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FLASH GENE
Symbol SENP1 contributors: mct/ - updated : 09-07-2019
HGNC name SUMO1/sentrin specific peptidase 1
HGNC id 17927
Location 12q13.11      Physical location : 48.436.757 - 48.499.641
Synonym name
  • sentrin specific protease
  • sentrin/SUMO-specific protease 1
  • Synonym symbol(s) SuPr-2
    EC.number 3.4.22.68
    DNA
    TYPE functioning gene
    STRUCTURE 62.88 kb     18 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
    18 - 4726 73.2 643 - 2018 30305424
    18 - 4456 - 644 - 2018 30305424
    18 - 4803 - 644 - 2018 30305424
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   moderately
    Digestivemouthtongue  moderately
    Endocrinepancreas    
    Lymphoid/Immunelymph node   moderately
     thymus   highly
    Nervousbrain    
    Reproductivemale systemprostate  highly Homo sapiens
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a catalytic domain (SENP1C) that can determine the substrate specificity towards SUMO-1, -2 and -3
  • HOMOLOGY
    interspecies homolog to yeast Smt3-s specific protease
    ortholog to murine Senp1
    Homologene
    FAMILY
  • peptidase C48 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm
    intracellular,nuclear envelope
    text
  • its localization is influenced by expression and localization of SUMO1-conjugated target proteins within the cell
  • SUMO-specific isopeptidases SENP1 and SENP2 are targeted to kinetochores in mitosis
  • basic FUNCTION
  • sentrin-specific protease that preferentially removes sentrin from sentrinized proteins in the nucleus
  • SUMO-specific proteases involved in the regulation of apoptosis
  • degrading UBL1 and SMT3H2 conjugates and releases the monomers
  • acting on sumoylated PML
  • acting as a thiol protease
  • involved in Ubl conjugation pathway
  • enhancing the transcription activity of c-Jun
  • playing a role in desumoylation
  • promotes stress-induced apoptosis by interacting with and desumoylating SIRT1
  • playing a key role in the regulation of the hypoxic response through regulation of HIF1alpha stability
  • controlling Epo production
  • may itself be a target for SUMO1 modification occurring at a nonconsensus site
  • lacks a clear preference for any particular SUMO isoform
  • important role in the de-SUMOylation of ELK1, and therefore an integral role in determining the ELK1-dependent transcriptional programme
  • important role in the regulation of ELK1-mediated gene expression in response to mitogenic signalling cues
  • could abrogate CAPN2 sumoylation, causing an inhibition on calpain-2-dependent activity and cell motility
  • alters VEGF levels by directly regulating HIF1A stability during fetal development
  • participates in the development of prostate neoplasia
  • regulates VEGF expression via modulating the nuclear stability of HIF1A and initiates the onset of angiogenesis in DYNLL1
  • is essential for the development of early T and B cells
  • essential role of SENP1 in PPARGC1A transcriptional activity and also in mitochondrial biogenesis
  • is essential for expression of nuclear mitochondrial genes
  • SENP1 can promote the expression of mitochondrial genes through de-SUMOylation
  • critical role for SENP1-mediated deSUMOylation in promoting PIN1 function during tumorigenesis
  • chromosome segregation depends on precise spatial and temporal control of sumoylation in mitosis and SENP1 and SENP2 are important mediators of this control
  • is a novel regulator in adipogenesis
  • is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation
  • SENP1 and the chromatin remodeler CHD3 interact and jointly affect chromatin accessibility and gene expression
  • SENP1 is an essential regulator of the balance between SUMOylation and deSUMOylation during lung development, specifically affecting the proliferation and differentiation status of AT2 cells
  • SENP1 promotes sepsis via activating the TGFBR2 signaling
  • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • markedly enhances the transcription activity of JUN (independent of the sumoylation and phosphorylation status of JUN but is critically dependent on the desumoylation activity of SENP1)
  • interacting with EP300 (essential for SENP1 to enhance JUN-dependent transcription because SENP1 can desumoylate the CRD1 domain of EP300, thereby releasing the cis-repression of CRD1 on EP300)
  • promotes GATA1 activation and subsequent erythropoiesis by deSUMOylating GATA1
  • reverses SUMOylation of MAML1 and potentiates the transcription factor activity of MAML1
  • STAT5B is a key regulator of lymphoid development, that is modified by SUMO-2 and is specifically regulated by SENP1
  • crucial role of SENP1 in the regulation of STAT5B activation during early lymphoid development
  • both SENP1 and -2 induce deSUMOylation of gJA1
  • NUP153 binds to both SENP1 and SENP2 and does so by interacting with the unique N-terminal domain of NUP153 as well as a specific region within the C-terminal FG-rich region
  • SENP1 is a specific SUMO protease to regulate SUMOylation status of PPARGC1A
  • SUMOylation of PPARGC1A controlled by SENP1 plays an important role in mitochondrial biogenesis and function
  • SENP1 is a specific de-SUMOylation protease for BHLHE41, a repressor for PPARG transcription and adipogenesis
  • SENP1 can deSUMOylate SUMOylated HMGN2, and PIAS1 is the E3 ligase responsible for SUMOylation of HMGN2
  • key role for SENP1 in IL6 induced proliferation and survival of multiple myeloma cells
  • SENP1-mediated IKBKG deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression
  • SUMO1 conjugation of RB1 and LMNA is modulated by the SUMO protease SENP1 and sumoylation of both proteins is required for their interaction
  • SENP1 deconjugates SUMO from modified proteins
  • SENP1 likely plays a neuroprotective role in I/R injury by inhibiting apoptosis through decreasing SUMO1 conjugation
  • only NUP153 is needed for proper nuclear import of TP53BP1 and SENP1-dependent sumoylation of TP53BP1
  • SENP1 is the specific deSUMOylation enzyme for GLI1, and negatively regulate SHH signaling
  • SENP1 attenuates the liver fibrosis through down-regulating the expression of SMAD2
  • SENP1 physically interacts with the chromatin remodeler chromodomain helicase DNA-binding protein 3 (CHD3)
  • SENP1 is a crucial MYC deSUMOylating enzyme that positively regulates MYC stability and activity
  • interaction of SENP1 with SUMO2 (C-terminal motif (QQTGG) of SUMO2 is stabilized by a number of specific bonding interactions that enable it to protrude into the catalytic triad of SENP1 and provide the arrangement necessary for maturation of SUMO and deSUMOylation activity)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in NPM-ALK positive anaplastic large cells lymphoma
    tumoral     --over  
    in prostate cancer and correlates with hypoxia-inducing factor 1&945; (HIF1A) expression
    constitutional   deletion    
    SENP1 deletion in adipocytes enhances SUMOylation of the NFKB1 essential molecule, IKBKG, at lysine 277/309, leading to increased NFKB1 activity, cytokine production and pancreatic inflammation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    may be a potential new therapeutic target in multiple myeloma
    ANIMAL & CELL MODELS
    Senp1 (-/-) mouse embryos show severe fetal anemia stemming from deficient Erythropoietin production and die midgestation