Required for DNA repair. Binds to DDB1 to form the UV- damaged DNA-binding protein complex (the UV-DDB complex). The UV- DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1- CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4- ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair. Component of the UV-DDB complex which includes DDB1 and DDB2. The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit. Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4- ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1), which includes CUL4A or CUL4B, DDB1, DDB2 and RBX1. DDB2 may function as the substrate recognition module within this complex. The DDB1- CUL4-ROC1 complex may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex. A large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces DDB2. These targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Isoform D1 and isoform D2 do not interact with DDB1. Expression is induced in response to treatment with IR or UV and this requires p53/TP53 activity. Ubiquitously expressed; with highest levels in corneal endothelium and lowest levels in brain. Isoform D1 is highly expressed in brain and heart. Isoform D2, isoform D3 and isoform D4 are weakly expressed. Belongs to the WD repeat DDB2/WDR76 family. 5 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage
Chromosomal Location of Human Ortholog: 11p12-p11
Cellular Component: nucleoplasm; protein complex
Molecular Function: protein binding; DNA binding; damaged DNA binding; ubiquitin-protein ligase activity
Biological Process: protein autoubiquitination; protein polyubiquitination; nucleotide-excision repair; pyrimidine dimer repair; nucleotide-excision repair, DNA damage removal; DNA repair; response to UV
Alt. Names/Synonyms: damage-specific DNA binding protein 2, 48kDa; Damage-specific DNA-binding protein 2; DDB p48 subunit; DDB2; DDBb; DNA damage-binding protein 2; FLJ34321; UV-damaged DNA-binding protein 2; UV-DDB 2; UV-DDB2; xeroderma pigmentosum group E protein
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.