InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NEDD4

Summary

InnateDB Protein

IDBP-13240.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

NEDD4

Protein Name

neural precursor cell expressed, developmentally down-regulated 4

Synonyms

NEDD4-1; RPF1;

Species

Homo sapiens

Ensembl Protein

ENSP00000345530

InnateDB Gene

IDBG-13236 (NEDD4)

Protein Structure

UniProt Annotation

Function

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. Involved in the pathway leading to the degradation of VEGFR- 2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2. Involved in the ubiquitination of ebola virus VP40 protein and this ubiquitination plays a role in facilitating viral budding. {ECO:0000269PubMed:11598133, ECO:0000269PubMed:17218260, ECO:0000269PubMed:18305167, ECO:0000269PubMed:18562292, ECO:0000269PubMed:20086093, ECO:0000269PubMed:21399620, ECO:0000269PubMed:21765395}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Recruited to the plasma membrane by GRB10. Once complexed with GRB10 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity). May be recruited to exosomes by NDFIP1. {ECO:0000250, ECO:0000269PubMed:18819914}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 333 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.

Experimentally validated
Total	333 [view]
Protein-Protein	333 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	29 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0016874	ligase activity
GO:0019871	sodium channel inhibitor activity
GO:0019904	protein domain specific binding
GO:0031698	beta-2 adrenergic receptor binding
GO:0043130	ubiquitin binding
GO:0050815	phosphoserine binding
GO:0050816	phosphothreonine binding
GO:0070063	RNA polymerase binding
GO:0070064	proline-rich region binding

Biological Process

GO:0006622	protein targeting to lysosome
GO:0007041	lysosomal transport
GO:0010766	negative regulation of sodium ion transport
GO:0010768	negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0016567	protein ubiquitination
GO:0019089	transmission of virus
GO:0019221	cytokine-mediated signaling pathway
GO:0030948	negative regulation of vascular endothelial growth factor receptor signaling pathway
GO:0031175	neuron projection development
GO:0031623	receptor internalization
GO:0032801	receptor catabolic process
GO:0034644	cellular response to UV
GO:0034765	regulation of ion transmembrane transport
GO:0042391	regulation of membrane potential
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0042921	glucocorticoid receptor signaling pathway
GO:0043162	ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
GO:0044111	development involved in symbiotic interaction
GO:0045732	positive regulation of protein catabolic process
GO:0046824	positive regulation of nucleocytoplasmic transport
GO:0048814	regulation of dendrite morphogenesis
GO:0050847	progesterone receptor signaling pathway
GO:0051592	response to calcium ion
GO:0070534	protein K63-linked ubiquitination
GO:1901016	regulation of potassium ion transmembrane transporter activity

Cellular Component

GO:0000151	ubiquitin ligase complex
GO:0000785	chromatin
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005938	cell cortex
GO:0016327	apicolateral plasma membrane
GO:0048471	perinuclear region of cytoplasm