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FLASH GENE
Symbol DDB1 contributors: mct/pgu - updated : 19-05-2021
HGNC name damage-specific DNA binding protein 1, 127kDa
HGNC id 2717
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • BPA and BPC domains
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Ddb1 (98.7 pc)
    homolog to murine Ddb1 (99.4 pc)
    Homologene
    FAMILY
  • DDB1 family
    • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • playing a role in DNA pyrimidine-dimer repair, global genomic nucleotide excision repair (NER) and transcription-coupled repair (TCR) of oxidative lesions
  • required for histone H3 and histone H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair
  • playing an important role in development by controlling levels of cell cycle regulators and thereby maintaining genomic stability
  • may functionally regulate mitotic exit by modulating APC/CDH1 activity
  • conserved protein component of the damaged DNA binding protein complex (DDB) that recognizes UV-induced DNA lesions and initiates the nucleotide excision repair process
  • contributes to the activation of DNA repair mechanisms and could be a key factor in regulating the cell cycle in response to UV-induced DNA damage
  • essential role likely in Sertoli cell proliferation and normal remodeling of testis cords via TGFB1 pathway
  • has a critical function in the development of growth plates, and is essential for the skeleton development by controlling chondrocyte proliferation and differentiation
  • DDB1 functions in a complex with CUL4B and PHIP
  • A key function of DDB1 is to recognize and bind to areas of UV-induced DNA damage
    • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, repair, nucleotide excision repair
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text
  • modulator of UV-induced apoptosis
    • PATHWAY
    metabolism
    signaling
  • DDB1-CUL4A and MLL1 complexes constitute a novel pathway that mediates CDKN2A activation during oncogenic checkpoint response and is repressed by the polycomb repression complexes during normal growth of young cells
    • a component
  • DDB is a heterodimeric complex comprising DDB1 and DDB2 subunits and binds to a wide spectrum of DNA lesions
  • DDB1-DDB2 complex serves in the initial detection of UV lesions
  • component of the RBX1-CUL4-DDB2 ubiquitin ligase machinery
  • FBXW5/DDB1/CUL4A/RBX1 may function to regulate the homeostasis of TSC complexes instead of mediating a specific cellular growth condition
  • CRL4 is a multisubunit protein complex, comprising cullin4A (CUL4A), RING H2 finger protein (RBX1), and DNA damage-binding protein 1 (DDB1)
  • CUL4A-DDB1 complex is a novel post-translational regulator of stem and progenitor maintenance and differentiation
    • INTERACTION
    DNA binding tightly to damaged DNA after UV-irradiation
    RNA
    small molecule
    protein
  • interacting with Simian virus 5 protein V
  • interacting with HBV protein X
  • interaction with XPA (the physical interaction between DDB1 and 2 and XPA plays an important role in the DDB-mediated NER reaction)
  • capable of binding the WD40 domains of CDH1, but not of CDC20, through its BPA and BPC domains
  • DDB1 interacts with the INO80 complex providing a mechanistic link between chromatin remodeling activity and the initiating step of nucleotide excision repair
  • DYRK2-associated DDB1-UBR5-VPRBP E3 ligase inhibits telomerase by TERT degradation
  • SETMAR decreases CHEK1 interaction with DDB1, and decreases CHEK1 ubiquitination
  • CDH1 promotes nucleotide excision repair through positively regulating the expression of xeroderma pigmentosum complementation group C (XPC) and DNA damage-binding protein 1 (DDB1)
  • DDB1 is acetylated and acetylation promotes DDB1 binding to CUL4B
  • nucleolar sirtuin 7 (SIRT7) is a major deacetylase that negatively regulates DDB1-CUL4B interaction
    • cell & other
    REGULATION
    Other proteosomal degradation after UV-irradiation
    ASSOCIATED DISORDERS
    corresponding disease(s) HIDDA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    prevents hepatocytes to replicate DNA, induces compensatory proliferation of DDB1-expressing hepatocytes, and eventually leads to development of hepatocellular carcinoma
    constitutional        
    DDB1 silencing activates TP53 pathway and leads to significant effects on cell cycle progression and rapid apoptosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS