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FLASH GENE
Symbol SMURF2 contributors: mct - updated : 14-03-2014
HGNC name SMAD specific E3 ubiquitin protein ligase 2
HGNC id 16809
Location 17q24.1      Physical location : 62.540.734 - 62.658.386
Synonym name
  • E3 ubiquitin ligase SMURF2
  • smad ubiquitination regulatory factor 2
  • Synonym symbol(s) H16, MGC138150, DKFZp686F0270
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 117.65 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3866 - 748 - 2008 18181147
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivestomach   highly
    Hearing/Equilibriumear   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text
  • expression of Smurf2 in placental villi was the highest during the first trimester and decreased as the pregnancy progressed
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one C2 domain
  • two WW domains
  • one HECT type E3 ubiquitin-protein ligase domain
  • HOMOLOGY
    Homologene
    FAMILY HECT domain ubiquitin ligase family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text cytoplasmic in the presence of SMAD7
    basic FUNCTION
  • E3 ubiquitin ligases, which suppress transforming growth factor-beta (TGFB) family signaling through degradation of Smads and receptors for TGFB and bone morphogenetic proteins
  • act in the same direction as SMURF1 in TGFB family signaling but play opposite roles in cell migration
  • induces ubiquitin-dependent degradation of SMURF1 to prevent migration of breast cancer cells
  • involved in protein modification, ubiquitin cycle
  • plays critical roles in the regulation of transforming growth factor-beta (TGF-beta)-Smad signaling via ubiquitin-dependent degradation of SMAD2 and SMAD7
  • important regulator of the TGF-beta signaling pathway, targeting TGF-beta receptors and various Smads for proteasome-mediated degradation
  • has a physiological role during embryo implantation, especially in trophoblast invasion, and this function may involve downregulation of TGF-beta type I receptor.
  • inducing degradation of GSK-3beta and upregulating beta-catenin in chondrocytes
  • important role for SMURF2 binding to TRAF2 in determining specific signalling outputs of TNFRSF1B
  • important regulator of TNFSF1B-mediated responses
  • promotes TP53 degradation by enhancing the activity of the E3 ligase MDM2
  • functions as a factor to stabilize MDM2 protein rather than as a direct E3 ligase in regulation of TP53 degradation
  • enhances heterodimerization of the MDM2-MDM4 but inhibits homodimerization of MDM2
  • plays a significant role in the pathomechanism of progressive supranuclear palsy by causing abnormal redistribution of neuronal nuclear SMAD2/3 to the cytoplasm
  • inducing multiple mono-ubiquitination of SMAD3
  • negatively regulates TGFB signalling by attenuating the activity of SMAD3 rather than promoting its degradation
  • SMURF2, one of the Smad ubiquitin regulator factor proteins, is an important negative regulator of virus-triggered type I IFN signaling, which targets at the MAVS level
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • crucial part of the ubiquitin-proteasome pathway (UPP) that regulates cellular signal transduction via ubiquitin-dependent degradation of some substrates and receptors
  • a component
  • TNFRSF1B/SMURF2 complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with SMAD1, SMAD2, SMAD3, SMAD6 and SMAD7 but not SMAD4
  • interacting with TRAF2 and TNFRSF1B (SMURF2-induced TNFRSF1B ubiquitination and subcellular relocalization of TNFRSF1B and TRAF2 enables the specific activation of the JNK pathway)
  • MTOR pathway is required to counteract the SMURF2-initiated degradation of RAP1B during the establishment of neuronal polarity
  • interacted with SMURF1 and induced its ubiquitination and degradation, whereas SMURF1 failed to induce degradation of SMURF2
  • can interact with SMAD proteins and promote their ubiquitin-dependent degradation, thereby controlling the cellular levels of these signalling mediators
  • is an E3 ubiquitin ligase for AXIN1
  • TRIB3 triggering the degradation of SMAD ubiquitin regulatory factor 2 (SMURF2), which resulted in a decrease in the degradation of SMAD2 and phosphorylated SMAD3
  • E3 ligase that ubiquitinates ID1 and ID3 (SMURF2-mediated ubiquitination and consequent degradation of ID1 or ID3 plays an important role in the regulation of Id expression in senescent cells
  • interacting protein of KLF5
  • interaction between SMURF2 and HSPB1, which suggested that SMURF2 mediated ubiquitylation-dependent degradation of HSPB1
  • RLIM directly bind to SMURF2, enhancing TGFB responsiveness in osteosarcoma U2OS cells
  • has a tumor suppression function that normally maintains genomic stability by controlling the epigenetic landscape of histone modifications through RNF20
  • SMURF2 forms complexes and functionally cooperates with SIK1
  • SMURF1 interaction with EFNB1 prevents the association with SMURF2 and precludes EFNB1 from ubiquitination and degradation, since it is a substantially weaker substrate for SMURF1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    during replicative senescence in response to telomere shortening, and induces senescence when expressed adventitiously in early passage or telomerase-immortalized fibroblasts
    tumoral     --over  
    correlates with poor prognosis in patients with esophageal squamous cell carcinoma
    constitutional     --over  
    in human osteoarthritis (OA) tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • adult Col2a1-Smurf2 mice have an osteoarthritis-like phenotype in knee joints