id: Q16531 gene_symbol: DDB1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: DDB1 (DNA damage-binding protein 1; p127, UV-DDB1, XAP-1) is a large (1140 aa) WD40 beta-propeller protein built from three seven-bladed beta-propeller domains (BPA, BPB and BPC) that serves as the central adaptor of CUL4-RING E3 ubiquitin ligases (CRL4). Its BPB propeller docks onto the N-terminus of the cullin scaffold CUL4A or CUL4B (assembled with the RING protein RBX1/ROC1), while a cleft between the BPA and BPC propellers, together with a helix-loop-helix (H-box) surface, captures a large family of interchangeable substrate-receptor subunits known as DCAFs (DDB1- and CUL4-associated factors), most of which engage DDB1 through a conserved WDxR motif on their own WD40 propeller. DDB1 itself is not catalytic and is not the direct nucleic-acid-binding subunit; by interchanging DCAF receptors it confers substrate specificity on numerous distinct DCX (DDB1-CUL4-X-box) ligase complexes that ubiquitinate and target their substrates for proteasomal degradation, and cullin-RING ligases as a class account for roughly a fifth of regulated proteasomal protein turnover. Systematic interactome studies (BioID/AP-MS/pulse-SILAC) indicate that only a minority of candidate WD40 proteins are bona fide DDB1/CUL4 receptors under any given condition, so DDB1's functional output is strongly context- and stimulus-dependent and is largely encoded by which DCAF is conditionally recruited. Structurally, DDB1's BPB propeller binds the CUL4 N-terminus while the BPA-BPC double-propeller cleft (with an H-box helical surface) captures receptors and viral hijackers; receptors that are intrinsically disordered (e.g. AMBRA1) become stabilized upon DDB1 engagement. With its dedicated receptor DDB2, DDB1 forms the UV-DDB complex that recognizes UV-induced photolesions (cyclobutane pyrimidine dimers and 6-4 photoproducts), apurinic sites and mismatches in chromatin and initiates global-genome nucleotide excision repair, in part by ubiquitinating histones (H2A, H3, H4) and XPC at damage sites; in a noncanonical capacity UV-DDB also stimulates base-excision-repair enzymes (e.g. OGG1, MUTYH, APE1 and the glycosylase SMUG1), promoting turnover of oxidative DNA lesions. With the DCAF ERCC8/CSA, DDB1-CUL4 contributes to transcription-coupled repair by ubiquitinating stalled RNA polymerase II and CSB/ERCC6. Other DDB1-CUL4 complexes regulate DNA replication licensing (CDT1, p21 via DTL/CDT2), cell-cycle progression through the DCAF AMBRA1 (which directs ubiquitination of cyclin D/cyclin D1), the circadian clock (CRY1), histone methylation, and many additional substrates. DDB1 is predominantly cytoplasmic at steady state and translocates to the nucleus after UV irradiation, accumulating at sites of DNA damage; the two cullin scaffolds it uses show partitioning tendencies (CUL4B largely nuclear, CUL4A more cytoplasmic) so that DDB1-containing CRL4 assemblies can act in distinct compartments depending on scaffold usage. It is a frequent target of viral hijacking (e.g. paramyxovirus V, HBV HBx, HIV Vpr/Vpx, HCMV proteins), which redirect CRL4 toward host antiviral or restriction factors; during influenza A virus infection the CRL4 interactome is rewired and DDB1 (with DCAF11/DCAF12L1) participates in non-degradative polyubiquitination of the viral polymerase subunit PB2. DDB1 is also the platform exploited by thalidomide/lenalidomide molecular-glue degraders acting through the DCAF cereblon (CRBN) and, more broadly, is an actionable induced-proximity node for targeted protein degradation, with surface residues such as Arg928 (a validated molecular-glue hotspot, e.g. in CDK12-cyclin K degrader ternary complexes) and Cys173 (engaged by covalent DDB1 recruiters) used to direct CRL4-dependent degradation of clinically relevant proteins including BRD4 and the androgen receptor. Monoallelic de novo DDB1 missense variants cause a recessive-DNA-repair-related neurodevelopmental syndrome (WHIKERS). alternative_products: - name: '1' id: Q16531-1 - name: '2' id: Q16531-2 sequence_note: VSP_055540 existing_annotations: - term: id: GO:0006281 label: DNA repair evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: DDB1 functions in DNA repair via the UV-DDB complex (parent of nucleotide excision repair). action: ACCEPT reason: Correct core process; UV-DDB initiates NER. Redundant with the more specific NER terms. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: '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' - term: id: GO:0035861 label: site of double-strand break evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: IBA 'site of double-strand break' localization; DDB1's documented genome-stability role is via UV-photolesion (NER) recognition, not DSB sites. action: MARK_AS_OVER_ANNOTATED reason: Phylogenetically inferred; DDB1's direct DNA-damage activity is global-genome NER through UV-DDB, so DSB-site localization over-reaches. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates. action: ACCEPT reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0003676 label: nucleic acid binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Generic nucleic acid binding (InterPro IEA); DDB1 itself is not a sequence/nucleic-acid-binding protein, DNA recognition is via the DDB2 subunit of UV-DDB. action: REMOVE reason: DDB1 is the adaptor/scaffold subunit of UV-DDB and the DCX(DDB1-CUL4) ligases; it does not itself bind nucleic acid. Direct lesion/DNA contact in UV-DDB is made by the DDB2 subunit. This InterPro2GO electronic mapping (GO_REF:0000002) is a false-positive attribution of a DNA-binding function to the wrong subunit and should be removed. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV. action: ACCEPT reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0034644 label: cellular response to UV evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: DDB1/UV-DDB mediates the cellular response to UV-induced DNA damage. action: ACCEPT reason: Core UV-response process; UV-DDB recognizes UV photolesions and recruits NER machinery. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:10777491 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16227264 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16473935 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17041588 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17314515 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17360488 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19109893 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19264781 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19651607 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19966799 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20562859 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20855601 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21113133 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21145461 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21988832 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22039351 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22157821 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22810585 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22822215 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23238014 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23314863 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24292623 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24412650 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24500646 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26131937 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26496610 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26909574 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29691401 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:30564455 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:30945288 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31391242 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:9418871 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0006511 label: ubiquitin-dependent protein catabolic process evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in review: summary: DDB1 enables ubiquitin-dependent protein catabolism as the CRL4 adaptor. action: ACCEPT reason: Core process (parent of proteasome-mediated catabolism); CRL4/DCX complexes target substrates for degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0016567 label: protein ubiquitination evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in review: summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes. action: ACCEPT reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0042752 label: regulation of circadian rhythm evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Context-specific downstream process (regulation of circadian rhythm) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1' - term: id: GO:0045722 label: positive regulation of gluconeogenesis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Context-specific downstream process (positive regulation of gluconeogenesis) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'DDB1- mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1- mediated gluconeogenesis in the liver' - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0000109 label: nucleotide-excision repair complex evidence_type: IPI original_reference_id: PMID:22118460 qualifier: part_of review: summary: DDB1 is part of the UV-DDB (DDB1-DDB2) nucleotide excision repair recognition complex. action: ACCEPT reason: Core component of the UV-DDB complex that recognizes UV-induced DNA damage and recruits NER factors. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:14751237 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005634 label: nucleus evidence_type: NAS original_reference_id: PMID:22118460 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0006289 label: nucleotide-excision repair evidence_type: NAS original_reference_id: PMID:22118460 qualifier: involved_in review: summary: DDB1, as part of UV-DDB, functions in nucleotide excision repair of UV lesions. action: ACCEPT reason: Core biological process; UV-DDB recognizes UV photolesions and initiates global-genome NER. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0006974 label: DNA damage response evidence_type: ISS original_reference_id: GO_REF:0000114 qualifier: involved_in review: summary: DDB1 acts in the DNA damage response through UV-DDB lesion recognition and CRL4-mediated damage signaling. action: ACCEPT reason: Core process; UV-DDB recognizes damage and CRL4(DDB2/DTL) couples damage to ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0006974 label: DNA damage response evidence_type: EXP original_reference_id: PMID:22118460 qualifier: involved_in review: summary: DDB1 acts in the DNA damage response through UV-DDB lesion recognition and CRL4-mediated damage signaling. action: ACCEPT reason: Core process; UV-DDB recognizes damage and CRL4(DDB2/DTL) couples damage to ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0007283 label: spermatogenesis evidence_type: NAS original_reference_id: PMID:29907856 qualifier: involved_in review: summary: Context-specific downstream process (spermatogenesis) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0008283 label: cell population proliferation evidence_type: NAS original_reference_id: PMID:30945288 qualifier: involved_in review: summary: Context-specific downstream process (cell population proliferation) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0010506 label: regulation of autophagy evidence_type: NAS original_reference_id: PMID:31267705 qualifier: involved_in review: summary: Context-specific downstream process (regulation of autophagy) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0030174 label: regulation of DNA-templated DNA replication initiation evidence_type: NAS original_reference_id: PMID:16861906 qualifier: involved_in review: summary: Context-specific downstream process (regulation of DNA replication initiation) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0031297 label: replication fork processing evidence_type: NAS original_reference_id: PMID:30018425 qualifier: involved_in review: summary: Context-specific downstream process (replication fork processing) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0031297 label: replication fork processing evidence_type: NAS original_reference_id: PMID:33503431 qualifier: involved_in review: summary: Context-specific downstream process (replication fork processing) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:16861906 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:16949367 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IPI original_reference_id: PMID:22118460 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: EXP original_reference_id: PMID:22118460 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:25108355 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:25499913 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:27113764 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:28212551 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:29691401 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:30945288 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IPI original_reference_id: PMID:31693891 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IPI original_reference_id: PMID:34595758 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:16861906 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:16949367 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:22118460 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:25108355 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:25499913 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: IPI original_reference_id: PMID:27113764 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:29691401 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:30945288 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:31452512 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:33898171 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:34595758 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0032814 label: regulation of natural killer cell activation evidence_type: NAS original_reference_id: PMID:31452512 qualifier: involved_in review: summary: Context-specific downstream process (regulation of natural killer cell activation) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0034644 label: cellular response to UV evidence_type: ISS original_reference_id: GO_REF:0000114 qualifier: involved_in review: summary: DDB1/UV-DDB mediates the cellular response to UV-induced DNA damage. action: ACCEPT reason: Core UV-response process; UV-DDB recognizes UV photolesions and recruits NER machinery. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0034644 label: cellular response to UV evidence_type: EXP original_reference_id: PMID:22118460 qualifier: involved_in review: summary: DDB1/UV-DDB mediates the cellular response to UV-induced DNA damage. action: ACCEPT reason: Core UV-response process; UV-DDB recognizes UV photolesions and recruits NER machinery. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0040029 label: epigenetic regulation of gene expression evidence_type: NAS original_reference_id: PMID:30111536 qualifier: involved_in review: summary: Context-specific downstream process (epigenetic regulation of gene expression) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0040029 label: epigenetic regulation of gene expression evidence_type: NAS original_reference_id: PMID:34429321 qualifier: involved_in review: summary: Context-specific downstream process (epigenetic regulation of gene expression) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0040029 label: epigenetic regulation of gene expression evidence_type: NAS original_reference_id: PMID:34720086 qualifier: involved_in review: summary: Context-specific downstream process (epigenetic regulation of gene expression) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0042127 label: regulation of cell population proliferation evidence_type: NAS original_reference_id: PMID:33869224 qualifier: involved_in review: summary: Context-specific downstream process (regulation of cell population proliferation) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0042981 label: regulation of apoptotic process evidence_type: NAS original_reference_id: PMID:33898171 qualifier: involved_in review: summary: Context-specific downstream process (regulation of apoptotic process) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0045995 label: regulation of embryonic development evidence_type: NAS original_reference_id: PMID:30111536 qualifier: involved_in review: summary: Context-specific downstream process (regulation of embryonic development) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0060964 label: regulation of miRNA-mediated gene silencing evidence_type: NAS original_reference_id: PMID:34065512 qualifier: involved_in review: summary: Context-specific downstream process (regulation of miRNA-mediated gene silencing) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0070914 label: UV-damage excision repair evidence_type: IDA original_reference_id: PMID:14751237 qualifier: involved_in review: summary: DDB1/UV-DDB participates in UV-damage excision repair (global-genome NER of UV photoproducts). action: ACCEPT reason: Core process directly supported; UV-DDB recognizes CPD/6-4PP lesions to initiate repair. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches - term: id: GO:0080135 label: regulation of cellular response to stress evidence_type: NAS original_reference_id: PMID:31586112 qualifier: involved_in review: summary: Context-specific downstream process (regulation of cellular response to stress) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:1901987 label: regulation of cell cycle phase transition evidence_type: NAS original_reference_id: PMID:16861906 qualifier: involved_in review: summary: Context-specific downstream process (regulation of cell cycle phase transition) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:1901987 label: regulation of cell cycle phase transition evidence_type: NAS original_reference_id: PMID:25499913 qualifier: involved_in review: summary: Context-specific downstream process (regulation of cell cycle phase transition) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:1902412 label: regulation of mitotic cytokinesis evidence_type: NAS original_reference_id: PMID:34758320 qualifier: involved_in review: summary: Context-specific downstream process (regulation of mitotic cytokinesis) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:1904178 label: negative regulation of adipose tissue development evidence_type: NAS original_reference_id: PMID:27113764 qualifier: involved_in review: summary: Context-specific downstream process (negative regulation of adipose tissue development) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:2000036 label: regulation of stem cell population maintenance evidence_type: NAS original_reference_id: PMID:29691401 qualifier: involved_in review: summary: Context-specific downstream process (regulation of stem cell population maintenance) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:2000036 label: regulation of stem cell population maintenance evidence_type: NAS original_reference_id: PMID:30442713 qualifier: involved_in review: summary: Context-specific downstream process (regulation of stem cell population maintenance) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0005654 label: nucleoplasm evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:10777491 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:11673459 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005737 label: cytoplasm evidence_type: EXP original_reference_id: PMID:10777491 qualifier: located_in review: summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV. action: ACCEPT reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005737 label: cytoplasm evidence_type: EXP original_reference_id: PMID:11673459 qualifier: located_in review: summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV. action: ACCEPT reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:25970626 qualifier: is_active_in review: summary: DDB1 is active in the nucleus, where CRL4/UV-DDB complexes act on chromatin substrates and DNA damage. action: ACCEPT reason: Nuclear activity is well documented; DDB1 accumulates at DNA-damage sites and acts on nuclear substrates. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0032991 label: protein-containing complex evidence_type: IDA original_reference_id: PMID:25970626 qualifier: part_of review: summary: Generic protein-containing complex membership; subsumed by the specific CRL4/UV-DDB complex annotations. action: KEEP_AS_NON_CORE reason: Correct but uninformative; the specific CUL4-RING/UV-DDB complex terms better capture DDB1's complex roles. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process evidence_type: IDA original_reference_id: PMID:25970626 qualifier: involved_in review: summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates. action: ACCEPT reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0160072 label: ubiquitin ligase complex scaffold activity evidence_type: IDA original_reference_id: PMID:25970626 qualifier: contributes_to review: summary: DDB1 provides the scaffold/adaptor activity that links CUL4 to DCAF substrate receptors in CRL4 complexes. action: ACCEPT reason: Captures DDB1's central molecular role as the CRL4 adaptor scaffold; consistent with structural studies and with deep-research synthesis that DDB1 is a non-catalytic adaptor whose receptor (DCAF) identity sets substrate specificity. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 - reference_id: file:human/DDB1/DDB1-deep-research-falcon.md supporting_text: "DDB1’s primary biochemical role is not catalytic; rather, it is an E3-ligase adaptor/scaffold that couples the CUL4A/B cullin scaffold to substrate receptors (commonly termed DCAFs, for “DDB1- and CUL4-associated factors”), enabling substrate selection for ubiquitination by CRL4 complexes" - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:32355176 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:34526721 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:30111536 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:30111536 qualifier: is_active_in review: summary: DDB1 is active in the nucleus, where CRL4/UV-DDB complexes act on chromatin substrates and DNA damage. action: ACCEPT reason: Nuclear activity is well documented; DDB1 accumulates at DNA-damage sites and acts on nuclear substrates. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005730 label: nucleolus evidence_type: IDA original_reference_id: PMID:11673459 qualifier: is_active_in review: summary: Nucleolar localization reported (IDA); a secondary compartment relative to DDB1's main nuclear/cytoplasmic pools. action: KEEP_AS_NON_CORE reason: Plausible secondary localization (e.g. SIRT7/nucleolar regulation context); not the core site of DDB1 action. - term: id: GO:0007056 label: spindle assembly involved in female meiosis evidence_type: IDA original_reference_id: PMID:31492966 qualifier: involved_in review: summary: Context-specific downstream process (spindle assembly involved in female meiosis) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process evidence_type: IDA original_reference_id: PMID:30111536 qualifier: involved_in review: summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates. action: ACCEPT reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process evidence_type: IDA original_reference_id: PMID:31492966 qualifier: involved_in review: summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates. action: ACCEPT reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0044725 label: epigenetic programming in the zygotic pronuclei evidence_type: IDA original_reference_id: PMID:30111536 qualifier: involved_in review: summary: Context-specific downstream process (epigenetic programming in zygotic pronuclei) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:31492966 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0160072 label: ubiquitin ligase complex scaffold activity evidence_type: IDA original_reference_id: PMID:30111536 qualifier: enables review: summary: DDB1 provides the scaffold/adaptor activity that links CUL4 to DCAF substrate receptors in CRL4 complexes. action: ACCEPT reason: Captures DDB1's central molecular role as the CRL4 adaptor scaffold; consistent with structural studies. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 - term: id: GO:0160072 label: ubiquitin ligase complex scaffold activity evidence_type: IDA original_reference_id: PMID:31492966 qualifier: enables review: summary: DDB1 provides the scaffold/adaptor activity that links CUL4 to DCAF substrate receptors in CRL4 complexes. action: ACCEPT reason: Captures DDB1's central molecular role as the CRL4 adaptor scaffold; consistent with structural studies. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 - term: id: GO:0045732 label: positive regulation of protein catabolic process evidence_type: IDA original_reference_id: PMID:14739464 qualifier: involved_in review: summary: DDB1 positively regulates catabolism of CRL4 substrates by assembling functional ligase complexes. action: ACCEPT reason: Core regulatory aspect of DDB1's adaptor role in promoting substrate degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0097602 label: cullin family protein binding evidence_type: IDA original_reference_id: PMID:10585395 qualifier: enables review: summary: DDB1 directly binds the cullin scaffold (CUL4A/CUL4B), the basis of its adaptor function. action: ACCEPT reason: Cullin binding is a specific, informative molecular interaction underlying CRL4 assembly. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:10585395 qualifier: is_active_in review: summary: DDB1 is active in the nucleus, where CRL4/UV-DDB complexes act on chromatin substrates and DNA damage. action: ACCEPT reason: Nuclear activity is well documented; DDB1 accumulates at DNA-damage sites and acts on nuclear substrates. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0003684 label: damaged DNA binding evidence_type: IDA original_reference_id: PMID:22334663 qualifier: contributes_to review: summary: Damaged-DNA binding is contributed by the UV-DDB complex (DDB2 is the direct DNA-contacting subunit); DDB1 contributes within the complex. action: KEEP_AS_NON_CORE reason: DDB1 contributes to UV-damaged DNA recognition as part of UV-DDB, but DDB2 is the primary lesion-binding subunit; retained as a contributory, non-core function. The contributes_to qualifier is appropriate here, since deep-research synthesis confirms DDB2 directly binds the lesion while DDB1 is the partner scaffold. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches - reference_id: file:human/DDB1/DDB1-deep-research-falcon.md supporting_text: "within this heterodimer, DDB2 is the principal DNA-damage-binding subunit, whereas DDB1 acts as the partner subunit that supports downstream steps, including coupling to ubiquitination machinery" - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14739464 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26906416 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:31686031 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0016567 label: protein ubiquitination evidence_type: IDA original_reference_id: PMID:28886238 qualifier: involved_in review: summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes. action: ACCEPT reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:28886238 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0006511 label: ubiquitin-dependent protein catabolic process evidence_type: IMP original_reference_id: PMID:26431207 qualifier: involved_in review: summary: DDB1 enables ubiquitin-dependent protein catabolism as the CRL4 adaptor. action: ACCEPT reason: Core process (parent of proteasome-mediated catabolism); CRL4/DCX complexes target substrates for degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0016567 label: protein ubiquitination evidence_type: IDA original_reference_id: PMID:26431207 qualifier: involved_in review: summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes. action: ACCEPT reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0045722 label: positive regulation of gluconeogenesis evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Context-specific downstream process (positive regulation of gluconeogenesis) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'DDB1- mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1- mediated gluconeogenesis in the liver' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28437394 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0006974 label: DNA damage response evidence_type: IMP original_reference_id: PMID:16949367 qualifier: involved_in review: summary: DDB1 acts in the DNA damage response through UV-DDB lesion recognition and CRL4-mediated damage signaling. action: ACCEPT reason: Core process; UV-DDB recognizes damage and CRL4(DDB2/DTL) couples damage to ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0016567 label: protein ubiquitination evidence_type: IMP original_reference_id: PMID:28437394 qualifier: involved_in review: summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes. action: ACCEPT reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0032991 label: protein-containing complex evidence_type: IMP original_reference_id: PMID:28437394 qualifier: part_of review: summary: Generic protein-containing complex membership; subsumed by the specific CRL4/UV-DDB complex annotations. action: KEEP_AS_NON_CORE reason: Correct but uninformative; the specific CUL4-RING/UV-DDB complex terms better capture DDB1's complex roles. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0045732 label: positive regulation of protein catabolic process evidence_type: IMP original_reference_id: PMID:16949367 qualifier: involved_in review: summary: DDB1 positively regulates catabolism of CRL4 substrates by assembling functional ligase complexes. action: ACCEPT reason: Core regulatory aspect of DDB1's adaptor role in promoting substrate degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16949367 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0071987 label: WD40-repeat domain binding evidence_type: IPI original_reference_id: PMID:16949367 qualifier: enables review: summary: DDB1 binds the WD40-repeat domains of DCAF substrate receptors via its beta-propeller surface. action: ACCEPT reason: WD40-repeat binding is the specific mechanism by which DDB1 recruits DCAF receptors; informative MF. supported_by: - reference_id: PMID:16949367 supporting_text: "the interaction of WD40-containing DCAFs with Ddb1 requires a \nconserved \"WDXR\" motif." - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IMP original_reference_id: PMID:16949367 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IPI original_reference_id: PMID:14739464 qualifier: enables review: summary: DDB1 acts as the molecular adaptor bridging CUL4 and substrate-receptor (DCAF) modules. action: ACCEPT reason: Adaptor activity is the defining DDB1 molecular function; better than bare protein binding. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:14739464 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process evidence_type: IMP original_reference_id: PMID:14739464 qualifier: involved_in review: summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates. action: ACCEPT reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0097602 label: cullin family protein binding evidence_type: IPI original_reference_id: PMID:14739464 qualifier: enables review: summary: DDB1 directly binds the cullin scaffold (CUL4A/CUL4B), the basis of its adaptor function. action: ACCEPT reason: Cullin binding is a specific, informative molecular interaction underlying CRL4 assembly. supported_by: - reference_id: PMID:14739464 supporting_text: "human DET1 (hDET1) promotes ubiquitination and \ndegradation of the proto-oncogenic transcription factor c-Jun by assembling a \nmultisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), \ncullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively \nphotomorphogenic-1." - term: id: GO:0010498 label: proteasomal protein catabolic process evidence_type: IMP original_reference_id: PMID:25970626 qualifier: acts_upstream_of_or_within review: summary: DDB1/CUL4B complex activity drives proteasomal catabolism of substrates (e.g. RGS2). action: ACCEPT reason: Core process supported by IMP; DDB1-containing CRL4 complexes promote substrate degradation. supported_by: - reference_id: PMID:25970626 supporting_text: "we identified a novel \nE3 ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1 \n(DDB1) and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation." - term: id: GO:0044877 label: protein-containing complex binding