{"gene":"DCAF13","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":2018,"finding":"CRL4-DCAF13 acts as an E3 ubiquitin ligase complex that targets SUV39H1 for polyubiquitination and proteasomal degradation, thereby facilitating H3K9me3 removal and enabling zygotic gene expression during preimplantation embryonic development. Dcaf13 knockout mice arrest at the 8-16 cell stage with elevated H3K9me3.","method":"Dcaf13 knockout mice, ubiquitination assays, co-immunoprecipitation, western blotting, immunofluorescence for H3K9me3","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, in vivo knockout with defined molecular phenotype (H3K9me3 elevation), ubiquitination assay, replicated in both murine and human embryo contexts","pmids":["30111536"],"is_preprint":false},{"year":2018,"finding":"DCAF13 is a nucleolar protein that functions as a component of the rRNA-processing complex essential for 18S rRNA processing in growing oocytes. DCAF13 interacts with the box C/D ribonucleoprotein component fibrillarin. Conditional knockout of Dcaf13 causes pre-rRNA accumulation, ribosome assembly disorder, reduced global protein synthesis, and arrest of oocyte NSN-to-SN chromatin configuration transition.","method":"Conditional knockout mice, co-immunoprecipitation (DCAF13-fibrillarin interaction), northern blotting for pre-rRNA, ribosome assembly analysis, protein synthesis assays","journal":"Cell death and differentiation","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined molecular phenotype, reciprocal Co-IP with fibrillarin, rRNA processing and ribosome assembly assays, multiple orthogonal methods","pmids":["30283081"],"is_preprint":false},{"year":2017,"finding":"CRL4B-DCAF13 E3 ligase complex (comprising CUL4B, DDB1, and DCAF13) targets PTEN for ubiquitination and proteasomal degradation in osteosarcoma cells. Disruption of this complex causes PTEN accumulation.","method":"Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, siRNA knockdown, DCAF13 overexpression","journal":"Molecular therapy. Nucleic acids","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP establishing ternary complex, in vitro and in vivo ubiquitination assays, single lab with multiple orthogonal methods","pmids":["29499938"],"is_preprint":false},{"year":2019,"finding":"CRL4-DCAF13 targets PTEN for polyubiquitination and proteasomal degradation in oocytes, thereby maintaining PI3K signaling pathway activity required for meiotic resumption. Dcaf13 knockout oocytes show decreased CDK1 activity, chromosome condensation defects, spindle assembly checkpoint activation, and arrest at prometaphase I.","method":"Oocyte-specific Dcaf13 knockout, ubiquitination assays, PI3K pathway activity measurement, CDK1 kinase assay, immunofluorescence for spindle/chromosome alignment","journal":"Cellular and molecular life sciences : CMLS","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined molecular phenotype, ubiquitination assay, kinase activity assay, multiple orthogonal readouts in single lab","pmids":["31492966"],"is_preprint":false},{"year":2019,"finding":"Maternal DCAF13, highly expressed in the growing oocyte nucleolus, is required for chromatin tightness in fully grown germinal vesicle oocytes and for proper chromosome condensation at MII. Loss of maternal DCAF13 leads to loose chromatin structure in GV oocytes, improperly condensed MII chromosomes, abnormal nuclear/nucleolar reorganization, and inactive transcription in zygotes, causing two-cell stage arrest.","method":"Oocyte-specific conditional knockout, RNA-seq of MII oocytes and 2-cell embryos, mRNA injection rescue attempt, immunofluorescence","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined chromatin phenotype, RNA-seq, failed rescue experiment; single lab","pmids":["31000741"],"is_preprint":false},{"year":2020,"finding":"DCAF13 functions as an RNA-binding protein (RBP) that binds to the AU-rich element (ARE) in the 3'UTR of DTX3 mRNA to accelerate its degradation, thereby activating NOTCH4 signaling (since DTX3 normally promotes ubiquitination and degradation of NOTCH4) and promoting triple-negative breast cancer metastasis.","method":"RNA immunoprecipitation (RIP), mRNA stability assays, overexpression and knockdown, migration/invasion assays, NOTCH4 ubiquitination assay","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RIP assay establishing DCAF13-ARE binding, mRNA stability analysis, functional rescue, single lab with multiple methods","pmids":["33300431"],"is_preprint":false},{"year":2022,"finding":"CRL4-DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation in breast cancer cells. Co-immunoprecipitation showed DCAF13 and DDB1 directly interact with PERP, and DDB1 overexpression significantly increased PERP polyubiquitination. DCAF13 deletion causes both mRNA and protein accumulation of PERP, leading to apoptosis and senescence.","method":"CRISPR/Cas9 knockout, co-immunoprecipitation (DCAF13-DDB1-PERP), ubiquitination assay with DDB1 overexpression, genome-wide RNAseq, western blotting","journal":"Cancer science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP establishing ternary complex, ubiquitination assay, CRISPR KO, single lab with multiple orthogonal methods","pmids":["35178836"],"is_preprint":false},{"year":2023,"finding":"DCAF13 is identified as the substrate receptor (DDB1- and Cullin-associated factor) of the CRL4 ubiquitin ligase that recognizes TOP1-DNA-protein crosslinks (TOP1-DPCs) for ubiquitination and proteasomal degradation during replication-coupled repair. The CUL4-RBX1 complex undergoes auto-NEDD8 modification and acts on TOP1-DPCs.","method":"Chemical genetic screens, co-immunoprecipitation, ubiquitination assays, TOP1-DPC repair assays in CRC cells and patient-derived organoids, xenograft models, pevonedistat (NEDD8 inhibitor) combination studies","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, ubiquitination assay, genetic screens, organoids, xenografts), rigorous mechanistic dissection in peer-reviewed journal","pmids":["37353483"],"is_preprint":false},{"year":2023,"finding":"DCAF13 promotes NPM1 phase separation in nucleolar condensates to accelerate pre-rRNA enrichment and recruitment of the endonuclease UTP23, thereby facilitating 18S rRNA maturation and rapid T cell proliferation. DCAF13 depletion in T cells causes 18S rRNA maturation failure, abnormal ribosome assembly in nucleoli, and insufficient nascent protein production.","method":"Conditional knockout (T cell-specific), phase separation assays, rRNA processing analysis, ribosome assembly assays, nascent protein synthesis assay, immunofluorescence","journal":"The Journal of cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined molecular phenotype, phase separation assays, rRNA processing analysis; single lab with multiple methods","pmids":["37615668"],"is_preprint":false},{"year":2024,"finding":"CRL4-DCAF13 E3 ubiquitin ligase targets MeCP2 (methyl-CpG-binding protein 2) for polyubiquitination and proteasomal degradation in growing oocytes. Dcaf13-null oocytes accumulate MeCP2 protein, leading to transcription dysregulation and DNA hypermethylation; partial rescue of follicle growth arrest was achieved by MeCP2 knockdown.","method":"Dcaf13-null oocytes (conditional KO), ubiquitination assay in cells and oocytes, MeCP2 knockdown rescue, RNA-seq, DNA methylation analysis","journal":"Cellular and molecular life sciences : CMLS","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined substrate accumulation, ubiquitination assay, genetic rescue experiment, RNA-seq, multiple orthogonal methods in single lab","pmids":["38578457"],"is_preprint":false},{"year":2024,"finding":"DCAF13 promotes p53 K48-linked ubiquitination and proteasomal degradation in lung adenocarcinoma cells, acting as a negative regulator of the p53 signaling pathway and suppressing p53 downstream targets including p21, BAX, FAS, and PIDD1.","method":"Co-immunoprecipitation (DCAF13-p53 binding), ubiquitination assay (K48-linked), RNA-sequencing, chromatin immunoprecipitation-qPCR, immunofluorescence, knockdown/overexpression assays","journal":"Journal of experimental & clinical cancer research : CR","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP, K48-specific ubiquitination assay, RNA-seq pathway analysis, ChIP-qPCR; single lab with multiple orthogonal methods","pmids":["38163876"],"is_preprint":false},{"year":2024,"finding":"DCAF13 promotes p53 ubiquitination and degradation in mantle cell lymphoma, and STAT5B transcriptionally activates DCAF13 expression. DCAF13-mediated p53 degradation leads to upregulation of xCT and suppression of ferroptosis in MCL cells.","method":"STAT5B silencing, DCAF13 overexpression/silencing, ubiquitination assay with MG132, luciferase reporter for STAT5B-DCAF13 transcription, tumor-bearing nude mouse model","journal":"Biologics : targets & therapy","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — ubiquitination assay with proteasome inhibitor, transcriptional reporter, in vivo model; single lab, moderate mechanistic depth","pmids":["38979130"],"is_preprint":false},{"year":2024,"finding":"CRL4-DCAF13 targets Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation in ovarian cancer cells. FRAS1 accumulation (upon DCAF13 knockout) inhibits the focal adhesion kinase (FAK) signaling pathway, suppressing proliferation and migration.","method":"CRISPR/Cas9 knockout of DCAF13, ubiquitination assays, FAK signaling pathway analysis (western blot), co-immunoprecipitation, xenograft mouse model","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO, ubiquitination assay, pathway activity measurement, in vivo xenograft; single lab with multiple methods","pmids":["39367995"],"is_preprint":false},{"year":2025,"finding":"DCAF13 promotes RNA polymerase I (Pol I) transcription by facilitating K63-linked ubiquitination of RPA194 (the largest Pol I subunit), a non-degradative modification that stimulates Pol I transcriptional activity, thereby enhancing ribosome biogenesis and global protein synthesis in breast cancer cells.","method":"Multi-omics analysis, ubiquitination assays (K63-specific), Pol I transcription assays, co-immunoprecipitation, in vitro and in vivo proliferation assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — K63-specific ubiquitination assay, Pol I transcription assay, in vitro and in vivo functional validation, multiple orthogonal methods in peer-reviewed journal","pmids":["39788980"],"is_preprint":false},{"year":2025,"finding":"DCAF13 directly interacts with TAF1A, a component of the RNA polymerase I preinitiation complex, and this interaction is necessary for preinitiation complex assembly and rDNA transcription. DCAF13 knockdown impairs rDNA transcription, ribosome biogenesis, and protein synthesis in non-small cell lung cancer cells.","method":"Co-immunoprecipitation (DCAF13-TAF1A), rDNA transcription assays, ribosome biogenesis analysis, protein synthesis assay, DCAF13 knockdown","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP establishing direct interaction, functional transcription assay, ribosome biogenesis analysis; single lab","pmids":["40902972"],"is_preprint":false},{"year":2025,"finding":"DCAF13 directly binds RRS1 (a ribosome biogenesis factor) and catalyzes K27-linked polyubiquitination of RRS1, a non-degradative modification that enhances RRS1 protein stability, thereby supporting ribosome assembly and protein synthesis in hematopoietic stem cells. Conditional deletion of Dcaf13 causes severe pancytopenia, HSC depletion, and activates the p53 pathway; Trp53 ablation only partially rescues this phenotype.","method":"Conditional knockout in hematopoietic cells, co-immunoprecipitation (DCAF13-RRS1), K27-specific ubiquitination assay, ribosome assembly analysis, protein synthesis assay, Trp53 double knockout epistasis","journal":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with in vivo phenotype, Co-IP, K27-specific ubiquitination assay, epistasis with p53, multiple orthogonal methods","pmids":["41787937"],"is_preprint":false},{"year":2025,"finding":"In the uterus, DCAF13 deficiency leads to elevated H3K9me3 levels (associated with increased SUV39H2 transcription), dysregulated estrogen and progesterone receptor expression, and insufficient endometrial cell proliferation, causing embryo implantation failure and infertility.","method":"Uterine conditional knockout of Dcaf13, RNA-seq, immunofluorescence for H3K9me3, hormone receptor western blot, in vivo implantation assay","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with defined molecular phenotype (H3K9me3, hormone receptors), RNA-seq, in vivo implantation assay; single lab","pmids":["40750792"],"is_preprint":false},{"year":2026,"finding":"In cranial neural crest cells, DCAF13 deficiency causes PTEN accumulation (a substrate it normally degrades), which suppresses PI3K/AKT signaling, thereby impairing proliferation and differentiation of CNC-derived cells and causing craniofacial malformations.","method":"Neural crest-specific conditional knockout of Dcaf13, western blot for PTEN and AKT phosphorylation, immunofluorescence, skeletal staining","journal":"Genesis (New York, N.Y. : 2000)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — conditional KO with PTEN substrate accumulation and PI3K/AKT pathway activity measurement; single lab","pmids":["41492083"],"is_preprint":false},{"year":2025,"finding":"DCAF13 interacts with glucose-6-phosphate dehydrogenase (G6PD) to enhance glycolytic flux in hepatocellular carcinoma cells. The stability of DCAF13 mRNA is maintained by METTL3-mediated m6A modification and YTHDF1 binding.","method":"Co-immunoprecipitation (DCAF13-G6PD), molecular dynamics simulation, MeRIP-qPCR and RIP assays for m6A/YTHDF1, CRISPR/Cas9 knockout, glycolysis flux assays","journal":"Journal of gastroenterology and hepatology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP and molecular dynamics for DCAF13-G6PD interaction; single lab, m6A regulation inferred from RIP; limited mechanistic depth in abstract","pmids":["40708455"],"is_preprint":false}],"current_model":"DCAF13 is a multifunctional nucleolar WD40-repeat protein that acts primarily as a substrate receptor (adaptor) for the CRL4 (CUL4-DDB1-RBX1) E3 ubiquitin ligase complex, directing polyubiquitination and proteasomal degradation of diverse substrates—including SUV39H1, PTEN, PERP, MeCP2, p53, FRAS1, and TOP1-DPCs—in a context-dependent manner; independently of its E3 adaptor role, DCAF13 supports ribosome biogenesis by interacting with fibrillarin, NPM1, UTP23, and TAF1A to facilitate 18S rRNA processing and Pol I preinitiation complex assembly, and can also catalyze non-degradative K27-linked ubiquitination of RRS1 to stabilize it, or K63-linked ubiquitination of RPA194 to stimulate Pol I transcription, collectively making DCAF13 an essential regulator of epigenetic reprogramming, translational capacity, and cell proliferation in development and cancer."