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).
Proposed New Ontology Terms
positive regulation of base-excision repair glycosylase activity
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.
non-proteolytic protein polyubiquitination by CRL4 ligase
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.
Summary: DDB1 functions in DNA repair via the UV-DDB complex (parent of nucleotide excision repair).
Reason: Correct core process; UV-DDB initiates NER. Redundant with the more specific NER terms.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
Summary: IBA 'site of double-strand break' localization; DDB1's documented genome-stability role is via UV-photolesion (NER) recognition, not DSB sites.
Reason: Phylogenetically inferred; DDB1's direct DNA-damage activity is global-genome NER through UV-DDB, so DSB-site localization over-reaches.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates.
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
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.
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.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
Summary: DDB1/UV-DDB mediates the cellular response to UV-induced DNA damage.
Reason: Core UV-response process; UV-DDB recognizes UV photolesions and recruits NER machinery.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:10777491
Nuclear transport of human DDB protein induced by ultraviole...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:16227264
Simian virus 5 V protein acts as an adaptor, linking DDB1 to...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:16473935
The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderm...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:17041588
CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repe...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:17314515
HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:17360488
HIV-1 Vpr function is mediated by interaction with the damag...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:19109893
Structural basis of UV DNA-damage recognition by the DDB1-DD...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:19264781
The human immunodeficiency virus type 2 Vpx protein usurps t...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:19966799
A promiscuous alpha-helical motif anchors viral hijackers an...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:20562859
Network organization of the human autophagy system.
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:20855601
INO80 chromatin remodeling complex promotes the removal of U...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:21113133
RNAi-based screening identifies the Mms22L-Nfkbil2 complex a...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:21145461
Dynamics of cullin-RING ubiquitin ligase network revealed by...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:21988832
Toward an understanding of the protein interaction network o...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:22039351
Regulation of nucleotide excision repair by UV-DDB: prioriti...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:22157821
VprBP binds full-length RAG1 and is required for B-cell deve...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:22810585
Viral immune modulators perturb the human molecular network ...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:22822215
Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) ...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:23238014
CRL4B catalyzes H2AK119 monoubiquitination and coordinates w...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:23314863
SCFFbxw5 mediates transient degradation of actin remodeller ...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:24292623
The myeloma drug lenalidomide promotes the cereblon-dependen...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:24412650
Premature activation of the SLX4 complex by Vpr promotes G2/...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:24500646
Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with ...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:26131937
Lenalidomide induces ubiquitination and degradation of CK1Ξ± ...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:26909574
Structural basis of lenalidomide-induced CK1Ξ± degradation by...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:28514442
Architecture of the human interactome defines protein commun...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:30564455
Structural insights into DDA1 function as a core component o...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:9418871
DDB, a putative DNA repair protein, can function as a transc...
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Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
GO:0006511
ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000120
ACCEPT
Summary: DDB1 enables ubiquitin-dependent protein catabolism as the CRL4 adaptor.
Reason: Core process (parent of proteasome-mediated catabolism); CRL4/DCX complexes target substrates for degradation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
Summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes.
Reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The DDB1-CUL4A-DTL
E3 ligase complex regulates the circadian clock function by mediating
the ubiquitination and degradation of CRY1
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1-
mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-
mediated gluconeogenesis in the liver
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1 is part of the UV-DDB (DDB1-DDB2) nucleotide excision repair recognition complex.
Reason: Core component of the UV-DDB complex that recognizes UV-induced DNA damage and recruits NER factors.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
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
Summary: DDB1 acts in the DNA damage response through UV-DDB lesion recognition and CRL4-mediated damage signaling.
Reason: Core process; UV-DDB recognizes damage and CRL4(DDB2/DTL) couples damage to ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
EXP
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1 acts in the DNA damage response through UV-DDB lesion recognition and CRL4-mediated damage signaling.
Reason: Core process; UV-DDB recognizes damage and CRL4(DDB2/DTL) couples damage to ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:29907856
Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) ge...
KEEP AS NON CORE
Summary: Context-specific downstream process (spermatogenesis) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
KEEP AS NON CORE
Summary: Context-specific downstream process (cell population proliferation) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:31267705
Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase ...
KEEP AS NON CORE
Summary: Context-specific downstream process (regulation of autophagy) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:0030174
regulation of DNA-templated DNA replication initiation
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:30018425
The replication initiation determinant protein (RepID) modul...
KEEP AS NON CORE
Summary: Context-specific downstream process (replication fork processing) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:33503431
DCAF14 promotes stalled fork stability to maintain genome in...
KEEP AS NON CORE
Summary: Context-specific downstream process (replication fork processing) mediated by a particular DCAF-defined CRL4 complex; ancillary to DDB1's core adaptor/NER roles.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
EXP
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:25108355
Structure of the human Cereblon-DDB1-lenalidomide complex re...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:27113764
The antiobesity factor WDTC1 suppresses adipogenesis via the...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:28212551
NRIP/DCAF6 stabilizes the androgen receptor protein by displ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:31693891
Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:34595758
The CRL4(DCAF1) cullin-RING ubiquitin ligase is activated fo...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:25108355
Structure of the human Cereblon-DDB1-lenalidomide complex re...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:27113764
The antiobesity factor WDTC1 suppresses adipogenesis via the...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:31452512
Systematic identification of cancer cell vulnerabilities to ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:33898171
OTUD1 Activates Caspase-Independent and Caspase-Dependent Ap...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
NAS
PMID:34595758
The CRL4(DCAF1) cullin-RING ubiquitin ligase is activated fo...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0032814
regulation of natural killer cell activation
NAS
PMID:31452512
Systematic identification of cancer cell vulnerabilities to ...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
Summary: DDB1/UV-DDB mediates the cellular response to UV-induced DNA damage.
Reason: Core UV-response process; UV-DDB recognizes UV photolesions and recruits NER machinery.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
EXP
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1/UV-DDB mediates the cellular response to UV-induced DNA damage.
