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FLASH GENE
Symbol USP28 contributors: mct - updated : 03-11-2014
HGNC name ubiquitin specific peptidase 28
HGNC id 12625
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Digestivemouth   highly
Reproductivefemale systemuteruscervix predominantly
Respiratoryrespiratory tracttrachea  moderately
Urinarybladder   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  moderately
Muscular   moderately
cell lineage
cell lines
fluid/secretion
at STAGE
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