InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMURF2

Summary

InnateDB Protein

IDBP-64878.6

Last Modified

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

Gene Symbol

SMURF2

Protein Name

SMAD specific E3 ubiquitin protein ligase 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000262435

InnateDB Gene

IDBG-64876 (SMURF2)

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. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level. {ECO:0000269PubMed:11389444, ECO:0000269PubMed:12717440}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:12717440}. Cytoplasm {ECO:0000269PubMed:12717440}. Cell membrane {ECO:0000269PubMed:12717440}. Membrane raft {ECO:0000269PubMed:12717440}. Note=Cytoplasmic in the presence of SMAD7. Colocalizes with CAV1, SMAD7 and TGF-beta receptor in membrane rafts.

Disease Associations

Tissue Specificity

Widely expressed.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 226 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	226 [view]
Protein-Protein	226 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	11 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005160	transforming growth factor beta receptor binding
GO:0005515	protein binding
GO:0016874	ligase activity
GO:0042802	identical protein binding
GO:0046332	SMAD binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006351	transcription, DNA-templated
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0010467	gene expression
GO:0017015	regulation of transforming growth factor beta receptor signaling pathway
GO:0030509	BMP signaling pathway
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030579	ubiquitin-dependent SMAD protein catabolic process
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0045892	negative regulation of transcription, DNA-templated

Cellular Component

GO:0000151	ubiquitin ligase complex
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0045121	membrane raft