{"gene":"DCAF7","run_date":"2026-06-09T23:54:41","timeline":{"discoveries":[{"year":2006,"finding":"WDR68 (DCAF7) interacts with DYRK1A and DYRK1B kinases and is required for craniofacial development in zebrafish; a GFP-WDR68 fusion protein localizes to the nucleus with DYRK1A, whereas a loss-of-function mutant (Wdr68-T284F) fails to accumulate in the nucleus and fails to rescue wdr68 mutant animals, placing WDR68 upstream of the edn1 pathway.","method":"Zebrafish insertional mutagenesis screen, GFP fusion localization, rescue experiments","journal":"BMC developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis in zebrafish with localization experiments and rescue assay, single lab","pmids":["16759393"],"is_preprint":false},{"year":2010,"finding":"HAN11 (DCAF7) acts as a scaffold protein that directly binds HIPK2, DYRK1A, DYRK1B, and MEKK1 in vitro, and is required to couple MEKK1 to DYRK1/HIPK2; knockdown lowers the threshold and amplitude of HIPK2- and MEKK1-triggered signaling, while overexpression impairs stoichiometrically assembled signaling complexes.","method":"In vitro direct binding assays, co-immunoprecipitation, knockdown in human cells and C. elegans, transcriptional reporter assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct binding in vitro, reciprocal co-IP, functional knockdown in multiple organisms with defined signaling phenotypes","pmids":["20940704"],"is_preprint":false},{"year":2010,"finding":"C. elegans SWAN-1 (DCAF7 ortholog) physically interacts with EGL-9 (prolyl hydroxylase) by yeast two-hybrid and co-immunoprecipitation; genetic evidence places the DYRK kinase MBK-1 downstream of SWAN-1 to promote HIF-1-mediated transcription and resistance to P. aeruginosa.","method":"Yeast two-hybrid, co-immunoprecipitation, forward genetic screen, epistasis analysis","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP and genetic epistasis in C. elegans, single lab","pmids":["20865124"],"is_preprint":false},{"year":2006,"finding":"SWAN-1 (DCAF7 ortholog in C. elegans) physically associates with Rac GTPases and the LIM domains of the Rac effector UNC-115/abLIM; swan-1 loss-of-function suppresses ced-10 (Rac) hypomorphic defects and enhances constitutively active Rac phenotypes, identifying SWAN-1 as a negative regulator of Rac GTPase function in cytoskeletal organization.","method":"Yeast two-hybrid, genetic epistasis in C. elegans, transgenic overexpression in C. elegans neurons and cultured mammalian fibroblasts","journal":"Genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast two-hybrid, genetic epistasis in multiple contexts, single lab","pmids":["16980389"],"is_preprint":false},{"year":2011,"finding":"WDR68 (DCAF7) binds DYRK1A and DYRK1B (but not DYRK2, 3, or 4) via DYRK1A's N-terminal domain (not the kinase domain); co-expression of wild-type or kinase-dead DYRK1A drives nuclear accumulation of WDR68, indicating that binding (not phosphorylation) mediates nuclear translocation; WDR68 depletion induces cell apoptosis.","method":"Co-immunoprecipitation, immunofluorescence, RNAi knockdown, domain deletion mapping","journal":"Biochimica et biophysica acta","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP, domain mapping, multiple orthogonal methods, functional consequence defined","pmids":["21777625"],"is_preprint":false},{"year":2013,"finding":"Nuclear access is required for WDR68 function in craniofacial development: a nuclear-export-signal (NES) fusion of WDR68 fails to rescue craniofacial defects and redistributes DYRK1A to the cytoplasm; a transcriptional activation domain fusion rescues development whereas a transcriptional repression domain fusion does not; WDR68 promotes myogenin promoter activity in C2C12 cells.","method":"Zebrafish rescue experiments, NES fusion constructs, co-localization by immunofluorescence, reporter assay in C2C12 cells","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic rescue with engineered constructs, reporter assay, localization with functional consequence, single lab","pmids":["23349862"],"is_preprint":false},{"year":2014,"finding":"The molecular chaperone TRiC/CCT binds WDR68 via three of its seven β-propeller blades; TRiC/CCT knockdown causes abnormal WDR68 folding, reduces DYRK1A-binding activity, suppresses nuclear accumulation of WDR68, and causes WDR68 aggregation upon overexpression. Phosphorylation sites in both WDR68 and TRiC/CCT were identified.","method":"Phosphoproteomic pulldown/MS, co-immunoprecipitation, siRNA knockdown, structural modeling, deletion mutant analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — MS-identified interaction confirmed by co-IP, siRNA functional validation, structural modeling with deletion mutants, multiple orthogonal methods","pmids":["25342745"],"is_preprint":false},{"year":2016,"finding":"DCAF7 (WDR68/HAN11) acts as an adaptor that bridges adenovirus E1A to DYRK1A and HIPK2; a 12-amino-acid DCAF7-binding motif in the N-terminal domain of class 1 DYRKs is functionally conserved across species; a similar sequence mediates DCAF7 binding to HIPK2, whereas HIPK1 does not bind DCAF7; DCAF7 is required for hyperphosphorylation of E1A by DYRK1A or HIPK2, defining it as a substrate-recruiting subunit.","method":"Co-immunoprecipitation, GST pulldown, domain mutagenesis, hyperphosphorylation assay in overexpressing cells","journal":"Scientific reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal co-IP plus pulldown, mutagenesis of binding motif, functional phosphorylation assay, multiple interactors tested","pmids":["27307198"],"is_preprint":false},{"year":2016,"finding":"DCAF7 is the specificity/substrate-recognition factor for the Cul4-DDB1 E3 ubiquitin ligase complex that targets DNA ligase I for ubiquitylation and degradation; three ubiquitylated lysine residues on DNA ligase I were mapped, and mutation of these residues reduced in vitro ubiquitylation by Cul4-DDB1-DCAF7; DCAF7 knockdown reduced DNA ligase I degradation upon inhibition of proliferation.","method":"Proteomic ubiquitylation-site mapping, co-immunoprecipitation, in vitro ubiquitylation assay, siRNA knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro ubiquitylation reconstitution, site-directed mutagenesis of ubiquitylation sites, co-IP, siRNA knockdown with functional readout","pmids":["27573245"],"is_preprint":false},{"year":2006,"finding":"HAN11 (DCAF7) binds the FH2 actin-binding domain of mDia1; overexpression of mDia1 or active RhoA causes translocation of HAN11 from nucleus to cytoplasm; HAN11 and mDia1 together repress DYRK1A-dependent GLI1 transcriptional activity.","method":"TAP-tag purification, GST pulldown, luciferase transcriptional assay, immunofluorescence microscopy","journal":"Journal of dermatological science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — TAP-tag pulldown confirmed by GST pulldown, transcriptional reporter assay, localization study, single lab","pmids":["16887337"],"is_preprint":false},{"year":2017,"finding":"DCAF7 (Dcaf7/WDR68) is a component of neuronal stigmoid bodies that interacts with Huntingtin-associated protein 1 (Hap1); Hap1 competes with DYRK1A for cytoplasmic binding to Dcaf7, thereby regulating Dcaf7 nuclear translocation; depleting Hap1 promotes DYRK1A-Dcaf7 interaction, increases DYRK1A protein levels, and overexpression of DYRK1A in hypothalamus causes delayed postnatal growth in mice.","method":"Subcellular fractionation, immunoprecipitation from mouse brain, transgenic mouse overexpression, co-immunoprecipitation","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP from brain fraction, competitive binding assay, transgenic mouse phenotype, single lab","pmids":["28137862"],"is_preprint":false},{"year":2018,"finding":"WDR68 (DCAF7) is required for normal protein levels of DYRK1A and DYRK1B: deletion of Wdr68 reduces DYRK1A/1B protein without affecting Dyrk1a mRNA levels or proteasome-dependent degradation; overexpression of WDR68 increases DYRK1A protein; DYRK1A and DYRK1B are each required for the transition from proliferation to differentiation in C2C12 cells.","method":"CRISPR/engineered knockout cell lines, mRNA quantification, proteasome inhibition, overexpression, differentiation assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function and gain-of-function in engineered cell lines, multiple controls, single lab","pmids":["30496304"],"is_preprint":false},{"year":2018,"finding":"WDR68 (DCAF7) is an integral component of the PRC1-AUTS2 complex and is required for PRC1-AUTS2-mediated transcriptional activation; deletion of Wdr68 in mouse embryonic stem cells causes defects in neuronal differentiation without affecting self-renewal, with down-regulation of PRC1-AUTS2 target neuronal genes.","method":"Complex co-immunoprecipitation, Wdr68 deletion in mESCs, transcriptomic analysis, differentiation assays","journal":"Stem cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP showing complex membership, genetic deletion with transcriptomic readout, single lab","pmids":["30448639"],"is_preprint":false},{"year":2019,"finding":"DYRK1A exists in a complex with DCAF7 that stabilizes DYRK1A and tethers it to RNA Pol II; this DYRK1A-DCAF7 complex phosphorylates the CTD of Pol II and co-migrates with Pol II along myogenic gene loci to stimulate myogenic transcription after P-TEFb is eliminated during myoblast differentiation.","method":"Co-immunoprecipitation, ChIP-seq, Pol II CTD phosphorylation assay, knockdown with transcriptional and differentiation readouts","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP, ChIP-seq, biochemical CTD kinase assay, loss-of-function with defined transcriptional phenotype, multiple orthogonal methods","pmids":["30864669"],"is_preprint":false},{"year":2019,"finding":"DCAF7 interacts with the ERCC1-XPF endonuclease complex (primarily with XPF); DCAF7 knockdown reduces cellular ERCC1-XPF protein levels partly via proteasomal degradation and impairs nucleotide excision repair of UV-induced (6-4) photoproducts; depletion of TRiC/CCT also reduces ERCC1-XPF levels, linking chaperone-assisted DCAF7 folding to NER capacity.","method":"Mass spectrometry after tandem purification, co-immunoprecipitation, siRNA knockdown, UV damage repair assay, ectopic overexpression rescue","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — MS identification confirmed by co-IP, functional knockdown with repair assay and rescue, single lab","pmids":["31493872"],"is_preprint":false},{"year":2022,"finding":"DCAF7 proximally interacts with IRS1 (insulin/IGF1 signaling adaptor) as well as DYRK1A and DYRK1B; DCAF7 knockdown in HepG2 cells attenuates insulin-stimulated AKT phosphorylation, promotes nuclear localization of FOXO1, induces FOXO1 target genes involved in G2 cell cycle inhibition, and causes G2 arrest; in Drosophila, wing-specific knockdown of DCAF7/wap reduces wing cell number, rescued by co-knockdown of dfoxo.","method":"BioID proximity labeling, siRNA knockdown, AKT phosphorylation assay, FOXO1 localization, gene expression analysis, Drosophila genetic epistasis","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID interaction, functional siRNA with signaling readout, Drosophila epistasis, multiple orthogonal approaches, single lab","pmids":["36248734"],"is_preprint":false},{"year":2023,"finding":"CUL4B and DCAF7 form a CRL4B E3 ubiquitin ligase complex that binds MEN1 (menin), catalyzes its ubiquitylation, and promotes its proteasomal degradation; neddylation activates this pathway; DCAF7 knockdown restores MEN1 levels and re-sensitizes everolimus-resistant PanNET cells to mTOR inhibition, with effects reversible by simultaneous MEN1 knockdown.","method":"Co-immunoprecipitation, ubiquitylation assay, siRNA knockdown, neddylation inhibitor (MLN4924), in vitro and in vivo tumor models, rescue experiments","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Strong — co-IP, ubiquitylation assay, genetic rescue in vitro and in vivo, pharmacological validation, multiple orthogonal methods","pmids":["36939378"],"is_preprint":false},{"year":2024,"finding":"DCAF7 acts as a scaffold protein that facilitates interaction between deubiquitinase USP10 and G3BP1; this leads to removal of K48-linked ubiquitin from Lys76 of G3BP1, preventing its proteasomal degradation and promoting stress granule-like structure formation; G3BP1 knockdown reverses the pro-tumorigenic effects of DCAF7 in nasopharyngeal carcinoma cells.","method":"Co-immunoprecipitation, ubiquitylation site mapping, siRNA knockdown with rescue, stress granule formation assay, in vitro and in vivo tumor models","journal":"Advanced science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, ubiquitylation analysis, functional rescue, single lab","pmids":["38973296"],"is_preprint":false},{"year":2025,"finding":"DCAF7 acts as the substrate recognition receptor of a CRL4B (CUL4B-RBX1-DDB1-DCAF7) E3 ligase that promotes K48-linked polyubiquitination of influenza A virus polymerase subunit PA at Lys609 and its proteasomal degradation, thereby restricting IAV replication; viral NS1 protein decreases DCAF7 levels to counteract this restriction.","method":"Co-immunoprecipitation, ubiquitylation assay with site-specific mutagenesis (K609), siRNA knockdown and overexpression, MLN4924 pharmacological inhibition in vivo, etoposide activation of CUL4B in vivo","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro ubiquitylation with site mutagenesis, co-IP, pharmacological and genetic in vivo validation, multiple orthogonal methods","pmids":["40145735"],"is_preprint":false},{"year":2025,"finding":"DCAF7 recruits deubiquitinase USP2 to inhibit clockophagy (selective autophagic degradation of BMAL1 via p62/SQSTM1) by reducing BMAL1 K63-linked polyubiquitination; loss of DCAF7 or USP2 triggers clockophagy-induced ferroptosis through the HIF1α-SLC7A11 axis in hepatocellular carcinoma cells.","method":"Co-immunoprecipitation, ubiquitylation assay, genetic ablation, pharmacological inhibition, in vitro and in vivo tumor models","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP, ubiquitylation analysis, genetic and pharmacological loss-of-function with mechanistic pathway, single lab","pmids":["40877242"],"is_preprint":false},{"year":2025,"finding":"WDR68 (DCAF7) is required for mouse embryonic development; WDR68 null embryos show intrauterine growth retardation and die in utero; WDR68 deficiency activates the HIF-1 pathway and deregulates developmental gene expression; co-immunoprecipitation/MS confirmed interaction of WDR68 with AUTS2 and PCGF5 (PRC1 components) in mouse embryos.","method":"Gene targeting (knockout mouse), single-cell RNA-seq, whole-embryo transcriptomics, co-immunoprecipitation/mass spectrometry","journal":"Journal of translational medicine","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic knockout with lethal phenotype, transcriptomic analysis, co-IP/MS for interactors, single lab","pmids":["40462101"],"is_preprint":false}],"current_model":"DCAF7 (WDR68/HAN11) is an evolutionarily conserved, catalytically inactive WD40-repeat scaffold/adaptor protein that (1) binds DYRK1A and DYRK1B via their N-terminal domains—an interaction requiring TRiC/CCT chaperone-assisted proper folding of DCAF7—and stabilizes these kinases while driving their nuclear translocation; (2) serves as the substrate-recognition subunit of CUL4B-DDB1 E3 ubiquitin ligase complexes, directing ubiquitylation and proteasomal degradation of substrates including DNA ligase I, MEN1, and viral PA polymerase; (3) acts as a scaffold coupling additional kinases (HIPK2, MEKK1) and deubiquitinases (USP10, USP2) to their targets; (4) is an integral component of the transcriptionally active PRC1-AUTS2 complex required for neuronal differentiation; and (5) controls cell proliferation, myogenesis, craniofacial development, and stress responses through these mechanistically distinct protein complexes."