Reason: Core UV-response process; UV-DDB recognizes UV photolesions and recruits NER machinery.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0040029
epigenetic regulation of gene expression
NAS
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:0040029
epigenetic regulation of gene expression
NAS
PMID:34429321
Systematic Profiling of DNMT3A Variants Reveals Protein Inst...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:0040029
epigenetic regulation of gene expression
NAS
PMID:34720086
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate d...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:0042127
regulation of cell population proliferation
NAS
PMID:33869224
Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:33898171
OTUD1 Activates Caspase-Independent and Caspase-Dependent Ap...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:0060964
regulation of miRNA-mediated gene silencing
NAS
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
IDA
PMID:14751237
Human DDB2 splicing variants are dominant negative inhibitor...
ACCEPT
Summary: DDB1/UV-DDB participates in UV-damage excision repair (global-genome NER of UV photoproducts).
Reason: Core process directly supported; UV-DDB recognizes CPD/6-4PP lesions to initiate repair.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches
GO:0080135
regulation of cellular response to stress
NAS
PMID:31586112
TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DC...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:1901987
regulation of cell cycle phase transition
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:1901987
regulation of cell cycle phase transition
NAS
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates ...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
NAS
PMID:34758320
Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquit...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:1904178
negative regulation of adipose tissue development
NAS
PMID:27113764
The antiobesity factor WDTC1 suppresses adipogenesis via the...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:2000036
regulation of stem cell population maintenance
NAS
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:2000036
regulation of stem cell population maintenance
NAS
PMID:30442713
Proteolysis of methylated SOX2 protein is regulated by L3MBT...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
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
IDA
PMID:25970626
FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends...
ACCEPT
Summary: DDB1 provides the scaffold/adaptor activity that links CUL4 to DCAF substrate receptors in CRL4 complexes.
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.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1
file:human/DDB1/DDB1-deep-research-falcon.md
DDB1βs 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 βDDB1- and CUL4-associated factorsβ), enabling substrate selection for ubiquitination by CRL4 complexes
IDA
PMID:32355176
The cooperative action of CSB, CSA, and UVSSA target TFIIH t...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:34526721
Structural basis of human transcription-DNA repair coupling.
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IDA
PMID:11673459
UV-damaged DNA-binding proteins are targets of CUL-4A-mediat...
KEEP AS NON CORE
Summary: Nucleolar localization reported (IDA); a secondary compartment relative to DDB1's main nuclear/cytoplasmic pools.
Reason: Plausible secondary localization (e.g. SIRT7/nucleolar regulation context); not the core site of DDB1 action.
GO:0007056
spindle assembly involved in female meiosis
IDA
PMID:31492966
The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic ...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
ACCEPT
Summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates.
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
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:31492966
The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic ...
ACCEPT
Summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates.
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
GO:0044725
epigenetic programming in the zygotic pronuclei
IDA
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
IDA
PMID:31492966
The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
ACCEPT
Summary: DDB1 provides the scaffold/adaptor activity that links CUL4 to DCAF substrate receptors in CRL4 complexes.
Reason: Captures DDB1's central molecular role as the CRL4 adaptor scaffold; consistent with structural studies.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1
IDA
PMID:31492966
The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic ...
ACCEPT
Summary: DDB1 provides the scaffold/adaptor activity that links CUL4 to DCAF substrate receptors in CRL4 complexes.
Reason: Captures DDB1's central molecular role as the CRL4 adaptor scaffold; consistent with structural studies.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1
GO:0045732
positive regulation of protein catabolic process
IDA
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: DDB1 positively regulates catabolism of CRL4 substrates by assembling functional ligase complexes.
Reason: Core regulatory aspect of DDB1's adaptor role in promoting substrate degradation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:22334663
Monoubiquitinated histone H2A destabilizes photolesion-conta...
KEEP AS NON CORE
Summary: Damaged-DNA binding is contributed by the UV-DDB complex (DDB2 is the direct DNA-contacting subunit); DDB1 contributes within the complex.
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.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches
file:human/DDB1/DDB1-deep-research-falcon.md
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
IPI
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:26906416
Characterization of the mammalian family of DCN-type NEDD8 E...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IDA
PMID:31686031
Structural complementarity facilitates E7820-mediated degrad...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:28886238
SIRT7 deacetylates DDB1 and suppresses the activity of the C...
ACCEPT
Summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes.
Reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:28886238
SIRT7 deacetylates DDB1 and suppresses the activity of the C...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0006511
ubiquitin-dependent protein catabolic process
IMP
PMID:26431207
CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activ...
ACCEPT
Summary: DDB1 enables ubiquitin-dependent protein catabolism as the CRL4 adaptor.
Reason: Core process (parent of proteasome-mediated catabolism); CRL4/DCX complexes target substrates for degradation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:26431207
CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activ...
ACCEPT
Summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes.
Reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1-
mediated CRY1 degradation promotes FOXO1 protein stability and FOXO1-
mediated gluconeogenesis in the liver
IPI
PMID:28437394
Selective degradation of splicing factor CAPERΞ± by anticance...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IMP
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: DDB1 acts in the DNA damage response through UV-DDB lesion recognition and CRL4-mediated damage signaling.
Reason: Core process; UV-DDB recognizes damage and CRL4(DDB2/DTL) couples damage to ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IMP
PMID:28437394
Selective degradation of splicing factor CAPERΞ± by anticance...
ACCEPT
Summary: DDB1 is required for protein ubiquitination by CRL4/DCX E3 ligase complexes.
Reason: Core process; DDB1 adaptor function is essential for CRL4-mediated substrate ubiquitination.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IMP
PMID:28437394
Selective degradation of splicing factor CAPERΞ± by anticance...
KEEP AS NON CORE
Summary: Generic protein-containing complex membership; subsumed by the specific CRL4/UV-DDB complex annotations.
Reason: Correct but uninformative; the specific CUL4-RING/UV-DDB complex terms better capture DDB1's complex roles.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0045732
positive regulation of protein catabolic process
IMP
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: DDB1 positively regulates catabolism of CRL4 substrates by assembling functional ligase complexes.
Reason: Core regulatory aspect of DDB1's adaptor role in promoting substrate degradation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IMP
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: DDB1 acts as the molecular adaptor bridging CUL4 and substrate-receptor (DCAF) modules.
Reason: Adaptor activity is the defining DDB1 molecular function; better than bare protein binding.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1
IDA
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
IMP
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates.
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
human DET1 (hDET1) promotes ubiquitination and
degradation of the proto-oncogenic transcription factor c-Jun by assembling a
multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1),
cullin 4A (CUL4A), Regulator of Cullins-1 (ROC1), and constitutively
photomorphogenic-1.
we identified a novel
E3 ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1
(DDB1) and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation.
IDA
PMID:21628527
Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:22334663
Monoubiquitinated histone H2A destabilizes photolesion-conta...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:1901990
regulation of mitotic cell cycle phase transition
IMP
PMID:17088560
DNA nucleotide excision repair-dependent signaling to checkp...
KEEP AS NON CORE
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.
Reason: DDB1 contributes via substrate-specific CRL4 complexes, but this is a pleiotropic downstream outcome rather than DDB1's core molecular function.
IDA
PMID:18381890
WD40 protein FBW5 promotes ubiquitination of tumor suppresso...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:17932509
Proteomic and functional analysis of Argonaute-containing mR...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IDA
PMID:12732143
The ubiquitin ligase activity in the DDB2 and CSA complexes ...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
GO:0043161
proteasome-mediated ubiquitin-dependent protein catabolic process
IMP
PMID:20223979
Identification of a primary target of thalidomide teratogeni...
ACCEPT
Summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates.
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
IDA
PMID:18794347
PCNA-dependent regulation of p21 ubiquitylation and degradat...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:20129063
CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to pro...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:20223979
Identification of a primary target of thalidomide teratogeni...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IDA
PMID:18794347
PCNA-dependent regulation of p21 ubiquitylation and degradat...
ACCEPT
Summary: DDB1 is a core (adaptor) subunit of CUL4A/CUL4B-RING E3 ubiquitin ligase (CRL4/DCX) complexes; correct core localization/complex membership.
Reason: DDB1 forms the adaptor of CRL4 complexes (DDB1-CUL4A/B-RBX1) that dock DCAF substrate receptors; well supported structurally and biochemically.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:16964240
Molecular architecture and assembly of the DDB1-CUL4A ubiqui...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
IPI
PMID:20223979
Identification of a primary target of thalidomide teratogeni...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
GO:0006511
ubiquitin-dependent protein catabolic process
IDA
PMID:11673459
UV-damaged DNA-binding proteins are targets of CUL-4A-mediat...
ACCEPT
Summary: DDB1 enables ubiquitin-dependent protein catabolism as the CRL4 adaptor.
Reason: Core process (parent of proteasome-mediated catabolism); CRL4/DCX complexes target substrates for degradation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
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
IPI
PMID:12732143
The ubiquitin ligase activity in the DDB2 and CSA complexes ...
KEEP AS NON CORE
Summary: Bare protein binding from interaction studies (DCAFs, cullins, viral hijackers, substrates); real but uninformative.
Reason: Per curation guidelines bare protein binding is uninformative; DDB1's specific interactions are captured by the adaptor/scaffold, cullin-binding and complex annotations.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
DDB1 may recruit specific substrate targeting subunits to the DCX complex
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
TAS
PMID:8798680
Mutations specific to the xeroderma pigmentosum group E Ddb-...
KEEP AS NON CORE
Summary: DNA binding attributed historically to the UV-damaged DNA-binding factor (DDB); the direct lesion-binding subunit is DDB2.
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.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches
TAS
PMID:8407967
Characterization of a human DNA damage binding protein impli...
KEEP AS NON CORE
Summary: Damaged-DNA binding is contributed by the UV-DDB complex (DDB2 is the direct DNA-contacting subunit); DDB1 contributes within the complex.
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.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches
TAS
PMID:8798680
Mutations specific to the xeroderma pigmentosum group E Ddb-...
ACCEPT
Summary: DDB1 functions in DNA repair via the UV-DDB complex (parent of nucleotide excision repair).
Reason: Correct core process; UV-DDB initiates NER. Redundant with the more specific NER terms.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Protein, which is both involved in DNA repair and protein
ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box)
complexes, respectively
Core Functions
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.
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
file:human/DDB1/DDB1-uniprot.txt
The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1
file:human/DDB1/DDB1-deep-research-falcon.md
DDB1βs 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 βDDB1- and CUL4-associated factorsβ), enabling substrate selection for ubiquitination by CRL4 complexes
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.
Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta
propeller Ddb1 adaptor protein, but few substrate receptors have been
identified.
file:human/DDB1/DDB1-deep-research-falcon.md
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
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.
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
file:human/DDB1/DDB1-uniprot.txt
The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches
References
file:human/DDB1/DDB1-deep-research-falcon.md
Falcon deep research report for human DDB1
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.
"DDB1βs 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 βDDB1- and CUL4-associated factorsβ), enabling substrate selection for ubiquitination by CRL4 complexes"
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.
"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"
Within UV-DDB, DDB2 is the direct DNA-damage-binding subunit while DDB1 is the partner scaffold that supports downstream NER and ubiquitination steps.
"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"
UV-DDB has a noncanonical role stimulating base-excision-repair enzymes on oxidative lesions (OGG1, MUTYH, APE1, SMUG1).
"UV-DDB was reported to stimulate several BER enzymes, including OGG1 (~3-fold), MUTYH (4β5-fold), and APE1 (8-fold), and specifically to stimulate SMUG1 excision activity by 4β5-fold"
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.
