Protein / target
DNA damage-binding protein 1
Protein at a glance
Biological role
Ubiquitin ligase complex scaffold activity
Primary system
Immune system
Strongest disease association
White-Kernohan syndrome
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
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, PubMed:25970626). 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, PubMed:32355176, PubMed:38316879). 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)
Subcellular location
Domains and Gene Ontology detail (55)Hide
Gene Ontology
- Cchromosome, telomeric region
- CCul4-RING E3 ubiquitin ligase complex
- CCul4A-RING E3 ubiquitin ligase complex
- CCul4B-RING E3 ubiquitin ligase complex
- Ccytoplasm
- Cextracellular exosome
- Cextracellular space
- Cnucleolus
- Cnucleoplasm
- Cnucleus
- Cprotein-containing complex
- Csite of double-strand break
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Protein, which is both involved in DNA repair and protein ubiquitination, as part of the…
- ·epigenetic regulation of gene expression
- ·Transcription-Coupled Nucleotide Excision Repair (TC-NER)
Immune signalling
- ·positive regulation by virus of viral protein levels in host cell
- ·regulation of mitotic cytokinesis
- ·viral release from host cell
Apoptosis & cell death
- ·regulation of apoptotic process
View underlying pathways (10)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Appears in clinical studies involving plasma cell myeloma, immune system disorder, prostate cancer, non-small cell lung carcinoma
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Appears in clinical studies involving anemia, mantle cell lymphoma, myelodysplastic syndrome, plasma cell myeloma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 392 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 4 total
plasma cell myeloma · sarcoidosis · systemic lupus erythematosus
anemia · mantle cell lymphoma · myelodysplastic syndrome
plasma cell myeloma · systemic sclerosis · immune system disorder
plasma cell myeloma · immune system disorder · prostate cancer
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Industry developmentAdvanced hierarchical ZnFe-LDH@MnO₂ nanostructures for sensitive voltammetric determination of lenalidomide
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- Regulatory approval
Approval: LENALIDOMIDE (ANDA201452)
- Regulatory approval
Approval: Thalidomide Lipomed (EMA)
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Label change
Label change: LENALIDOMIDE (NDA021880)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.