DNA damage-binding protein 1

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. 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. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. 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. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. 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. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. 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. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1. 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).

Classification

Family (Pfam)

PF10433 Beta-prop_RSE1_1st, PF23726 Beta-prop_RSE1_2nd, PF03178 CPSF_A

InterPro

Beta-prop_RSE1/DDB1/CPSF1_1st, Beta-prop_RSE1/DDB1/CPSF1_2nd, RSE1/DDB1/CFT1, RSE1/DDB1/CPSF1_C, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf

Functional cluster

Zinc-Finger & Ubiquitination Proteins

Experimental structures · PDB · 181

• 2B5L X-ray 2.85A
• 2B5M X-ray 2.92A
• 2B5N X-ray 2.80A
• 2HYE X-ray 3.10A
• 3E0C X-ray 2.41A
• 3EI1 X-ray 2.80A
• 3EI2 X-ray 2.60A
• 3EI3 X-ray 2.30A
• 3EI4 X-ray 3.30A
• 3I7H X-ray 2.90A
• 3I7K X-ray 2.80A
• 3I7L X-ray 2.80A
• … and 169 more

A predicted model is available from AlphaFold.

Gene Ontology · 55

• GO:0000781 chromosome, telomeric region
• GO:0080008 Cul4-RING E3 ubiquitin ligase complex
• GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
• GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
• GO:0005737 cytoplasm
• GO:0070062 extracellular exosome
• GO:0005615 extracellular space
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:0035861 site of double-strand break
• GO:0097602 cullin family protein binding
• GO:0003684 damaged DNA binding
• GO:0003677 DNA binding
• GO:0044877 protein-containing complex binding
• GO:0030674 protein-macromolecule adaptor activity
• GO:0160072 ubiquitin ligase complex scaffold activity
• GO:0071987 WD40-repeat domain binding
• GO:0051702 biological process involved in interaction with symbiont
• GO:0008283 cell population proliferation
• GO:0034644 cellular response to UV
• GO:0006974 DNA damage response
• GO:0006281 DNA repair
• GO:0044725 epigenetic programming in the zygotic pronuclei
• GO:0040029 epigenetic regulation of gene expression
• GO:1904178 negative regulation of adipose tissue development
• GO:0006289 nucleotide-excision repair
• GO:0046726 positive regulation by virus of viral protein levels in host cell
• GO:0045722 positive regulation of gluconeogenesis
• GO:0045732 positive regulation of protein catabolic process
• GO:0045070 positive regulation of viral genome replication
• GO:0010498 proteasomal protein catabolic process
• GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
• GO:0016567 protein ubiquitination
• GO:0042981 regulation of apoptotic process
• GO:0010506 regulation of autophagy
• GO:1901987 regulation of cell cycle phase transition
• GO:0042127 regulation of cell population proliferation
• GO:0080135 regulation of cellular response to stress
• GO:0042752 regulation of circadian rhythm
• GO:0030174 regulation of DNA-templated DNA replication initiation
• GO:0045995 regulation of embryonic development
• GO:0060964 regulation of miRNA-mediated gene silencing
• GO:1901990 regulation of mitotic cell cycle phase transition
• GO:1902412 regulation of mitotic cytokinesis
• GO:0032814 regulation of natural killer cell activation
• GO:2000036 regulation of stem cell population maintenance
• GO:0031297 replication fork processing
• GO:0048511 rhythmic process
• GO:0007283 spermatogenesis
• GO:0007056 spindle assembly involved in female meiosis
• GO:0006511 ubiquitin-dependent protein catabolic process
• GO:0070914 UV-damage excision repair
• GO:0019076 viral release from host cell

Disease associations

• White-Kernohan syndrome MONDO:0859169

Drugs targeting this protein · 5

• IBERDOMIDE modulator
• POMALIDOMIDE inhibitor
• THALIDOMIDE inhibitor
• LENALIDOMIDE HYDROCHLORIDE MONOHYDRATE modulator
• LENALIDOMIDE inhibitor

Related proteins · sequence + function similarity

• DNA damage-binding protein 1 1.00
• DNA damage-binding protein 1 1.00
• DNA damage-binding protein 1 1.00
• DNA damage-binding protein 1 1.00
• DNA damage-binding protein 1 1.00
• DNA damage-binding protein 1 1.00
• DNA damage-binding protein 1 0.99
• DNA damage-binding protein 1b 0.95
• DNA damage-binding protein 1a 0.94
• DNA damage-binding protein 1 0.94
• DNA damage-binding protein 1 0.94
• DNA damage-binding protein 1 0.93

Co-cited proteins · studied together in the literature

• DNA damage-binding protein 2 19 shared papers
• Protein UL145 2 shared papers
• DET1- and DDB1-associated protein 1 8 shared papers
• Protein X 2 shared papers
• Cullin-4A 16 shared papers
• DDB1- and CUL4-associated factor 15 8 shared papers
• RNA-binding protein 39 7 shared papers
• Non-structural protein V 3 shared papers
• Protein RL1 1 shared papers
• BRCA1-associated protein 1 shared papers
• DNA damage-binding protein 2 2 shared papers
• DNA damage-binding protein 1 1 shared papers

Literature · 72 cited papers

• Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair. Nat. Struct. Mol. Biol. · 2024
• Insight into Viral Hijacking of CRL4 Ubiquitin Ligase through Structural Analysis of the pUL145-DDB1 Complex. J. Virol. · 2022
• Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. Proc. Natl. Acad. Sci. U.S.A. · 2022
• Structural basis of human transcription-DNA repair coupling. Nature · 2021
• A DNA repair disorder caused by de novo monoallelic DDB1 variants is associated with a neurodevelopmental syndrome. Am. J. Hum. Genet. · 2021
• The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. Nat. Commun. · 2020
• The Human Cytomegalovirus pUL145 Isoforms Act as Viral DDB1-Cullin-Associated Factors to Instruct Host Protein Degradation to Impede Innate Immunity. Cell Rep. · 2020
• Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex. Nat. Chem. Biol. · 2020
• Structural basis and kinetic pathway of RBM39 recruitment to DCAF15 by a sulfonamide molecular glue E7820. Structure · 2019
• Aryl sulfonamides degrade RBM39 and RBM23 by recruitment to CRL4-DCAF15. Cell Rep. · 2019
• Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat. Chem. Biol. · 2020
• The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation. Cell. Mol. Life Sci. · 2020
• … and 60 more in the literature graph