Falcon deep research report for human DDB1
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DDB1 is best annotated as a non-catalytic adaptor/scaffold that couples the CUL4A/B cullin to interchangeable DCAF substrate receptors, so receptor identity (not DDB1 itself) sets substrate specificity.
"DDB1’s primary biochemical role is not catalytic; rather, it is an E3-ligase adaptor/scaffold that couples the CUL4A/B cullin scaffold to substrate receptors (commonly termed DCAFs, for “DDB1- and CUL4-associated factors”), enabling substrate selection for ubiquitination by CRL4 complexes"
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Only a minority of candidate WD40 proteins are bona fide DDB1/CUL4 receptors under a given condition, so DDB1's functional output is highly DCAF- and stimulus-dependent.
"only a subset appear to be robust DDB1/CUL4-associated receptors under particular conditions. A 2023 systematic analysis characterized 58 DCAFs and observed that DDB1/CUL4A/B were detected as interactors for 15/58 tested putative DCAFs, with 10 enriched for both DDB1 and CUL4A/B"
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Within UV-DDB, DDB2 is the direct DNA-damage-binding subunit while DDB1 is the partner scaffold that supports downstream NER and ubiquitination steps.
"within this heterodimer, DDB2 is the principal DNA-damage-binding subunit, whereas DDB1 acts as the partner subunit that supports downstream steps, including coupling to ubiquitination machinery"
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UV-DDB has a noncanonical role stimulating base-excision-repair enzymes on oxidative lesions (OGG1, MUTYH, APE1, SMUG1).
"UV-DDB was reported to stimulate several BER enzymes, including OGG1 (~3-fold), MUTYH (4–5-fold), and APE1 (8-fold), and specifically to stimulate SMUG1 excision activity by 4–5-fold"
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DDB1 is an actionable induced-proximity node for targeted protein degradation, with the Arg928 molecular-glue hotspot and a Cys173 covalent recruiter enabling DDB1-dependent degradation of BRD4 and the androgen receptor.
"Covalent recruiter bound DDB1 at C173 and supported BRD4 and AR degradation that was proteasome-, NEDDylation-, and DDB1-dependent; DDB1 noted as essential, potentially limiting resistance"
Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Manual transfer of experimentally-verified manual GO annotation data to homologous complexes by curator judgment of sequence, composition and function similarity
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Cullin 4A associates with the UV-damaged DNA-binding protein DDB.
Nuclear transport of human DDB protein induced by ultraviolet light.
Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo.
UV-damaged DNA-binding proteins are targets of CUL-4A-mediated ubiquitination and degradation.
The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage.
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.
Human DDB2 splicing variants are dominant negative inhibitors of UV-damaged DNA repair.
Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1.
The DDB1-CUL4ADDB2 ubiquitin ligase is deficient in xeroderma pigmentosum group E and targets histone H2A at UV-damaged DNA sites.
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage.
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1.
Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery.
CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation.
DNA nucleotide excision repair-dependent signaling to checkpoint activation.
HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase.
HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1.
Proteomic and functional analysis of Argonaute-containing mRNA-protein complexes in human cells.
WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase.
The cullin 4B-based UV-damaged DNA-binding protein ligase binds to UV-damaged chromatin and ubiquitinates histone H2A.
PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex.
Large-scale proteomics and phosphoproteomics of urinary exosomes.
Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex.
Purification of proteins associated with specific genomic Loci.
The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection.
Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in ApcMin/+ mice with natural ligands.
A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.
CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis.
Identification of a primary target of thalidomide teratogenicity.
Network organization of the human autophagy system.
INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway.
RNAi-based screening identifies the Mms22L-Nfkbil2 complex as a novel regulator of DNA replication in human cells.
Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.
Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin-conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex.
Toward an understanding of the protein interaction network of the human liver.
Regulation of nucleotide excision repair by UV-DDB: prioritization of damage recognition to internucleosomal DNA.
The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture, targeting, and activation.
VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity.
Monoubiquitinated histone H2A destabilizes photolesion-containing nucleosomes with concomitant release of UV-damaged DNA-binding protein E3 ligase.
Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach.