"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"
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Manual transfer of experimentally-verified manual GO annotation data to homologous complexes by curator judgment of sequence, composition and function similarity
The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection.
Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.
ERCC3-facilitated RNA Pol II backtracking in TC-NER
Suggested Questions for Experts
Q: 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)?
Q: 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?
Q: 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?
Q: 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
Experiment: 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.
Experiment: 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.
Experiment: 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.
Deep Research
Falcon
(DDB1-deep-research-falcon.md)
Research Report: Human **DDB1** (UniProt **Q16531**) β Functional Annotation, Pathways, and Translational RelevanceFalconEdison Scientific Literature18 citations2 artifacts2026-06-13T07:10:24.526464
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Research Report: Human DDB1 (UniProt Q16531) β Functional Annotation, Pathways, and Translational Relevance
0) Target verification (gene/protein identity)
The literature analyzed here consistently refers to human DNA damage-binding protein 1 (DDB1) as a triple Ξ²-propeller WD40-like adaptor that serves as (i) the non-DNA-binding subunit of the UV-DDB damage-recognition factor and (ii) the core adaptor of CUL4A/BβRING E3 ubiquitin ligases (CRL4), matching the provided UniProt entry (Q16531) in name, organism, family, and domain architecture (raisch2023pulsesilacandinteractomics pages 1-3, liu2023structureofthe pages 1-2).
1) Key concepts and definitions (current understanding)
1.1 DDB1 as an adaptor in CRL4 ubiquitin ligases
DDB1βs 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 βDDB1- and CUL4-associated factorsβ), enabling substrate selection for ubiquitination by CRL4 complexes (raisch2023pulsesilacandinteractomics pages 1-3, liu2023structureofthe pages 1-2).
Mechanistically, DDB1 is described as containing three WD40-like Ξ²-propeller domains (BPA/BPB/BPC). In a CRL4 context, BPB contacts the N-terminus of CUL4A/B, while DDB1 also provides an H-box interaction surface used to bind WD40 substrate receptors (DCAFs), thereby organizing a modular ubiquitin ligase in which receptor identity largely determines substrate specificity (raisch2023pulsesilacandinteractomics pages 1-3).
1.2 UV-DDB (DDB1βDDB2) and global-genome NER
UV-DDB is a lesion-recognition factor in global-genome nucleotide excision repair (GG-NER) composed of DDB1 and DDB2; 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 (raja2023understandingtherole pages 1-6, raisch2023pulsesilacandinteractomics pages 16-17).
1.3 DCAFs and the βCRL4βDDB1βDCAFβ modular paradigm
A key concept for functional annotation is that a substantial number of WD40 proteins can be candidate DCAFs, but 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 (raisch2023pulsesilacandinteractomics pages 8-11). In the same study, only 14/58 (23%) DCAFs were enriched in DDB1/CUL4 assays (raisch2023pulsesilacandinteractomics pages 14-15). This emphasizes that DDB1βs functional output is highly dependent on which DCAF/receptor is engaged, and often on stimulus context (e.g., UV damage for DDB2) (raisch2023pulsesilacandinteractomics pages 8-11).
2) Molecular function, structure, and localization
2.1 Structural basis for receptor binding and scaffold function
A high-resolution recent example of DDB1βs scaffold role is provided by Liu et al., Nature Communications (published Nov 2023; https://doi.org/10.1038/s41467-023-43174-6), which solved a cryo-EM structure at 3.08 Γ of DDB1 bound to the substrate receptor AMBRA1 (liu2023structureofthe pages 1-2). The structure shows how DDB1βs double-propeller architecture engages AMBRA1 features to form a platform for substrate recruitment and ubiquitination, and functional assays show that DDB1-binding-defective AMBRA1 mutants disrupt Cyclin D1 ubiquitination and promote cell-cycle progression (liu2023structureofthe pages 1-2).
2.2 Subcellular localization (evidence and limitations)
In the retrieved full-text evidence, direct, explicit localization statements for DDB1 (e.g., nuclear vs cytosolic partitioning) were limited. However, the 2023 proteomics work notes functional specialization and distinct localization tendencies of the CUL4 paralogs (CUL4B nuclear; CUL4A cytoplasmic), implying DDB1-containing CRL4 assemblies can act in different cellular compartments depending on scaffold usage (raisch2023pulsesilacandinteractomics pages 1-3). Where more granular DDB1 localization is needed, additional sources (e.g., OpenCell resource articles) would be appropriate; the Raisch et al. study explicitly points to endogenous tagging/localization resources as useful for mapping subcellular associations (raisch2023pulsesilacandinteractomics pages 16-17).
3) Biological processes and pathways involving DDB1
3.1 DNA damage recognition and repair: GG-NER and ubiquitination-linked steps
DDB1 participates in DNA damage response through its presence in UV-DDB and CRL4 complexes. The proteomics synthesis and cited literature indicate UV-induced ubiquitination steps in GG-NER can involve UV-DDBβubiquitin ligase activity, including UV-induced ubiquitylation of XPC mediated by UV-DDB-associated ligase machinery (raisch2023pulsesilacandinteractomics pages 16-17, raisch2023pulsesilacandinteractomics pages 17-17). In this framework, DDB1βs mechanistic role is to help assemble the relevant CRL4 complex and engage the appropriate receptor/adaptors that connect lesion recognition to ubiquitylation-mediated remodeling of repair factors (raisch2023pulsesilacandinteractomics pages 16-17).
3.2 Noncanonical DNA repair roles: UV-DDB promotes base excision repair enzyme activity
A 2023 mechanistic synthesis on UV-DDB in oxidative DNA repair reports noncanonical roles for UV-DDB (DDB1βDDB2) in base excision repair (BER). UV-DDB was reported to stimulate several BER enzymes, including OGG1 (~3-fold), MUTYH (4β5-fold), and APE1 (8-fold), and specifically to stimulate SMUG1 excision activity by 4β5-fold. Single-molecule analysis indicated UV-DDB can reduce SMUG1 residence time on DNA, decreasing SMUG1 half-life on DNA by >8-fold (raja2023understandingtherole pages 1-6). Although this evidence centers on UV-DDB as a complex, it places DDB1 within a broader conceptual role in DNA repair beyond canonical UV-lesion GG-NER (raja2023understandingtherole pages 1-6).
3.3 Chromatin/replication-related roles: cohesion and genome stability
DDB1-containing CRL4 complexes are implicated in genomic stability through chromatin-associated mechanisms. The 2023 DDB1/CUL4 interactomics synthesis highlights CRL4βDDB1 involvement in chromatin-linked processes including replication-coupled sister chromatid cohesion, via regulation of the cohesin acetyltransferase pathway (e.g., Esco2-linked regulation is cited in the evidence synthesis) (raisch2023pulsesilacandinteractomics pages 16-17, raisch2023pulsesilacandinteractomics pages 17-17).
3.4 Hostβpathogen interfaces: influenza A virus rewiring of CRL4/DDB1 interactomes
A recent Mol Cell Proteomics study (published Nov 2024; https://doi.org/10.1016/j.mcpro.2024.100856) reported that during influenza A virus (IAV) infection, the CRL4 interactome is rewired, with functional consequences tied to viral replication. In their model, DDB1 together with DCAF11 and DCAF12L1 mediates non-degradative poly-ubiquitination of the viral polymerase subunit PB2, and these components were required for optimal in vitro infection. The study reports IAV-induced disruption of CRL4 interactions including a global loss of DDB1 and DCAF11 interactions and increased DCAF12L1 associations (dugied2024profilingcullin4e3ligases pages 1-3).
4) Recent developments (2023β2024 emphasis) and emerging research themes
4.1 Systems-level mapping of DDB1βCUL4 receptor usage and substrates (2023)
A central 2023 advance for functional annotation is the integration of BioID, AP-MS, and pulse-SILAC to profile DDB1/CUL4-associated receptor usage and candidate substrates. This work (published Oct 2023; https://doi.org/10.1016/j.mcpro.2023.100644) both supports canonical roles (DNA repair) and expands cell-biology contexts via network mapping. It provides quantitative constraints on receptor engagement (e.g., 14/58 enriched DCAFs) and suggests that DDB1βs functional diversification is largely encoded through conditional recruitment of distinct DCAFs and subcomplexes (raisch2023pulsesilacandinteractomics pages 14-15, raisch2023pulsesilacandinteractomics pages 8-11).
4.2 Structural biology of non-canonical DDB1 receptors in cell-cycle regulation (2023)
The 3.08 Γ cryo-EM structure of DDB1 bound to AMBRA1 provides a contemporary structural framework for understanding how intrinsically disordered or dynamic receptor proteins can stabilize upon DDB1 engagement to assemble active CRL4 ligases. HDX-MS showed extensive AMBRA1 stabilization upon DDB1 interaction (203 peptides; 98.8% coverage), offering detailed, experimentally supported structureβfunction annotation for this DDB1 receptor axis (liu2023structureofthe pages 1-2).
4.3 Molecular glues and targeted protein degradation: DDB1 as an induced-proximity node (2024)
A high-impact 2024 review in Cell Chemical Biology (published Jun 2024; https://doi.org/10.1016/j.chembiol.2024.04.002) summarizes extensive medicinal chemistry and structural work on small molecules that promote target recruitment to ubiquitin ligases. For DDB1-linked degradation, it highlights cyclin K degraders that form ternary complexes with CDK12βcyclin K and DDB1/CRL4 and identifies Arg928 of DDB1 as a validated hotspot residue enabling Ο-cation (and related) interactions used by βmolecular glueβ chemotypes (konstantinidou2024moleculargluesfor pages 10-11). The summarized dataset is quantitatively substantial: >90 compounds screened by TR-FRET for ternary complex formation, 40 with <100 nM biochemical affinity, and 28 ternary complex crystal structures solved; biochemical ternary affinity correlated with cellular degradation (konstantinidou2024moleculargluesfor pages 10-11).
5) Current applications and real-world implementations
A 2024 dissertation/monograph on chemoproteomic platforms reports a DDB1-directed induced-proximity strategy: cysteine chemoproteomics identified a covalent DDB1 recruiter (EN223) binding DDB1 at Cys173, which was elaborated into heterobifunctional degraders that induced degradation of BRD4 (preferentially the short isoform) and the androgen receptor (AR) in prostate cancer cells. Mechanistically, degradation was shown to be proteasome-, NEDDylation-, and DDB1-dependent, consistent with functional recruitment of the CUL4AβDDB1 axis (meyers2024leveragingchemoproteomicplatforms pages 71-75). This provides a direct bridge from DDB1 functional annotation (core adaptor of CRL4) to therapeutic modality development (targeted protein degradation) (meyers2024leveragingchemoproteomicplatforms pages 71-75, meyers2024leveragingchemoproteomicplatforms pages 1-6).
5.2 Molecular glueβstyle engagement of DDB1: cyclin K degradation and drug discovery strategy
The 2024 molecular-glue review frames DDB1 as an actionable interface for induced proximity, with explicit expert analysis that Arg928 is a βhotspot residueβ and that successful glues typically combine (i) a kinase hinge-binding motif and (ii) an aromatic βgluingβ moiety that extends to engage DDB1. The extent of the interface contribution (~20% of the PPI interface) and the strong structureβactivity and structureβfunction linkages (28 structures) underpin a rational design approach for DDB1-involving degraders (konstantinidou2024moleculargluesfor pages 10-11).
The IAV CRL4 interactome rewiring data suggest DDB1-centered complexes may be leveraged as host-directed antiviral intervention points, since DDB1 and specific DCAFs were mechanistically required for aspects of infection and virus-linked ubiquitination patterns (dugied2024profilingcullin4e3ligases pages 1-3). While not yet a therapeutic, this constitutes a real-world application direction in infection biology (dugied2024profilingcullin4e3ligases pages 1-3).
