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FLASH GENE
Symbol UBR5 contributors: SGE/npt - updated : 28-02-2015
HGNC name ubiquitin protein ligase E3 component n-recognin 5
HGNC id 16806
Location 8q22.3      Physical location : 103.265.568 - 103.424.495
Synonym name
  • ubiquitin-protein ligase
  • hyperplastic discs protein homolog
  • E3 ubiquitin protein ligase, HECT domain containing, 1
  • progestin-induced protein
  • E3 identified by differential display
  • E3 ubiquitin-protein ligase UBR5
  • Synonym symbol(s) HYD, DD5, KIAA0896, EDD, MGC57263, EDD1, FLJ11310
    EC.number 6.3.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 150.45 kb     59 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    59 - 10897 - 2798 - -
    59 - 10900 309.2 2799 - 2008 18349819
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunelymph node   highly
    Nervousspinal cord    
    Reproductivemale systemtestis  highly
    Respiratoryrespiratory tractlarynx   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one HECT domain
  • one UBR1-type zinc finger, 70-AAs UBR box functioning as a common structural element essential for binding to all known destabilizing N-terminal residues (Tasaki 2009)
  • ubiquitin-associated domain, each of which indicates involvement in ubiquitinylation pathways
  • a PABC domain that is present in poly(A)-binding protein (PABP)
  • HOMOLOGY
    interspecies ortholog to Drosophila tumor suppressor gene hypoplastic discs, Hyd
    Homologene
    FAMILY
  • HECT family (homology to E6-AP carboxyl terminal)
  • ubiquitin E3 ligase of the HECT family
  • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,nucleus,nucleoplasm
    text
  • UBR5 and MCRS1 co-localize in the nucleus
  • basic FUNCTION
  • HECT domain E3 ubiquitin protein-ligase playing a role in regulation of cell proliferation or differentiation
  • playing a role in progesterone receptor signaling but also, in carcinogenesis through DNA damage response pathways
  • regulating transcription independently of its E3 ligase activity
  • necessary role for G(1)/S and intra S phase DNA damage checkpoint activation and for the maintenance of G(2)/M arrest after double strand DNA breaks (Munoz 2007)
  • playing a role in the maintenance of genomic stability, emphasising the potential importance of dysregulated UBR5 expression and/or function in the evolution of cancer (Munoz 2007)
  • specifically enhancing trans-activation of smooth muscle-specific promoters by the myocardin family of proteins
  • can attenuate MYOCD protein degradation (Hu 2010)
  • activator os smooth muscle differentiation (Hu 2010)
  • progestin-regulated gene in breast cancer cells
  • TRIP12 and UBR5, two HECT domain ubiquitin E3 ligases, control accumulation of RNF168, a rate-limiting component of a pathway that ubiquitylates histones after DNA breakage
  • HECT-domain containing ubiquitin ligase that plays a role in cell proliferation, differentiation and DNA damage response
  • multiple functions, including E3 ligase activity based on a conserved cysteine residue at the C-terminus
  • UBR5, a protein commonly amplified in breast cancer, is a novel regulator of ESR1 protein levels and transcriptional activity
  • UBR5-mediated ATMIN ubiquitination is a vital event for ATM pathway selection and activation in response to DNA damage
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text putative role in cell growth and differentiation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ZN2+
  • protein
  • interacts with importin alpha 5 through consensus basic nuclear localization signals
  • binding to TOPBP1
  • interacting with MYOCD (Hu 2010)
  • in addition to PPP2CA, IGBP1 interacts with UBR5 and PABPC1, suggesting its involvement in multiple steps in the MTOR pathway that leads to translation initiation and cell-cycle progression
  • increased TP53 levels upon UBR5 depletion cause a G(1) arrest, as co-depletion of UBR5 and TP53 completely rescues this effect on cell cycle progression
  • is a novel MCRS1-interacting protein, that negatively regulates MCRS1 protein stability
  • DYRK2-associated DDB1-UBR5-VPRBP E3 ligase inhibits telomerase by TERT degradation
  • IGBP1 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PPP2CA) to regulate PP2A activity, and to poly(A)-binding protein (PABPC1) and progestin-inducible UBR5
  • negative regulation of ACVRL1 gene expression by UBR5 that is exerted at the promoter
  • post-translational regulation of NR1I2 via phosphorylation-facilitated ubiquitination by DYRK2 and UBR5
  • interacts with ATMIN and catalyzes ubiquitination of ATMIN at lysine 238 in an IR-stimulated manner, which decreases ATMIN interaction with ATM and promotes MRN-mediated signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in hepatocellular carcinoma, squamous cell carcinoma of the tongue, metastatic melanoma
    tumoral     --over  
    in breast carcinoma
    tumoral somatic mutation      
    recurrently mutated in mantle cell lymphoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS