DDB1

UniProt ID: Q16531
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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).

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.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0006281 DNA repair
IBA
GO_REF:0000033
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
GO:0035861 site of double-strand break
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
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.
Reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal 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
GO:0003676 nucleic acid binding
IEA
GO_REF:0000002
REMOVE
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
GO:0005634 nucleus
IEA
GO_REF:0000120
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV.
Reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
GO:0034644 cellular response to UV
IEA
GO_REF:0000117
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:0005515 protein binding
IPI
PMID:10777491
Nuclear transport of human DDB protein induced by ultraviole...
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:0005515 protein binding
IPI
PMID:16227264
Simian virus 5 V protein acts as an adaptor, linking DDB1 to...
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:0005515 protein binding
IPI
PMID:16473935
The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderm...
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:0005515 protein binding
IPI
PMID:17041588
CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repe...
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:0005515 protein binding
IPI
PMID:17314515
HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a...
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:0005515 protein binding
IPI
PMID:17360488
HIV-1 Vpr function is mediated by interaction with the damag...
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:0005515 protein binding
IPI
PMID:19109893
Structural basis of UV DNA-damage recognition by the DDB1-DD...
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:0005515 protein binding
IPI
PMID:19264781
The human immunodeficiency virus type 2 Vpx protein usurps t...
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:0005515 protein binding
IPI
PMID:19651607
Aryl hydrocarbon receptor suppresses intestinal carcinogenes...
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:0005515 protein binding
IPI
PMID:19966799
A promiscuous alpha-helical motif anchors viral hijackers an...
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:0005515 protein binding
IPI
PMID:20562859
Network organization of the human autophagy system.
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:0005515 protein binding
IPI
PMID:20855601
INO80 chromatin remodeling complex promotes the removal of 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
GO:0005515 protein binding
IPI
PMID:21113133
RNAi-based screening identifies the Mms22L-Nfkbil2 complex a...
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:0005515 protein binding
IPI
PMID:21145461
Dynamics of cullin-RING ubiquitin ligase network revealed by...
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:0005515 protein binding
IPI
PMID:21988832
Toward an understanding of the protein interaction network o...
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:0005515 protein binding
IPI
PMID:22039351
Regulation of nucleotide excision repair by UV-DDB: prioriti...
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:0005515 protein binding
IPI
PMID:22157821
VprBP binds full-length RAG1 and is required for B-cell deve...
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:0005515 protein binding
IPI
PMID:22810585
Viral immune modulators perturb the human molecular network ...
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:0005515 protein binding
IPI
PMID:22822215
Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) ...
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:0005515 protein binding
IPI
PMID:23238014
CRL4B catalyzes H2AK119 monoubiquitination and coordinates w...
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:0005515 protein binding
IPI
PMID:23314863
SCFFbxw5 mediates transient degradation of actin remodeller ...
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:0005515 protein binding
IPI
PMID:24292623
The myeloma drug lenalidomide promotes the cereblon-dependen...
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:0005515 protein binding
IPI
PMID:24412650
Premature activation of the SLX4 complex by Vpr promotes G2/...
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:0005515 protein binding
IPI
PMID:24500646
Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with ...
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:0005515 protein binding
IPI
PMID:26131937
Lenalidomide induces ubiquitination and degradation of CK1Ξ± ...
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:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
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:0005515 protein binding
IPI
PMID:26909574
Structural basis of lenalidomide-induced CK1Ξ± degradation by...
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:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun...
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:0005515 protein binding
IPI
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
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:0005515 protein binding
IPI
PMID:30564455
Structural insights into DDA1 function as a core component o...
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:0005515 protein binding
IPI
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
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:0005515 protein binding
IPI
PMID:31391242
DCAF8, a novel MuRF1 interaction partner, promotes muscle at...
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:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
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:0005515 protein binding
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
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
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:0005515 protein binding
IPI
PMID:9418871
DDB, a putative DNA repair protein, can function as a transc...
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
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