evidence_type: IPI original_reference_id: PMID:11564863 qualifier: enables review: summary: Binds the STAGA/protein complex; more informative than bare protein binding but ancillary. action: KEEP_AS_NON_CORE reason: Records association with a multiprotein complex; subsidiary to the core adaptor/complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0000781 label: chromosome, telomeric region evidence_type: HDA original_reference_id: PMID:19135898 qualifier: located_in review: summary: Telomeric chromatin localization from high-throughput locus-proteomics (HDA); peripheral to core function. action: KEEP_AS_NON_CORE reason: High-throughput chromatin-association data; a context-specific localization, not a core DDB1 compartment. - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:23137809 qualifier: located_in review: summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV. action: ACCEPT reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0019076 label: viral release from host cell evidence_type: IMP original_reference_id: PMID:23137809 qualifier: involved_in review: summary: 'Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1''s endogenous function.' action: KEEP_AS_NON_CORE reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role. - term: id: GO:0045070 label: positive regulation of viral genome replication evidence_type: IMP original_reference_id: PMID:23137809 qualifier: involved_in review: summary: 'Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1''s endogenous function.' action: KEEP_AS_NON_CORE reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role. - term: id: GO:0046726 label: positive regulation by virus of viral protein levels in host cell evidence_type: IMP original_reference_id: PMID:23137809 qualifier: involved_in review: summary: 'Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1''s endogenous function.' action: KEEP_AS_NON_CORE reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role. - term: id: GO:0051702 label: biological process involved in interaction with symbiont evidence_type: IDA original_reference_id: PMID:23137809 qualifier: involved_in review: summary: 'Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1''s endogenous function.' action: KEEP_AS_NON_CORE reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role. - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:21628527 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:22334663 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0070914 label: UV-damage excision repair evidence_type: IDA original_reference_id: PMID:22334663 qualifier: involved_in review: summary: DDB1/UV-DDB participates in UV-damage excision repair (global-genome NER of UV photoproducts). action: ACCEPT reason: Core process directly supported; UV-DDB recognizes CPD/6-4PP lesions to initiate repair. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches - term: id: GO:0005576 label: extracellular region evidence_type: HDA original_reference_id: PMID:22664934 qualifier: located_in review: summary: Extracellular/exosome localization from large-scale proteomics; DDB1 is a nuclear/cytoplasmic CRL4 adaptor. action: MARK_AS_OVER_ANNOTATED reason: High-throughput body-fluid/exosome proteomics detections do not reflect DDB1's functional nuclear/cytoplasmic localization. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: Extracellular/exosome localization from large-scale proteomics; DDB1 is a nuclear/cytoplasmic CRL4 adaptor. action: MARK_AS_OVER_ANNOTATED reason: High-throughput body-fluid/exosome proteomics detections do not reflect DDB1's functional nuclear/cytoplasmic localization. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:1901990 label: regulation of mitotic cell cycle phase transition evidence_type: IMP original_reference_id: PMID:17088560 qualifier: involved_in review: summary: Context-specific downstream process (regulation of mitotic cell cycle phase transition) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles. action: KEEP_AS_NON_CORE reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5652005 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5652009 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5689317 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5689861 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5690213 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5690988 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5690990 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5690991 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5690996 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5691000 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5691006 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5696655 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5696664 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5696670 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6781833 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6781867 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782004 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782069 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782131 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782138 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782141 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782204 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782208 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782211 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782224 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782227 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782234 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6782943 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6790454 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6790487 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8952638 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8952639 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8955245 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8955285 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8956045 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-9684118 qualifier: located_in review: summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity. action: KEEP_AS_NON_CORE reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:18381890 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17932509 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:12732143 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process evidence_type: IMP original_reference_id: PMID:20223979 qualifier: involved_in review: summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates. action: ACCEPT reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:18794347 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:20129063 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:20223979 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:18794347 qualifier: part_of review: summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership. action: ACCEPT reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16964240 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20223979 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:20223979 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:20223979 qualifier: located_in review: summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV. action: ACCEPT reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0006511 label: ubiquitin-dependent protein catabolic process evidence_type: IDA original_reference_id: PMID:11673459 qualifier: involved_in review: summary: DDB1 enables ubiquitin-dependent protein catabolism as the CRL4 adaptor. action: ACCEPT reason: Core process (parent of proteasome-mediated catabolism); CRL4/DCX complexes target substrates for degradation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:18593899 qualifier: located_in review: summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV. action: ACCEPT reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:18593899 qualifier: located_in review: summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV. action: ACCEPT reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 'Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)' - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12732143 qualifier: enables review: summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative. action: KEEP_AS_NON_CORE reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - term: id: GO:0006289 label: nucleotide-excision repair evidence_type: TAS original_reference_id: PMID:8407967 qualifier: involved_in review: summary: DDB1, as part of UV-DDB, functions in nucleotide excision repair of UV lesions. action: ACCEPT reason: Core biological process; UV-DDB recognizes UV photolesions and initiates global-genome NER. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - term: id: GO:0003677 label: DNA binding evidence_type: TAS original_reference_id: PMID:8798680 qualifier: enables review: summary: DNA binding attributed historically to the UV-damaged DNA-binding factor (DDB); the direct lesion-binding subunit is DDB2. action: KEEP_AS_NON_CORE reason: Reflects the historical UV-DDB damaged-DNA-binding activity; DDB1's contribution is as the complex scaffold rather than the direct DNA-contacting subunit. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches - term: id: GO:0003684 label: damaged DNA binding evidence_type: TAS original_reference_id: PMID:8407967 qualifier: enables review: summary: Damaged-DNA binding is contributed by the UV-DDB complex (DDB2 is the direct DNA-contacting subunit); DDB1 contributes within the complex. action: KEEP_AS_NON_CORE reason: DDB1 contributes to UV-damaged DNA recognition as part of UV-DDB, but DDB2 is the primary lesion-binding subunit; retained as a contributory, non-core function. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches - term: id: GO:0006281 label: DNA repair evidence_type: TAS original_reference_id: PMID:8798680 qualifier: involved_in review: summary: DDB1 functions in DNA repair via the UV-DDB complex (parent of nucleotide excision repair). action: ACCEPT reason: Correct core process; UV-DDB initiates NER. Redundant with the more specific NER terms. supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: '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' references: - id: file:human/DDB1/DDB1-deep-research-falcon.md title: Falcon deep research report for human DDB1 findings: - statement: DDB1 is best annotated as a non-catalytic adaptor/scaffold that couples the CUL4A/B cullin to interchangeable DCAF substrate receptors, so receptor identity (not DDB1 itself) sets substrate specificity. supporting_text: "DDB1’s primary biochemical role is not catalytic; rather, it is an E3-ligase adaptor/scaffold that couples the CUL4A/B cullin scaffold to substrate receptors (commonly termed DCAFs, for “DDB1- and CUL4-associated factors”), enabling substrate selection for ubiquitination by CRL4 complexes" - statement: Only a minority of candidate WD40 proteins are bona fide DDB1/CUL4 receptors under a given condition, so DDB1's functional output is highly DCAF- and stimulus-dependent. supporting_text: "only a subset appear to be robust DDB1/CUL4-associated receptors under particular conditions. A 2023 systematic analysis characterized 58 DCAFs and observed that DDB1/CUL4A/B were detected as interactors for 15/58 tested putative DCAFs, with 10 enriched for both DDB1 and CUL4A/B" - statement: Within UV-DDB, DDB2 is the direct DNA-damage-binding subunit while DDB1 is the partner scaffold that supports downstream NER and ubiquitination steps. supporting_text: "within this heterodimer, DDB2 is the principal DNA-damage-binding subunit, whereas DDB1 acts as the partner subunit that supports downstream steps, including coupling to ubiquitination machinery" - statement: UV-DDB has a noncanonical role stimulating base-excision-repair enzymes on oxidative lesions (OGG1, MUTYH, APE1, SMUG1). supporting_text: "UV-DDB was reported to stimulate several BER enzymes, including OGG1 (~3-fold), MUTYH (4–5-fold), and APE1 (8-fold), and specifically to stimulate SMUG1 excision activity by 4–5-fold" - statement: DDB1 is an actionable induced-proximity node for targeted protein degradation, with the Arg928 molecular-glue hotspot and a Cys173 covalent recruiter enabling DDB1-dependent degradation of BRD4 and the androgen receptor. supporting_text: "Covalent recruiter bound DDB1 at C173 and supported BRD4 and AR degradation that was proteasome-, NEDDylation-, and DDB1-dependent; DDB1 noted as essential, potentially limiting resistance" - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000114 title: Manual transfer of experimentally-verified manual GO annotation data to homologous complexes by curator judgment of sequence, composition and function similarity findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:10585395 title: Cullin 4A associates with the UV-damaged DNA-binding protein DDB. findings: [] - id: PMID:10777491 title: Nuclear transport of human DDB protein induced by ultraviolet light. findings: [] - id: PMID:11564863 title: Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo. findings: [] - id: PMID:11673459 title: UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract-only in cache; DDB1 (p125) associates with CUL4A and is itself a CUL4A ubiquitination substrate; primarily cytoplasmic with UV-induced nuclear translocation. Supports localization and CUL4 association. - id: PMID:12732143 title: The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. findings: [] - id: PMID:14739464 title: Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only in cache; shows DDB1 assembles a CUL4A-ROC1-DET1-COP1 ligase that ubiquitinates c-Jun. Source of adaptor activity, cullin binding and DCX complex annotations. - id: PMID:14751237 title: Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair. findings: [] - id: PMID:16227264 title: Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. findings: [] - id: PMID:16473935 title: The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: DDB1-CUL4A(DDB2) ubiquitinates histone H2A at UV-damaged sites and is XPE-deficient; supports the UV-DDB/NER histone-ubiquitination role. - id: PMID:16861906 title: L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. findings: [] - id: PMID:16949367 title: A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only in cache; defines DDB1 as the triple beta-propeller Cul4 adaptor and identifies the DCAF family bound via the WDxR motif. Source of WD40-repeat domain binding and DCAF/CUL4-complex annotations. - id: PMID:16964240 title: Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. findings: [] - id: PMID:17041588 title: CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. findings: [] - id: PMID:17088560 title: DNA nucleotide excision repair-dependent signaling to checkpoint activation. findings: [] - id: PMID:17314515 title: HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. findings: [] - id: PMID:17360488 title: HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1. findings: [] - id: PMID:17932509 title: Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells. findings: [] - id: PMID:18381890 title: WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. findings: [] - id: PMID:18593899 title: The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A. findings: [] - id: PMID:18794347 title: PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19109893 title: Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex; supports UV-DDB damaged-DNA recognition (DDB2 as the direct lesion-binding subunit). - id: PMID:19135898 title: Purification of proteins associated with specific genomic Loci. findings: [] - id: PMID:19264781 title: The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection. findings: [] - id: PMID:19651607 title: Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+ mice with natural ligands. findings: [] - id: PMID:19966799 title: A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery. findings: [] - id: PMID:20129063 title: CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. findings: [] - id: PMID:20223979 title: Identification of a primary target of thalidomide teratogenicity. findings: [] - id: PMID:20562859 title: Network organization of the human autophagy system. findings: [] - id: PMID:20855601 title: INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. findings: [] - id: PMID:21113133 title: RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells. findings: [] - id: PMID:21145461 title: Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. findings: [] - id: PMID:21628527 title: Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin-conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex. findings: [] - id: PMID:21988832 title: Toward an understanding of the protein interaction network of the human liver. findings: [] - id: PMID:22039351 title: 'Regulation of nucleotide excision repair by UV-DDB: prioritization of damage recognition to internucleosomal DNA.' findings: [] - id: PMID:22118460 title: The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only in cache; structural basis of CRL4(DDB2)/CSA showing DDB1-CUL4-RBX1 architecture with DCAF substrate receptors and DDB2-mediated NER. Source of complex-membership and NER annotations. - id: PMID:22157821 title: VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity. findings: [] - id: PMID:22334663 title: Monoubiquitinated histone H2A destabilizes photolesion-containing nucleosomes with concomitant release of UV-damaged DNA-binding protein E3 ligase. findings: [] - id: PMID:22664934 title: Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach. findings: [] - id: PMID:22810585 title: Viral immune modulators perturb the human molecular network by common and unique strategies. findings: [] - id: PMID:22822215 title: Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) dimerization and its roles in chromatinized DNA repair. findings: [] - id: PMID:23137809 title: DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication. findings: [] - id: PMID:23238014 title: CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis. findings: [] - id: PMID:23314863 title: SCFFbxw5 mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression. findings: [] - id: PMID:24292623 title: The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. findings: [] - id: PMID:24412650 title: Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing. findings: [] - id: PMID:24500646 title: Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons. findings: [] - id: PMID:25108355 title: Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. findings: [] - id: PMID:25499913 title: AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics. findings: [] - id: PMID:25970626 title: FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Full text available; identifies a CUL4B/DDB1/FBXO44 complex driving RGS2 proteasomal degradation. Supports proteasomal catabolism and scaffold annotations for an atypical (F-box) DCAF. - id: PMID:26131937 title: Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. findings: [] - id: PMID:26431207 title: CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activity by Promoting Ubiquitination-Dependent Degradation of the Mammalian CRY1. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: CUL4-DDB1-CDT2 promotes ubiquitin-dependent degradation of CRY1, linking DDB1 to circadian-clock regulation; supports a non-core circadian role. - id: PMID:26496610 title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances. findings: [] - id: PMID:26906416 title: Characterization of the mammalian family of DCN-type NEDD8 E3 ligases. findings: [] - id: PMID:26909574 title: Structural basis of lenalidomide-induced CK1α degradation by the CRL4(CRBN) ubiquitin ligase. findings: [] - id: PMID:27113764 title: The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase. findings: [] - id: PMID:28212551 title: NRIP/DCAF6 stabilizes the androgen receptor protein by displacing DDB2 from the CUL4A-DDB1 E3 ligase complex in prostate cancer. findings: [] - id: PMID:28437394 title: Selective degradation of splicing factor CAPERα by anticancer sulfonamides. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:28886238 title: SIRT7 deacetylates DDB1 and suppresses the activity of the CRL4 E3 ligase complexes. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract-only in cache; DDB1 acetylation promotes DDB1-CUL4 binding and is reversed by SIRT7, regulating CRL4 activity. Supports the adaptor role and a regulatory layer on DDB1-CUL4 assembly. - id: PMID:29691401 title: Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4(DCAF5) ubiquitin ligase. findings: [] - id: PMID:29907856 title: Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice. findings: [] - id: PMID:30018425 title: The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin. findings: [] - id: PMID:30111536 title: DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract-only in cache; CRL4-DCAF13 regulates SUV39H1 in early embryos. Supports a context-specific (epigenetic/embryonic) DCAF-defined CRL4 function, marked non-core. - id: PMID:30442713 title: Proteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4(DCAF5) ubiquitin ligase. findings: [] - id: PMID:30564455 title: Structural insights into DDA1 function as a core component of the CRL4-DDB1 ubiquitin ligase. findings: [] - id: PMID:30945288 title: Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer. findings: [] - id: PMID:31267705 title: Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient availability. findings: [] - id: PMID:31391242 title: DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy. findings: [] - id: PMID:31452512 title: Systematic identification of cancer cell vulnerabilities to natural killer cell-mediated immune surveillance. findings: [] - id: PMID:31492966 title: The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Full text available; CRL4-DCAF13 targets PTEN for degradation supporting oocyte meiotic resumption. Supports a context-specific DCAF-defined CRL4 function, marked non-core. - id: PMID:31586112 title: TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DCAF11 and promoting phosphorylation of p62. findings: [] - id: PMID:31686031 title: Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. findings: [] - id: PMID:31693891 title: Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15. findings: [] - id: PMID:32355176 title: The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: DDB1-CUL4(CSA/ERCC8) acts with CSB and UVSSA in transcription-coupled repair; supports the CRL4(ERCC8) TCR role. - id: PMID:33503431 title: DCAF14 promotes stalled fork stability to maintain genome integrity. findings: [] - id: PMID:33869224 title: 'Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View.' findings: [] - id: PMID:33898171 title: OTUD1 Activates Caspase-Independent and Caspase-Dependent Apoptosis by Promoting AIF Nuclear Translocation and MCL1 Degradation. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:34065512 title: CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation. findings: [] - id: PMID:34429321 title: Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor. findings: [] - id: PMID:34526721 title: Structural basis of human transcription-DNA repair coupling. findings: [] - id: PMID:34595758 title: The CRL4(DCAF1) cullin-RING ubiquitin ligase is activated following a switch in oligomerization state. findings: [] - id: PMID:34720086 title: Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine. findings: [] - id: PMID:34758320 title: Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] - id: PMID:8407967 title: Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E. findings: [] - id: PMID:8798680 title: Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype. findings: [] - id: PMID:9418871 title: DDB, a putative DNA repair protein, can function as a transcriptional partner of E2F1. findings: [] - id: Reactome:R-HSA-5652005 title: RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA findings: [] - id: Reactome:R-HSA-5652009 title: RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA findings: [] - id: Reactome:R-HSA-5689317 title: Formation of the pre-incision complex in GG-NER findings: [] - id: Reactome:R-HSA-5689861 title: Recruitment of XPA and release of CAK findings: [] - id: Reactome:R-HSA-5690213 title: DNA polymerases delta, epsilon or kappa bind the GG-NER site findings: [] - id: Reactome:R-HSA-5690988 title: 3'-incision of DNA by ERCC5 (XPG) in GG-NER findings: [] - id: Reactome:R-HSA-5690990 title: 5'- incision of DNA by ERCC1:ERCC4 in GG-NER findings: [] - id: Reactome:R-HSA-5690991 title: Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER findings: [] - id: Reactome:R-HSA-5690996 title: ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA findings: [] - id: Reactome:R-HSA-5691000 title: TFIIH binds GG-NER site to form a verification complex findings: [] - id: Reactome:R-HSA-5691006 title: XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site findings: [] - id: Reactome:R-HSA-5696655 title: PARP1 or PARP2 PARylates DDB2 and autoPARylates findings: [] - id: Reactome:R-HSA-5696664 title: PARP1 or PARP2 binds DDB2 at GG-NER site findings: [] - id: Reactome:R-HSA-5696670 title: CHD1L is recruited to GG-NER site findings: [] - id: Reactome:R-HSA-6781833 title: ERCC8 (CSA) binds stalled RNA Pol II findings: [] - id: Reactome:R-HSA-6781867 title: ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II findings: [] - id: Reactome:R-HSA-6782004 title: Assembly of the pre-incision complex in TC-NER findings: [] - id: Reactome:R-HSA-6782069 title: UVSSA:USP7 deubiquitinates ERCC6 findings: [] - id: Reactome:R-HSA-6782131 title: ERCC2-facilitated RNA Pol II backtracking in TC-NER findings: [] - id: Reactome:R-HSA-6782138 title: ERCC5 and RPA bind TC-NER site findings: [] - id: Reactome:R-HSA-6782141 title: Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER findings: [] - id: Reactome:R-HSA-6782204 title: 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER findings: [] - id: Reactome:R-HSA-6782208 title: Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER findings: [] - id: Reactome:R-HSA-6782211 title: DNA polymerases delta, epsilon or kappa bind the TC-NER site findings: [] - id: Reactome:R-HSA-6782224 title: 3' incision by ERCC5 (XPG) in TC-NER findings: [] - id: Reactome:R-HSA-6782227 title: Ligation of newly synthesized repair patch to incised DNA in TC-NER findings: [] - id: Reactome:R-HSA-6782234 title: Recovery of RNA synthesis after TC-NER findings: [] - id: Reactome:R-HSA-6782943 title: UV-DDB ubiquitinates XPC findings: [] - id: Reactome:R-HSA-6790454 title: SUMOylation of XPC findings: [] - id: Reactome:R-HSA-6790487 title: RNF111 ubiquitinates SUMOylated XPC findings: [] - id: Reactome:R-HSA-8952638 title: AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-8952639 title: NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-8955245 title: CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus findings: [] - id: Reactome:R-HSA-8955285 title: COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-8956045 title: COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-9684118 title: ERCC3-facilitated RNA Pol II backtracking in TC-NER findings: [] core_functions: - description: 'Adaptor/scaffold of CUL4-RING (CRL4) E3 ubiquitin ligases: DDB1 bridges the CUL4A/CUL4B-RBX1 catalytic scaffold to interchangeable DCAF substrate-receptor subunits, determining substrate specificity and enabling ubiquitination and proteasomal degradation of diverse targets.' molecular_function: id: GO:0160072 label: ubiquitin ligase complex scaffold activity locations: - id: GO:0005634 label: nucleus - id: GO:0005737 label: cytoplasm directly_involved_in: - id: GO:0043161 label: proteasome-mediated ubiquitin-dependent protein catabolic process supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 - reference_id: file:human/DDB1/DDB1-deep-research-falcon.md supporting_text: "DDB1’s primary biochemical role is not catalytic; rather, it is an E3-ligase adaptor/scaffold that couples the CUL4A/B cullin scaffold to substrate receptors (commonly termed DCAFs, for “DDB1- and CUL4-associated factors”), enabling substrate selection for ubiquitination by CRL4 complexes" - description: 'Substrate-receptor (DCAF) docking adaptor: DDB1 recruits DCAF/WD40-repeat receptor proteins onto the CUL4 ligase via its beta-propeller surface, acting as a protein-macromolecule adaptor.' molecular_function: id: GO:0030674 label: protein-macromolecule adaptor activity locations: - id: GO:0005634 label: nucleus directly_involved_in: - id: GO:0016567 label: protein ubiquitination supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: DDB1 may recruit specific substrate targeting subunits to the DCX complex - reference_id: PMID:16949367 supporting_text: "Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta \npropeller Ddb1 adaptor protein, but few substrate receptors have been \nidentified." - reference_id: file:human/DDB1/DDB1-deep-research-falcon.md supporting_text: "only a subset appear to be robust DDB1/CUL4-associated receptors under particular conditions. A 2023 systematic analysis characterized 58 DCAFs and observed that DDB1/CUL4A/B were detected as interactors for 15/58 tested putative DCAFs, with 10 enriched for both DDB1 and CUL4A/B" - description: 'UV-damaged DNA recognition for nucleotide excision repair: as the core subunit of the UV-DDB (DDB1-DDB2) complex, DDB1 helps recognize UV photolesions in chromatin and recruit NER factors to initiate global-genome repair.' molecular_function: id: GO:0030674 label: protein-macromolecule adaptor activity locations: - id: GO:0005634 label: nucleus directly_involved_in: - id: GO:0006289 label: nucleotide-excision repair - id: GO:0070914 label: UV-damage excision repair supported_by: - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: 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 - reference_id: file:human/DDB1/DDB1-uniprot.txt supporting_text: The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches proposed_new_terms: - proposed_name: positive regulation of base-excision repair glycosylase activity proposed_definition: Any process, here mediated by the UV-DDB (DDB1-DDB2) complex, that increases the catalytic activity or turnover of base-excision-repair DNA glycosylases/AP endonucleases (e.g. OGG1, MUTYH, APE1, SMUG1) on oxidative or other base lesions. Current GO has terms for base-excision repair and for damaged-DNA binding, but no specific term capturing a complex acting in trans to stimulate BER enzyme activity, which is the reported noncanonical UV-DDB role. - proposed_name: non-proteolytic protein polyubiquitination by CRL4 ligase proposed_definition: Assembly by a DDB1-CUL4 (CRL4) E3 ligase complex of a polyubiquitin signal on a substrate that does not target it for proteasomal degradation but instead modulates its activity, localization or interactions (e.g. the reported non-degradative polyubiquitination of the influenza A virus polymerase subunit PB2). Distinguishes the regulatory, non-degradative ubiquitin output of CRL4 from the canonical proteasome-targeting branch. suggested_questions: - question: Which DCAF-defined CRL4 complexes represent the physiologically dominant DDB1 functions across tissues, and how is DCAF exchange on the DDB1 propeller cluster regulated (e.g. by CAND1, neddylation, or DDB1 acetylation)? - question: How separable are DDB1's UV-DDB/NER role and its broader CRL4 adaptor role, given that NER-defective DDB1 phenotypes (e.g. the WHIKERS neurodevelopmental syndrome) may also reflect loss of DCAF-dependent substrate turnover? - question: Is the noncanonical stimulation of base-excision-repair enzymes (OGG1, MUTYH, APE1, SMUG1) by UV-DDB attributable to DDB1 itself or solely to the DDB2 subunit, and does it require an assembled CRL4 ligase or only the UV-DDB heterodimer? - question: Under which infections or stresses does DDB1-CUL4 switch from degradative to non-degradative (regulatory) ubiquitination of substrates such as influenza PB2, and which DCAFs (e.g. DCAF11, DCAF12L1) determine that switch? suggested_experiments: - description: Degron/auxin-inducible depletion of DDB1 followed by quantitative ubiquitinome and proteome profiling, with and without UV, to define the endogenous substrate repertoire attributable to each major DCAF and to separate NER from non-NER CRL4 functions. - description: Structure-guided point mutations in the DDB1 BPB propeller cleft that selectively block DCAF (WDxR-motif) docking while preserving CUL4 binding, to test which phenotypes depend on substrate-receptor recruitment versus UV-DDB lesion recognition. - description: Reconstitute purified UV-DDB (DDB1-DDB2) with and without DDB1, plus recombinant BER enzymes (OGG1, MUTYH, APE1, SMUG1), and use single-molecule and ensemble kinetics to determine whether DDB1 is required for the reported stimulation of BER enzyme activity and lesion handoff.