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FLASH GENE
Symbol SENP3 contributors: mct - updated : 10-10-2017
HGNC name SUMO1/sentrin/SMT3 specific peptidase 3
HGNC id 17862
Location 17p13.1      Physical location : 7.465.318 - 7.475.285
Synonym name
  • sentrin/SUMO-specific protease 3
  • sentrin/SUMO-specific protease SENP3
  • Synonym symbol(s) SMT3IP1, SSP3, SUSP3, DKFZP586K0919, DKFZp762A152
    EC.number 3.4.22.68
    DNA
    TYPE functioning gene
    STRUCTURE 9.97 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2499 - 574 - PMID: 18639523
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  moderately
     mouthtongue  moderately
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunelymph node   moderately
     spleen   moderately
    Reproductivefemale systemuteruscervix highly
     male systemtestis  moderately Mus musculus
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    Epithelial    
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousepithelial cell
    ReproductiveSertoli cell Mus musculus
    Reproductivespermatocyte Mus musculus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text liver, eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal region required for both nucleolar localization and interaction with NPM1 in cells
  • HOMOLOGY
    interspecies homolog to yeast Ulp1p
    ortholog to murine Senp3
    Homologene
    FAMILY
  • peptidase C48 family
  • SUMO-specific protease family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • relocating from the nucleoli to the nucleoplasm upon stabilization by ROS, and thus regulating nuclear events
  • sequestrated MDM2 in the nucleolus, and appeared to bind preferentially to MDM2 rather than TP53
  • basic FUNCTION
  • releasing UBL1, SMT3H1 and SMT3H2 monomers from sumoylated substrates
  • acting as a thiol protease
  • might regulate the sumoylation of other substrates through directly binding or mediating association with NPM1 at the nucleolus and other subcellular compartments
  • acting as an essential factor for ribosome biogenesis ,
  • redox sensor that regulates HIF-1 transcriptional activity under oxidative stress through the de-SUMOylation of p300
  • Hsp90/SENP3 association protects SENP3 from STUB1-mediated ubiquitination and subsequent degradation, but this effect of Hsp90 requires the presence of STUB1
  • controls the TP53–MDM2 pathway
  • may play important roles in the pathophysiology of spinal cord injury (SCI)
  • essential for cell proliferation and ribosomal RNA processing
  • might play an important role in the regulation of epithelial ovarian cancer progression
  • might be a novel determinant of multiple pathways governing blood-testis barrier (BTB) dynamics in testis to support germ cells development in mammals
  • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • Ubl conjugation pathway
  • SENP3-DLX3 pathway dictates osteogenic differentiation of human stem cells, thus delineating the importance of balanced SUMOylation for epigenetic control of gene expression programs
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • UBL1
  • SMT3H1
  • nucleophosmin (NPM1) is an SENP3-binding partner (SENP3-mediated desumoylation might control NPM1 physiological functions at both the nucleolus and other subcellular compartments)
  • specific interaction partner of CDCA8 and catalyzes the removal of SUMO2/3 from CDCA8
  • interacts with STUB1 and Hsp90 in differential modes under non-stress and oxidative stress conditions
  • interacts with TP53 and MDM2, desumoylates both proteins and bound to the acidic domain of MDM2, which also mediates the TP53 interaction, and competed with TP53 for binding
  • PELP1 and the PELP1-associated factor LAS1L are SENP3-sensitive targets of SUMO
  • LAS1L interacts with PELP1, and WDR18, the mammalian homologues of the budding yeast Rix1 complex, along with NOL9 and SENP3, to form a novel nucleolar complex that cofractionates with the 60S preribosomal subunit
  • key target for SENP3-mediated deSUMOylation is the GTPase DNM1L, which plays a major role in regulating mitochondrial fission
  • nutrient-sensing MTOR kinase pathway controls the nucleolar targeting of SENP3 by regulating its interaction with NPM1
  • regulates the global protein turnover and the SP1 level via antagonizing SUMO2/3-targeted ubiquitination and degradation
  • SENP3 could thus enhance STAT3 phosphorylation by de-conjugating the SUMO2/3 modification of STAT3
  • SENP3-mediated deSUMOylation of DNM1L facilitates interaction with MFF to promote cell death
  • MAP2K7, which selectively phosphorylates MAPK8, is a SENP3 substrate and SENP3-mediated deSUMOylation of MAP2K7 may favor its binding to MAPK8
  • cell & other
    REGULATION
    Other sophisticatedly regulated by STUB1 and Hsp90
    constitutively degraded by STUB1, which serves as an ubiquitin E3 ligase under resting conditions, and SENP3 is thus maintained at a low basal level
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    suppressed MDM2-mediated TP53 ubiquitination and subsequent proteasomal degradation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • could serve as a potential biomarker for epithelial ovarian cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    promising therapeutic target against epithelial ovarian cancer
    ANIMAL & CELL MODELS