InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: NEDD4L

Summary

InnateDB Protein

IDBP-371225.5

Last Modified

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

Gene Symbol

NEDD4L

Protein Name

neural precursor cell expressed, developmentally down-regulated 4-like

Synonyms

hNEDD4-2; NEDD4-2; NEDD4.2; RSP5;

Species

Homo sapiens

Ensembl Protein

ENSP00000411947

InnateDB Gene

IDBG-3835 (NEDD4L)

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. 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, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. {ECO:0000269PubMed:12911626, ECO:0000269PubMed:15040001, ECO:0000269PubMed:15217910, ECO:0000269PubMed:15489223, ECO:0000269PubMed:15496141, ECO:0000269PubMed:15576372, ECO:0000269PubMed:19144635}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:15496141, ECO:0000269PubMed:18819914}. Note=May be recruited to exosomes by NDFIP1.

Disease Associations

Tissue Specificity

Ubiquitously expressed, with highest levels in prostate, pancreas and kidney. {ECO:0000269PubMed:14615060, ECO:0000269PubMed:15496141, ECO:0000269PubMed:19664597}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 190 experimentally validated interaction(s) in this database.
They are also associated with 13 interaction(s) predicted by orthology.

Experimentally validated
Total	190 [view]
Protein-Protein	188 [view]
Protein-DNA	1 [view]
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	13 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0015459	potassium channel regulator activity
GO:0016874	ligase activity
GO:0017080	sodium channel regulator activity
GO:0019870	potassium channel inhibitor activity
GO:0019871	sodium channel inhibitor activity
GO:0044325	ion channel binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0003254	regulation of membrane depolarization
GO:0006351	transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006814	sodium ion transport
GO:0006883	cellular sodium ion homeostasis
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007588	excretion
GO:0010038	response to metal ion
GO:0010467	gene expression
GO:0016032	viral process
GO:0016567	protein ubiquitination
GO:0019058	viral life cycle
GO:0030104	water homeostasis
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0034220	ion transmembrane transport
GO:0034765	regulation of ion transmembrane transport
GO:0042176	regulation of protein catabolic process
GO:0042391	regulation of membrane potential
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0045807	positive regulation of endocytosis
GO:0055085	transmembrane transport
GO:0060306	regulation of membrane repolarization
GO:0070936	protein K48-linked ubiquitination
GO:0086005	ventricular cardiac muscle cell action potential
GO:1901016	regulation of potassium ion transmembrane transporter activity
GO:1901017	negative regulation of potassium ion transmembrane transporter activity
GO:1901380	negative regulation of potassium ion transmembrane transport
GO:1902306	negative regulation of sodium ion transmembrane transport
GO:2000009	negative regulation of protein localization to cell surface
GO:2000650	negative regulation of sodium ion transmembrane transporter activity
GO:2001288	positive regulation of caveolin-mediated endocytosis

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0070062	extracellular vesicular exosome