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FLASH GENE
Symbol SMURF1 contributors: mct - updated : 26-06-2015
HGNC name SMAD specific E3 ubiquitin protein ligase 1
HGNC id 16807
Location 7q22.1      Physical location : 98.625.063 - 98.741.723
Synonym name
  • E3 ubiquitin ligase SMURF1
  • Smad ubiquitination regulatory factor 1 isoform 1
  • E3 ubiquitin ligase Smad ubiquitin regulatory factor 1
  • Synonym symbol(s) H25, KIAA1625
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 116.68 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    BRI3 7q22.1 brain protein I3 LOC55971 7q22.1 insulin receptor tyrosine kinase substrate NPTX2 7q21.3-q22.1 neuronal pentraxin II DKFZp761L1417 7q22.1 hypothetical protein DKFZp761L1417 TRRAP 7q21.3-q22.1 transformation/transcription domain-associated protein SMURF1 7q21.1-q31.1 transformation/transcription domain-associated protein LOC389539 7 similar to importin alpha 1b ARPC1A 7q22.1-q31.33 actin related protein 2/3 complex, subunit 1A, 41kDa ARPC1B 7q22.1-q31.33 actin related protein 2/3 complex, subunit 1B, 41kDa PDAP1 7q11.21 PDGFA associated protein 1 G10 7q11.21 PDGFA associated protein 1 CPSF4 7q22.1 cleavage and polyadenylation specific factor 4, 30kDa KIAA0632 7q22.1 cleavage and polyadenylation specific factor 4, 30kDa ATP5J2 7q21.3-q22 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit f, isoform 2 LOC285989 7q22.1 hypothetical protein LOC285989 ZNF394 7q22.1 zinc finger protein 394 ZFP95 7q22 zinc finger protein 95 homolog (mouse) DKFZp727G131 7q22.1 hypothetical protein DKFZp727G131 VIK 7q22.1 vav-1 interacting Kruppel-like protein ZNF498 7q22.1 zinc finger protein 498 CYP3A5 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 CYP3A5P1 7q21.3-q22.1 cytochrome P450, family 3, subfamily A, polypeptide 5 pseudogene 1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 5737 - 757 - 2007 17510966
    18 - 5659 - 731 - 2007 17510966
    18 - 5694 - 728 - 2007 17510966
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     mouthtongue  highly
    Respiratoryrespiratory tractlarynx  highly
    Skeletonaxialskullfacemandible 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one C2 domain, with ARHGEF9-binding domain, essential for SMURF1-regulated protrusion formation but not BMP signaling , that is critical for targeting Axin for ubiquitination
  • two WW domains, mediating the interaction with KLF2
  • and WW2 domain of SMURF1 is sufficient and necessary for the interaction of USP9X
  • one HECT (homologous to E6-AP C terminus) domain, with ING2 binding domain , essential for its E3 ubiquitin ligase activity
  • HOMOLOGY
    interspecies ortholog to murine Smurf1
    Homologene
    FAMILY
  • Hect domain family of E3 ubiquitin ligases
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    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
  • regulates cell polarity and protrusive activity by inducing ubiquitination and subsequent proteasomal degradation of the small GTPase RHOA
  • potentially playing a crucial role in the spatiotemporal regulation of Rho GTPase family members
  • involved in protein modification and ubiquitin cycle
  • mediating the protein degradation of the osteoblast-specific transcription factor RUNX2 and playing a specific role in osteoblast differentiation and bone formation
  • promote RhoA ubiquitination and degradation and regulate cell motility, suggesting its involvement in cancer progression
  • act in the same direction as SMURF2 in TGFB family signaling but play opposite roles in cell migration
  • regulates talin head degradation and ultimately cell migration, and CDK5-mediated phosphorylation of the head prevents SMURF1 action on talin
  • critical role in regulating ING2 protein stability
  • plays a pivotal role in control of cell polarity, maintenance of bone homeostasis and regulation of tumorigenesis through targeting BMP-Smad, Wnt and RhoA signalling pathways
  • 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
  • functions as an E3 ligase to promote the ubiquitination and proteasomal degradation of KLF2
  • represses the transcriptional factor activity of KLF2 and regulates its down-stream genes such as SELL and WEE1