6) Statistics and quantitative highlights (recent evidence)
CRLsβ proteostasis contribution: Cullin-RING ligases are described as accounting for approximately ~20% of proteasomal protein degradation (raisch2023pulsesilacandinteractomics pages 1-3).
DCAF landscape and selectivity: In a targeted evaluation of 58 DCAFs, DDB1/CUL4A/B interactors were found for 15/58, with 10 enriched for both DDB1 and CUL4A/B (raisch2023pulsesilacandinteractomics pages 8-11). In a related analysis, only 14/58 (23%) DCAFs were enriched in DDB1/CUL4 assays (raisch2023pulsesilacandinteractomics pages 14-15).
Noncanonical BER stimulation by UV-DDB: UV-DDB stimulated BER enzyme activities with fold-changes of ~3Γ (OGG1), 4β5Γ (MUTYH), 8Γ (APE1), 4β5Γ (SMUG1), and reduced SMUG1 DNA residence time with >8Γ decrease in half-life (raja2023understandingtherole pages 1-6).
DDB1-directed PROTAC recruiter: Covalent recruiter binds DDB1 at Cys173, enabling DDB1-dependent degradation of BRD4 and AR (meyers2024leveragingchemoproteomicplatforms pages 71-75).
7) Visual evidence (structure and complex organization)
The following figure panels from Liu et al. (Nature Communications, Nov 2023) illustrate DDB1βs adaptor architecture and its receptor-binding role in CRL4 assemblies: schematic architecture of the CRL4βDDB1βRBX1βAMBRA1 complex and cryo-EM structural views of the DDB1βAMBRA1 interface (liu2023structureofthe media 06cbf119, liu2023structureofthe media 0d66b2f6, liu2023structureofthe media 6096d8f9).
8) Summary of core functional annotation
DDB1 (Q16531) is best annotated as an essential, multi-domain adaptor/scaffold that (i) supports UV-damage recognition/NER via the UV-DDB complex and (ii) acts as the central adaptor of CRL4 E3 ubiquitin ligases, recruiting diverse DCAF substrate receptors to drive ubiquitin-mediated remodeling or degradation of target proteins. Recent structural biology (cryo-EM 3.08 Γ DDB1βAMBRA1) and systems proteomics (DDB1βCUL4βDCAF interactome/degradome) support a model in which DDB1βs pleiotropic phenotypes arise from context-specific assembly of distinct CRL4 receptor modules. Translationally, DDB1 is increasingly viewed as an induced-proximity node for targeted protein degradation, both via DDB1-surface hotspots (Arg928) exploited by molecular glues and via direct covalent recruitment (Cys173) enabling DDB1-dependent degradation of clinically relevant proteins such as BRD4 and AR (raisch2023pulsesilacandinteractomics pages 1-3, liu2023structureofthe pages 1-2, meyers2024leveragingchemoproteomicplatforms pages 71-75, konstantinidou2024moleculargluesfor pages 10-11).
Evidence map (complexes, functions, and quantitative highlights)
Complex/Axis
DDB1 role
Key partner(s)
Biological process
Type of evidence (structure/proteomics/review)
Quantitative/statistical highlight
Key citation IDs
UV-DDB / GG-NER
Non-DNA-binding subunit of UV-DDB; scaffolds damage-recognition machinery with DDB2 and links lesion sensing to ubiquitylation steps
DDB2, XPC, CUL4
Recognition of UV-induced DNA lesions and initiation of global-genome nucleotide excision repair
Review/proteomics-supported functional synthesis
DDB2-associated DCAF interaction can be stimulus-specific under UV damage; myc-BirA*-DDB2 cells showed 12 proteins decreased at 16 h in pulse-SILAC workflow (raisch2023pulsesilacandinteractomics pages 8-11)
Central adaptor linking CUL4A/B scaffold to WD40 substrate receptors (DCAFs) through H-box recognition; organizes CRL4 E3 ligase architecture
CUL4A, CUL4B, ROC1/RBX1, DCAFs
Ubiquitin-dependent proteostasis across DNA repair, replication, cell cycle, tumorigenesis
Structure + proteomics
CRLs account for ~20% of proteasomal protein degradation; 58 DCAFs characterized, 15/58 showed DDB1/CUL4 interactions, and 10 were enriched for both DDB1 and CUL4A/B (raisch2023pulsesilacandinteractomics pages 1-3, raisch2023pulsesilacandinteractomics pages 8-11)
CRL4-DDB1 complex component supporting chromatin-associated regulation beyond DNA damage recognition
Esco2, DDA1, CUL4
Replication-coupled sister chromatid cohesion and genome stability
Proteomics/literature synthesis
Reported as a genomic-stability pathway linked to DDB1-CUL4 complexes; no direct effect size given in provided context (raisch2023pulsesilacandinteractomics pages 16-17, raisch2023pulsesilacandinteractomics pages 17-17)
Noncanonical oxidative DNA repair support via UV-DDB
Within UV-DDB, supports DDB2-centered stimulation of BER enzymes at oxidative lesions
DDB2, SMUG1, OGG1, MUTYH, APE1
Base excision repair of oxidative damage / lesion handoff
Primary mechanistic study summarized in provided context
UV-DDB stimulated OGG1 ~3-fold, MUTYH 4β5-fold, APE1 8-fold, and SMUG1 4β5-fold; reduced SMUG1 DNA residence time by >8-fold (raja2023understandingtherole pages 1-6)
(raja2023understandingtherole pages 1-6)
Influenza A virusβrewired CRL4 axis
Core adaptor in host CRL4 complexes rewired during infection; supports non-degradative ubiquitination of viral factor PB2
DCAF11, DCAF12L1, PB2
Hostβvirus interaction and antiviral/ proviral ubiquitin signaling
Proteomics
IAV caused a global loss of DDB1 and DCAF11 interactions while increasing DCAF12L1 associations; DDB1/DCAF11/DCAF12L1 required for optimal in vitro infection (dugied2024profilingcullin4e3ligases pages 1-3)
(dugied2024profilingcullin4e3ligases pages 1-3)
Induced proximity / DDB1-directed degraders
Direct small-molecule engagement point for induced-proximity chemistry; can serve as recruiter in DDB1-dependent degradation
Targeted protein degradation / chemical biology applications
Chemoproteomics + cellular degradation
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 (meyers2024leveragingchemoproteomicplatforms pages 71-75, meyers2024leveragingchemoproteomicplatforms pages 1-6)
DDB1 provides a gluable surface in ternary complexes that drive cyclin K degradation
CDK12, cyclin K, CRL4
Molecular-glue-induced targeted degradation
Review of structural/biochemical studies
>90 compounds screened; 40 had <100 nM biochemical affinity; 28 ternary crystal structures solved; DDB1 Arg928 identified as hotspot residue and degraders contributed ~20% of the PPI interface (konstantinidou2024moleculargluesfor pages 10-11)
(konstantinidou2024moleculargluesfor pages 10-11)
Table: This table summarizes the main experimentally supported DDB1 complexes, adaptor roles, and biological functions relevant to human DDB1/Q16531. It emphasizes recent structural, proteomic, and induced-proximity findings, including quantitative highlights useful for functional annotation.