GO:0016567 protein ubiquitination
IEA
GO_REF:0000120
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
GO:0042752 regulation of circadian rhythm
IEA
GO_REF:0000107
KEEP AS NON CORE
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
GO:0045722 positive regulation of gluconeogenesis
IEA
GO_REF:0000107
KEEP AS NON CORE
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
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
IEA
GO_REF:0000120
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:0000109 nucleotide-excision repair complex
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
GO:0005634 nucleus
IDA
PMID:14751237
Human DDB2 splicing variants are dominant negative inhibitor...
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005634 nucleus
NAS
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0006289 nucleotide-excision repair
NAS
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: DDB1, as part of UV-DDB, functions in nucleotide excision repair of UV lesions.
Reason: Core biological process; UV-DDB recognizes UV photolesions and initiates global-genome NER.
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:0006974 DNA damage response
ISS
GO_REF:0000114
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
GO:0006974 DNA damage response
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
GO:0007283 spermatogenesis
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.
GO:0008283 cell population proliferation
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.
GO:0010506 regulation of autophagy
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.
GO:0031297 replication fork processing
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.
GO:0031297 replication fork processing
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.
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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.
GO:0034644 cellular response to UV
ISS
GO_REF:0000114
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:0034644 cellular response to UV
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.
GO:0042981 regulation of apoptotic process
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.
GO:0045995 regulation of embryonic development
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.
GO:0070914 UV-damage excision repair
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.
GO:1902412 regulation of mitotic cytokinesis
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.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005634 nucleus
EXP
PMID:10777491
Nuclear transport of human DDB protein induced by ultraviole...
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005634 nucleus
EXP
PMID:11673459
UV-damaged DNA-binding proteins are targets of CUL-4A-mediat...
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005737 cytoplasm
EXP
PMID:10777491
Nuclear transport of human DDB protein induced by ultraviole...
ACCEPT
Summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV.
Reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
GO:0005737 cytoplasm
EXP
PMID:11673459
UV-damaged DNA-binding proteins are targets of CUL-4A-mediat...
ACCEPT
Summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV.
Reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
GO:0005634 nucleus
IDA
PMID:25970626
FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends...
ACCEPT
Summary: DDB1 is active in the nucleus, where CRL4/UV-DDB complexes act on chromatin substrates and DNA damage.
Reason: Nuclear activity is well documented; DDB1 accumulates at DNA-damage sites and acts on nuclear substrates.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0032991 protein-containing complex
IDA
PMID:25970626
FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends...
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:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:25970626
FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends...
ACCEPT
Summary: DDB1, as the CRL4 adaptor, drives proteasome-mediated ubiquitin-dependent degradation of DCAF-recruited substrates.
Reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal 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
GO:0160072 ubiquitin ligase complex scaffold activity
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
DDB1’s primary biochemical role is not catalytic; rather, it is an E3-ligase adaptor/scaffold that couples the CUL4A/B cullin scaffold to substrate receptors (commonly termed DCAFs, for β€œDDB1- and CUL4-associated factors”), enabling substrate selection for ubiquitination by CRL4 complexes
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
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
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
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
GO:0005515 protein binding
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
GO:0005634 nucleus
IDA
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
ACCEPT
Summary: DDB1 is active in the nucleus, where CRL4/UV-DDB complexes act on chromatin substrates and DNA damage.
Reason: Nuclear activity is well documented; DDB1 accumulates at DNA-damage sites and acts on nuclear substrates.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005730 nucleolus
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.
Reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal 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
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.
Reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal 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
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.
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
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
GO:0160072 ubiquitin ligase complex scaffold activity
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
GO:0160072 ubiquitin ligase complex scaffold activity
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
GO:0097602 cullin family protein binding
IDA
PMID:10585395
Cullin 4A associates with the UV-damaged DNA-binding protein...
ACCEPT
Summary: DDB1 directly binds the cullin scaffold (CUL4A/CUL4B), the basis of its adaptor function.
Reason: Cullin binding is a specific, informative molecular interaction underlying CRL4 assembly.
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:0005634 nucleus
IDA
PMID:10585395
Cullin 4A associates with the UV-damaged DNA-binding protein...
ACCEPT
Summary: DDB1 is active in the nucleus, where CRL4/UV-DDB complexes act on chromatin substrates and DNA damage.
Reason: Nuclear activity is well documented; DDB1 accumulates at DNA-damage sites and acts on nuclear substrates.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0003684 damaged DNA binding
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
GO:0005515 protein binding
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
GO:0005515 protein binding
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
GO:0080008 Cul4-RING E3 ubiquitin ligase 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
GO:0016567 protein ubiquitination
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
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
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
GO:0016567 protein ubiquitination
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
GO:0045722 positive regulation of gluconeogenesis
ISS
GO_REF:0000024
KEEP AS NON CORE
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
GO:0005515 protein binding
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
GO:0006974 DNA damage response
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
GO:0016567 protein ubiquitination
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
GO:0032991 protein-containing complex
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
GO:0005515 protein binding
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
GO:0071987 WD40-repeat domain binding
IPI
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: DDB1 binds the WD40-repeat domains of DCAF substrate receptors via its beta-propeller surface.
Reason: WD40-repeat binding is the specific mechanism by which DDB1 recruits DCAF receptors; informative MF.
Supporting Evidence:
PMID:16949367
the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif.
GO:0080008 Cul4-RING E3 ubiquitin ligase 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
GO:0030674 protein-macromolecule adaptor activity
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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.
Reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal 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
GO:0097602 cullin family protein binding
IPI
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: DDB1 directly binds the cullin scaffold (CUL4A/CUL4B), the basis of its adaptor function.
Reason: Cullin binding is a specific, informative molecular interaction underlying CRL4 assembly.
Supporting Evidence:
PMID:14739464
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.
GO:0010498 proteasomal protein catabolic process
IMP
PMID:25970626
FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends...
ACCEPT
Summary: DDB1/CUL4B complex activity drives proteasomal catabolism of substrates (e.g. RGS2).
Reason: Core process supported by IMP; DDB1-containing CRL4 complexes promote substrate degradation.
Supporting Evidence:
PMID:25970626
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.
GO:0044877 protein-containing complex binding
IPI
PMID:11564863
Human STAGA complex is a chromatin-acetylating transcription...
KEEP AS NON CORE
Summary: Binds the STAGA/protein complex; more informative than bare protein binding but ancillary.
Reason: Records association with a multiprotein complex; subsidiary to the core adaptor/complex annotations.
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:0000781 chromosome, telomeric region
HDA
PMID:19135898
Purification of proteins associated with specific genomic Lo...
KEEP AS NON CORE
Summary: Telomeric chromatin localization from high-throughput locus-proteomics (HDA); peripheral to core function.
Reason: High-throughput chromatin-association data; a context-specific localization, not a core DDB1 compartment.
GO:0005737 cytoplasm
IDA
PMID:23137809
DDB1 is a cellular substrate of NS3/4A protease and required...
ACCEPT
Summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV.
Reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
GO:0019076 viral release from host cell
IMP
PMID:23137809
DDB1 is a cellular substrate of NS3/4A protease and required...
KEEP AS NON CORE
Summary: Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1's endogenous function.
Reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role.
GO:0045070 positive regulation of viral genome replication
IMP
PMID:23137809
DDB1 is a cellular substrate of NS3/4A protease and required...
KEEP AS NON CORE
Summary: Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1's endogenous function.
Reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role.
GO:0046726 positive regulation by virus of viral protein levels in host cell
IMP
PMID:23137809
DDB1 is a cellular substrate of NS3/4A protease and required...
KEEP AS NON CORE
Summary: Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1's endogenous function.
Reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role.
GO:0051702 biological process involved in interaction with symbiont
IDA
PMID:23137809
DDB1 is a cellular substrate of NS3/4A protease and required...
KEEP AS NON CORE
Summary: Viral-hijacking phenotype: pathogens redirect the DDB1-CUL4 ligase; ancillary to DDB1's endogenous function.
Reason: Reflects viral usurpation of the CRL4 adaptor (e.g. HCV NS3/4A context); a host-pathogen interaction outcome, not a core endogenous role.
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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:0070914 UV-damage excision repair
IDA
PMID:22334663
Monoubiquitinated histone H2A destabilizes photolesion-conta...
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:0005576 extracellular region
HDA
PMID:22664934
Comparison of tear protein levels in breast cancer patients ...
MARK AS OVER ANNOTATED
Summary: Extracellular/exosome localization from large-scale proteomics; DDB1 is a nuclear/cytoplasmic CRL4 adaptor.
Reason: High-throughput body-fluid/exosome proteomics detections do not reflect DDB1's functional nuclear/cytoplasmic localization.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
GO:0070062 extracellular exosome
HDA
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exos...
MARK AS OVER ANNOTATED
Summary: Extracellular/exosome localization from large-scale proteomics; DDB1 is a nuclear/cytoplasmic CRL4 adaptor.