},"narrative":{"mechanistic_narrative":"DCAF13 is a nucleolar WD40-repeat protein that serves as a substrate receptor for the CRL4 (CUL4–DDB1–RBX1) E3 ubiquitin ligase and, independently, as a ribosome biogenesis factor, making it an essential regulator of epigenetic reprogramming, translational capacity, and proliferation in development and cancer [PMID:30111536, PMID:30283081, PMID:37353483]. As a CRL4 adaptor it directs polyubiquitination and proteasomal degradation of a context-dependent set of substrates: SUV39H1 to lower H3K9me3 and license zygotic gene expression [PMID:30111536], PTEN to sustain PI3K/AKT signaling required for meiotic resumption and neural crest development [PMID:31492966, PMID:41492083], MeCP2 to restrain DNA methylation in growing oocytes [PMID:38578457], the TOP1–DNA-protein crosslink for replication-coupled repair [PMID:37353483], PERP, FRAS1, and p53 in various cancers [PMID:35178836, PMID:39367995, PMID:38163876]. Beyond degradative ubiquitination, DCAF13 catalyzes non-degradative chain types that promote ribosome production—K63-linked ubiquitination of the Pol I subunit RPA194 to stimulate rDNA transcription, and K27-linked ubiquitination of RRS1 to stabilize it during hematopoietic ribosome assembly [PMID:39788980, PMID:41787937]. It also supports 18S rRNA processing through interactions with fibrillarin, NPM1/UTP23, and the Pol I preinitiation factor TAF1A, the latter two coupling DCAF13 to nucleolar condensate formation and preinitiation complex assembly [PMID:30283081, PMID:37615668, PMID:40902972]. Loss of DCAF13 produces ribosome biogenesis failure, p53 pathway activation, and developmental arrest across oocytes, embryos, hematopoietic stem cells, and uterine tissue [PMID:30283081, PMID:41787937, PMID:40750792].","teleology":[{"year":2017,"claim":"Established that DCAF13 functions catalytically as a CRL4 substrate receptor, defining its first degradation target and demonstrating it assembles into a CUL4B–DDB1 ligase.","evidence":"Co-IP, in vitro/in vivo ubiquitination, knockdown and overexpression in osteosarcoma cells targeting PTEN","pmids":["29499938"],"confidence":"High","gaps":["Degron/substrate recognition motif on PTEN not defined","Specificity vs other DCAFs not addressed"]},{"year":2018,"claim":"Connected DCAF13 to epigenetic reprogramming by showing CRL4-DCAF13 degrades the H3K9 methyltransferase SUV39H1 to erase repressive marks and enable zygotic gene activation in vivo.","evidence":"Dcaf13 knockout mice, reciprocal Co-IP, ubiquitination assays, H3K9me3 immunofluorescence","pmids":["30111536"],"confidence":"High","gaps":["Whether SUV39H2 is also a substrate not resolved here","Direct enzymatic specificity vs indirect effects on H3K9me3"]},{"year":2018,"claim":"Revealed a degradation-independent role in ribosome biogenesis, placing DCAF13 in the nucleolar rRNA-processing machinery via fibrillarin interaction.","evidence":"Oocyte conditional KO, Co-IP with fibrillarin, northern blot for pre-rRNA, ribosome assembly and protein synthesis assays","pmids":["30283081"],"confidence":"High","gaps":["Direct rRNA cleavage role vs scaffolding not separated","Molecular basis of fibrillarin binding unknown"]},{"year":2019,"claim":"Linked DCAF13-mediated PTEN degradation to a physiological signaling outcome—maintaining PI3K activity and CDK1 for oocyte meiotic resumption.","evidence":"Oocyte-specific KO, ubiquitination assays, PI3K and CDK1 activity measurement, spindle/chromosome imaging","pmids":["31492966"],"confidence":"High","gaps":["How DCAF13 substrate choice is restricted to PTEN in this context unclear"]},{"year":2019,"claim":"Showed maternal DCAF13 is required for higher-order chromatin organization and nucleolar reorganization in oocytes, broadening its role beyond single-substrate effects.","evidence":"Oocyte conditional KO, RNA-seq of MII oocytes and 2-cell embryos, mRNA rescue attempt, immunofluorescence","pmids":["31000741"],"confidence":"Medium","gaps":["mRNA rescue failed, leaving causal mechanism for chromatin tightness incomplete","Molecular link between nucleolar function and chromatin not defined"]},{"year":2020,"claim":"Proposed an RNA-binding activity distinct from ubiquitin ligation, with DCAF13 destabilizing DTX3 mRNA via ARE binding to drive NOTCH4 signaling in cancer.","evidence":"RIP, mRNA stability assays, migration/invasion assays, NOTCH4 ubiquitination in TNBC cells","pmids":["33300431"],"confidence":"Medium","gaps":["Direct vs indirect ARE binding not structurally confirmed","Relationship of RBP activity to WD40 scaffold unknown"]},{"year":2022,"claim":"Extended the CRL4-DCAF13 substrate repertoire to PERP in breast cancer, coupling its degradation to apoptosis and senescence suppression.","evidence":"CRISPR KO, Co-IP of DCAF13–DDB1–PERP ternary complex, DDB1-dependent ubiquitination, RNA-seq","pmids":["35178836"],"confidence":"Medium","gaps":["mRNA accumulation of PERP upon KO implies an additional transcriptional layer not explained","Degron not mapped"]},{"year":2023,"claim":"Defined DCAF13 as the CRL4 receptor recognizing TOP1-DPCs for replication-coupled repair, with the complex undergoing auto-NEDDylation and exploitable by NEDD8 inhibition.","evidence":"Chemical genetic screens, Co-IP, ubiquitination assays, DPC repair in CRC cells, organoids, xenografts, pevonedistat combination","pmids":["37353483"],"confidence":"High","gaps":["How DCAF13 discriminates crosslinked TOP1 from native TOP1 unresolved"]},{"year":2023,"claim":"Showed DCAF13 drives nucleolar phase separation through NPM1 to recruit UTP23 and accelerate 18S rRNA maturation, linking ribosome biogenesis to rapid proliferation.","evidence":"T cell-specific KO, phase separation assays, rRNA processing, ribosome assembly and nascent protein synthesis assays","pmids":["37615668"],"confidence":"Medium","gaps":["Whether DCAF13 itself undergoes phase separation or only promotes NPM1 condensation unclear","Direct UTP23 contact not shown"]},{"year":2024,"claim":"Identified MeCP2 as an oocyte CRL4-DCAF13 substrate, connecting its degradation to control of DNA methylation, validated by genetic rescue.","evidence":"Dcaf13-null oocytes, ubiquitination assays, MeCP2 knockdown rescue, RNA-seq, DNA methylation analysis","pmids":["38578457"],"confidence":"High","gaps":["Only partial rescue indicates additional substrates contribute to phenotype"]},{"year":2024,"claim":"Established DCAF13 as a negative regulator of p53 across cancers, promoting K48-linked p53 degradation and, downstream, ferroptosis suppression via xCT.","evidence":"Co-IP, K48-linked ubiquitination assays, RNA-seq, ChIP-qPCR in lung adenocarcinoma; STAT5B reporter, ubiquitination and xenografts in mantle cell lymphoma","pmids":["38163876","38979130"],"confidence":"Medium","gaps":["Whether p53 ubiquitination is CRL4-dependent not formally shown in both contexts","Direct vs scaffolded p53 recognition unresolved"]},{"year":2024,"claim":"Added FRAS1 as a CRL4-DCAF13 substrate whose degradation sustains FAK signaling and tumor cell proliferation/migration in ovarian cancer.","evidence":"CRISPR KO, ubiquitination assays, FAK pathway western blots, Co-IP, xenografts","pmids":["39367995"],"confidence":"Medium","gaps":["Mechanism linking FRAS1 level to FAK activity not detailed"]},{"year":2025,"claim":"Demonstrated non-degradative ubiquitination as a DCAF13 mechanism, with K63-linked modification of RPA194 stimulating Pol I transcription, and direct TAF1A binding required for preinitiation complex assembly.","evidence":"K63-specific ubiquitination and Pol I transcription assays in breast cancer (RPA194); Co-IP and rDNA transcription assays in NSCLC (TAF1A)","pmids":["39788980","40902972"],"confidence":"High","gaps":["Whether RPA194 K63 ubiquitination uses the CRL4 scaffold or a different E3 unclear","Coordination between RPA194 and TAF1A roles not integrated"]},{"year":2025,"claim":"Identified a third ubiquitin chain type—K27-linked stabilization of RRS1—and showed DCAF13 sustains hematopoietic stem cell ribosome assembly upstream of the p53 pathway.","evidence":"Hematopoietic conditional KO, Co-IP, K27-specific ubiquitination assays, ribosome assembly assays, Trp53 epistasis","pmids":["41787937"],"confidence":"High","gaps":["Only partial p53-independent rescue; full downstream effector set undefined","How chain-type selectivity (K27 vs K48 vs K63) is achieved unknown"]},{"year":2025,"claim":"Extended DCAF13's developmental requirement to uterine receptivity, where its loss raises H3K9me3 and dysregulates hormone receptors to cause implantation failure.","evidence":"Uterine conditional KO, RNA-seq, H3K9me3 immunofluorescence, hormone receptor western blot, implantation assay","pmids":["40750792"],"confidence":"Medium","gaps":["Direct substrate driving SUV39H2/H3K9me3 change not pinpointed in uterus"]},{"year":2025,"claim":"Proposed a metabolic role via G6PD interaction enhancing glycolysis, with DCAF13 mRNA itself under m6A/YTHDF1 control in hepatocellular carcinoma.","evidence":"Co-IP, molecular