},"narrative":{"mechanistic_narrative":"DCAF7 (WDR68/HAN11) is an evolutionarily conserved, catalytically inactive WD40-repeat scaffold and substrate-recognition adaptor that organizes distinct kinase- and ubiquitin-ligase complexes controlling differentiation, proliferation, and development [PMID:20940704, PMID:27573245]. Its best-defined role is as a dedicated partner of the class 1 DYRK kinases DYRK1A and DYRK1B: it binds a conserved 12-residue motif in their N-terminal (non-catalytic) domain rather than the kinase domain, and this binding—not phosphorylation—drives their nuclear accumulation, stabilizes DYRK protein levels, and recruits substrates such as adenoviral E1A for hyperphosphorylation [PMID:21777625, PMID:27307198, PMID:30496304]. Through the same scaffolding logic DCAF7 also couples HIPK2 and MEKK1 into stoichiometric signaling complexes [PMID:20940704, PMID:27307198]. Proper folding of DCAF7 by the TRiC/CCT chaperonin, which engages three of its β-propeller blades, is a prerequisite for DYRK1A binding and nuclear localization [PMID:25342745]. In the nucleus DCAF7 functions in transcription: it is an integral subunit of the transcriptionally active PRC1-AUTS2 complex required for neuronal differentiation [PMID:30448639, PMID:40462101], and the DYRK1A-DCAF7 complex phosphorylates the RNA Pol II CTD and tracks along myogenic loci to sustain myogenic transcription [PMID:30864669]. Independently, DCAF7 serves as the substrate-recognition receptor of CUL4-DDB1/CRL4B E3 ubiquitin ligases, directing K48-linked ubiquitylation and proteasomal degradation of DNA ligase I, MEN1/menin, and influenza A virus PA polymerase [PMID:27573245, PMID:36939378, PMID:40145735], and conversely it can scaffold deubiquitinases (USP10 toward G3BP1, USP2 toward BMAL1) to protect targets from degradation [PMID:38973296, PMID:40877242]. Loss of DCAF7 is embryonic-lethal in mice with intrauterine growth retardation and aberrant HIF-1-pathway activation [PMID:40462101], consistent with its requirement for craniofacial development, myogenesis, and the proliferation-to-differentiation transition across model systems [PMID:16759393, PMID:23349862, PMID:30496304].","teleology":[{"year":2006,"claim":"Established DCAF7 as a physiological partner of DYRK kinases and a developmental regulator, framing the question of how a WD40 protein influences signaling output.","evidence":"Zebrafish insertional mutagenesis, GFP-fusion localization, and rescue placing WDR68 upstream of the edn1 pathway; parallel C. elegans work linking the SWAN-1 ortholog to Rac GTPase regulation and mDia1 binding","pmids":["16759393","16980389","16887337"],"confidence":"Medium","gaps":["Did not define whether DCAF7 acts as kinase scaffold versus transcriptional effector","Molecular basis of the DYRK1A interaction unresolved","Rac/mDia1 connections come from invertebrate genetics without mammalian biochemical reconstitution"]},{"year":2010,"claim":"Defined DCAF7 as a direct scaffold that couples multiple kinases, explaining how it shapes signaling thresholds rather than acting catalytically.","evidence":"In vitro direct binding, reciprocal co-IP, and knockdown in human cells and C. elegans with transcriptional reporter readouts (HIPK2, DYRK1A/1B, MEKK1); separate epistasis placing the DYRK MBK-1 downstream of SWAN-1 in HIF-1-mediated immunity","pmids":["20940704","20865124"],"confidence":"High","gaps":["Did not map the binding motifs on each kinase","Stoichiometry of assembled complexes not structurally resolved"]},{"year":2011,"claim":"Showed that DCAF7 binds DYRK1A/1B through their N-terminal domain and that binding alone (not phosphorylation) drives DCAF7 nuclear translocation, separating localization control from kinase activity.","evidence":"Co-IP, immunofluorescence, RNAi, and domain-deletion mapping using wild-type and kinase-dead DYRK1A","pmids":["21777625"],"confidence":"High","gaps":["Mechanism by which the DYRK1A-DCAF7 pair traverses the nuclear envelope not defined","Apoptosis upon depletion not mechanistically dissected"]},{"year":2013,"claim":"Demonstrated that nuclear access and a transcription-activating function are required for DCAF7's developmental role, tying its localization to transcriptional output.","evidence":"Zebrafish rescue with NES and transcriptional activation/repression domain fusions plus myogenin promoter reporter in C2C12 cells","pmids":["23349862"],"confidence":"Medium","gaps":["Direct transcriptional targets not identified at this stage","Whether DCAF7 itself contacts chromatin unresolved"]},{"year":2014,"claim":"Identified TRiC/CCT chaperonin as required for DCAF7 folding, establishing that competent DYRK1A binding and nuclear accumulation depend on chaperone-assisted β-propeller assembly.","evidence":"Phosphoproteomic pulldown/MS, co-IP, siRNA knockdown, structural modeling, and deletion mutants","pmids":["25342745"],"confidence":"High","gaps":["Functional role of identified phosphosites not tested","Whether folding is regulated to control activity unknown"]},{"year":2016,"claim":"Defined DCAF7 as a substrate-recruiting adaptor in two arenas: bridging E1A to DYRK1A/HIPK2 for hyperphosphorylation, and serving as the specificity factor of a Cul4-DDB1 ligase that degrades DNA ligase I.","evidence":"Co-IP, GST pulldown, binding-motif mutagenesis, hyperphosphorylation assay; and ubiquitylation-site mapping with in vitro Cul4-DDB1-DCAF7 ubiquitylation and siRNA","pmids":["27307198","27573245"],"confidence":"High","gaps":["Did not establish how DCAF7 partitions between kinase-scaffold and E3-adaptor roles","Selectivity rules for ligase substrates unresolved"]},{"year":2017,"claim":"Showed that competition for cytoplasmic DCAF7 binding regulates DYRK1A nuclear translocation and stability, identifying Hap1 as a tuning factor at stigmoid bodies.","evidence":"Subcellular fractionation, co-IP from mouse brain, competitive binding, and transgenic DYRK1A overexpression causing growth phenotype","pmids":["28137862"],"confidence":"Medium","gaps":["Physiological stimulus governing Hap1-DCAF7 competition unknown","Direct structural overlap of Hap1 and DYRK1A binding sites not mapped"]},{"year":2018,"claim":"Established that DCAF7 sustains DYRK1A/1B protein levels post-transcriptionally and is required for the proliferation-to-differentiation switch, and that DCAF7 is a genuine subunit of the PRC1-AUTS2 transcriptional complex.","evidence":"CRISPR knockout cell lines with mRNA quantification, proteasome inhibition, and differentiation assays; complex co-IP and Wdr68 deletion in mESCs with transcriptomics","pmids":["30496304","30448639"],"confidence":"Medium","gaps":["Mechanism of DYRK stabilization independent of proteasome not defined","How DCAF7 contributes to PRC1-AUTS2 activation unresolved"]},{"year":2019,"claim":"Demonstrated a direct chromatin-associated transcriptional mechanism: the DYRK1A-DCAF7 complex phosphorylates Pol II CTD and travels with Pol II to drive myogenic transcription after P-TEFb loss.","evidence":"Co-IP, ChIP-seq, Pol II CTD phosphorylation assay, and knockdown with transcriptional/differentiation readouts; plus DCAF7 interaction with ERCC1-XPF affecting NER capacity","pmids":["30864669","31493872"],"confidence":"High","gaps":["Whether DCAF7 directly contacts DNA versus tethering kinase unresolved","ERCC1-XPF link relies on knockdown without reconstitution"]},{"year":2022,"claim":"Connected DCAF7 to insulin/IGF1 signaling, showing it is required for insulin-stimulated AKT activation and restraint of FOXO1, linking the scaffold to proliferation control.","evidence":"BioID proximity labeling, siRNA with AKT phosphorylation and FOXO1 localization readouts, and Drosophila wing epistasis rescued by dfoxo co-knockdown","pmids":["36248734"],"confidence":"Medium","gaps":["Direct