| Aspect | Key findings | Best supporting sources | Publication details |
|---|---|---|---|
| identity/domains | • Verified target is human **DDA1 / DET1- and DDB1-associated protein 1** (UniProt Q9BW61), not Drosophila dDA1 receptor or chemical "DDA-1" • Conserved **DDA1 family** protein and basal CRL4-associated component • UniProt-consistent function in DDB1/CUL4 systems supported by multiple human studies (pqac-00000006, pqac-00000016) | (pqac-00000006, pqac-00000016) | 2018, *Cell Discovery*, https://doi.org/10.1038/s41421-018-0064-8; 2007, *Molecular and Cellular Biology*, https://doi.org/10.1128/mcb.02432-06 |
| complex membership | • Stable member of mammalian **DET1–DDB1–DDA1 (DDD)** core complex • Also an integral component of **CRL4^CSA** in TC-NER; binds CSA and DDB1 • Present in **DCAF15:DDA1:DDB1** ligase assemblies used by molecular glues, but not detected in CRL4^DDB2 in the cited TC-NER proteomics (pqac-00000016, pqac-00000017, pqac-00000020, pqac-00000026) | (pqac-00000016, pqac-00000017, pqac-00000020, pqac-00000026) | 2007, *Molecular and Cellular Biology*, https://doi.org/10.1128/mcb.02432-06; 2023, *Research Square*, https://doi.org/10.21203/rs.3.rs-3385435/v1; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7; 2024, *bioRxiv*, https://doi.org/10.1101/2023.02.03.526954 |
| molecular function | • Functions as a **small structural/regulatory subunit** of DDB1-CUL4 E3 ligases rather than an enzyme with its own catalytic reaction • In DDD-E2 context, negatively regulates **Cul4A-dependent polyubiquitin chain assembly** in vitro • In TC-NER, coordinates **ubiquitination dynamics** and supports efficient turnover/progression at stalled RNAPII (pqac-00000001, pqac-00000002, pqac-00000005) | (pqac-00000001, pqac-00000002, pqac-00000005) | 2007, *Molecular and Cellular Biology*, https://doi.org/10.1128/mcb.02432-06; 2023, *Research Square*, https://doi.org/10.21203/rs.3.rs-3385435/v1; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7 |
| structural determinants | • **N-terminal 1–28 aa** (or broader 2–75 aa in CRL4^CSA map) mediates direct DDB1 engagement • DDB1-binding site lies on the **BPA propeller**; key residues include **Pro9, Asn15, Phe16, Arg18, Phe19** • Reported affinities/resolution: **Kd ~45 nM** for DDA1-NT by BLI; alternate summaries report **FL Kd 28 nM vs NT Kd 663 nM**; crystal/cryo-EM resolutions **3.1–3.4 Å** (pqac-00000011, pqac-00000013, pqac-00000014, pqac-00000018) | (pqac-00000011, pqac-00000013, pqac-00000014, pqac-00000018) | 2018, *Cell Discovery*, https://doi.org/10.1038/s41421-018-0064-8; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7 |
| localization/compartment | • Functional evidence places DDA1 mainly in **nuclear CRL4 complexes** involved in DNA repair • TC-NER role implies action at **DNA damage-stalled RNA polymerase II/chromatin** • Direct localization evidence in retrieved texts is limited; compartment inference is strongest from CRL4^CSA structure/function rather than standalone imaging of DDA1 (pqac-00000002, pqac-00000005, pqac-00000007) | (pqac-00000002, pqac-00000005, pqac-00000007) | 2023, *Research Square*, https://doi.org/10.21203/rs.3.rs-3385435/v1; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7 |
| pathways/biological processes | • Participates in **CRL4 ubiquitin ligase regulation** • Key human pathway link is **transcription-coupled nucleotide excision repair (TC-NER)**, affecting ubiquitination of TC-NER factors such as RNAPII/UVSSA/CSB through CRL4^CSA context • Foundational work also links DDA1-containing complexes to **UV-induced CDT1 stability** and broader CRL4 control (pqac-00000001, pqac-00000002, pqac-00000020) | (pqac-00000001, pqac-00000002, pqac-00000020) | 2007, *Molecular and Cellular Biology*, https://doi.org/10.1128/mcb.02432-06; 2023, *Research Square*, https://doi.org/10.21203/rs.3.rs-3385435/v1; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7 |
| recent 2023-2024 advances | • 2023 preprint/2024 paper established DDA1 as a **CSA-interacting protein** and **integral CRL4^CSA component** • Cryo-EM of CSA–DDB1–DDA1-containing complex reached **3.4 Å** • DDA1 gave a modest but reproducible **~1 °C thermal stabilization** of CSA-DDB1; assays used **2 µM** protein in nanoDSF and in vitro ubiquitination conditions including **1.5 µM UVSSA, 0.2 µM UBA1, 1 µM UBE2E1, 20 µM ubiquitin** (pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000021) | (pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000021) | 2023, *Research Square*, https://doi.org/10.21203/rs.3.rs-3385435/v1; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7 |
| applications | • **Drug-discovery assays** now use DDB1-interaction peptides/FP displacement to find antagonists of DDB1 complexes relevant to antiviral/anticancer discovery • DDA1-containing **DCAF15:DDA1:DDB1** complexes are used in **targeted protein degradation** studies with RBM39 molecular glues (E7820, indisulam) • Native MS can resolve DDA1-containing ternary complexes and stoichiometric changes, enabling practical TPD analytics (pqac-00000026, pqac-00000028, pqac-00000029) | (pqac-00000026, pqac-00000028, pqac-00000029) | 2024, *bioRxiv*, https://doi.org/10.1101/2023.02.03.526954; 2024, *Biochemistry*, https://doi.org/10.1021/acs.biochem.4c00044 |
| quantitative statistics | • DDA1–DDB1 affinity: **Kd ~45 nM** (BLI, DDA1-NT); alternate reported values **28 nM FL** and **663 nM NT** • Structures: **3.1 Å** DDB1–DDA1-NT crystal; **3.4 Å** CRL4^CSA cryo-EM • Screening/TPD metrics: **FITC-DCAF15 L49A Kd 68 nM**, **Z-factor 0.73**, DCAF15:DDA1:DDB1 self-association at **100 mM** ammonium acetate and dissociation/1:1:1 ternary complex at **500 mM** ammonium acetate or upon MG+POI addition; OpenTargets association scores include **neurodegenerative disease 0.3696**, **atrial fibrillation 0.1274**, **hypertension 0.1170**, **neoplasm 0.1101**, **lung cancer 0.0799** (pqac-00000011, pqac-00000014, pqac-00000018, pqac-00000026, pqac-00000028, pqac-00000000) | (pqac-00000011, pqac-00000014, pqac-00000018, pqac-00000026, pqac-00000028, pqac-00000000) | 2018, *Cell Discovery*, https://doi.org/10.1038/s41421-018-0064-8; 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-50584-7; 2024, *bioRxiv*, https://doi.org/10.1101/2023.02.03.526954; 2024, *Biochemistry*, https://doi.org/10.1021/acs.biochem.4c00044; OpenTargets platform context (pqac-00000000) |


*Table: This table summarizes the strongest available functional annotation evidence for human DDA1 (UniProt Q9BW61), emphasizing experimentally supported complex membership, structural mechanism, TC-NER function, and translational relevance. It consolidates recent and foundational quantitative findings useful for downstream gene/protein annotation.*