Viral immune modulators perturb the human molecular network by common and unique strategies.
Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) dimerization and its roles in chromatinized DNA repair.
DDB1 is a cellular substrate of NS3/4A protease and required for hepatitis C virus replication.
CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis.
SCFFbxw5 mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression.
The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins.
Premature activation of the SLX4 complex by Vpr promotes G2/M arrest and escape from innate immune sensing.
Ubiquitin ligase defect by DCAF8 mutation causes HMSN2 with giant axons.
Structure of the human Cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs.
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics.
FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex.
Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS.
CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activity by Promoting Ubiquitination-Dependent Degradation of the Mammalian CRY1.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
Characterization of the mammalian family of DCN-type NEDD8 E3 ligases.
Structural basis of lenalidomide-induced CK1α degradation by the CRL4(CRBN) ubiquitin ligase.
The antiobesity factor WDTC1 suppresses adipogenesis via the CRL4WDTC1 E3 ligase.
NRIP/DCAF6 stabilizes the androgen receptor protein by displacing DDB2 from the CUL4A-DDB1 E3 ligase complex in prostate cancer.
Selective degradation of splicing factor CAPERα by anticancer sulfonamides.
Architecture of the human interactome defines protein communities and disease networks.
SIRT7 deacetylates DDB1 and suppresses the activity of the CRL4 E3 ligase complexes.
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4(DCAF5) ubiquitin ligase.
Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) gene causes spermatogenesis defects and male infertility in mice.
The replication initiation determinant protein (RepID) modulates replication by recruiting CUL4 to chromatin.
DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development.
Proteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4(DCAF5) ubiquitin ligase.
Structural insights into DDA1 function as a core component of the CRL4-DDB1 ubiquitin ligase.
Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.
Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient availability.
DCAF8, a novel MuRF1 interaction partner, promotes muscle atrophy.
Systematic identification of cancer cell vulnerabilities to natural killer cell-mediated immune surveillance.
The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation.
TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DCAF11 and promoting phosphorylation of p62.
Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15.
Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15.
The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II.
DCAF14 promotes stalled fork stability to maintain genome integrity.
Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View.
OTUD1 Activates Caspase-Independent and Caspase-Dependent Apoptosis by Promoting AIF Nuclear Translocation and MCL1 Degradation.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor.
Structural basis of human transcription-DNA repair coupling.
The CRL4(DCAF1) cullin-RING ubiquitin ligase is activated following a switch in oligomerization state.
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine.
Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquitination and degradation of CENP-A during the cell cycle.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Multimodal cell maps as a foundation for structural and functional genomics.
Characterization of a human DNA damage binding protein implicated in xeroderma pigmentosum E.
Mutations specific to the xeroderma pigmentosum group E Ddb- phenotype.
DDB, a putative DNA repair protein, can function as a transcriptional partner of E2F1.
RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA
RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA
Formation of the pre-incision complex in GG-NER
Recruitment of XPA and release of CAK
DNA polymerases delta, epsilon or kappa bind the GG-NER site
3'-incision of DNA by ERCC5 (XPG) in GG-NER
5'- incision of DNA by ERCC1:ERCC4 in GG-NER
Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER
ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA
TFIIH binds GG-NER site to form a verification complex
XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site
PARP1 or PARP2 PARylates DDB2 and autoPARylates
PARP1 or PARP2 binds DDB2 at GG-NER site
CHD1L is recruited to GG-NER site
ERCC8 (CSA) binds stalled RNA Pol II
ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II
Assembly of the pre-incision complex in TC-NER
UVSSA:USP7 deubiquitinates ERCC6
ERCC2-facilitated RNA Pol II backtracking in TC-NER
ERCC5 and RPA bind TC-NER site
Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER
5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER
Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER
DNA polymerases delta, epsilon or kappa bind the TC-NER site
3' incision by ERCC5 (XPG) in TC-NER
Ligation of newly synthesized repair patch to incised DNA in TC-NER
Recovery of RNA synthesis after TC-NER
RNF111 ubiquitinates SUMOylated XPC
AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex
NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex
CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus
COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex
COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex
ERCC3-facilitated RNA Pol II backtracking in TC-NER