versus indirect IRS1 interaction not resolved (proximity labeling)","Mechanistic step between DCAF7 and AKT unclear"]},{"year":2023,"claim":"Extended the CRL4B substrate-receptor function to a disease context, showing DCAF7-directed degradation of MEN1 controls mTOR-inhibitor sensitivity in neuroendocrine tumors.","evidence":"Co-IP, ubiquitylation assay, siRNA rescue in vitro and in vivo, and neddylation inhibition (MLN4924)","pmids":["36939378"],"confidence":"High","gaps":["Determinants of MEN1 recognition by DCAF7 not mapped","Crosstalk with DCAF7's kinase-scaffold roles untested"]},{"year":2024,"claim":"Revealed a deubiquitinase-scaffolding mode in which DCAF7 bridges USP10 to G3BP1, stabilizing it and promoting stress-granule-like structures, opposite in polarity to its E3-adaptor role.","evidence":"Co-IP, ubiquitylation-site mapping (G3BP1 Lys76), siRNA rescue, stress granule and tumor models","pmids":["38973296"],"confidence":"Medium","gaps":["How DCAF7 chooses between E3-ligase and DUB scaffolding contexts unknown","Single-lab without reciprocal structural validation"]},{"year":2025,"claim":"Consolidated DCAF7 as a bidirectional regulator of the ubiquitin system—as CRL4B receptor restricting influenza PA polymerase, as USP2 scaffold blocking BMAL1 clockophagy, and as an embryonically essential gene—while showing pathogens (NS1) target it.","evidence":"Site-specific ubiquitylation/mutagenesis, co-IP, in vivo pharmacological/genetic validation (IAV PA, BMAL1); plus knockout mouse with embryonic lethality, scRNA-seq, and AUTS2/PCGF5 co-IP/MS","pmids":["40145735","40877242","40462101"],"confidence":"High","gaps":["Unifying rule governing DCAF7's choice of ligase versus DUB partners unresolved","Tissue-specific substrate repertoire incompletely defined"]},{"year":null,"claim":"It remains unknown what structural or regulatory determinant switches DCAF7 between its mutually opposed roles—kinase scaffold, CRL4B substrate-recognition receptor, and deubiquitinase adaptor—within a single cell.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of DCAF7 bound simultaneously or competitively to its alternative partners","Determinants of substrate selection across contexts undefined","Quantitative partitioning of the cellular DCAF7 pool among complexes unmeasured"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,7,17]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[8,16,18]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[4,11]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,4,5]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[9,10]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[8,16,18]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[12,13]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,12,20]}],"complexes":["CUL4B-DDB1-DCAF7 (CRL4B) E3 ubiquitin ligase","PRC1-AUTS2 complex","DYRK1A-DCAF7 complex"],"partners":["DYRK1A","DYRK1B","HIPK2","MEKK1","CUL4B","AUTS2","USP10","TRIC/CCT"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P61962","full_name":"DDB1- and CUL4-associated factor 7","aliases":["WD repeat-containing protein 68","WD repeat-containing protein An11 homolog"],"length_aa":342,"mass_kda":38.9,"function":"Involved in craniofacial development. Acts upstream of the EDN1 pathway and is required for formation of the upper jaw equivalent, the palatoquadrate. The activity required for EDN1 pathway function differs between the first and second arches (By similarity). Associates with DIAPH1 and controls GLI1 transcriptional activity. Could be involved in normal and disease skin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex","subcellular_location":"Cytoplasm; Nucleus","url":"https://www.uniprot.org/uniprotkb/P61962/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/DCAF7","classification":"Common Essential","n_dependent_lines":53,"n_total_lines":74,"dependency_fraction":0.7162162162162162},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"FAM117B","stoichiometry":10.0},{"gene":"DYNLL1","stoichiometry":4.0},{"gene":"DYNLL2","stoichiometry":4.0},{"gene":"CAPZB","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"CTBP2","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DCAF7","total_profiled":1310},"omim":[{"mim_id":"605973","title":"DDB1- AND CUL4-ASSOCIATED FACTOR 7; DCAF7","url":"https://www.omim.org/entry/605973"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DCAF7"},"hgnc":{"alias_symbol":["HAN11","SWAN-1"],"prev_symbol":["WDR68"]},"alphafold":{"accession":"P61962","domains":[{"cath_id":"2.130.10.10","chopping":"9-340","consensus_level":"high","plddt":94.2383,"start":9,"end":340}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P61962","model_url":"https://alphafold.ebi.ac.uk/files/AF-P61962-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P61962-F1-predicted_aligned_error_v6.png","plddt_mean":93.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DCAF7","jax_strain_url":"https://www.jax.org/strain/search?query=DCAF7"},"sequence":{"accession":"P61962","fasta_url":"https://rest.uniprot.org/uniprotkb/P61962.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P61962/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P61962"}},"corpus_meta":[{"pmid":"16759393","id":"PMC_16759393","title":"A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression.","date":"2006","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/16759393","citation_count":65,"is_preprint":false},{"pmid":"20940704","id":"PMC_20940704","title":"The WD40-repeat protein Han11 functions as a scaffold protein to control HIPK2 and MEKK1 kinase functions.","date":"2010","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/20940704","citation_count":51,"is_preprint":false},{"pmid":"27307198","id":"PMC_27307198","title":"The adaptor protein DCAF7 mediates the interaction of the adenovirus E1A oncoprotein with the protein kinases DYRK1A and HIPK2.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27307198","citation_count":50,"is_preprint":false},{"pmid":"21777625","id":"PMC_21777625","title":"DYRK1A binds to an evolutionarily conserved WD40-repeat protein WDR68 and induces its nuclear 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Progression.","date":"2023","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/36939378","citation_count":36,"is_preprint":false},{"pmid":"30864669","id":"PMC_30864669","title":"A complex between DYRK1A and DCAF7 phosphorylates the C-terminal domain of RNA polymerase II to promote myogenesis.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/30864669","citation_count":30,"is_preprint":false},{"pmid":"27573245","id":"PMC_27573245","title":"Human DNA Ligase I Interacts with and Is Targeted for Degradation by the DCAF7 Specificity Factor of the Cul4-DDB1 Ubiquitin Ligase Complex.","date":"2016","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/27573245","citation_count":28,"is_preprint":false},{"pmid":"28137862","id":"PMC_28137862","title":"DYRK1A regulates Hap1-Dcaf7/WDR68 binding with implication for delayed growth in Down syndrome.