id: Q5QP82 gene_symbol: DCAF10 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: DCAF10 (DDB1- and CUL4-associated factor 10; also known as WD repeat-containing protein 32, WDR32) is a WD40-repeat protein predicted to fold into a beta-propeller. It is a member of the DCAF family of substrate-recognition receptors that dock onto the DDB1 adaptor of CRL4 (DDB1-CUL4-RBX1) cullin-RING E3 ubiquitin ligase complexes via a conserved WD40 surface. By analogy to other DCAFs, DCAF10 presents substrates to the CRL4 ligase for ubiquitination. Direct biochemical evidence supports its association with DDB1/CUL4, and it is defined as a component of CRL4-DCAF10 complexes (CUL4A and CUL4B variants). A reconstituted CUL4A-DDB1-DCAF10 complex has been shown to directly ubiquitinate substrate proteins, and one study reports DCAF10 acting as an N-recognin that recognizes an N-terminally acetylated glycine (Ac-Gly) degron through a pocket in its WD40 beta-propeller, targeting Src-family kinases (Lyn, Fyn, Src) whose N-myristoylation is omitted; this proposed Ac-Gly N-degron activity awaits independent replication. Other single studies have proposed additional substrates and contexts, including a CUL4A-DDB1-DCAF10 complex stabilized by the deubiquitinase OTUD1 promoting degradation of the anti-apoptotic protein MCL1 in esophageal squamous cell carcinoma, degradation of RUVBL1/2 AAA+ ATPases when the complex is co-opted by adenovirus E1A, and degradation of the lipoxygenase ALOX15B in KRAS-mutant pancreatic cancer. Each of these substrate and pathway links rests on a single report and has not been independently replicated. DCAF10 is also notably enriched in testis at the transcript level, suggesting a possible specialized role in spermatogenesis that remains uncharacterized. The N-terminal region is disordered and carries several phosphoserine and methylarginine sites identified in large-scale proteomics, with no functional characterization. alternative_products: - name: '1' id: Q5QP82-1 - name: '2' id: Q5QP82-2 sequence_note: VSP_028513 existing_annotations: - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: Phylogenetic (IBA) inference of CRL4 complex membership from the PANTHER DCAF family tree. Consistent with the well-supported assignment of DCAF10 as a DDB1/CUL4-associated WD40 substrate receptor and with direct biochemical evidence (PMID:16949367). Recent primary work synthesized in the falcon deep-research report further establishes DCAF10 as a bona fide substrate receptor of reconstituted CUL4A-DDB1-DCAF10 complexes (Kremer et al. 2026, PMID:41484149), reinforcing this complex-membership annotation. This represents the core cellular-component role of the gene. action: ACCEPT reason: DCAF10 is established as a CRL4-associated WD40 factor; complex membership is supported phylogenetically, by direct DDB1/CUL4 co-purification, and by reconstitution of an active CUL4A-DDB1-DCAF10 ligase. supported_by: - reference_id: PMID:16949367 supporting_text: Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: DCAF10 functions as a substrate receptor (specificity factor) for Cullin 4-RING E3 ubiquitin ligase (CRL4) complexes, comprising CUL4A (or CUL4B), DDB1, DCAF10, and the catalytic subunit RBX1 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Bare "protein binding" from a high-throughput binary interactome screen (HuRI), with partner LHX4 (UniProtKB:Q969G2). This term is uninformative as a molecular function and the partner is not a CRL4 component, so it does not illuminate DCAF10 function. action: MARK_AS_OVER_ANNOTATED reason: Generic protein binding from a large-scale interactome screen conveys no specific molecular function and the partner (LHX4) does not establish a defined activity; per curation guidance, bare protein binding should not be retained as informative. supported_by: - reference_id: PMID:32296183 supporting_text: A reference map of the human binary protein interactome. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Bare "protein binding" from large-scale affinity-purification interactome (BioPlex), with partners DNAJA2, PPIL2, and MYG1. Uninformative as a molecular function; none of these partners are CRL4 core components. action: MARK_AS_OVER_ANNOTATED reason: Generic protein binding from a high-throughput interactome network does not specify a molecular function and should not be retained as an informative annotation. supported_by: - reference_id: PMID:33961781 supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables review: summary: Bare "protein binding" from a multimodal cell-map interactome study, partner DNAJA2. Uninformative as a molecular function. action: MARK_AS_OVER_ANNOTATED reason: Generic protein binding from a large-scale mapping study does not specify a molecular function and should not be retained as informative. supported_by: - reference_id: PMID:40205054 supporting_text: Multimodal cell maps as a foundation for structural and functional genomics. - term: id: GO:0016567 label: protein ubiquitination evidence_type: IEA original_reference_id: GO_REF:0000041 qualifier: involved_in review: summary: Process annotation transferred by UniPathway mapping (UPA00143). DCAF10 is a non-catalytic substrate-recognition subunit; the ubiquitin-transfer chemistry is performed by the CRL4 complex. Although this specific annotation is inferred via pathway mapping (IEA), the underlying process (DCAF10 participation in substrate ubiquitination as a CRL4 substrate receptor) is now directly supported by primary biochemistry reported in the falcon deep-research synthesis (Kremer et al. 2026, Nat Commun PMID:41484149), in which reconstituted CUL4A-DDB1-DCAF10 directly ubiquitinated immunoprecipitated substrate proteins. This upgrades the involvement of DCAF10 in protein ubiquitination from a purely homology/pathway inference to a function with direct experimental backing, even though no single endogenous substrate has been broadly replicated. action: ACCEPT reason: DCAF10 is a CRL4 substrate-recognition subunit and its involvement in protein ubiquitination is now supported by direct in vitro evidence that a reconstituted CUL4A-DDB1-DCAF10 complex ubiquitinates substrate proteins (PMID:41484149, via falcon synthesis), in addition to the pathway-vocabulary (IEA) mapping; this is a core process for the gene. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: 'PATHWAY: Protein modification; protein ubiquitination.' - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: In vitro ubiquitination assays with reconstituted CUL4A-DDB1-DCAF10 complexes directly ubiquitinated immunoprecipitated Lyn, Fyn, and Src proteins - term: id: GO:0031464 label: Cul4A-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:16949367 qualifier: part_of review: summary: ComplexPortal-defined membership in the CUL4A-variant CRL4-DCAF10 complex (CPX-2817), traced to the founding DCAF discovery paper that showed DCAF10 co-purifies with DDB1/CUL4. A more specific (CUL4A paralog) refinement of the general Cul4-RING annotation; well supported as complex membership. action: ACCEPT reason: DCAF10 is a defined component of the CRL4-DCAF10 CUL4A-variant complex (ComplexPortal CPX-2817), consistent with direct DDB1/CUL4 association. supported_by: - reference_id: PMID:16949367 supporting_text: DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: ComplexPortal; CPX-2817; CRL4-DCAF10 E3 ubiquitin ligase complex, CUL4A variant. - term: id: GO:0031465 label: Cul4B-RING E3 ubiquitin ligase complex evidence_type: NAS original_reference_id: PMID:33898171 qualifier: part_of review: summary: ComplexPortal-defined membership in the CUL4B-variant CRL4-DCAF10 complex (CPX-2819). CRL4 ligases assemble with either CUL4A or CUL4B, so a CUL4B-variant complex is plausible for DCAF10 as a DDB1-docking DCAF. Notably the cited paper (PMID:33898171) describes a CUL4A (not CUL4B) DCAF10 complex; the CUL4B assignment here rests on the general interchangeability of CUL4A/CUL4B rather than direct data for the B variant. action: KEEP_AS_NON_CORE reason: Plausible by analogy with CUL4A/CUL4B interchangeability and supported by ComplexPortal CPX-2819, but the cited study specifically demonstrates a CUL4A complex; retain as non-core given the absence of direct CUL4B-specific evidence. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: ComplexPortal; CPX-2819; CRL4-DCAF10 E3 ubiquitin ligase complex, CUL4B variant. - term: id: GO:0042981 label: regulation of apoptotic process evidence_type: NAS original_reference_id: PMID:33898171 qualifier: involved_in review: summary: Derived from a single study reporting that OTUD1 stabilizes DCAF10 and recruits a CUL4A-DDB1-DCAF10 complex to promote MCL1 degradation, thereby activating caspase-dependent apoptosis in esophageal squamous cell carcinoma. This is the only report proposing an apoptosis-related role and a specific substrate (MCL1), placing DCAF10 as a downstream/secondary player; it is not independently replicated. action: KEEP_AS_NON_CORE reason: A single, non-replicated cancer-context study links a DCAF10-containing CRL4 to MCL1 degradation and apoptosis; the role is plausible but context-specific and indirect, so it is retained as non-core rather than core or removed. supported_by: - reference_id: PMID:33898171 supporting_text: OTUD1 stabilizes DDB1 and CUL4 associated factor 10 (DCAF10) and recruits the cullin 4A (CUL4A)-damage specific DNA binding protein 1 (DDB1) complex to promote myeloid cell leukemia sequence 1 (MCL1) degradation, thereby activating caspase-dependent apoptotic signaling. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8952638 qualifier: located_in review: summary: Nucleoplasm localization asserted via a generic Reactome CRL4 neddylation/assembly reaction (AcM-UBE2M transfers NEDD8 to CRL4) in which DCAF10 stands in as one of many possible interchangeable DCAFs. Not DCAF10-specific experimental localization. action: KEEP_AS_NON_CORE reason: Localization is inferred from generic CRL4 pathway reactions rather than direct DCAF10 evidence; plausible but non-core. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8952639 qualifier: located_in review: summary: Nucleoplasm localization from a generic Reactome CRL4 reaction (NEDD8:AcM-UBE2M binds CRL4) where DCAF10 represents a generic DCAF; not DCAF10-specific localization evidence. action: KEEP_AS_NON_CORE reason: Inferred from a generic CRL4 neddylation reaction rather than direct DCAF10 data; plausible but non-core. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8955245 qualifier: located_in review: summary: Nucleoplasm localization from a generic Reactome CRL4 reaction (CAND1 binds CRL4 in the nucleus) where DCAF10 represents a generic DCAF; not DCAF10-specific localization evidence. action: KEEP_AS_NON_CORE reason: Inferred from a generic CRL4 assembly reaction rather than direct DCAF10 data; plausible but non-core. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8955285 qualifier: located_in review: summary: Nucleoplasm localization from a generic Reactome CRL4 reaction (COMMDs displace CAND1 from CRL4) where DCAF10 represents a generic DCAF; not DCAF10-specific localization evidence. action: KEEP_AS_NON_CORE reason: Inferred from a generic CRL4 assembly reaction rather than direct DCAF10 data; plausible but non-core. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8956045 qualifier: located_in review: summary: Nucleoplasm localization from a generic Reactome CRL4 reaction (COP9 signalosome deneddylates nuclear CRL4) where DCAF10 represents a generic DCAF; not DCAF10-specific localization evidence. action: KEEP_AS_NON_CORE reason: Inferred from a generic CRL4 deneddylation reaction rather than direct DCAF10 data; plausible but non-core. supported_by: - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - term: id: GO:0080008 label: Cul4-RING E3 ubiquitin ligase complex evidence_type: IDA original_reference_id: PMID:16949367 qualifier: part_of review: summary: Direct experimental (IDA) evidence of CRL4 complex membership from the founding DCAF study, which identified DCAF10 by mass spectrometry as a DDB1/CUL4-associated factor and demonstrated WD40-DCAF docking onto DDB1. This is the strongest direct evidence for the core cellular-component role of DCAF10. action: ACCEPT reason: Direct biochemical co-purification establishes DCAF10 as a CRL4 (DDB1/CUL4)-associated component; this is a core function. supported_by: - reference_id: PMID:16949367 supporting_text: Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. core_functions: - description: Substrate-recognition receptor subunit of CRL4 (DDB1-CUL4-RBX1) cullin-RING E3 ubiquitin ligase complexes; a WD40 beta-propeller protein that docks onto the DDB1 adaptor (via WDxR motifs) to present substrates for ubiquitination. Beyond the original homology-based assignment, a reconstituted CUL4A-DDB1-DCAF10 complex has now been shown to directly ubiquitinate substrate proteins, establishing DCAF10 as a functional substrate receptor rather than only a putative one. supported_by: - reference_id: PMID:16949367 supporting_text: Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: 'FUNCTION: May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.' - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: As a substrate receptor, DCAF10 recruits specific target proteins to the E3 ligase complex, facilitating their ubiquitination and subsequent proteasomal degradation proposed_new_terms: - proposed_name: N-terminally-acetylated-glycine-degron-binding substrate-receptor activity proposed_definition: Binding to an N-terminal alpha-amino-acetylated glycine (Ac-Gly) residue of a substrate protein, recognizing it as a degradation signal (N-degron), so as to recruit the substrate to a cullin-RING E3 ubiquitin ligase (CRL4) for ubiquitination and subsequent proteasomal degradation; an N-recognin activity. justification: A primary study (Kremer et al. 2026, Nat Commun, PMID:41484149), synthesized in the falcon deep-research report, reports that DCAF10 recognizes an N-terminally acetylated glycine degron through a pocket in its WD40 beta-propeller and thereby directs substrate ubiquitination by reconstituted CUL4A-DDB1-DCAF10. No existing GO molecular-function term captures this specific Ac-Gly N-recognin activity. Proposed cautiously pending independent replication and verification against the primary full text (not in the