DDB1
Domain
The core of the protein consists of three WD40 beta-propeller domains.
Function
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:14739464, PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16407252, PubMed:16482215, PubMed:16940174, PubMed:17079684). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:25043012, PubMed:25108355, PubMed:28886238). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:25043012, PubMed:25108355). DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (PubMed:16473935, PubMed:16678110, PubMed:17041588, PubMed:18593899). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (PubMed:16473935, PubMed:16678110, PubMed:17041588, PubMed:18593899). DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER (PubMed:15882621). DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication (PubMed:17041588). DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR) (PubMed:12732143). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). DDB1-mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-mediated gluconeogenesis in the liver (By similarity). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (By similarity). Maternal factor required for proper zygotic genome activation and genome reprogramming (By similarity).
Involvement in disease
White-Kernohan syndrome
WHIKERS
An autosomal dominant disorder characterized by global developmental delay, variably impaired intellectual development, hypotonia, and characteristic facial features. Some patients may have genitourinary and skeletal abnormalities.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Phosphorylated by ABL1.
Ubiquitinated by CUL4A. Subsequently degraded by ubiquitin-dependent proteolysis.
Acetylated, promoting interaction with CUL4 (CUL4A or CUL4B) and subsequent formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes (PubMed:28886238). Deacetylation by SIRT7 impairs the interaction with CUL4 (CUL4A or CUL4B) and formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes (PubMed:28886238).
Sequence Similarities
Belongs to the DDB1 family.
Cellular localization
- Cytoplasm
- Nucleus
- Primarily cytoplasmic (PubMed:10777491, PubMed:11673459). Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459). More concentrated in nuclei than in cytoplasm in germinal vesicle (GV) stage oocytes, zygotes and the 2-cell stage, but distributed in the cytoplasm at the MII-stage oocytes (By similarity).
Alternative names
XAP1, DDB1, DNA damage-binding protein 1, DDB p127 subunit, DNA damage-binding protein a, Damage-specific DNA-binding protein 1, HBV X-associated protein 1, UV-damaged DNA-binding factor, UV-damaged DNA-binding protein 1, XPE-binding factor, Xeroderma pigmentosum group E-complementing protein, DDBa, XAP-1, UV-DDB 1, XPE-BF, XPCe
Database links
swissprot:Q16531 omim:600045 entrezGene:1642 entrezGene:100290337
Other research areas
- Oncology