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Protein / target

DNA damage-binding protein 1

Encoded byDDB1Q16531Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Ubiquitin ligase complex scaffold

Strongest disease association

White-Kernohan syndrome

Via encoding gene DDB1 · Genetic evidence · score 0.77

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

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.

View complete UniProt function annotation

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

CytoplasmNucleus
Domains and Gene Ontology detail (55)

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

1140 aa · 127 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOCell-cycle regulationGOTranscriptional regulationUniProt · GO · Reactome
View supporting evidence

Cell proliferation & survival

  • ·cell population proliferation
  • ·regulation of cell population proliferation

Cell-cycle regulation

  • ·regulation of cell cycle phase transition
  • ·regulation of mitotic cell cycle phase transition

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)
View underlying pathways (10)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

ERCC8DCAF1ENSP00…CUL4ADCAF4DDA1DDB2DCAF11FBXW5RBX1DDB1

10 strongest partners — larger node and heavier line mean higher confidence

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.

Approved medicines with mapped indications

3 medicines · 5 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Immune System Diseases3 medicines
Multiple Myeloma3 medicines
Anemia1 medicine
Lymphoma, Mantle-Cell1 medicine
Myelodysplastic Syndromes1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Thalidomide
ApprovedInhibitor

CRL4(CRBN) E3 ubiquitin ligase inhibitor

Indicated for Immune System Diseases, Multiple Myeloma

Acts on a complex — shared with CRBN, CUL4A, RBX1 · 1 of 4 recorded protein targets

lenalidomide
ApprovedInhibitor

CRL4(CRBN) E3 ubiquitin ligase inhibitor

Indicated for Anemia, Immune System Diseases, Lymphoma, Mantle-Cell, Multiple Myeloma

Acts on a complex — shared with CRBN, CUL4A, RBX1 · 1 of 4 recorded protein targets

pomalidomide
ApprovedInhibitor

CRL4(CRBN) E3 ubiquitin ligase inhibitor

Indicated for Immune System Diseases, Multiple Myeloma

Acts on a complex — shared with CRBN, CUL4A, RBX1 · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene DDB1

Gene-level evidence surfaced through the gene DDB1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

White-Kernohan syndrome
0.77Well supported

Genetic evidence dominant · Open Targets 0.65

Multiple Myeloma
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.61

Myelodysplastic syndrome
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Lymphoma, Mantle-Cell
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

Lymphoma, Large B-Cell, Diffuse
0.52Moderately supported

Clinical evidence dominant · Open Targets 0.41

View evidence synthesis (5)
White-Kernohan syndromeWell supported
0.77
agreement 0.630.91
Genetic100%Literature0%Genetic literaturedup

Open Targets aggregate 0.65 · 2 independent evidence families · 1 not counted as duplicate

Multiple MyelomaModerately supported
0.75
agreement 0.590.90
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

Myelodysplastic syndromeModerately supported
0.69
agreement 0.540.85
Clinical100%Literature0%

Open Targets aggregate 0.56 · 2 independent evidence families

Lymphoma, Mantle-CellModerately supported
0.68
agreement 0.530.83
Clinical99%Literature1%

Open Targets aggregate 0.55 · 2 independent evidence families

Lymphoma, Large B-Cell, DiffuseModerately supported
0.52
agreement 0.360.67
Clinical97%Literature3%

Open Targets aggregate 0.41 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
White-Kernohan syndrome0.65
Multiple Myeloma0.61
Myelodysplastic syndrome0.56
Lymphoma, Mantle-Cell0.55
Neurodegenerative Diseases0.45
Lymphoma, Large B-Cell, Diffuse0.41

Drug development

4 compounds recorded · 3 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (4)
IBERDOMIDEPhase 3
LENALIDOMIDEApproval
POMALIDOMIDEApproval
THALIDOMIDEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (8)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-07-31

    A Phase 3b, Multicenter, Open-label, Daratumumab Long-term Extension Study

    Status changed to Active, not recruiting · ClinicalTrials.gov · via lenalidomide

  2. Trial status changed2026-07-30

    64407564MMY3009: A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pom

    Status changed to Active, not recruiting · ClinicalTrials.gov · via pomalidomide

  3. Label change2026-07-22

    Label change: LENALIDOMIDE (NDA021880)

    fda · regulatory · fda · via lenalidomide

  4. Trial status changed2026-07-20

    A Phase II Trial of Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma

    Status changed to Active, not recruiting · ClinicalTrials.gov · via lenalidomide

  5. Label change2026-06-15

    Label change: LENALIDOMIDE (ANDA201452)

    fda · regulatory · fda · via lenalidomide

  6. Supplemental approval2026-04-27

    Supplemental approval: LENALIDOMIDE (ANDA201452)

    fda · regulatory · fda · via lenalidomide

  7. Supplemental approval2026-04-27

    Supplemental approval: LENALIDOMIDE (NDA021880)

    fda · regulatory · fda · via lenalidomide

  8. New publication2022-03-01
    Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2022 · 38 citations · Europe PMC · via pomalidomide

  9. Safety communication2016-05-10

    Drug Safety Update: Pomalidomide (Imnovid▼): risk of hepatitis B reactivation

    mhra · safety · mhra · via pomalidomide

  10. Safety communication2014-12-11

    Drug Safety Update: Lenalidomide (Revlimid): risk of serious hepatic adverse drug reactions

    mhra · safety · mhra · via lenalidomide

  11. Safety communication2014-12-11

    Drug Safety Update: Lenalidomide (Revlimid▼): update on risk of second primary malignancy

    mhra · safety · mhra · via lenalidomide

  12. Safety communication2014-12-11

    Drug Safety Update: Lenalidomide: risk of thrombosis and thromboembolism

    mhra · safety · mhra · via lenalidomide

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.