O43165
• Q3LSM7
• Q7Z5F1
• Q7Z5F2
• Q7Z5N3
• Q8N5A7
• Q8WUU9
• Q9BW58
• Q9H2W4
• Q9NT88

Gene Name

• NEDD4L

Ensembl ID

• ENST00000256830
• ENSP00000256830
• ENSG00000049759
• ENST00000356462
• ENSP00000348847
• ENST00000357895
• ENSP00000350569
• ENST00000382850
• ENSP00000372301
• ENST00000400345
• ENSP00000383199
• ENST00000431212
• ENSP00000389406
• ENST00000435432
• ENSP00000393395
• ENST00000456173
• ENSP00000405440
• ENST00000456986
• ENSP00000411947
• ENST00000586263
• ENSP00000468546

Symbol

• KIAA0439
• NEDL3
• RSP5
• PVNH7
• NEDD4-2
• NEDD4.2
• hNEDD4-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
transcription factor perturbation	0.98
transcription factor binding site profile	0.92
virus perturbation	0.92
transcription factor	0.91

Protein Classes

PANTHER Classes

Protein / Ligase / Ubiquitin-protein Ligase / E3 Ubiquitin-protein Ligase Nedd4-like

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / E3 Ubiquitin-protein Ligase Nedd4-like

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 475.52   (req: < 5)

Gene RIFs: 105   (req: <= 3)

Antibodies: 216   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 475.52   (req: >= 5)

Gene RIFs: 105   (req: > 3)

Antibodies: 216   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 39

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (440)

Explore Interacting Targets

1 – 10 of 440

• See Interactions on String-DB

FAM189B

Tbio

Novelty:  0.21064304

p_int:  0.999997253

p_ni:  0.000002747

Score:  0.192

Data Source:  BioPlex,STRINGDB

FAM189A2

Tdark

Novelty:  0.41335428

p_int:  0.99999444

p_ni:  0.00000556

Data Source:  BioPlex

WBP1

Tbio

Novelty:  1.24967974

p_int:  0.999982703

p_ni:  0.000017297

Score:  0.384

Data Source:  BioPlex,STRINGDB

DLG3

Tbio

Novelty:  0.01196565

p_int:  0.999982044

p_ni:  0.000017956

Score:  0.329

Data Source:  BioPlex,STRINGDB

TMEM51

Tdark

Novelty:  0.54147214

p_int:  0.999944392

p_ni:  0.000055608

Data Source:  BioPlex

ILDR1

Tbio

Novelty:  0.05462229

p_int:  0.999942351

p_ni:  0.000057649

Score:  0.201

Data Source:  BioPlex,STRINGDB

LDLRAD4

Tbio

Novelty:  0.04881486

p_int:  0.999940227

p_ni:  0.000059773

Score:  0.316

Data Source:  BioPlex,STRINGDB

KLF5

Tchem

Family:  TF

Novelty:  0.00384971

p_int:  0.999878953

p_ni:  0.000121047

Data Source:  BioPlex

TMEM171

Tdark

Novelty:  2.00247773

p_int:  0.999756253

p_ni:  0.000243747

Data Source:  BioPlex

SUSD6

Tbio

Novelty:  0.08836898

p_int:  0.999495716

p_ni:  0.000504284

Score:  0.235

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (10)

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Upstream (1)

Downstream (9)

1 – 1 of 1

NR3C2

Tclin

Family:  Nuclear Receptor

KEGG Distance:  2

Common Pathways:  1

1: Aldosterone-regulated sodium reabsorption

Pathways (37)

Reactome (23)

KEGG (4)

PathwayCommons (4)

UniProt (1)

WikiPathways (5)

Adaptive Immune System (R-HSA-1280218)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	Budding and maturation of HIV virion	28 targets	R-HSA-162588
Reactome	Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Reactome	Disease	1105 targets	R-HSA-1643685

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Budding and maturation of HIV virion	28 targets	R-HSA-162588
Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Disease	1105 targets	R-HSA-1643685

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (46)

Functions (7)

Components (7)

Processes (32)

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1 – 7 of 7

GO Term	Evidence	Assigned by
ubiquitin-protein transferase activity	Inferred from Experiment (EXP)	Reactome
potassium channel inhibitor activity	Inferred from Direct Assay (IDA)	BHF-UCL
potassium channel regulator activity	Inferred from Direct Assay (IDA)	BHF-UCL
sodium channel inhibitor activity	Inferred from Direct Assay (IDA)	BHF-UCL
sodium channel regulator activity	Inferred from Direct Assay (IDA)	UniProtKB
ion channel binding	Inferred from Physical Interaction (IPI)	BHF-UCL
ubiquitin protein ligase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations ()

No disease associations found

GWAS Traits (14)

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1 – 5 of 14

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
serum gamma-glutamyl transferase measurement	EFO_0004532	4	7	7	3.6	99.4
serum alanine aminotransferase measurement	EFO_0004735	2	3	2	13	93.8
alkaline phosphatase measurement	EFO_0004533	2	4	3	9.2	93.6
mathematical ability	EFO_0004875	4	3	4		89.8
aspartate aminotransferase measurement	EFO_0004736	2	2	1	7.8	80.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 14

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
serum gamma-glutamyl transferase measurement	EFO_0004532	7	3.6	99.4
serum alanine aminotransferase measurement	EFO_0004735	2	13	93.8
alkaline phosphatase measurement	EFO_0004533	3	9.2	93.6
mathematical ability	EFO_0004875	4		89.8
aspartate aminotransferase measurement	EFO_0004736	1	7.8	80.2

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
Complete proteome
Cytoplasm
Differentiation
Direct protein sequencing
Endosome
Golgi apparatus
Host-virus interaction

GWAS Trait Find Similar Targets

No Header	No Header
alkaline phosphatase measurement
apolipoprotein A 1 measurement
appendicitis
aspartate aminotransferase measurement
cognitive function measurement
diastolic blood pressure
high density lipoprotein cholesterol measurement
IGF-1 measurement
mathematical ability
platelet count

MGI Phenotype Find Similar Targets

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behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase		455443
Macaque	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase		700282
Mouse	neural precursor cell expressed, developmentally down-regulated gene 4-like	MGI:1933754	83814
Rat	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase	RGD:735047	291553
Dog	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase	VGNC:43721	476189

Species	Name	OMA	EggNOG	Inparanoid
Chimp	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
Macaque	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
Mouse	neural precursor cell expressed, developmentally down-regulated gene 4-like
Rat	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
Dog	neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase

Publication Statistics

PubMed Score 475.52

PubMed score by year

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PubTator Score 174.39

PubTator score by year

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Related Publications

Text Mined References (150)

GeneRif Annotations (105)

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PMID	Year	Title