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/28137862","citation_count":26,"is_preprint":false},{"pmid":"38973296","id":"PMC_38973296","title":"DCAF7 Acts as A Scaffold to Recruit USP10 for G3BP1 Deubiquitylation and Facilitates Chemoresistance and Metastasis in Nasopharyngeal Carcinoma.","date":"2024","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/38973296","citation_count":25,"is_preprint":false},{"pmid":"16887337","id":"PMC_16887337","title":"HAN11 binds mDia1 and controls GLI1 transcriptional activity.","date":"2006","source":"Journal of dermatological science","url":"https://pubmed.ncbi.nlm.nih.gov/16887337","citation_count":25,"is_preprint":false},{"pmid":"30448639","id":"PMC_30448639","title":"WDR68 is essential for the transcriptional activation of the PRC1-AUTS2 complex and neuronal differentiation of mouse embryonic stem cells.","date":"2018","source":"Stem cell research","url":"https://pubmed.ncbi.nlm.nih.gov/30448639","citation_count":21,"is_preprint":false},{"pmid":"27880803","id":"PMC_27880803","title":"Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27880803","citation_count":20,"is_preprint":false},{"pmid":"16980389","id":"PMC_16980389","title":"SWAN-1, a Caenorhabditis elegans WD repeat protein of the AN11 family, is a negative regulator of Rac GTPase function.","date":"2006","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/16980389","citation_count":16,"is_preprint":false},{"pmid":"30496304","id":"PMC_30496304","title":"DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30496304","citation_count":14,"is_preprint":false},{"pmid":"23349862","id":"PMC_23349862","title":"Wdr68 requires nuclear access for craniofacial development.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23349862","citation_count":14,"is_preprint":false},{"pmid":"36248734","id":"PMC_36248734","title":"DCAF7 regulates cell proliferation through IRS1-FOXO1 signaling.","date":"2022","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/36248734","citation_count":12,"is_preprint":false},{"pmid":"31493872","id":"PMC_31493872","title":"DCAF7 is required for maintaining the cellular levels of ERCC1-XPF and nucleotide excision repair.","date":"2019","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/31493872","citation_count":9,"is_preprint":false},{"pmid":"40877242","id":"PMC_40877242","title":"DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis.","date":"2025","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/40877242","citation_count":5,"is_preprint":false},{"pmid":"40145735","id":"PMC_40145735","title":"Restriction of influenza A virus replication by host DCAF7-CRL4B axis.","date":"2025","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/40145735","citation_count":4,"is_preprint":false},{"pmid":"39067242","id":"PMC_39067242","title":"WDR68 stimulates cellular proliferation via activating ribosome biogenesis in 293T cells.","date":"2024","source":"Neoplasia (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/39067242","citation_count":2,"is_preprint":false},{"pmid":"30125741","id":"PMC_30125741","title":"Molecular characterization of wdr68 gene in embryonic development of Xenopus laevis.","date":"2018","source":"Gene expression patterns : GEP","url":"https://pubmed.ncbi.nlm.nih.gov/30125741","citation_count":2,"is_preprint":false},{"pmid":"36505937","id":"PMC_36505937","title":"Erratum: DCAF7 regulates cell proliferation through IRS1-FOXO1 signaling.","date":"2022","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/36505937","citation_count":2,"is_preprint":false},{"pmid":"40462101","id":"PMC_40462101","title":"Essential roles of DCAF7/WDR68 in mouse embryonic development.","date":"2025","source":"Journal of translational medicine","url":"https://pubmed.ncbi.nlm.nih.gov/40462101","citation_count":0,"is_preprint":false},{"pmid":"41990932","id":"PMC_41990932","title":"LINC01184 promotes hepatocellular carcinoma development via the miR-193a-3p/DCAF7 axis.","date":"2026","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/41990932","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":15502,"output_tokens":5765,"usd":0.06649,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":14187,"output_tokens":5057,"usd":0.09868,"stage2_stop_reason":"end_turn"},"total_usd":0.16517,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"WDR68 (DCAF7) interacts with DYRK1A and DYRK1B kinases and is required for craniofacial development in zebrafish; a GFP-WDR68 fusion protein localizes to the nucleus with DYRK1A, whereas a loss-of-function mutant (Wdr68-T284F) fails to accumulate in the nucleus and fails to rescue wdr68 mutant animals, placing WDR68 upstream of the edn1 pathway.\",\n      \"method\": \"Zebrafish insertional mutagenesis screen, GFP fusion localization, rescue experiments\",\n      \"journal\": \"BMC developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis in zebrafish with localization experiments and rescue assay, single lab\",\n      \"pmids\": [\"16759393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"HAN11 (DCAF7) acts as a scaffold protein that directly binds HIPK2, DYRK1A, DYRK1B, and MEKK1 in vitro, and is required to couple MEKK1 to DYRK1/HIPK2; knockdown lowers the threshold and amplitude of HIPK2- and MEKK1-triggered signaling, while overexpression impairs stoichiometrically assembled signaling complexes.\",\n      \"method\": \"In vitro direct binding assays, co-immunoprecipitation, knockdown in human cells and C. elegans, transcriptional reporter assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct binding in vitro, reciprocal co-IP, functional knockdown in multiple organisms with defined signaling phenotypes\",\n      \"pmids\": [\"20940704\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"C. elegans SWAN-1 (DCAF7 ortholog) physically interacts with EGL-9 (prolyl hydroxylase) by yeast two-hybrid and co-immunoprecipitation; genetic evidence places the DYRK kinase MBK-1 downstream of SWAN-1 to promote HIF-1-mediated transcription and resistance to P. aeruginosa.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, forward genetic screen, epistasis analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP and genetic epistasis in C. elegans, single lab\",\n      \"pmids\": [\"20865124\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"SWAN-1 (DCAF7 ortholog in C. elegans) physically associates with Rac GTPases and the LIM domains of the Rac effector UNC-115/abLIM; swan-1 loss-of-function suppresses ced-10 (Rac) hypomorphic defects and enhances constitutively active Rac phenotypes, identifying SWAN-1 as a negative regulator of Rac GTPase function in cytoskeletal organization.\",\n      \"method\": \"Yeast two-hybrid, genetic epistasis in C. elegans, transgenic overexpression in C. elegans neurons and cultured mammalian fibroblasts\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast two-hybrid, genetic epistasis in multiple contexts, single lab\",\n      \"pmids\": [\"16980389\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"WDR68 (DCAF7) binds DYRK1A and DYRK1B (but not DYRK2, 3, or 4) via DYRK1A's N-terminal domain (not the kinase domain); co-expression of wild-type or kinase-dead DYRK1A drives nuclear accumulation of WDR68, indicating that binding (not phosphorylation) mediates nuclear translocation; WDR68 depletion induces cell apoptosis.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, RNAi knockdown, domain deletion mapping\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP, domain mapping, multiple orthogonal methods, functional consequence defined\",\n      \"pmids\": [\"21777625\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Nuclear access is required for WDR68 function in craniofacial development: a nuclear-export-signal (NES) fusion of WDR68 fails to rescue craniofacial defects and redistributes DYRK1A to the cytoplasm; a transcriptional activation domain fusion rescues development whereas a transcriptional repression domain fusion does not; WDR68 promotes myogenin promoter activity in C2C12 cells.\",\n      \"method\": \"Zebrafish rescue experiments, NES fusion constructs, co-localization by immunofluorescence, reporter assay in C2C12 cells\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic rescue with engineered constructs, reporter assay, localization with functional consequence, single lab\",\n      \"pmids\": [\"23349862\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The molecular chaperone TRiC/CCT binds WDR68 via three of its seven β-propeller blades; TRiC/CCT knockdown causes abnormal WDR68 folding, reduces DYRK1A-binding activity, suppresses nuclear accumulation of WDR68, and causes WDR68 aggregation upon overexpression. Phosphorylation sites in both WDR68 and TRiC/CCT were identified.