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FLASH GENE
Symbol USP28 contributors: mct - updated : 03-11-2014
HGNC name ubiquitin specific peptidase 28
HGNC id 12625
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • presence of ubiquitin-binding domains in the N-terminal domain
  • an UIM (ubiquitin-interacting motif) repeat
  • HOMOLOGY
    interspecies homolog to rattus Usp28 (91.7pc)
    homolog to murine Usp28 (90.7pc)
    Homologene
    FAMILY
  • peptidase C19 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as a cysteine-type endopeptidase
  • acting as an ubiquitin thiolesterase
  • required to stabilize CHEK2 and TP53BP1 in response to DNA damage
  • required for MYC stability in tumour cells
  • FBXW7 and USP28 reciprocally regulated cell migration and angiogenesis in an HIF1A-dependent manner
  • govern the stability of multiple factors that are critical for diverse aspects of the DNA damage response (DDR)
  • is not a critical factor in double-strand break metabolism and is unlikely to be an attractive target for therapeutic intervention aimed at chemotherapy sensitization
  • deubiquitinating enzyme that has been implicated in the DNA damage response (DDR), the regulation of MYC signaling and cancer progression
  • has a chain preference activity for K11, K48 and K63 di-ubiquitin linkages
  • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism protein
    signaling
  • Ubl conjugation pathway
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • specifically antagonize the function of FBW7 alpha
  • interacted with and stabilized KDM1A via deubiquitination
  • is recruited to double-strand breaks in a manner that requires the tandem BRCT domains of the DDR protein TP53BP1
  • antagonizes the ubiquitin-dependent degradation of MYC, a known USP28 substrate
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colon and breast carcinoma
    tumoral     --over  
    correlated with KDM1A upregulation in multiple cancer cell lines and breast tumor samples
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    inhibition of the enzymatic activity of USP28 may be a potential target for cancer therapy
    ANIMAL & CELL MODELS
  • mice lacking Usp28 had no apparent adverse phenotypes, but exhibited reduced intestinal proliferation and impaired differentiation of secretory lineage cells