(liu2023structureofthe pages 1-2): Ming Liu, Yang Wang, Fei Teng, Xinyi Mai, Xi Wang, Ming-Yuan Su, and Goran Stjepanovic. Structure of the ddb1-ambra1 e3 ligase receptor complex linked to cell cycle regulation. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43174-6, doi:10.1038/s41467-023-43174-6. This article has 21 citations and is from a highest quality peer-reviewed journal.
(raja2023understandingtherole pages 1-6): SJ Raja. Understanding the role of uv-ddb in the smug1-mediated repair of oxidative dna damage. Unknown journal, 2023.
(dugied2024profilingcullin4e3ligases pages 1-3): Guillaume Dugied, Thibaut Douche, Melanie dos Santos, Quentin Giai Gianetto.Q, Camille Cassonnet, Françoise Vuillier, Patricia Cassonnet, Yves Jacob, Sylvie van der Werf, Anastassia Komarova, Mariette Matondo, Marwah Karim, and Caroline Demeret. Profiling cullin4-e3 ligases interactomes and their rewiring in influenza a virus infection. Nov 2024. URL: https://doi.org/10.1016/j.mcpro.2024.100856, doi:10.1016/j.mcpro.2024.100856. This article has 3 citations and is from a domain leading peer-reviewed journal.
(konstantinidou2024moleculargluesfor pages 10-11): Markella Konstantinidou and Michelle R. Arkin. Molecular glues for protein-protein interactions: progressing toward a new dream. Jun 2024. URL: https://doi.org/10.1016/j.chembiol.2024.04.002, doi:10.1016/j.chembiol.2024.04.002. This article has 159 citations and is from a domain leading peer-reviewed journal.
(meyers2024leveragingchemoproteomicplatforms pages 71-75): ML Meyers. Leveraging chemo-proteomic platforms to expand the scope of induced proximity based. Unknown journal, 2024.
(meyers2024leveragingchemoproteomicplatforms pages 1-6): ML Meyers. Leveraging chemo-proteomic platforms to expand the scope of induced proximity based. Unknown journal, 2024.
(liu2023structureofthe media 06cbf119): Ming Liu, Yang Wang, Fei Teng, Xinyi Mai, Xi Wang, Ming-Yuan Su, and Goran Stjepanovic. Structure of the ddb1-ambra1 e3 ligase receptor complex linked to cell cycle regulation. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43174-6, doi:10.1038/s41467-023-43174-6. This article has 21 citations and is from a highest quality peer-reviewed journal.
(liu2023structureofthe media 0d66b2f6): Ming Liu, Yang Wang, Fei Teng, Xinyi Mai, Xi Wang, Ming-Yuan Su, and Goran Stjepanovic. Structure of the ddb1-ambra1 e3 ligase receptor complex linked to cell cycle regulation. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43174-6, doi:10.1038/s41467-023-43174-6. This article has 21 citations and is from a highest quality peer-reviewed journal.
(liu2023structureofthe media 6096d8f9): Ming Liu, Yang Wang, Fei Teng, Xinyi Mai, Xi Wang, Ming-Yuan Su, and Goran Stjepanovic. Structure of the ddb1-ambra1 e3 ligase receptor complex linked to cell cycle regulation. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43174-6, doi:10.1038/s41467-023-43174-6. This article has 21 citations and is from a highest quality peer-reviewed journal.
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).
Consistency: Mostly consistent on biology (central CRL4 adaptor/scaffold; UV-DDB NER; AMBRA1/BECN1 K63 ubiquitination role appears in the description), but a mapping-category contradiction: the review correctly classifies DDB1 as a SCAFFOLD and uses GO:0160072 (ubiquitin ligase complex scaffold activity) + GO:0030674 as its core MF, whereas the PN "Cullin adaptor" node maps it to GO:1990756 (substrate-adaptor activity). Those are different MF categories.
PN story / NEW pressure: PN projects GO:1990756 as "more_specific_than_existing_goa," but DDB1's GOA ALREADY contains the correct GO:0160072 (scaffold, IDA) and GO:0030674 (both verified real via OLS); the review ACCEPTs GO:0160072 as core. GO:1990756 (defn: brings ligase together with its SUBSTRATE; F-box/BTB proteins) is biologically wrong for DDB1 β DDB1 bridges CUL4 to DCAF receptors (scaffold), it is not the substrate receptor. Verdict: over-reaches / already captured by the better GO:0160072.