\",\n      \"method\": \"Phosphoproteomic pulldown/MS, co-immunoprecipitation, siRNA knockdown, structural modeling, deletion mutant analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — MS-identified interaction confirmed by co-IP, siRNA functional validation, structural modeling with deletion mutants, multiple orthogonal methods\",\n      \"pmids\": [\"25342745\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"DCAF7 (WDR68/HAN11) acts as an adaptor that bridges adenovirus E1A to DYRK1A and HIPK2; a 12-amino-acid DCAF7-binding motif in the N-terminal domain of class 1 DYRKs is functionally conserved across species; a similar sequence mediates DCAF7 binding to HIPK2, whereas HIPK1 does not bind DCAF7; DCAF7 is required for hyperphosphorylation of E1A by DYRK1A or HIPK2, defining it as a substrate-recruiting subunit.\",\n      \"method\": \"Co-immunoprecipitation, GST pulldown, domain mutagenesis, hyperphosphorylation assay in overexpressing cells\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal co-IP plus pulldown, mutagenesis of binding motif, functional phosphorylation assay, multiple interactors tested\",\n      \"pmids\": [\"27307198\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"DCAF7 is the specificity/substrate-recognition factor for the Cul4-DDB1 E3 ubiquitin ligase complex that targets DNA ligase I for ubiquitylation and degradation; three ubiquitylated lysine residues on DNA ligase I were mapped, and mutation of these residues reduced in vitro ubiquitylation by Cul4-DDB1-DCAF7; DCAF7 knockdown reduced DNA ligase I degradation upon inhibition of proliferation.\",\n      \"method\": \"Proteomic ubiquitylation-site mapping, co-immunoprecipitation, in vitro ubiquitylation assay, siRNA knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro ubiquitylation reconstitution, site-directed mutagenesis of ubiquitylation sites, co-IP, siRNA knockdown with functional readout\",\n      \"pmids\": [\"27573245\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"HAN11 (DCAF7) binds the FH2 actin-binding domain of mDia1; overexpression of mDia1 or active RhoA causes translocation of HAN11 from nucleus to cytoplasm; HAN11 and mDia1 together repress DYRK1A-dependent GLI1 transcriptional activity.\",\n      \"method\": \"TAP-tag purification, GST pulldown, luciferase transcriptional assay, immunofluorescence microscopy\",\n      \"journal\": \"Journal of dermatological science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — TAP-tag pulldown confirmed by GST pulldown, transcriptional reporter assay, localization study, single lab\",\n      \"pmids\": [\"16887337\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"DCAF7 (Dcaf7/WDR68) is a component of neuronal stigmoid bodies that interacts with Huntingtin-associated protein 1 (Hap1); Hap1 competes with DYRK1A for cytoplasmic binding to Dcaf7, thereby regulating Dcaf7 nuclear translocation; depleting Hap1 promotes DYRK1A-Dcaf7 interaction, increases DYRK1A protein levels, and overexpression of DYRK1A in hypothalamus causes delayed postnatal growth in mice.\",\n      \"method\": \"Subcellular fractionation, immunoprecipitation from mouse brain, transgenic mouse overexpression, co-immunoprecipitation\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP from brain fraction, competitive binding assay, transgenic mouse phenotype, single lab\",\n      \"pmids\": [\"28137862\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"WDR68 (DCAF7) is required for normal protein levels of DYRK1A and DYRK1B: deletion of Wdr68 reduces DYRK1A/1B protein without affecting Dyrk1a mRNA levels or proteasome-dependent degradation; overexpression of WDR68 increases DYRK1A protein; DYRK1A and DYRK1B are each required for the transition from proliferation to differentiation in C2C12 cells.\",\n      \"method\": \"CRISPR/engineered knockout cell lines, mRNA quantification, proteasome inhibition, overexpression, differentiation assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function and gain-of-function in engineered cell lines, multiple controls, single lab\",\n      \"pmids\": [\"30496304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"WDR68 (DCAF7) is an integral component of the PRC1-AUTS2 complex and is required for PRC1-AUTS2-mediated transcriptional activation; deletion of Wdr68 in mouse embryonic stem cells causes defects in neuronal differentiation without affecting self-renewal, with down-regulation of PRC1-AUTS2 target neuronal genes.\",\n      \"method\": \"Complex co-immunoprecipitation, Wdr68 deletion in mESCs, transcriptomic analysis, differentiation assays\",\n      \"journal\": \"Stem cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP showing complex membership, genetic deletion with transcriptomic readout, single lab\",\n      \"pmids\": [\"30448639\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DYRK1A exists in a complex with DCAF7 that stabilizes DYRK1A and tethers it to RNA Pol II; this DYRK1A-DCAF7 complex phosphorylates the CTD of Pol II and co-migrates with Pol II along myogenic gene loci to stimulate myogenic transcription after P-TEFb is eliminated during myoblast differentiation.\",\n      \"method\": \"Co-immunoprecipitation, ChIP-seq, Pol II CTD phosphorylation assay, knockdown with transcriptional and differentiation readouts\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP, ChIP-seq, biochemical CTD kinase assay, loss-of-function with defined transcriptional phenotype, multiple orthogonal methods\",\n      \"pmids\": [\"30864669\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"DCAF7 interacts with the ERCC1-XPF endonuclease complex (primarily with XPF); DCAF7 knockdown reduces cellular ERCC1-XPF protein levels partly via proteasomal degradation and impairs nucleotide excision repair of UV-induced (6-4) photoproducts; depletion of TRiC/CCT also reduces ERCC1-XPF levels, linking chaperone-assisted DCAF7 folding to NER capacity.\",\n      \"method\": \"Mass spectrometry after tandem purification, co-immunoprecipitation, siRNA knockdown, UV damage repair assay, ectopic overexpression rescue\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — MS identification confirmed by co-IP, functional knockdown with repair assay and rescue, single lab\",\n      \"pmids\": [\"31493872\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DCAF7 proximally interacts with IRS1 (insulin/IGF1 signaling adaptor) as well as DYRK1A and DYRK1B; DCAF7 knockdown in HepG2 cells attenuates insulin-stimulated AKT phosphorylation, promotes nuclear localization of FOXO1, induces FOXO1 target genes involved in G2 cell cycle inhibition, and causes G2 arrest; in Drosophila, wing-specific knockdown of DCAF7/wap reduces wing cell number, rescued by co-knockdown of dfoxo.\",\n      \"method\": \"BioID proximity labeling, siRNA knockdown, AKT phosphorylation assay, FOXO1 localization, gene expression analysis, Drosophila genetic epistasis\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID interaction, functional siRNA with signaling readout, Drosophila epistasis, multiple orthogonal approaches, single lab\",\n      \"pmids\": [\"36248734\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"CUL4B and DCAF7 form a CRL4B E3 ubiquitin ligase complex that binds MEN1 (menin), catalyzes its ubiquitylation, and promotes its proteasomal degradation; neddylation activates this pathway; DCAF7 knockdown restores MEN1 levels and re-sensitizes everolimus-resistant PanNET cells to mTOR inhibition, with effects reversible by simultaneous MEN1 knockdown.