local publications cache). supported_by: - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: Recent breakthrough research by Kremer et al. (2026) identified DCAF10 as an N-recognin for proteins bearing N-terminally acetylated glycine (Ac-Gly) residues, particularly those that normally undergo N-myristoylation suggested_questions: - question: What endogenous substrate(s) does DCAF10 present to the CRL4 ligase, and is the proposed MCL1 substrate (from the OTUD1/ESCC study) reproducible in other cell types and under physiological conditions? - question: Does DCAF10 assemble with both CUL4A and CUL4B in cells, or does it preferentially use one paralog? - question: Are the N-terminal phosphorylation (S53/S63/S89/S92/S349) and R134 methylation sites functionally relevant to DCAF10 stability, DDB1 docking, or substrate selection? - question: Is the proposed Ac-Gly/MO N-degron activity of DCAF10 (recognition of N-terminally acetylated glycine on myristoylation-omitted Src-family kinases; Kremer et al. 2026, PMID:41484149) reproducible by independent groups and physiologically operative in tissues with high DCAF10 expression such as testis, and does it warrant a dedicated GO molecular-function term? suggested_experiments: - description: Affinity purification-mass spectrometry of endogenous (or epitope-tagged) DCAF10 followed by ubiquitin-remnant (diGly) proteomics in DCAF10-knockout vs wild-type cells to identify bona fide substrates. - description: Structural or mutational mapping of the DCAF10 WD40 surface and its WDxR/DWD motif to confirm and characterize DDB1 docking. - description: Quantitative proteomics of MCL1 and AIF-pathway components in DCAF10-knockout cells across multiple lineages to test the proposed apoptosis-regulatory role independently of the original ESCC context. knowledge_gaps: - gap_statement: >- The breadth and physiological specificity of DCAF10's Ac-Gly/MO N-degron substrate-recognition activity remain unresolved. A recent primary study supports direct recognition and ubiquitination of acetylated Src-family kinases, but it is still unclear how broadly DCAF10 recognizes N-terminally acetylated glycine degrons across the proteome, which endogenous clients are core substrates, and how this activity should be represented by a precise GO molecular-function term. boundary: >- DCAF10 is established as a CRL4 substrate receptor, and the current review accepts protein ubiquitination/CRL4 complex membership while proposing a more specific Ac-Gly N-recognin term cautiously. The gap is the scope and term-level precision of the substrate-recognition activity, not whether DCAF10 can associate with DDB1/CUL4. gap_kind: - BIOLOGY - ONTOLOGY - CURATION dark_aspect: MF_DARK status: OPEN significance: >- Resolving this gap would determine whether DCAF10 should receive a specific N-degron-recognin molecular-function annotation, how broadly that annotation applies beyond Lyn/Fyn/Src, and which proposed pathway/process annotations should be treated as direct DCAF10 biology rather than context-specific substrate leads. resolution: >- Independent replication of Ac-Gly binding and CUL4A-DDB1-DCAF10 ubiquitination with endogenous substrates, proteome-wide Ac-Gly candidate testing, degron mutagenesis, and substrate-rescue assays would define the direct substrate class and support a precise GO term request. provenance: - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: Recent breakthrough research by Kremer et al. (2026) identified DCAF10 as an N-recognin for proteins bearing N-terminally acetylated glycine (Ac-Gly) residues, particularly those that normally undergo N-myristoylation - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: The recognition motif is not simply Ac-Gly but includes downstream residues, with a preference for serine at position 6 and lysine at position 7 - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: It is useful for separating direct DCAF10 substrates from cases, such as IRF3, where the evidence currently supports indirect regulation. - gap_statement: >- DCAF10's normal testis and spermatogenesis role is still largely undefined. Transcript-level evidence points to strong testis/sperm expression, but the relevant germ-cell substrates, developmental stage, and reproductive phenotype have not been resolved. boundary: >- The review treats testis enrichment as a biological lead rather than as a curated spermatogenesis process annotation. DCAF10's established CRL4 substrate-receptor function provides a plausible mechanism, but not a specific reproductive process or substrate set. gap_kind: - BIOLOGY - CURATION dark_aspect: BP_DARK status: OPEN significance: >- This gap controls whether DCAF10 should acquire biological-process annotations for spermatogenesis, germ-cell proteostasis, or male