dynamics, MeRIP-qPCR and RIP, CRISPR KO, glycolysis flux assays","pmids":["40708455"],"confidence":"Low","gaps":["Single Co-IP plus simulation; functional dependence of glycolysis on direct DCAF13–G6PD binding not established","m6A regulation inferred indirectly"]},{"year":null,"claim":"How DCAF13 selects among degradative (K48), and non-degradative (K63, K27) ubiquitin chain types and switches between its E3 adaptor and ribosome biogenesis functions remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of substrate or chain-type determinants","Mechanism partitioning DCAF13 between CRL4 and nucleolar machinery unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,2,3,6,7,9,10,12,13,15]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,7]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[1,5]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[13,14]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[1,4,8]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,9]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[1,8,13,14,15]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,2,7,9,10]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[7]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[0,16]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3]}],"complexes":["CRL4 (CUL4-DDB1-RBX1) E3 ubiquitin ligase","Pol I preinitiation complex"],"partners":["DDB1","CUL4B","FBL","NPM1","UTP23","TAF1A","RRS1","RPA194"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NV06","full_name":"DDB1- and CUL4-associated factor 13","aliases":["WD repeat and SOF domain-containing protein 1"],"length_aa":445,"mass_kda":51.4,"function":"Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Participates in the 18S rRNA processing in growing oocytes, being essential for oocyte nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) transition (PubMed:30283081) Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that plays a key role in embryo preimplantation and is required for normal meiotic cycle progression in oocytes (PubMed:16949367, PubMed:30111536, PubMed:31492966). Acts as a maternal factor that regulates oocyte and zygotic chromatin tightness during maternal to zygotic transition (By similarity). Also involved in the transformation of the endometrium into the decidua, known as decidualization, providing a solid foundation for implantation of blastocysts (PubMed:35932979). Recognizes the histone methyltransferases SUV39H1 and SUV39H2 and directs them to polyubiquitination and proteasomal degradation, which facilitates the H3K9me3 removal and early zygotic gene expression, essential steps for progressive genome reprogramming and the establishment of pluripotency during preimplantation embryonic development (PubMed:30111536). Supports the spindle assembly and chromosome condensation during oocyte meiotic division by targeting the polyubiquitination and degradation of PTEN, a lipid phosphatase that inhibits PI3K pathway as well as oocyte growth and maturation (PubMed:31492966). Targets PMP22 for polyubiquitination and proteasomal degradation (By similarity)","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q9NV06/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DCAF13","classification":"Common Essential","n_dependent_lines":77,"n_total_lines":77,"dependency_fraction":1.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"IPO5","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DCAF13","total_profiled":1310},"omim":[{"mim_id":"616196","title":"DDB1- AND CUL4-ASSOCIATED FACTOR 13; DCAF13","url":"https://www.omim.org/entry/616196"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Nucleoli","reliability":"Supported"},{"location":"Cell Junctions","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DCAF13"},"hgnc":{"alias_symbol":["DKFZP564O0463","Gm83","HSPC064","Sof1"],"prev_symbol":["WDSOF1"]},"alphafold":{"accession":"Q9NV06","domains":[{"cath_id":"-","chopping":"38-58_365-393","consensus_level":"medium","plddt":96.3628,"start":38,"end":393},{"cath_id":"2.130.10.10","chopping":"59-354","consensus_level":"medium","plddt":92.7512,"start":59,"end":354}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NV06","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NV06-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NV06-F1-predicted_aligned_error_v6.png","plddt_mean":92.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DCAF13","jax_strain_url":"https://www.jax.org/strain/search?query=DCAF13"},"sequence":{"accession":"Q9NV06","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NV06.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NV06/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NV06"}},"corpus_meta":[{"pmid":"30111536","id":"PMC_30111536","title":"DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during early embryonic development.","date":"2018","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/30111536","citation_count":67,"is_preprint":false},{"pmid":"30283081","id":"PMC_30283081","title":"Mammalian nucleolar protein DCAF13 is essential for ovarian follicle maintenance and oocyte growth by mediating rRNA processing.","date":"2018","source":"Cell death and differentiation","url":"https://pubmed.ncbi.nlm.nih.gov/30283081","citation_count":62,"is_preprint":false},{"pmid":"29499938","id":"PMC_29499938","title":"MicroRNA-300 Regulates the Ubiquitination of PTEN through the CRL4BDCAF13 E3 Ligase in Osteosarcoma Cells.","date":"2017","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/29499938","citation_count":60,"is_preprint":false},{"pmid":"31492966","id":"PMC_31492966","title":"The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation.","date":"2019","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/31492966","citation_count":44,"is_preprint":false},{"pmid":"35178836","id":"PMC_35178836","title":"DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression.","date":"2022","source":"Cancer science","url":"https://pubmed.ncbi.nlm.nih.gov/35178836","citation_count":36,"is_preprint":false},{"pmid":"34775691","id":"PMC_34775691","title":"Doxorubicin promotes breast cancer cell migration and invasion via DCAF13.","date":"2021","source":"FEBS open bio","url":"https://pubmed.ncbi.nlm.nih.gov/34775691","citation_count":35,"is_preprint":false},{"pmid":"37353483","id":"PMC_37353483","title":"Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37353483","citation_count":29,"is_preprint":false},{"pmid":"33300431","id":"PMC_33300431","title":"DCAF13 promotes triple-negative breast cancer metastasis by mediating DTX3 mRNA degradation.","date":"2020","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/33300431","citation_count":28,"is_preprint":false},{"pmid":"38163876","id":"PMC_38163876","title":"DCAF13 inhibits the p53 signaling pathway by promoting p53 ubiquitination modification in lung adenocarcinoma.","date":"2024","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/38163876","citation_count":27,"is_preprint":false},{"pmid":"37615668","id":"PMC_37615668","title":"T cell proliferation requires ribosomal maturation in nucleolar condensates dependent on DCAF13.","date":"2023","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/37615668","citation_count":16,"is_preprint":false},{"pmid":"31000741","id":"PMC_31000741","title":"Maternal DCAF13 Regulates Chromatin Tightness to Contribute to Embryonic Development.","date":"2019","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31000741","citation_count":16,"is_preprint":false},{"pmid":"36884358","id":"PMC_36884358","title":"A multidimensional pan-cancer analysis of DCAF13 and its protumorigenic effect in lung adenocarcinoma.","date":"2023","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/36884358","citation_count":13,"is_preprint":false},{"pmid":"35932979","id":"PMC_35932979","title":"DCAF13 is essential for the pathogenesis of preeclampsia through its involvement in endometrial decidualization.","date":"2022","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/35932979","citation_count":11,"is_preprint":false},{"pmid":"20601284","id":"PMC_20601284","title":"Identification of non-synonymous polymorphisms in the WDSOF1 gene as novel susceptibility markers for low bone mineral density in Japanese postmenopausal women.","date":"2010","source":"Bone","url":"https://pubmed.ncbi.nlm.nih.gov/20601284","citation_count":10,"is_preprint":false},{"pmid":"38578457","id":"PMC_38578457","title":"CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.","date":"2024","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/38578457","citation_count":9,"is_preprint":false},{"pmid":"38979130","id":"PMC_38979130","title":"STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression.","date":"2024","source":"Biologics : targets & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/38979130","citation_count":6,"is_preprint":false},{"pmid":"39367995","id":"PMC_39367995","title":"DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.","date":"2024","source":"Cellular and molecular life sciences : CMLS","url":"https://pubmed.ncbi.nlm.nih.gov/39367995","citation_count":5,"is_preprint":false},{"pmid":"37855431","id":"PMC_37855431","title":"DCAF13 and RNF114 participate in the regulation of early porcine embryo development.","date":"2023","source":"Reproduction (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/37855431","citation_count":5,"is_preprint":false},{"pmid":"36797467","id":"PMC_36797467","title":"A biallelic variant of DCAF13 implicated in a neuromuscular disorder in humans.","date":"2023","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/36797467","citation_count":5,"is_preprint":false},{"pmid":"39788980","id":"PMC_39788980","title":"DCAF13-mediated K63-linked ubiquitination of RNA polymerase I promotes uncontrolled proliferation in Breast Cancer.","date":"2025","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39788980","citation_count":4,"is_preprint":false},{"pmid":"40603761","id":"PMC_40603761","title":"DCAF13 Regulates Cell Proliferation and Immune Escape of Hepatocellular Carcinoma Through Activating the NF-κB Pathway.","date":"2025","source":"Cell biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/40603761","citation_count":3,"is_preprint":false},{"pmid":"40708455","id":"PMC_40708455","title":"m6A Modification-Mediated Regulation of DCAF13 Promotes Glycolytic Metabolism and Drives Hepatocellular Carcinoma Progression via Interaction With G6PD.","date":"2025","source":"Journal of gastroenterology and hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/40708455","citation_count":2,"is_preprint":false},{"pmid":"40268788","id":"PMC_40268788","title":"DCAF13 influences breast cancer chemotherapy resistance through metabolic reprogramming by regulating c-Myc expression.","date":"2025","source":"Medical oncology (Northwood, London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/40268788","citation_count":2,"is_preprint":false},{"pmid":"30003937","id":"PMC_30003937","title":"Whole exome sequencing reveals novel NOV and DCAF13 variants in a Chinese pedigree with familial cortical myoclonic tremor with epilepsy.","date":"2018","source":"Neuroscience letters","url":"https://pubmed.ncbi.nlm.nih.gov/30003937","citation_count":2,"is_preprint":false},{"pmid":"36217444","id":"PMC_36217444","title":"DCAF-13 is required for C. elegans growth, development, and fertility.","date":"2022","source":"microPublication biology","url":"https://pubmed.ncbi.nlm.nih.gov/36217444","citation_count":2,"is_preprint":false},{"pmid":"40902972","id":"PMC_40902972","title":"Nucleolar protein DCAF13 promotes non-small cell lung cancer cell proliferation via facilitating rDNA transcription and ribosome biogenesis.","date":"2025","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/40902972","citation_count":1,"is_preprint":false},{"pmid":"40750792","id":"PMC_40750792","title":"DCAF13 is essential for mouse uterine function and fertility.","date":"2025","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/40750792","citation_count":1,"is_preprint":false},{"pmid":"41787937","id":"PMC_41787937","title":"DCAF13 Safeguards Hematopoietic Stem Cells via RRS1-Regulated Ribosome Biogenesis.","date":"2026","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/41787937","citation_count":0,"is_preprint":false},{"pmid":"41492083","id":"PMC_41492083","title":"The E3 Ubiquitin Ligase DCAF13 Is Essential for Craniofacial Development.","date":"2026","source":"Genesis (New York, N.Y. : 2000)","url":"https://pubmed.ncbi.nlm.nih.gov/41492083","citation_count":0,"is_preprint":false},{"pmid":"41797888","id":"PMC_41797888","title":"Pro-tumourigenic effects of DCAF13 on the progression of colorectal cancer.","date":"2026","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/41797888","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":17113,"output_tokens":5188,"usd":0.064579,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":13610,"output_tokens":5130,"usd":0.09815,"stage2_stop_reason":"end_turn"},"total_usd":0.162729,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"CRL4-DCAF13 acts as an E3 ubiquitin ligase complex that targets SUV39H1 for polyubiquitination and proteasomal degradation, thereby facilitating H3K9me3 removal and enabling zygotic gene expression during preimplantation embryonic development. Dcaf13 knockout mice arrest at the 8-16 cell stage with elevated H3K9me3.\",\n      \"method\": \"Dcaf13 knockout mice, ubiquitination assays, co-immunoprecipitation, western blotting, immunofluorescence for H3K9me3\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, in vivo knockout with defined molecular phenotype (H3K9me3 elevation), ubiquitination assay, replicated in both murine and human embryo contexts\",\n      \"pmids\": [\"30111536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DCAF13 is a nucleolar protein that functions as a component of the rRNA-processing complex essential for 18S rRNA processing in growing oocytes. DCAF13 interacts with the box C/D ribonucleoprotein component fibrillarin. Conditional knockout of Dcaf13 causes pre-rRNA accumulation, ribosome assembly disorder, reduced global protein synthesis, and arrest of oocyte NSN-to-SN chromatin configuration transition.\",\n      \"method\": \"Conditional knockout mice, co-immunoprecipitation (DCAF13-fibrillarin interaction), northern blotting for pre-rRNA, ribosome assembly analysis, protein synthesis assays\",\n      \"journal\": \"Cell death and differentiation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined molecular phenotype, reciprocal Co-IP with fibrillarin, rRNA processing and ribosome assembly assays, multiple orthogonal methods\",\n      \"pmids\": [\"30283081\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CRL4B-DCAF13 E3 ligase complex (comprising CUL4B, DDB1, and DCAF13) targets PTEN for ubiquitination and proteasomal degradation in osteosarcoma cells. Disruption of this complex causes PTEN accumulation.\",\n      \"method\": \"Co-immunoprecipitation, in vitro and in vivo ubiquitination assays, siRNA knockdown, DCAF13 overexpression\",\n      \"journal\": \"Molecular therapy. Nucleic acids\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP establishing ternary complex, in vitro and in vivo ubiquitination assays, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"29499938\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CRL4-DCAF13 targets PTEN for polyubiquitination and proteasomal degradation in oocytes, thereby maintaining PI3K signaling pathway activity required for meiotic resumption. Dcaf13 knockout oocytes show decreased CDK1 activity, chromosome condensation defects, spindle assembly checkpoint activation, and arrest at prometaphase I.