Reason: High-throughput body-fluid/exosome proteomics detections do not reflect DDB1's functional nuclear/cytoplasmic localization.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
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.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5652005
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5652009
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5689317
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5689861
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690213
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690988
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690990
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690991
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690996
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5691000
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5691006
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5696655
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5696664
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5696670
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6781833
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6781867
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782004
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782069
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782131
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782138
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782141
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782204
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782208
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782211
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782224
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782227
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782234
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782943
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6790454
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6790487
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8952638
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8952639
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8955245
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8955285
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8956045
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9684118
KEEP AS NON CORE
Summary: Nucleoplasm localization (Reactome/IDA), a sub-compartment consistent with nuclear CRL4/NER activity.
Reason: Correct nuclear sub-localization; subsumed by the nucleus annotations and Reactome NER/CRL4 pathway context.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
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
GO:0005515 protein binding
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase 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.
Reason: Core biological process; numerous DCX(DDB1-CUL4-X) complexes ubiquitinate substrates for proteasomal 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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
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
GO:0005515 protein binding
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
GO:0005515 protein binding
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:0005634 nucleus
IDA
PMID:20223979
Identification of a primary target of thalidomide teratogeni...
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005737 cytoplasm
IDA
PMID:20223979
Identification of a primary target of thalidomide teratogeni...
ACCEPT
Summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV.
Reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
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
GO:0005634 nucleus
IDA
PMID:18593899
The cullin 4B-based UV-damaged DNA-binding protein ligase bi...
ACCEPT
Summary: Nuclear localization, consistent with DDB1's UV-DDB/CRL4 functions on chromatin; DDB1 accumulates in nuclei after UV.
Reason: Well-supported localization; DDB1 translocates to and acts in the nucleus at DNA-damage sites.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Translocates to the nucleus following UV irradiation and subsequently accumulates at sites of DNA damage (PubMed:10777491, PubMed:11673459)
GO:0005737 cytoplasm
IDA
PMID:18593899
The cullin 4B-based UV-damaged DNA-binding protein ligase bi...
ACCEPT
Summary: Cytoplasmic localization; DDB1 is primarily cytoplasmic at steady state and translocates to the nucleus after UV.
Reason: Directly supported; DDB1 is primarily cytoplasmic and relocates to nuclei following UV irradiation.
Supporting Evidence:
file:human/DDB1/DDB1-uniprot.txt
Primarily cytoplasmic (PubMed:10777491, PubMed:11673459)
GO:0005515 protein binding
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
GO:0006289 nucleotide-excision repair
TAS
PMID:8407967
Characterization of a human DNA damage binding protein impli...
ACCEPT
Summary: DDB1, as part of UV-DDB, functions in nucleotide excision repair of UV lesions.
Reason: Core biological process; UV-DDB recognizes UV photolesions and initiates global-genome NER.
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:0003677 DNA binding
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
GO:0003684 damaged DNA binding
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
GO:0006281 DNA repair
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.

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
  • 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
    DDB1’s primary biochemical role is not catalytic; rather, it is an E3-ligase adaptor/scaffold that couples the CUL4A/B cullin scaffold to substrate receptors (commonly termed DCAFs, for β€œDDB1- and CUL4-associated factors”), 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.

Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • file:human/DDB1/DDB1-uniprot.txt
    DDB1 may recruit specific substrate targeting subunits to the DCX complex
  • PMID:16949367
    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.

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
  • 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

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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)

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πŸ“š Additional Documentation

Pn Notes

(DDB1-pn-notes.md)

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