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FLASH GENE
Symbol DDB2 contributors: mct - updated : 04-12-2017
HGNC name damage-specific DNA binding protein 2, 48kDa
HGNC id 2718
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
 stomach   highly
Endocrinepancreas    
Lymphoid/Immunetonsils   highly
Reproductivefemale systemuteruscervix highly
Respiratorylung    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • G protein beta with five WD40 repeats
  • conjugated Other
    mono polymer heteromer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • WD repeat DDB2/WDR76 family
  • CATEGORY regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • pyrimidine-dimer repair, global genomic nucleotide excision repair (NER) and transcription-coupled repair (TCR) of oxidative lesions
  • participates in NER by regulating the cellular levels of CDKN1A
  • involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation
  • can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer
  • having an intrinsic damaged DNA binding activity but neither DDB2 nor complexes that contain DDB2 (UV-DDB, CUL4A, and COP9) participate in nucleotide excision repair carried out by the six-factor human excision nuclease
  • regulates negatively the constitutive expression of the SOD2 gene in breast cancer cells and exerts, at least in part, a control of breast cacner cell growth
  • transcriptional regulator
  • upon oxidative stress, functions in a positive feedback loop by repressing the antioxidant genes to cause persistent accumulation of ROS and induce premature senescence
  • in addition to stimulating NER, plays a significant role in terminating DNA damage checkpoint, allowing cells with extensive DNA damage to undergo apoptosis
  • likely has evolved to participate in transcriptional repression of the antioxidant genes to ensure that cells harboring DNA damage do not replicate
  • is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER)
  • DDB2 and XPC, two early UV damage recognition factors, are required for the damage-specific ATR and ATM recruitment and phosphorylation
  • DDB2 has been implicated in promoting cell-cycle progression by regulating gene expression
  • is a protein playing an essential role in the lesion recognition step of the global genome sub-pathway of nucleotide excision repair (GG-NER) process
  • DDB2 exhibits a high affinity toward UV-damaged DNA, and it is involved in the initial steps of global genome nucleotide excision repair
  • participates in both nucleotide excision repair and mRNA transcription
  • is modified by SUMOylation upon UV irradiation, and this post-translational modification plays an important role in the initial recognition and processing of UVR (UV radiation)-induced DNA damage occurring within the context of chromatin
  • is both a partner and regulator of WNT signaling, with an important role in suppressing colon cancer development
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, repair, nucleotide excision repair
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text modulator of UV-induced apoptosis
    PATHWAY
    metabolism
    signaling
    nucleotide-excision repair
    a component
  • DDB is a heterodimeric complex comprising DDB1 and DDB2 subunits and binds to a wide spectrum of DNA lesions
  • at least four forms in the cell: monomeric DDB2, DDB1-DDB2 heterodimer (UV-DDB), and as a protein associated with both the Cullin 4A (CUL4A) complex and the COP9 signalosome
  • DDB1-DDB2 complex serves in the initial detection of UV lesions
  • INTERACTION
    DNA binding tightly to damaged DNA after UV irradiation
    RNA
    small molecule
    protein
  • CUL4A (target of CUL4A)
  • interaction with XPA (the physical interaction between DDB1 and 2 and XPA plays an important role in the DDB-mediated NER reaction)
  • is a novel androgen receptor (AR)-interacting protein, mediating contact with AR and CUL4A-DDB1 complex for AR ubiquitination/degradation
  • PARP1 is a novel DDB2-associated factor
  • PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of CHD1L
  • is a novel regulator of NFKB1 and breast tumor invasion
  • DDB2 is involved in the CUL4-DDB1 complex mediating CDKN1A degradation
  • DDB2 is a PCNA-binding protein, and that this association is required for DDB2 proteolytic degradation
  • XPC allows DDB2 to initiate multiple rounds of repair events, thereby contributing to the persistence of cellular DNA repair capacity
  • UVRAG is a regulator of CRL4(DDB2)-mediated NER, suggesting that its expression levels may influence melanoma predisposition
  • DDB2 is critical for chromatin association of XRCC5/XRCC6 in the absence of DNA damage and provide evidence that XRCC5/XRCC6 are functional partners of DDB2 in its transcriptional stimulatory activity
  • PARP1 plays an additional DDB2-independent direct role in recruitment and stabilization of XPC at the UV-induced DNA lesions to promote nucleotide excision repair (GG-NER)
  • is critical for CTNNB1-mediated activation of RNF43, which restricts WNT signaling by removing WNT receptors from the cell surface
  • cell & other
  • regulating the pool of hepatitis B virus through interaction with the viral X protein
  • REGULATION
    activated by TP53 (directly)
    repressed by proteosomal degradation after UV-irradiation
    ASSOCIATED DISORDERS
    corresponding disease(s) XPE
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional        
    in xeroderma pigmentosum, type E
    Susceptibility to progressive supranuclear palsy (PSP)
    Variant & Polymorphism SNP increasing the risk of progressive supranuclear palsy (PSP)
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    may be a potential regimen for prostate cancer treatment, especially in androgen-refractory patients harboring high amount of AR who cannot be cured by androgen ablation
    ANIMAL & CELL MODELS
  • DDB2/ mice are susceptible to UV-induced skin carcinogenesis
  • mice genetically deficient in Ddb2 exhibited increased susceptibility to colon tumor development in a manner associated with higher abundance of the Wnt receptor-expressing cells and greater activation of the downstream Wnt pathway