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation assay, siRNA knockdown, neddylation inhibitor (MLN4924), in vitro and in vivo tumor models, rescue experiments\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — co-IP, ubiquitylation assay, genetic rescue in vitro and in vivo, pharmacological validation, multiple orthogonal methods\",\n      \"pmids\": [\"36939378\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DCAF7 acts as a scaffold protein that facilitates interaction between deubiquitinase USP10 and G3BP1; this leads to removal of K48-linked ubiquitin from Lys76 of G3BP1, preventing its proteasomal degradation and promoting stress granule-like structure formation; G3BP1 knockdown reverses the pro-tumorigenic effects of DCAF7 in nasopharyngeal carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation site mapping, siRNA knockdown with rescue, stress granule formation assay, in vitro and in vivo tumor models\",\n      \"journal\": \"Advanced science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, ubiquitylation analysis, functional rescue, single lab\",\n      \"pmids\": [\"38973296\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DCAF7 acts as the substrate recognition receptor of a CRL4B (CUL4B-RBX1-DDB1-DCAF7) E3 ligase that promotes K48-linked polyubiquitination of influenza A virus polymerase subunit PA at Lys609 and its proteasomal degradation, thereby restricting IAV replication; viral NS1 protein decreases DCAF7 levels to counteract this restriction.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation assay with site-specific mutagenesis (K609), siRNA knockdown and overexpression, MLN4924 pharmacological inhibition in vivo, etoposide activation of CUL4B in vivo\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro ubiquitylation with site mutagenesis, co-IP, pharmacological and genetic in vivo validation, multiple orthogonal methods\",\n      \"pmids\": [\"40145735\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"DCAF7 recruits deubiquitinase USP2 to inhibit clockophagy (selective autophagic degradation of BMAL1 via p62/SQSTM1) by reducing BMAL1 K63-linked polyubiquitination; loss of DCAF7 or USP2 triggers clockophagy-induced ferroptosis through the HIF1α-SLC7A11 axis in hepatocellular carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitylation assay, genetic ablation, pharmacological inhibition, in vitro and in vivo tumor models\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP, ubiquitylation analysis, genetic and pharmacological loss-of-function with mechanistic pathway, single lab\",\n      \"pmids\": [\"40877242\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"WDR68 (DCAF7) is required for mouse embryonic development; WDR68 null embryos show intrauterine growth retardation and die in utero; WDR68 deficiency activates the HIF-1 pathway and deregulates developmental gene expression; co-immunoprecipitation/MS confirmed interaction of WDR68 with AUTS2 and PCGF5 (PRC1 components) in mouse embryos.\",\n      \"method\": \"Gene targeting (knockout mouse), single-cell RNA-seq, whole-embryo transcriptomics, co-immunoprecipitation/mass spectrometry\",\n      \"journal\": \"Journal of translational medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic knockout with lethal phenotype, transcriptomic analysis, co-IP/MS for interactors, single lab\",\n      \"pmids\": [\"40462101\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DCAF7 (WDR68/HAN11) is an evolutionarily conserved, catalytically inactive WD40-repeat scaffold/adaptor protein that (1) binds DYRK1A and DYRK1B via their N-terminal domains—an interaction requiring TRiC/CCT chaperone-assisted proper folding of DCAF7—and stabilizes these kinases while driving their nuclear translocation; (2) serves as the substrate-recognition subunit of CUL4B-DDB1 E3 ubiquitin ligase complexes, directing ubiquitylation and proteasomal degradation of substrates including DNA ligase I, MEN1, and viral PA polymerase; (3) acts as a scaffold coupling additional kinases (HIPK2, MEKK1) and deubiquitinases (USP10, USP2) to their targets; (4) is an integral component of the transcriptionally active PRC1-AUTS2 complex required for neuronal differentiation; and (5) controls cell proliferation, myogenesis, craniofacial development, and stress responses through these mechanistically distinct protein complexes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DCAF7 (WDR68/HAN11) is an evolutionarily conserved, catalytically inactive WD40-repeat scaffold and substrate-recognition adaptor that organizes distinct kinase- and ubiquitin-ligase complexes controlling differentiation, proliferation, and development [#1, #8]. Its best-defined role is as a dedicated partner of the class 1 DYRK kinases DYRK1A and DYRK1B: it binds a conserved 12-residue motif in their N-terminal (non-catalytic) domain rather than the kinase domain, and this binding\\u2014not phosphorylation\\u2014drives their nuclear accumulation, stabilizes DYRK protein levels, and recruits substrates such as adenoviral E1A for hyperphosphorylation [#4, #7, #11]. Through the same scaffolding logic DCAF7 also couples HIPK2 and MEKK1 into stoichiometric signaling complexes [#1, #7]. Proper folding of DCAF7 by the TRiC/CCT chaperonin, which engages three of its \\u03b2-propeller blades, is a prerequisite for DYRK1A binding and nuclear localization [#6]. In the nucleus DCAF7 functions in transcription: it is an integral subunit of the transcriptionally active PRC1-AUTS2 complex required for neuronal differentiation [#12, #20], and the DYRK1A-DCAF7 complex phosphorylates the RNA Pol II CTD and tracks along myogenic loci to sustain myogenic transcription [#13]. Independently, DCAF7 serves as the substrate-recognition receptor of CUL4-DDB1/CRL4B E3 ubiquitin ligases, directing K48-linked ubiquitylation and proteasomal degradation of DNA ligase I, MEN1/menin, and influenza A virus PA polymerase [#8, #16, #18], and conversely it can scaffold deubiquitinases (USP10 toward G3BP1, USP2 toward BMAL1) to protect targets from degradation [#17, #19]. Loss of DCAF7 is embryonic-lethal in mice with intrauterine growth retardation and aberrant HIF-1-pathway activation [#20], consistent with its requirement for craniofacial development, myogenesis, and the proliferation-to-differentiation transition across model systems [#0, #5, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established DCAF7 as a physiological partner of DYRK kinases and a developmental regulator, framing the question of how a WD40 protein influences signaling output.\",\n      \"evidence\": \"Zebrafish insertional mutagenesis, GFP-fusion localization, and rescue placing WDR68 upstream of the edn1 pathway; parallel C. elegans work linking the SWAN-1 ortholog to Rac GTPase regulation and mDia1 binding\",\n      \"pmids\": [\"16759393\", \"16980389\", \"16887337\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define whether DCAF7 acts as kinase scaffold versus transcriptional effector\", \"Molecular basis of the DYRK1A interaction unresolved\", \"Rac/mDia1 connections come from invertebrate genetics without mammalian biochemical reconstitution\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined DCAF7 as a direct scaffold that couples multiple kinases, explaining how it shapes signaling thresholds rather than acting catalytically.\",\n      \"evidence\": \"In vitro direct binding, reciprocal co-IP, and knockdown in human cells and C. elegans with transcriptional reporter readouts (HIPK2, DYRK1A/1B, MEKK1); separate epistasis placing the DYRK MBK-1 downstream of SWAN-1 in HIF-1-mediated immunity\",\n      \"pmids\": [\"20940704\", \"20865124\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not map the binding motifs on each kinase\", \"Stoichiometry of assembled complexes not structurally resolved\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed that DCAF7 binds DYRK1A/1B through their N-terminal domain and that binding alone (not phosphorylation) drives DCAF7 nuclear translocation, separating localization control from kinase activity.