\",\n      \"method\": \"Oocyte-specific Dcaf13 knockout, ubiquitination assays, PI3K pathway activity measurement, CDK1 kinase assay, immunofluorescence for spindle/chromosome alignment\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined molecular phenotype, ubiquitination assay, kinase activity assay, multiple orthogonal readouts in single lab\",\n      \"pmids\": [\"31492966\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Maternal DCAF13, highly expressed in the growing oocyte nucleolus, is required for chromatin tightness in fully grown germinal vesicle oocytes and for proper chromosome condensation at MII. Loss of maternal DCAF13 leads to loose chromatin structure in GV oocytes, improperly condensed MII chromosomes, abnormal nuclear/nucleolar reorganization, and inactive transcription in zygotes, causing two-cell stage arrest.\",\n      \"method\": \"Oocyte-specific conditional knockout, RNA-seq of MII oocytes and 2-cell embryos, mRNA injection rescue attempt, immunofluorescence\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined chromatin phenotype, RNA-seq, failed rescue experiment; single lab\",\n      \"pmids\": [\"31000741\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"DCAF13 functions as an RNA-binding protein (RBP) that binds to the AU-rich element (ARE) in the 3'UTR of DTX3 mRNA to accelerate its degradation, thereby activating NOTCH4 signaling (since DTX3 normally promotes ubiquitination and degradation of NOTCH4) and promoting triple-negative breast cancer metastasis.\",\n      \"method\": \"RNA immunoprecipitation (RIP), mRNA stability assays, overexpression and knockdown, migration/invasion assays, NOTCH4 ubiquitination assay\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RIP assay establishing DCAF13-ARE binding, mRNA stability analysis, functional rescue, single lab with multiple methods\",\n      \"pmids\": [\"33300431\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CRL4-DCAF13 E3 ligase targets PERP for ubiquitination and proteasomal degradation in breast cancer cells. Co-immunoprecipitation showed DCAF13 and DDB1 directly interact with PERP, and DDB1 overexpression significantly increased PERP polyubiquitination. DCAF13 deletion causes both mRNA and protein accumulation of PERP, leading to apoptosis and senescence.\",\n      \"method\": \"CRISPR/Cas9 knockout, co-immunoprecipitation (DCAF13-DDB1-PERP), ubiquitination assay with DDB1 overexpression, genome-wide RNAseq, western blotting\",\n      \"journal\": \"Cancer science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP establishing ternary complex, ubiquitination assay, CRISPR KO, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"35178836\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DCAF13 is identified as the substrate receptor (DDB1- and Cullin-associated factor) of the CRL4 ubiquitin ligase that recognizes TOP1-DNA-protein crosslinks (TOP1-DPCs) for ubiquitination and proteasomal degradation during replication-coupled repair. The CUL4-RBX1 complex undergoes auto-NEDD8 modification and acts on TOP1-DPCs.\",\n      \"method\": \"Chemical genetic screens, co-immunoprecipitation, ubiquitination assays, TOP1-DPC repair assays in CRC cells and patient-derived organoids, xenograft models, pevonedistat (NEDD8 inhibitor) combination studies\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, ubiquitination assay, genetic screens, organoids, xenografts), rigorous mechanistic dissection in peer-reviewed journal\",\n      \"pmids\": [\"37353483\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DCAF13 promotes NPM1 phase separation in nucleolar condensates to accelerate pre-rRNA enrichment and recruitment of the endonuclease UTP23, thereby facilitating 18S rRNA maturation and rapid T cell proliferation. DCAF13 depletion in T cells causes 18S rRNA maturation failure, abnormal ribosome assembly in nucleoli, and insufficient nascent protein production.\",\n      \"method\": \"Conditional knockout (T cell-specific), phase separation assays, rRNA processing analysis, ribosome assembly assays, nascent protein synthesis assay, immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined molecular phenotype, phase separation assays, rRNA processing analysis; single lab with multiple methods\",\n      \"pmids\": [\"37615668\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CRL4-DCAF13 E3 ubiquitin ligase targets MeCP2 (methyl-CpG-binding protein 2) for polyubiquitination and proteasomal degradation in growing oocytes. Dcaf13-null oocytes accumulate MeCP2 protein, leading to transcription dysregulation and DNA hypermethylation; partial rescue of follicle growth arrest was achieved by MeCP2 knockdown.\",\n      \"method\": \"Dcaf13-null oocytes (conditional KO), ubiquitination assay in cells and oocytes, MeCP2 knockdown rescue, RNA-seq, DNA methylation analysis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined substrate accumulation, ubiquitination assay, genetic rescue experiment, RNA-seq, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"38578457\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DCAF13 promotes p53 K48-linked ubiquitination and proteasomal degradation in lung adenocarcinoma cells, acting as a negative regulator of the p53 signaling pathway and suppressing p53 downstream targets including p21, BAX, FAS, and PIDD1.\",\n      \"method\": \"Co-immunoprecipitation (DCAF13-p53 binding), ubiquitination assay (K48-linked), RNA-sequencing, chromatin immunoprecipitation-qPCR, immunofluorescence, knockdown/overexpression assays\",\n      \"journal\": \"Journal of experimental & clinical cancer research : CR\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP, K48-specific ubiquitination assay, RNA-seq pathway analysis, ChIP-qPCR; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"38163876\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DCAF13 promotes p53 ubiquitination and degradation in mantle cell lymphoma, and STAT5B transcriptionally activates DCAF13 expression. DCAF13-mediated p53 degradation leads to upregulation of xCT and suppression of ferroptosis in MCL cells.\",\n      \"method\": \"STAT5B silencing, DCAF13 overexpression/silencing, ubiquitination assay with MG132, luciferase reporter for STAT5B-DCAF13 transcription, tumor-bearing nude mouse model\",\n      \"journal\": \"Biologics : targets & therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — ubiquitination assay with proteasome inhibitor, transcriptional reporter, in vivo model; single lab, moderate mechanistic depth\",\n      \"pmids\": [\"38979130\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"CRL4-DCAF13 targets Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation in ovarian cancer cells. FRAS1 accumulation (upon DCAF13 knockout) inhibits the focal adhesion kinase (FAK) signaling pathway, suppressing proliferation and migration.\",\n      \"method\": \"CRISPR/Cas9 knockout of DCAF13, ubiquitination assays, FAK signaling pathway analysis (western blot), co-immunoprecipitation, xenograft mouse model\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO, ubiquitination assay, pathway activity measurement, in vivo xenograft; single lab with multiple methods\",\n      \"pmids\": [\"39367995\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DCAF13 promotes RNA polymerase I (Pol I) transcription by facilitating K63-linked ubiquitination of RPA194 (the largest Pol I subunit), a non-degradative modification that stimulates Pol I transcriptional activity, thereby enhancing ribosome biogenesis and global protein synthesis in breast cancer cells.\",\n      \"method\": \"Multi-omics analysis, ubiquitination assays (K63-specific), Pol I transcription assays, co-immunoprecipitation, in vitro and in vivo proliferation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — K63-specific ubiquitination assay, Pol I transcription assay, in vitro and in vivo functional validation, multiple orthogonal methods in peer-reviewed journal\",\n      \"pmids\": [\"39788980\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DCAF13 directly interacts with TAF1A, a component of the RNA polymerase I preinitiation complex, and this interaction is necessary for preinitiation complex assembly and rDNA transcription. DCAF13 knockdown impairs rDNA transcription, ribosome biogenesis, and protein synthesis in non-small cell lung cancer cells.