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DNA damage-binding protein 2; damage-specific DNA-binding protein 2; DDB p48 subunit; DDBb; UV-damaged DNA-binding protein 2; UV-DDB 2 (DDB2)

Function: - required for DNA repair - binds to DDB1 to form the UV-DDB complex (UV-damaged DNA-binding protein complex) - isoform D1 & isoform D2 inhibit UV-damaged DNA repair - protein modification; protein ubiquitination - ubiquitinated by CUL4A in response to UV irradiation - ubiquitination appears to both impair DNA-binding & promotes ubiquitin-dependent proteolysis - degradation of DDB2 at sites of DNA damage may be a prerequisite for their recognition by XPC & subsequent repair - CUL4A-mediated degradation appears to be promoted by ABL1/c-ABL - the UV-DDB complex interacts with monoubiquitinated histone H2A & binds to XPC via the DDB2 subunit - component of the DCX complex - DDB2 may function as the substrate recognition module within this complex. - a large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces DDB2 as a substrate recognition modue - these targeting subunits are generally known as - DCAF (DDB1-&-CUL4-associated factor) or - CDW (CUL4-DDB1-associated WD40-repeat) - isoform D1 & isoform D2 do not interact with DDB1 Structure: - the DWD box is required for interaction with DDB1 - belongs to the WD repeat DDB2/WDR76 family - contains 5 WD repeats Compartment: - nucleus - accumulates at sites of DNA damage following UV irradiation Alternative splicing: named isoforms=5; D1, D2, D3, D4 Expression: - ubiquitously expressed - highest levels in corneal endothelium - lowest levels in brain - isoform D1 is highly expressed in brain & heart - isoform D2, isoform D3 & isoform D4 are weakly expressed - induced in response to treatment with IR or UV & this requires p53 activity Pathology: - defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E)

General

dna damage binding protein phosphoprotein WD repeat protein family

Properties

SIZE: entity length = 427 aa MW = 48 kD COMPARTMENT: cell nucleus MOTIF: Ser phosphorylation site {S24} Ser phosphorylation site {S26} DDB1 interaction {68-79} DDB1 interaction {87-98} WD repeat {109-149} WD repeat {154-195} WD repeat {240-280} MOTIF: DWD box {256-274} WD repeat {286-325} WD repeat {389-426}

Database Correlations

OMIM correlations MORBIDMAP 600811 UniProt Q92466 Pfam PF00400 Entrez Gene 1643 Kegg hsa:1643

References

  1. UniProt :accession Q92466
  2. Allelic variations of the XP genes http://www.xpmutations.org/
  3. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/XPEID298.html
  4. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/DDB2
  5. NIEHS-SNPs http://egp.gs.washington.edu/data/ddb2/

Component-of

UV-damaged DNA-binding protein complex (UV-DDB complex)