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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
Corresponding disease
XPE xeroderma pigmentosum, complementation group E
Location 11p11.2      Physical location : 47.236.492 - 47.260.769
Synonym name
  • DDB p48 subunit
  • UV-damaged DNA-binding protein 2
  • xeroderma pigmentosum group E protein
  • Synonym symbol(s) FLJ34321, DDBB, UV-DDB, UV-DDB 2, XPE
    DNA
    TYPE functioning gene
    STRUCTURE 24.28 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    CREB3L1 11p11.2 cAMP responsive element binding protein 3-like 1 DGKZ 11p11.2 diacylglycerol kinase, zeta 104kDa MDK 11p11.2 midkine (neurite growth-promoting factor 2) CHRM4 11p12-p11.2 cholinergic receptor, muscarinic 4 LOC387765 11 LOC387765 FLJ20294 11p11.2 hypothetical protein FLJ20294 FLJ32675 11p11.2 hypothetical protein FLJ32675 KIAA0652 11p12-q11 hypothetical protein FLJ32675 ARHGAP1 11p12-q12 Rho GTPase activating protein 1 ZNF408 11p11.2 zinc finger protein 408 F2 11p11-q12 coagulation factor II (thrombin) ch-TOG 11p11.2 KIAA0097 gene product LRP4 11p12-p11.2 low density lipoprotein receptor-related protein 4 MGC4707 11p11.2 hypothetical protein MGC4707 ZNF289 11p11.2-p11.12 zinc finger protein 289, ID1 regulated PACSIN3 11p12-p11.2 protein kinase C and casein kinase substrate in neurons 3 DDB2 11p12-p11.2 damage-specific DNA binding protein 2, 48kDa ACP2 11p11.2 acid phosphatase 2, lysosomal NR1H3 11p11.2 nuclear receptor subfamily 1, group H, member 3 MADD 11p11.22-p11.21 MAP-kinase activating death domain MYBPC3 11p11.2 myosin binding protein C, cardiac SPI1 11p12 spleen focus forming virus (SFFV) proviral integration oncogene spi1 SLC39A13 11p11.2 solute carrier family 39 (zinc transporter), member 13 PSMC3 11p13-p12 proteasome (prosome, macropain) 26S subunit, ATPase, 3 RAPSN 11p11.2-p11.1 receptor-associated protein of the synapse, 43kD CUGBP1 11p11 CUG triplet repeat, RNA binding protein 1 KBTBD4 11p11.2 kelch repeat and BTB (POZ) domain containing 4 NDUFS3 11p11.11 NADH dehydrogenase (ubiquinone) Fe-S protein 3, 30kDa (NADH-coenzyme Q reductase) C1QTNF4 11q11 C1q and tumor necrosis factor related protein 4 MTCH2 11p11.2 mitochondrial carrier homolog 2 (C. elegans) FLJ23598 11p11.2 hypothetical protein FLJ23598 FNBP4 11q12.1 formin binding protein 4 NUP160 11q12.1 nucleoporin 160kDa PTPRJ 11p11.2 protein tyrosine phosphatase, receptor type, J
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - splicing 717 - 238 highly in brain and heart 2002 11852074
  • also called DDB2 ID1
  • dominant negative inhibitor of DNA repair, which is probably due to disruption of complex formation between DDB1 and DDB2-WT and of DDB1 nuclear import
  • not part of the damaged DNA-protein complex
  • 10 - 1870 48 427 - 2002 11852074
    interacting with ID1 and itself
    - splicing 960 - 156 - 2002 11852074
  • also called DDB2 ID2
  • dominant negative inhibitor of DNA repair, which is probably due to disruption of complex formation between DDB1 and DDB2-WT and of DDB1 nuclear import
  • not part of the damaged DNA-protein complex
  • - splicing 1092 - 363 - 2002 11852074
    also called DDB2 ID3
    - splicing 1106 - 244 - 2002 11852074
    also called DDB2 ID4
    6 - 1303 - 238 - 2002 11852074
  • variant (D1)
  • 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