SMURF2

SMURF2 (SMAD Specific E3 Ubiquitin Protein Ligase 2) is a Protein Coding gene. Among its related pathways are Metabolism of proteins and Innate Immune System. Gene Ontology (GO) annotations related to this gene include identical protein binding and ubiquitin-protein transferase activity. An important paralog of this gene is SMURF1.

Full Name

SMAD Specific E3 Ubiquitin Protein Ligase 2

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 (PubMed:11016919).
Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling (PubMed:11163210, PubMed:12717440).
In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1 (PubMed:18448069).
Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation (PubMed:11016919, PubMed:11158580, PubMed:11389444).
SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation (PubMed:11389444).
Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation (PubMed:30696809).
(Microbial infection) In case of filoviruses Ebola/EBOV and Marburg/MARV infection, the complex formed by viral matrix protein VP40 and SMURF2 facilitates virus budding.

Biological Process

Biological Process negative regulation of BMP signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Biological Process negative regulation of DNA-templated transcription1 PublicationNAS:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase IITAS:Reactome
Biological Process negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:CACAO
Biological Process positive regulation of canonical Wnt signaling pathwayTAS:Reactome
Biological Process positive regulation of trophoblast cell migrationManual Assertion Based On ExperimentIDA:CACAO
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process protein polyubiquitinationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process protein ubiquitinationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of transforming growth factor beta receptor signaling pathway1 PublicationNAS:UniProtKB
Biological Process ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process ubiquitin-dependent SMAD protein catabolic processManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process Wnt signaling pathway, planar cell polarity pathwayTAS:Reactome

Cellular Location

Nucleus
Cytoplasm
Cell membrane
Membrane raft
Cytoplasmic in the presence of SMAD7. Colocalizes with CAV1, SMAD7 and TGF-beta receptor in membrane rafts.

PTM

Auto-ubiquitinated and ubiquitinated in the presence of RNF11 and UBE2D1 (PubMed:19343052, PubMed:30696809).
Ubiquitinated by the SCF(FBXL15) complex and TTC3, leading to its degradation by the proteasome (PubMed:21572392, PubMed:30696809).
'Lys-48'-linked polyubiquitination mediated by TRAF4 at Lys-119 leads to SMURF2 proteasomal degradation (PubMed:31076633).