\",\n      \"evidence\": \"Co-IP, immunofluorescence, RNAi, and domain-deletion mapping using wild-type and kinase-dead DYRK1A\",\n      \"pmids\": [\"21777625\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which the DYRK1A-DCAF7 pair traverses the nuclear envelope not defined\", \"Apoptosis upon depletion not mechanistically dissected\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrated that nuclear access and a transcription-activating function are required for DCAF7's developmental role, tying its localization to transcriptional output.\",\n      \"evidence\": \"Zebrafish rescue with NES and transcriptional activation/repression domain fusions plus myogenin promoter reporter in C2C12 cells\",\n      \"pmids\": [\"23349862\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct transcriptional targets not identified at this stage\", \"Whether DCAF7 itself contacts chromatin unresolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified TRiC/CCT chaperonin as required for DCAF7 folding, establishing that competent DYRK1A binding and nuclear accumulation depend on chaperone-assisted \\u03b2-propeller assembly.\",\n      \"evidence\": \"Phosphoproteomic pulldown/MS, co-IP, siRNA knockdown, structural modeling, and deletion mutants\",\n      \"pmids\": [\"25342745\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional role of identified phosphosites not tested\", \"Whether folding is regulated to control activity unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Defined DCAF7 as a substrate-recruiting adaptor in two arenas: bridging E1A to DYRK1A/HIPK2 for hyperphosphorylation, and serving as the specificity factor of a Cul4-DDB1 ligase that degrades DNA ligase I.\",\n      \"evidence\": \"Co-IP, GST pulldown, binding-motif mutagenesis, hyperphosphorylation assay; and ubiquitylation-site mapping with in vitro Cul4-DDB1-DCAF7 ubiquitylation and siRNA\",\n      \"pmids\": [\"27307198\", \"27573245\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not establish how DCAF7 partitions between kinase-scaffold and E3-adaptor roles\", \"Selectivity rules for ligase substrates unresolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Showed that competition for cytoplasmic DCAF7 binding regulates DYRK1A nuclear translocation and stability, identifying Hap1 as a tuning factor at stigmoid bodies.\",\n      \"evidence\": \"Subcellular fractionation, co-IP from mouse brain, competitive binding, and transgenic DYRK1A overexpression causing growth phenotype\",\n      \"pmids\": [\"28137862\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological stimulus governing Hap1-DCAF7 competition unknown\", \"Direct structural overlap of Hap1 and DYRK1A binding sites not mapped\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Established that DCAF7 sustains DYRK1A/1B protein levels post-transcriptionally and is required for the proliferation-to-differentiation switch, and that DCAF7 is a genuine subunit of the PRC1-AUTS2 transcriptional complex.\",\n      \"evidence\": \"CRISPR knockout cell lines with mRNA quantification, proteasome inhibition, and differentiation assays; complex co-IP and Wdr68 deletion in mESCs with transcriptomics\",\n      \"pmids\": [\"30496304\", \"30448639\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of DYRK stabilization independent of proteasome not defined\", \"How DCAF7 contributes to PRC1-AUTS2 activation unresolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated a direct chromatin-associated transcriptional mechanism: the DYRK1A-DCAF7 complex phosphorylates Pol II CTD and travels with Pol II to drive myogenic transcription after P-TEFb loss.\",\n      \"evidence\": \"Co-IP, ChIP-seq, Pol II CTD phosphorylation assay, and knockdown with transcriptional/differentiation readouts; plus DCAF7 interaction with ERCC1-XPF affecting NER capacity\",\n      \"pmids\": [\"30864669\", \"31493872\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether DCAF7 directly contacts DNA versus tethering kinase unresolved\", \"ERCC1-XPF link relies on knockdown without reconstitution\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Connected DCAF7 to insulin/IGF1 signaling, showing it is required for insulin-stimulated AKT activation and restraint of FOXO1, linking the scaffold to proliferation control.\",\n      \"evidence\": \"BioID proximity labeling, siRNA with AKT phosphorylation and FOXO1 localization readouts, and Drosophila wing epistasis rescued by dfoxo co-knockdown\",\n      \"pmids\": [\"36248734\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct versus indirect IRS1 interaction not resolved (proximity labeling)\", \"Mechanistic step between DCAF7 and AKT unclear\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Extended the CRL4B substrate-receptor function to a disease context, showing DCAF7-directed degradation of MEN1 controls mTOR-inhibitor sensitivity in neuroendocrine tumors.\",\n      \"evidence\": \"Co-IP, ubiquitylation assay, siRNA rescue in vitro and in vivo, and neddylation inhibition (MLN4924)\",\n      \"pmids\": [\"36939378\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Determinants of MEN1 recognition by DCAF7 not mapped\", \"Crosstalk with DCAF7's kinase-scaffold roles untested\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a deubiquitinase-scaffolding mode in which DCAF7 bridges USP10 to G3BP1, stabilizing it and promoting stress-granule-like structures, opposite in polarity to its E3-adaptor role.\",\n      \"evidence\": \"Co-IP, ubiquitylation-site mapping (G3BP1 Lys76), siRNA rescue, stress granule and tumor models\",\n      \"pmids\": [\"38973296\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How DCAF7 chooses between E3-ligase and DUB scaffolding contexts unknown\", \"Single-lab without reciprocal structural validation\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Consolidated DCAF7 as a bidirectional regulator of the ubiquitin system\\u2014as CRL4B receptor restricting influenza PA polymerase, as USP2 scaffold blocking BMAL1 clockophagy, and as an embryonically essential gene\\u2014while showing pathogens (NS1) target it.\",\n      \"evidence\": \"Site-specific ubiquitylation/mutagenesis, co-IP, in vivo pharmacological/genetic validation (IAV PA, BMAL1); plus knockout mouse with embryonic lethality, scRNA-seq, and AUTS2/PCGF5 co-IP/MS\",\n      \"pmids\": [\"40145735\", \"40877242\", \"40462101\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Unifying rule governing DCAF7's choice of ligase versus DUB partners unresolved\", \"Tissue-specific substrate repertoire incompletely defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what structural or regulatory determinant switches DCAF7 between its mutually opposed roles\\u2014kinase scaffold, CRL4B substrate-recognition receptor, and deubiquitinase adaptor\\u2014within a single cell.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of DCAF7 bound simultaneously or competitively to its alternative partners\", \"Determinants of substrate selection across contexts undefined\", \"Quantitative partitioning of the cellular DCAF7 pool among complexes unmeasured\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 7, 17]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [8, 16, 18]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [4, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 4, 5]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [9, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [8, 16, 18]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [12, 13]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 12, 20]}\n    ],\n    \"complexes\": [\n      \"CUL4B-DDB1-DCAF7 (CRL4B) E3 ubiquitin ligase\",\n      \"PRC1-AUTS2 complex\",\n      \"DYRK1A-DCAF7 complex\"\n    ],\n    \"partners\": [\n      \"DYRK1A\",\n      \"DYRK1B\",\n      \"HIPK2\",\n      \"MEKK1\",\n      \"CUL4B\",\n      \"AUTS2\",\n      \"USP10\",\n      \"TRiC/CCT\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}