  • targets an ER-localized protein for degradation and is regulated by ER stress
  • ubiquitin ligase controling ubiquitination and stability of diverse cellular protein substrates
  • regulatory circuit between RUNX2 and SMURF1 controls RUNX2 expression and regulates odontoblastic differentiation in dental pulp stem cells (hDPSCs)
  • SMURF1 promotes LHX9 ubiquitylation and is involved in testosterone production in Leydig cells directly
  • CELLULAR PROCESS protein, degradation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS development , cellular trafficking transport
    text targeting the BMP pathway and affecting embryonic patterning
    PATHWAY
    metabolism
    signaling signal transduction
  • CDH1-ANAPC/SMURF1/RHOA pathway that mediates axonal growth suppression in the developing mammalian brain
  • a component
  • SMAD7-SMURF1 complex inhibited by FKBP12 to regulate the duration of the activin signal
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • receptor-regulated SMAD specific for the BMP pathway (MADH1 and MADH5)
  • XPO1 (CRM1)dependent nuclear export
  • interacts with PDLIM7
  • interacting wtith TGFBR1 through SMAD7 and inducing receptor degradation
  • targets osteogenic SMADs, SMAD1/5, for ubiquitin-mediated proteasomal degradation
  • interacting with SMURF2 but SMURF1 failed to induce degradation of SMURF2
  • interacting with ARHGEF9 (induces proteasomal degradation of ARHGEFG9 in cells)
  • interacting with Talin head
  • interacts with and targets ING2 for poly-ubiquitination and proteasomal degradation
  • interacts with and targets KLF2 for poly-ubiquitination and proteasomal degradation specifically in lung cancer
  • inhibited the transcriptional activity of KLF2 to control its target genes, WEE1 and SELL
  • WFS1 is a specific degradation substrate of SMURF1 (interacts with WFS1 at the ER and promotes the ubiquitination and proteasomal degradation of WFS1)
  • FBXL15 targets SMURF1 for ubiquitination and proteasomal degradation
  • interacting with RHOA (C2 domain of SMURF1 is necessary and sufficient for binding RHOA, and therefore is crucial for targeting RhHOA for ubiquitination)
  • CDH1 promotes the E3 ligase activity of SMURF1
  • SMURF1 interacted with STAT1 through the WW domains of SMURF1 and the PY motif in STAT1 and catalyzed K48-linked polyubiquitination of STAT1
  • PLEKHO1 is an activator of the SMURF1 ubiquitin ligase acting to promote the ubiquitylation of SMAD5 and MAP2K1
  • PLEKHO1 mediates the SMURF1-PSMC5 interaction and delivers the ubiquitylated substrates to the proteasome
  • USP9X interacts with SMURF1 and stabilizes SMURF1 through deubiquitination
  • growth-suppressive role of PLEKHO1 was dependent on the downregulation of the cell cycle-regulated oncogene SMURF1
  • FGFR3 facilitates BMPR1A to degradation through SMURF1-mediated ubiquitination pathway
  • dual role of SMURF1 C2 domain, recruiting SMURF1 to membrane for accessing Axin and mediating its interaction with Axin, and SMURF1-mediated Axin ubiquitination is subjected to the regulation of cell cycle
  • physically SMURF1 interacts with NEDD8 and UBE2M, forms a NEDD8-thioester intermediate, then catalyses its own neddylation on multiple lysine residues, and NEDD8 is critical for the activation of SMURF1 ubiquitin ligase in tumorigenesis
  • TRIB2 associated-BTRC, RFWD2 and SMURF1 reduced TCF4/CTNNB1 expression, and these effects could be enhanced by TRIB2
  • interacts with and targets SMURF1 for poly-ubiquitination and proteasomal degradation
  • SMURF1, an E3 ubiquitin ligase, targets LHX9 for ubiquitin-mediated proteasome degradation, thereby negatively modulating its function
  • cell & other
    REGULATION
    activated by XPO1 dependent for nuclear export
    RUNX2, in osteoblasts
    Other its stability is suppressed by SCF(FBXL15)-mediated ubiquitination
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in some cases of pancreatic adenocarcinoma
    tumoral       gain of function
    aberrant upregulation of SMURF1 promotes tumorigenesis by excessively targeting RHOB for degradation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS