DCAF11 (DDB1- and CUL4-associated factor 11; also called WD repeat-containing protein 23, WDR23) is a WD40-repeat protein that serves as a substrate-recognition receptor of the CRL4 (DDB1-CUL4-RBX1) cullin-RING E3 ubiquitin ligase. Through a conserved WDXR motif it docks onto the DDB1 adaptor of CUL4A- and CUL4B-based complexes and uses its C-terminal WD40 beta-propeller to present specific substrates for polyubiquitination and proteasomal degradation. Characterized substrates include the NRF2/NFE2L2 transcription factor (via the DIDLID sequence of its Neh2 domain), which links DCAF11 to the cellular antioxidant/oxidative-stress response, and the centromeric histone variant CENP-A, whose phospho-Ser68-primed degradation DCAF11 mediates to maintain centromere identity. The protein localizes predominantly to the nucleoplasm, consistent with its nuclear substrates. The orthologous receptor in C. elegans (WDR-23) controls the NRF/Nrf2 ortholog SKN-1, and DCAF11 has also been exploited as a recruited ligase in covalent molecular-glue targeted protein degradation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: DCAF11 is the substrate receptor of the CRL4(DCAF11) E3 ligase and targets multiple substrates for proteasomal degradation, including NRF2 and CENP-A, and additionally p21Cip1/CDKN1A (CRL4B-DCAF11) and the stem-loop binding protein SLBP at the end of S phase. This IBA term correctly captures the core role in ubiquitin-dependent proteolysis and is supported by direct experimental data on substrate degradation. Reason: Core biological process; supported phylogenetically and by direct degradation studies of NRF2 and CENP-A, with additional DCAF11-specific proteolytic substrates (p21Cip1, SLBP) reported in the primary literature and summarized in the falcon deep research. Supporting Evidence: PMID:34758320 Deletion of DCAF11 hampers CENP-A degradation and causes its mislocalization. PMID:31586112 DCAF11 and DDB1-Cul4/Roc1 bind to the DIDLID sequence of the Neh2 domain of Nrf2 to mediate its degradation. file:human/DCAF11/DCAF11-deep-research-falcon.md DCAF11 mediates the degradation of SLBP at the end of S phase through a phosphorylation-dependent mechanism |
| GO:0080008 Cul4-RING E3 ubiquitin ligase complex | IBA GO_REF:0000033 | ACCEPT | Summary: DCAF11 is an established component of the CRL4 (DDB1-CUL4) E3 ubiquitin ligase complex, acting as the DDB1-bound substrate receptor. This is the primary, well-supported complex membership annotation. Reason: Core complex membership; supported by IBA, by direct IDA in PMID:16949367, and by ComplexPortal entries CPX-2403/CPX-2404. Supporting Evidence: PMID:16949367 we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1. |
| GO:0005515 protein binding | IPI PMID:19109893 Structural basis of UV DNA-damage recognition by the DDB1-DD... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from an interactome dataset with DDB1 (Q16531). The specific, informative function (DDB1-docked substrate receptor) is captured better by other terms; bare protein binding is uninformative. Reason: Bare protein binding (GO:0005515) is uninformative; the meaningful DDB1 interaction is captured by the substrate-receptor MF and complex terms. Supporting Evidence: PMID:19109893 Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes. | MARK AS OVER ANNOTATED | Summary: Interaction with HIV-1 Vif (P12504) from a viral-host interactome screen. Represents viral hijacking of CRL machinery, not an endogenous DCAF11 function; the bare protein-binding term is uninformative. Reason: Xeno viral-host interactome hit; bare protein binding does not inform endogenous gene function. Supporting Evidence: PMID:22190034 Global landscape of HIV-human protein complexes. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation with DDB1 (Q16531) from a large-scale interactome map. Uninformative as a bare term; the DDB1 interaction is already captured by complex/substrate-receptor terms. Reason: Bare protein binding from high-throughput interactome; not specifically informative. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation from a binary (Y2H) interactome map with high-throughput partners (AGR2, TNNI1, TNNI2, RCN1, GPSM1) lacking functional follow-up. Bare protein binding is uninformative and these are likely non-physiological screen hits. Reason: High-throughput binary interactome partners without functional validation; bare protein binding uninformative. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation with DDB1 (Q16531) from a proteome-scale interactome dataset. Uninformative bare term; DDB1 interaction already represented by complex/substrate-receptor annotations. Reason: Bare protein binding from large-scale interactome; not specifically informative. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein-binding annotation with DDB1 (Q16531) from the OpenCell endogenous-tagging interactome. Uninformative as bare protein binding; the DDB1 interaction is captured by the substrate-receptor and complex terms. Reason: Bare protein binding from high-throughput interactome; not specifically informative. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | ACCEPT | Summary: DCAF11 functions in protein ubiquitination as the substrate receptor of the CRL4(DCAF11) ligase. This UniPathway-derived IEA term is consistent with direct evidence that DCAF11 mediates substrate ubiquitination. Reason: Correct process annotation, supported by experimental substrate ubiquitination data. Supporting Evidence: PMID:34758320 DCAF11 (DDB1 and CUL4 associated factor 11/WDR23) is the E3 ligase that specifically mediates the observed polyubiquitination. |
| GO:0031464 Cul4A-RING E3 ubiquitin ligase complex | NAS PMID:16949367 A family of diverse Cul4-Ddb1-interacting proteins includes ... | KEEP AS NON CORE | Summary: DCAF11 assembles into the CUL4A variant of the CRL4 complex (ComplexPortal CPX-2403). This more specific child of GO:0080008 is supported; keep as a valid but non-core specialization, with GO:0080008 as the core term. Reason: Valid CUL4A-variant complex membership (ComplexPortal CPX-2403); more specific than the core GO:0080008 annotation. Supporting Evidence: PMID:16949367 DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved WDXR motif. |
| GO:0031465 Cul4B-RING E3 ubiquitin ligase complex | NAS PMID:16949367 A family of diverse Cul4-Ddb1-interacting proteins includes ... | KEEP AS NON CORE | Summary: DCAF11 assembles into the CUL4B variant of the CRL4 complex (ComplexPortal CPX-2404). This more specific child of GO:0080008 is supported; keep as a valid but non-core specialization, with GO:0080008 as the core term. Reason: Valid CUL4B-variant complex membership (ComplexPortal CPX-2404); more specific than the core GO:0080008 annotation. Supporting Evidence: PMID:16949367 DCAFs interact with multiple surfaces on Ddb1, and the interaction of WD40-containing DCAFs with Ddb1 requires a conserved WDXR motif. |
| GO:0080135 regulation of cellular response to stress | NAS PMID:31586112 TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DC... | KEEP AS NON CORE | Summary: By targeting NRF2 for degradation, DCAF11 modulates the NRF2-driven antioxidant/oxidative-stress response. This regulatory process annotation is supported but is a downstream/indirect consequence of the core ligase function rather than a core activity. Reason: Supported via the NRF2/oxidative-stress axis but downstream of the core ubiquitin-ligase substrate-receptor function. Supporting Evidence: PMID:31586112 DCAF11 and DDB1-Cul4/Roc1 bind to the DIDLID sequence of the Neh2 domain of Nrf2 to mediate its degradation. |
| GO:1902412 regulation of mitotic cytokinesis | NAS PMID:34758320 Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquit... | MARK AS OVER ANNOTATED | Summary: The cited paper shows DCAF11 mediates phospho-Ser68 CENP-A degradation to maintain centromere identity and prevent ectopic CENP-A localization during the cell cycle; it does not demonstrate a role in cytokinesis. This label over-reaches the evidence. Reason: The publication concerns CENP-A/centromere homeostasis, not mitotic cytokinesis; the term is an imprecise over-interpretation. Supporting Evidence: PMID:34758320 the Ser68 phosphorylation plays an important role in regulating cellular CENP-A homeostasis via DCAF11-mediated degradation to prevent ectopic localization of CENP-A during the cell cycle. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence (HPA) localizes DCAF11 to the nucleoplasm, consistent with its nuclear substrates (NRF2, CENP-A) and with the nuclear CRL4 cycle. Reason: Direct immunofluorescence localization, consistent with nuclear substrate biology. Supporting Evidence: file:human/DCAF11/DCAF11-uniprot.txt GO; GO:0005654; C:nucleoplasm; IDA:HPA. |
| GO:0005515 protein binding | IPI PMID:16949367 A family of diverse Cul4-Ddb1-interacting proteins includes ... | MODIFY | Summary: This IPI captures the functionally meaningful interactions with DDB1 and the cullins (Q16531/Q13619/Q13620) that constitute CRL4(DCAF11) assembly. The specific, informative function is the DDB1-docked substrate-receptor activity rather than bare protein binding. Reason: The interaction with DDB1/CUL4 reflects the substrate-receptor adaptor role; replace uninformative protein binding with the specific MF term. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:16949367 we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. DCAFs interact with multiple surfaces on Ddb1. |
| GO:0005515 protein binding | IPI PMID:27018634 Quantitative Mass Spectrometry Identifies Novel Host Binding... | MARK AS OVER ANNOTATED | Summary: Interaction with an E. coli type III secretion system effector (Q8XB62) from a pathogen-effector screen. Not an endogenous DCAF11 function; the bare protein-binding term is uninformative. Reason: Pathogen effector interactome hit; bare protein binding does not inform endogenous gene function. Supporting Evidence: PMID:27018634 Quantitative Mass Spectrometry Identifies Novel Host Binding Partners for Pathogenic Escherichia coli Type III Secretion System Effectors. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8952638 | ACCEPT | Summary: Reactome places the CRL4 complex (here DCAF11) in the nucleoplasm during the neddylation/deneddylation regulatory cycle. Consistent with the IDA nucleoplasm localization. Reason: Nucleoplasm localization corroborated by independent IDA evidence. Supporting Evidence: file:human/DCAF11/DCAF11-uniprot.txt GO; GO:0005654; C:nucleoplasm; IDA:HPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8952639 | ACCEPT | Summary: Reactome places the CRL4 complex (here DCAF11) in the nucleoplasm during the neddylation regulatory cycle. Consistent with the IDA nucleoplasm localization. Reason: Nucleoplasm localization corroborated by independent IDA evidence. Supporting Evidence: file:human/DCAF11/DCAF11-uniprot.txt GO; GO:0005654; C:nucleoplasm; IDA:HPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8955245 | ACCEPT | Summary: Reactome places the CRL4 complex (here DCAF11) in the nucleoplasm during the CAND1 exchange cycle. Consistent with the IDA nucleoplasm localization. Reason: Nucleoplasm localization corroborated by independent IDA evidence. Supporting Evidence: file:human/DCAF11/DCAF11-uniprot.txt GO; GO:0005654; C:nucleoplasm; IDA:HPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8955285 | ACCEPT | Summary: Reactome places the CRL4 complex (here DCAF11) in the nucleoplasm during COMMD-mediated CAND1 displacement. Consistent with the IDA nucleoplasm localization. Reason: Nucleoplasm localization corroborated by independent IDA evidence. Supporting Evidence: file:human/DCAF11/DCAF11-uniprot.txt GO; GO:0005654; C:nucleoplasm; IDA:HPA. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8956045 | ACCEPT | Summary: Reactome places the CRL4 complex (here DCAF11) in the nucleoplasm during COP9 signalosome-mediated deneddylation. Consistent with the IDA nucleoplasm localization. Reason: Nucleoplasm localization corroborated by independent IDA evidence. Supporting Evidence: file:human/DCAF11/DCAF11-uniprot.txt GO; GO:0005654; C:nucleoplasm; IDA:HPA. |
| GO:0080008 Cul4-RING E3 ubiquitin ligase complex | IDA PMID:16949367 A family of diverse Cul4-Ddb1-interacting proteins includes ... | ACCEPT | Summary: Direct identification of DCAF11 in DDB1-CUL4A complexes by tandem-affinity purification and mass spectrometry establishes CRL4 complex membership. This is the core, experimentally grounded complex annotation. Reason: Core complex membership directly demonstrated by affinity purification/MS. Supporting Evidence: PMID:16949367 we identify 18 Ddb1- and Cul4-associated factors (DCAFs), including 14 containing WD40 repeats. |
Loading supporting content…
Download this section (compressed HTML)Q: What is the full repertoire of endogenous CRL4(DCAF11) substrates, and which degrons/recognition motifs does the DCAF11 WD40 propeller read?
Q: Does DCAF11 preferentially partner with CUL4A versus CUL4B in specific cellular contexts, and is there substrate specialization between the two variants?
Q: How is CRL4(DCAF11) activity itself regulated (neddylation/CAND1 exchange, expression control such as TFEB repression) under oxidative and proteotoxic stress?
Experiment: Define the CRL4(DCAF11) substrate landscape using global protein-stability profiling (e.g., quantitative diGly ubiquitinome and degradation/half-life proteomics) comparing DCAF11-knockout versus wild-type cells.
Experiment: Determine a cryo-EM or crystal structure of DCAF11 bound to DDB1 and to a substrate degron peptide (e.g., NRF2 Neh2 DIDLID or phospho-CENP-A) to map the recognition surface.
Experiment: Test for genetic separation of function between CUL4A- and CUL4B-based CRL4(DCAF11) complexes by selective depletion and substrate-stabilization readouts.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)