\",\n      \"method\": \"Co-immunoprecipitation (DCAF13-TAF1A), rDNA transcription assays, ribosome biogenesis analysis, protein synthesis assay, DCAF13 knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP establishing direct interaction, functional transcription assay, ribosome biogenesis analysis; single lab\",\n      \"pmids\": [\"40902972\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DCAF13 directly binds RRS1 (a ribosome biogenesis factor) and catalyzes K27-linked polyubiquitination of RRS1, a non-degradative modification that enhances RRS1 protein stability, thereby supporting ribosome assembly and protein synthesis in hematopoietic stem cells. Conditional deletion of Dcaf13 causes severe pancytopenia, HSC depletion, and activates the p53 pathway; Trp53 ablation only partially rescues this phenotype.\",\n      \"method\": \"Conditional knockout in hematopoietic cells, co-immunoprecipitation (DCAF13-RRS1), K27-specific ubiquitination assay, ribosome assembly analysis, protein synthesis assay, Trp53 double knockout epistasis\",\n      \"journal\": \"Advanced science (Weinheim, Baden-Wurttemberg, Germany)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with in vivo phenotype, Co-IP, K27-specific ubiquitination assay, epistasis with p53, multiple orthogonal methods\",\n      \"pmids\": [\"41787937\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In the uterus, DCAF13 deficiency leads to elevated H3K9me3 levels (associated with increased SUV39H2 transcription), dysregulated estrogen and progesterone receptor expression, and insufficient endometrial cell proliferation, causing embryo implantation failure and infertility.\",\n      \"method\": \"Uterine conditional knockout of Dcaf13, RNA-seq, immunofluorescence for H3K9me3, hormone receptor western blot, in vivo implantation assay\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with defined molecular phenotype (H3K9me3, hormone receptors), RNA-seq, in vivo implantation assay; single lab\",\n      \"pmids\": [\"40750792\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In cranial neural crest cells, DCAF13 deficiency causes PTEN accumulation (a substrate it normally degrades), which suppresses PI3K/AKT signaling, thereby impairing proliferation and differentiation of CNC-derived cells and causing craniofacial malformations.\",\n      \"method\": \"Neural crest-specific conditional knockout of Dcaf13, western blot for PTEN and AKT phosphorylation, immunofluorescence, skeletal staining\",\n      \"journal\": \"Genesis (New York, N.Y. : 2000)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional KO with PTEN substrate accumulation and PI3K/AKT pathway activity measurement; single lab\",\n      \"pmids\": [\"41492083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DCAF13 interacts with glucose-6-phosphate dehydrogenase (G6PD) to enhance glycolytic flux in hepatocellular carcinoma cells. The stability of DCAF13 mRNA is maintained by METTL3-mediated m6A modification and YTHDF1 binding.\",\n      \"method\": \"Co-immunoprecipitation (DCAF13-G6PD), molecular dynamics simulation, MeRIP-qPCR and RIP assays for m6A/YTHDF1, CRISPR/Cas9 knockout, glycolysis flux assays\",\n      \"journal\": \"Journal of gastroenterology and hepatology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP and molecular dynamics for DCAF13-G6PD interaction; single lab, m6A regulation inferred from RIP; limited mechanistic depth in abstract\",\n      \"pmids\": [\"40708455\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DCAF13 is a multifunctional nucleolar WD40-repeat protein that acts primarily as a substrate receptor (adaptor) for the CRL4 (CUL4-DDB1-RBX1) E3 ubiquitin ligase complex, directing polyubiquitination and proteasomal degradation of diverse substrates—including SUV39H1, PTEN, PERP, MeCP2, p53, FRAS1, and TOP1-DPCs—in a context-dependent manner; independently of its E3 adaptor role, DCAF13 supports ribosome biogenesis by interacting with fibrillarin, NPM1, UTP23, and TAF1A to facilitate 18S rRNA processing and Pol I preinitiation complex assembly, and can also catalyze non-degradative K27-linked ubiquitination of RRS1 to stabilize it, or K63-linked ubiquitination of RPA194 to stimulate Pol I transcription, collectively making DCAF13 an essential regulator of epigenetic reprogramming, translational capacity, and cell proliferation in development and cancer.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DCAF13 is a nucleolar WD40-repeat protein that serves as a substrate receptor for the CRL4 (CUL4–DDB1–RBX1) E3 ubiquitin ligase and, independently, as a ribosome biogenesis factor, making it an essential regulator of epigenetic reprogramming, translational capacity, and proliferation in development and cancer [#0, #1, #7]. As a CRL4 adaptor it directs polyubiquitination and proteasomal degradation of a context-dependent set of substrates: SUV39H1 to lower H3K9me3 and license zygotic gene expression [#0], PTEN to sustain PI3K/AKT signaling required for meiotic resumption and neural crest development [#3, #17], MeCP2 to restrain DNA methylation in growing oocytes [#9], the TOP1–DNA-protein crosslink for replication-coupled repair [#7], PERP, FRAS1, and p53 in various cancers [#6, #12, #10]. Beyond degradative ubiquitination, DCAF13 catalyzes non-degradative chain types that promote ribosome production—K63-linked ubiquitination of the Pol I subunit RPA194 to stimulate rDNA transcription, and K27-linked ubiquitination of RRS1 to stabilize it during hematopoietic ribosome assembly [#13, #15]. It also supports 18S rRNA processing through interactions with fibrillarin, NPM1/UTP23, and the Pol I preinitiation factor TAF1A, the latter two coupling DCAF13 to nucleolar condensate formation and preinitiation complex assembly [#1, #8, #14]. Loss of DCAF13 produces ribosome biogenesis failure, p53 pathway activation, and developmental arrest across oocytes, embryos, hematopoietic stem cells, and uterine tissue [#1, #15, #16].\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Established that DCAF13 functions catalytically as a CRL4 substrate receptor, defining its first degradation target and demonstrating it assembles into a CUL4B–DDB1 ligase.\",\n      \"evidence\": \"Co-IP, in vitro/in vivo ubiquitination, knockdown and overexpression in osteosarcoma cells targeting PTEN\",\n      \"pmids\": [\"29499938\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Degron/substrate recognition motif on PTEN not defined\", \"Specificity vs other DCAFs not addressed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected DCAF13 to epigenetic reprogramming by showing CRL4-DCAF13 degrades the H3K9 methyltransferase SUV39H1 to erase repressive marks and enable zygotic gene activation in vivo.\",\n      \"evidence\": \"Dcaf13 knockout mice, reciprocal Co-IP, ubiquitination assays, H3K9me3 immunofluorescence\",\n      \"pmids\": [\"30111536\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether SUV39H2 is also a substrate not resolved here\", \"Direct enzymatic specificity vs indirect effects on H3K9me3\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Revealed a degradation-independent role in ribosome biogenesis, placing DCAF13 in the nucleolar rRNA-processing machinery via fibrillarin interaction.\",\n      \"evidence\": \"Oocyte conditional KO, Co-IP with fibrillarin, northern blot for pre-rRNA, ribosome assembly and protein synthesis assays\",\n      \"pmids\": [\"30283081\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct rRNA cleavage role vs scaffolding not separated\", \"Molecular basis of fibrillarin binding unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Linked DCAF13-mediated PTEN degradation to a physiological signaling outcome—maintaining PI3K activity and CDK1 for oocyte meiotic resumption.