fertility, or whether testis expression should remain contextual evidence without direct functional annotation. resolution: >- Stage-resolved germ-cell expression, DCAF10 loss-of-function in spermatogenic systems, fertility phenotyping, and testis-specific substrate/ubiquitin-remnant proteomics would establish whether DCAF10 has a specialized reproductive role. provenance: - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: DCAF10 shows highest transcript levels in testis with very low expression in other tissues, suggesting a specialized role in spermatogenesis - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: Further research is needed to characterize DCAF10's specific role in spermatogenesis and whether defects in DCAF10 contribute to male infertility. - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: Expressed in sperm and 189 other cell types or tissues. - gap_statement: >- The compartment-specific and regulatory context of DCAF10 activity is underdetermined. GOA/Reactome place DCAF10 in nucleoplasm, the literature synthesis points to both nuclear and cytoplasmic substrate contexts, and the N-terminal region contains phosphoserine and methylarginine marks whose effects on DDB1 docking, substrate selection, localization, or stability are unknown. boundary: >- The review accepts CRL4-DCAF10 complex membership and keeps Reactome-derived nucleoplasm annotations as non-core. It does not yet define which cellular pools of DCAF10 perform which substrate-recognition functions, nor whether post-translational modifications regulate those pools. gap_kind: - BIOLOGY - CURATION dark_aspect: CC_DARK status: OPEN significance: >- Clarifying localization and regulatory PTMs would make DCAF10 annotations more precise, separating generic CRL4-pathway compartment projections from DCAF10-specific nuclear, cytoplasmic, or germ-cell substrate-recognition contexts. resolution: >- Endogenous localization under basal, N-myristoylation-stress, viral, cancer, and germ-cell conditions, paired with phosphosite/methylarginine mutagenesis and DDB1/CUL4/substrate-binding assays, would define the regulated active pools of DCAF10. provenance: - reference_id: file:human/DCAF10/DCAF10-deep-research-falcon.md supporting_text: DCAF10 functions in both nuclear and cytoplasmic compartments as part of the ubiquitin-proteasome system - reference_id: file:human/DCAF10/DCAF10-uniprot.txt supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - reference_id: file:human/DCAF10/DCAF10-notes.md supporting_text: N-terminal disordered region (1-119), with phosphoserine sites (S53, S63, S89, S92, S349) and methylarginine R134 from large-scale proteomics; no functional studies on these PTMs references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000041 title: Gene Ontology annotation based on UniPathway vocabulary mapping findings: [] - id: PMID:16949367 title: A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. findings: - statement: Identifies 18 DDB1- and CUL4-associated factors (DCAFs), including DCAF10, that co-purify with CUL4-DDB1; WD40-containing DCAFs dock onto DDB1 via a conserved WDXR motif and act as substrate receptors. supporting_text: Here, we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved "WDXR" motif. - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:33898171 title: OTUD1 Activates Caspase-Independent and Caspase-Dependent Apoptosis by Promoting AIF Nuclear Translocation and MCL1 Degradation. findings: - statement: Reports that OTUD1 deubiquitinates and stabilizes DCAF10 and recruits a CUL4A-DDB1-DCAF10 complex to promote MCL1 degradation, activating caspase-dependent apoptosis in esophageal squamous cell carcinoma; single, non-replicated study. supporting_text: OTUD1 stabilizes DDB1 and CUL4 associated factor 10 (DCAF10) and recruits the cullin 4A (CUL4A)-damage specific DNA binding protein 1 (DDB1) complex to promote myeloid cell leukemia sequence 1 (MCL1) degradation, thereby activating caspase-dependent apoptotic signaling. - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] - id: Reactome:R-HSA-8952638 title: AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-8952639 title: NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-8955245 title: CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus findings: [] - id: Reactome:R-HSA-8955285 title: COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex findings: [] - id: Reactome:R-HSA-8956045 title: COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex findings: [] - id: file:human/DCAF10/DCAF10-uniprot.txt title: UniProt record for human DCAF10 findings: - statement: UniProt summarizes DCAF10 as a possible CUL4-DDB1 substrate receptor that interacts with DDB1. supporting_text: May function as a substrate receptor for CUL4-DDB1 E3 - statement: UniProt carries a Bgee sperm expression cross-reference. supporting_text: Expressed in sperm and 189 other cell types or tissues. - statement: UniProt carries a Reactome-derived nucleoplasm GO annotation. supporting_text: GO; GO:0005654; C:nucleoplasm; TAS:Reactome. - statement: UniProt lists phosphoserine sites on DCAF10. supporting_text: Phosphoserine - statement: UniProt lists an omega-N-methylarginine site on DCAF10. supporting_text: Omega-N-methylarginine reference_review: relevance: HIGH correctness: VERIFIED review_notes: Local UniProt record used for stable protein summary, GO cross-references, expression cross-reference, and PTM feature evidence. - id: file:human/DCAF10/DCAF10-notes.md title: DCAF10 reviewer notes findings: - statement: Reviewer notes flag DCAF10 N-terminal phosphoserine and methylarginine sites as uncharacterized. supporting_text: N-terminal disordered region (1-119), with phosphoserine sites (S53, S63, S89, S92, S349) and methylarginine R134 from large-scale proteomics; no functional studies on these PTMs reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Local reviewer notes summarizing curation-relevant evidence gaps and provenance already checked against local UniProt and annotation files. - id: file:human/DCAF10/DCAF10-deep-research-falcon.md title: Falcon deep research report for DCAF10 findings: - statement: Synthesizes recent primary literature indicating DCAF10 acts as a substrate receptor of CRL4 (CUL4A/B-DDB1-RBX1) and, per Kremer et al. 2026, functions as an N-recognin recognizing N-terminally acetylated glycine (Ac-Gly) degrons, with reconstituted CUL4A-DDB1-DCAF10 directly ubiquitinating Src-family kinases (Lyn, Fyn, Src) in vitro. supporting_text: As a substrate receptor, DCAF10 recruits specific target proteins to the E3 ligase complex, facilitating their ubiquitination and subsequent proteasomal degradation reference_review: relevance: HIGH correctness: UNVERIFIED review_notes: LLM-synthesized deep-research report. The safe, well-supported framing it conveys is that DCAF10 is a WD40 beta-propeller substrate-recognition receptor of CRL4 (DDB1-CUL4) that docks DDB1 via WDxR motifs and contributes to substrate ubiquitination; this is consistent with the founding DCAF biochemistry (PMID:16949367) and is now reinforced by a primary paper defining DCAF10 as an N-recognin for N-terminally acetylated glycine (Ac-Gly) degrons (Kremer et al. 2026, Nat Commun, PMID:41484149, in vitro reconstitution + AlphaFold3). The specific substrate and pathway claims (Src-family kinases via the Ac-Gly/MO N-degron pathway; RUVBL1/2 in adenovirus E1A hijacking, Zemke et al. 2023, PMID:37962355; ALOX15B in KRAS-mutant PDAC, Li et al. 2025, PMID:40569151; high testis expression, Mistry et al. 2020, PMID:32867693) are each supported by single primary studies not yet independently replicated, and the underlying full texts are NOT in the local publications cache, so they have not been verified against source here and are treated as promising-but-provisional rather than established core functions. No specific substrate or pathway is attributed to DCAF10 in this review beyond what a primary paper directly demonstrates. - id: PMID:41484149 title: CUL4A-DDB1-DCAF10 is an N-recognin for N-terminally acetylated Src kinases. full_text_unavailable: true findings: - statement: Defines DCAF10 as the CRL4 substrate receptor (N-recognin) that recognizes an N-terminally acetylated glycine (Ac-Gly) degron via a pocket in its WD40 beta-propeller, and shows reconstituted CUL4A-DDB1-DCAF10 directly ubiquitinates Src-family kinases (Lyn, Fyn, Src) when N-myristoylation is impaired. Provides direct molecular-function and process evidence for DCAF10 as a CRL4 substrate-recognition subunit. Full text not in local cache; cited via the falcon deep-research synthesis and not independently verified here. supporting_text: Recent breakthrough research by Kremer et al. (2026) identified DCAF10 as an N-recognin for proteins bearing N-terminally acetylated glycine (Ac-Gly) residues, particularly those that normally undergo N-myristoylation - id: PMID:37962355 title: Adenovirus E1A binding to DCAF10 targets proteasomal degradation of RUVBL1/2 AAA+ ATPases required for quaternary assembly of multiprotein machines, innate immunity, and responses to metabolic stress. full_text_unavailable: true findings: [] - id: PMID:40569151 title: KRAS/ABHD17C/ALOX15B Axis Promotes Pancreatic Cancer Progression via Ferroptosis Evasion. full_text_unavailable: true findings: [] - id: PMID:32867693 title: Expression profiling of WD40 family genes including DDB1- and CUL4- associated factor (DCAF) genes in mice and human suggests important regulatory roles in testicular development and spermatogenesis. full_text_unavailable: true findings: []