Evidence alignment: Partial. PN UPS refs 19337321 / 19276361 (DCAF-discovery papers) are not individually in the review reference list, though the review cites the cognate DCAF/CUL4-DDB1 framework (PMID:16949367 and many complex-membership PMIDs). PN ALP ref (AMBRA1 review, tandfonline) is not in the review references; the AMBRA1-CRL4-BECN1 story is in the description but not anchored to that PMID.
Verdict: Biology consistent but PN MF mapping mis-categorized. Recommended edits: [MAP] retarget DDB1 "Cullin adaptor" node from GO:1990756 to GO:0160072 (scaffold), matching the review's accepted MF and existing GOA.
PN placement: two rows β (1) ALP|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct|Modulator of class 3 PI3K complex 1 activity|Modulator of BECN1 ubiquitination (all context_only, too_broad: GO:0035032 / GO:0016236); (2) UPS|E3 ubiquitin and UBL ligases|Cullin adaptor|DDB1 ; PN-node mapping (UPS): group "Cullin adaptor"=mapped, ok_for_propagation, GO:1990756 (substrate-adaptor MF); projected goa_status=more_specific_than_existing_goa.
Consistency: Mostly consistent on biology (central CRL4 adaptor/scaffold; UV-DDB NER; AMBRA1/BECN1 K63 ubiquitination role appears in the description), but a mapping-category contradiction: the review correctly classifies DDB1 as a SCAFFOLD and uses GO:0160072 (ubiquitin ligase complex scaffold activity) + GO:0030674 as its core MF, whereas the PN "Cullin adaptor" node maps it to GO:1990756 (substrate-adaptor activity). Those are different MF categories.
PN story / NEW pressure: PN projects GO:1990756 as "more_specific_than_existing_goa," but DDB1's GOA ALREADY contains the correct GO:0160072 (scaffold, IDA) and GO:0030674 (both verified real via OLS); the review ACCEPTs GO:0160072 as core. GO:1990756 (defn: brings ligase together with its SUBSTRATE; F-box/BTB proteins) is biologically wrong for DDB1 β DDB1 bridges CUL4 to DCAF receptors (scaffold), it is not the substrate receptor. Verdict: over-reaches / already captured by the better GO:0160072.
Mapping strategy: This gene SHOULD change the node. DDB1 is the scaffold that the DCAF receptors dock onto; GO:1990756 is the receptor MF. Recommend the "Cullin adaptor"/DDB1 node target GO:0160072, not GO:1990756 (parallels the DDA1 "receptor scaffold" node which correctly uses GO:0160072).
Evidence alignment: Partial. PN UPS refs 19337321 / 19276361 (DCAF-discovery papers) are not individually in the review reference list, though the review cites the cognate DCAF/CUL4-DDB1 framework (PMID:16949367 and many complex-membership PMIDs). PN ALP ref (AMBRA1 review, tandfonline) is not in the review references; the AMBRA1-CRL4-BECN1 story is in the description but not anchored to that PMID.
Verdict: Biology consistent but PN MF mapping mis-categorized. Recommended edits: [MAP] retarget DDB1 "Cullin adaptor" node from GO:1990756 to GO:0160072 (scaffold), matching the review's accepted MF and existing GOA.
PN Dossier Context
review_batch: proteostasis-batch-2026-06-13
review_yaml: genes/human/DDB1/DDB1-ai-review.yaml
PN workbook rows: 2
PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Class 3 PI3K complex 1, direct | Modulator of class 3 PI3K complex 1 activity | Modulator of BECN1 ubiquitination
UniProt: Q16531
In branches: ALP, UPS
Notes: CUL4A/B-DDB1-AMBRA1 complex mediates K63 ubiquitination of BECN1, increasing activity of VPS34
PN references (titles):
Full article: Connecting autophagy: AMBRA1 and its network of regulation (tandfonline.com)
PN-node mapping records (path + ancestors):
[subtype] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct|Modulator of class 3 PI3K complex 1 activity|Modulator of BECN1 ubiquitination
status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
[type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct|Modulator of class 3 PI3K complex 1 activity
status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
[group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct
status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
[class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
[branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
PN row 2: Ubiquitin Proteasome System | E3 ubiquitin and UBL ligases | Cullin adaptor | DDB1
UniProt: Q16531
In branches: ALP, UPS
Signature domains: (none)
Auxiliary domains: IPR015943
PN references (titles):
19337321
19276361
PN-node mapping records (path + ancestors):
[type] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cullin adaptor|DDB1
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower substrate-receptor, adaptor, domain, or family subdivision already covered by the curated parent adaptor/receptor mapping. No additional direct GO mapping is needed at this node.
[group] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|Cullin adaptor
status=mapped scope=ok_for_propagation_to_go GO=[GO:1990756 ubiquitin-like ligase-substrate adaptor activity]
rationale: This PN group captures substrate receptors/adaptors for cullin/UBL ligase systems. The shared GO molecular-function target is ubiquitin-like ligase-substrate adaptor activity.
[class] Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases
status=context_only scope=too_broad_to_propagate GO=[GO:0061630 ubiquitin protein ligase activity]
rationale: This class is a genuine E3-ligase context, but its descendants include catalytic ligases, cullin scaffolds, substrate receptors, adaptors, cofactors, regulators, and UBL modifier systems. A class-level propagation would over-annotate.
[branch] Ubiquitin Proteasome System
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
π View Raw YAML
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: "DDB1βs 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 βDDB1- and CUL4-associated factorsβ), 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: "DDB1βs 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 βDDB1- and CUL4-associated factorsβ), 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 (4β5-fold), and APE1 (8-fold), and specifically to stimulate SMUG1 excision activity by 4β5-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 CK1Ξ± 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 CK1Ξ± 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 CAPERΞ± 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: "DDB1βs 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 βDDB1- and CUL4-associated factorsβ), 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.