\",\n      \"evidence\": \"Oocyte-specific KO, ubiquitination assays, PI3K and CDK1 activity measurement, spindle/chromosome imaging\",\n      \"pmids\": [\"31492966\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How DCAF13 substrate choice is restricted to PTEN in this context unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed maternal DCAF13 is required for higher-order chromatin organization and nucleolar reorganization in oocytes, broadening its role beyond single-substrate effects.\",\n      \"evidence\": \"Oocyte conditional KO, RNA-seq of MII oocytes and 2-cell embryos, mRNA rescue attempt, immunofluorescence\",\n      \"pmids\": [\"31000741\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mRNA rescue failed, leaving causal mechanism for chromatin tightness incomplete\", \"Molecular link between nucleolar function and chromatin not defined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Proposed an RNA-binding activity distinct from ubiquitin ligation, with DCAF13 destabilizing DTX3 mRNA via ARE binding to drive NOTCH4 signaling in cancer.\",\n      \"evidence\": \"RIP, mRNA stability assays, migration/invasion assays, NOTCH4 ubiquitination in TNBC cells\",\n      \"pmids\": [\"33300431\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect ARE binding not structurally confirmed\", \"Relationship of RBP activity to WD40 scaffold unknown\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extended the CRL4-DCAF13 substrate repertoire to PERP in breast cancer, coupling its degradation to apoptosis and senescence suppression.\",\n      \"evidence\": \"CRISPR KO, Co-IP of DCAF13–DDB1–PERP ternary complex, DDB1-dependent ubiquitination, RNA-seq\",\n      \"pmids\": [\"35178836\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"mRNA accumulation of PERP upon KO implies an additional transcriptional layer not explained\", \"Degron not mapped\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined DCAF13 as the CRL4 receptor recognizing TOP1-DPCs for replication-coupled repair, with the complex undergoing auto-NEDDylation and exploitable by NEDD8 inhibition.\",\n      \"evidence\": \"Chemical genetic screens, Co-IP, ubiquitination assays, DPC repair in CRC cells, organoids, xenografts, pevonedistat combination\",\n      \"pmids\": [\"37353483\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How DCAF13 discriminates crosslinked TOP1 from native TOP1 unresolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Showed DCAF13 drives nucleolar phase separation through NPM1 to recruit UTP23 and accelerate 18S rRNA maturation, linking ribosome biogenesis to rapid proliferation.\",\n      \"evidence\": \"T cell-specific KO, phase separation assays, rRNA processing, ribosome assembly and nascent protein synthesis assays\",\n      \"pmids\": [\"37615668\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether DCAF13 itself undergoes phase separation or only promotes NPM1 condensation unclear\", \"Direct UTP23 contact not shown\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Identified MeCP2 as an oocyte CRL4-DCAF13 substrate, connecting its degradation to control of DNA methylation, validated by genetic rescue.\",\n      \"evidence\": \"Dcaf13-null oocytes, ubiquitination assays, MeCP2 knockdown rescue, RNA-seq, DNA methylation analysis\",\n      \"pmids\": [\"38578457\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Only partial rescue indicates additional substrates contribute to phenotype\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Established DCAF13 as a negative regulator of p53 across cancers, promoting K48-linked p53 degradation and, downstream, ferroptosis suppression via xCT.\",\n      \"evidence\": \"Co-IP, K48-linked ubiquitination assays, RNA-seq, ChIP-qPCR in lung adenocarcinoma; STAT5B reporter, ubiquitination and xenografts in mantle cell lymphoma\",\n      \"pmids\": [\"38163876\", \"38979130\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether p53 ubiquitination is CRL4-dependent not formally shown in both contexts\", \"Direct vs scaffolded p53 recognition unresolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Added FRAS1 as a CRL4-DCAF13 substrate whose degradation sustains FAK signaling and tumor cell proliferation/migration in ovarian cancer.\",\n      \"evidence\": \"CRISPR KO, ubiquitination assays, FAK pathway western blots, Co-IP, xenografts\",\n      \"pmids\": [\"39367995\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism linking FRAS1 level to FAK activity not detailed\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated non-degradative ubiquitination as a DCAF13 mechanism, with K63-linked modification of RPA194 stimulating Pol I transcription, and direct TAF1A binding required for preinitiation complex assembly.\",\n      \"evidence\": \"K63-specific ubiquitination and Pol I transcription assays in breast cancer (RPA194); Co-IP and rDNA transcription assays in NSCLC (TAF1A)\",\n      \"pmids\": [\"39788980\", \"40902972\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether RPA194 K63 ubiquitination uses the CRL4 scaffold or a different E3 unclear\", \"Coordination between RPA194 and TAF1A roles not integrated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified a third ubiquitin chain type—K27-linked stabilization of RRS1—and showed DCAF13 sustains hematopoietic stem cell ribosome assembly upstream of the p53 pathway.\",\n      \"evidence\": \"Hematopoietic conditional KO, Co-IP, K27-specific ubiquitination assays, ribosome assembly assays, Trp53 epistasis\",\n      \"pmids\": [\"41787937\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Only partial p53-independent rescue; full downstream effector set undefined\", \"How chain-type selectivity (K27 vs K48 vs K63) is achieved unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Extended DCAF13's developmental requirement to uterine receptivity, where its loss raises H3K9me3 and dysregulates hormone receptors to cause implantation failure.\",\n      \"evidence\": \"Uterine conditional KO, RNA-seq, H3K9me3 immunofluorescence, hormone receptor western blot, implantation assay\",\n      \"pmids\": [\"40750792\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct substrate driving SUV39H2/H3K9me3 change not pinpointed in uterus\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proposed a metabolic role via G6PD interaction enhancing glycolysis, with DCAF13 mRNA itself under m6A/YTHDF1 control in hepatocellular carcinoma.\",\n      \"evidence\": \"Co-IP, molecular dynamics, MeRIP-qPCR and RIP, CRISPR KO, glycolysis flux assays\",\n      \"pmids\": [\"40708455\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Single Co-IP plus simulation; functional dependence of glycolysis on direct DCAF13–G6PD binding not established\", \"m6A regulation inferred indirectly\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DCAF13 selects among degradative (K48), and non-degradative (K63, K27) ubiquitin chain types and switches between its E3 adaptor and ribosome biogenesis functions remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of substrate or chain-type determinants\", \"Mechanism partitioning DCAF13 between CRL4 and nucleolar machinery unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 2, 3, 6, 7, 9, 10, 12, 13, 15]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 7]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [13, 14]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [1, 4, 8]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [1, 8, 13, 14, 15]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 2, 7, 9, 10]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [0, 16]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"CRL4 (CUL4-DDB1-RBX1) E3 ubiquitin ligase\",\n      \"Pol I preinitiation complex\"\n    ],\n    \"partners\": [\n      \"DDB1\",\n      \"CUL4B\",\n      \"FBL\",\n      \"NPM1\",\n      \"UTP23\",\n      \"TAF1A\",\n      \"RRS1\",\n      \"RPA194\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}