| Claim/Topic | Direct evidence for DCAF12L2? (Yes/No) | Key details (concise, include mutations/residues/substrates) | Source (first author, year, venue) | Publication date (month/year) | URL/DOI |
|---|---|---|---|---|---|
| Identity / domains | Yes | Human target verified as DCAF12L2/WDR40C, a WD40-repeat DCAF family protein; one source states DCAF12L2 is composed of seven WD40 repeats and functions in a CRL4 context; this aligns with UniProt Q5VW00 annotation as DDB1- and CUL4-associated factor 12-like protein 2 (pqac-00000009) | Onireti, 2022, thesis/unknown venue | 2022 | Not clearly available in retrieved context |
| CRL4 substrate receptor role | Yes | Reported as CRL4DCAF12L2 substrate receptor; AP-MS identified associated candidate substrates, supporting assignment as a CRL4 substrate receptor rather than an enzyme or transporter (pqac-00000009) | Onireti, 2022, thesis/unknown venue | 2022 | Not clearly available in retrieved context |
| Known / predicted degron recognition | Yes | DCAF12L2 is reported to recognize a C-terminal di-glutamic acid (EE) degron; however, this evidence appears thesis-level and not independently validated here by structural biochemistry for DCAF12L2 itself (pqac-00000009) | Onireti, 2022, thesis/unknown venue | 2022 | Not clearly available in retrieved context |
| Experimentally identified substrates and ubiquitination | Yes | AP-MS identified MEKK4 and the WDR11 complex as two independent CRL4DCAF12L2 substrates; CRL4DCAF12L2 reportedly ubiquitylates FAM91A1, a component of the WDR11 complex, implicating regulation of WDR11-complex stability/function (pqac-00000009) | Onireti, 2022, thesis/unknown venue | 2022 | Not clearly available in retrieved context |
| Cancer-associated mutations and effect | Yes | Cancer-associated mutations in WD40 region include P334L, R335C, R335H, and mutation at/near residue 337; these mutations reportedly block DCAF12L2 binding to identified substrates, consistent with disruption of substrate recognition (pqac-00000009) | Onireti, 2022, thesis/unknown venue | 2022 | Not clearly available in retrieved context |
| Negative findings: DDB1 / MCMBP binding | Yes | In ortholog testing, DCAF12L2 showed no detectable binding to MCMBP; authors cite prior evidence that neither DCAF12L1 nor DCAF12L2 binds the C-terminal acidic end, and they did not detect significant DDB1 binding to DCAF12L2, leaving functional CRL4 assembly uncertain in that assay system (pqac-00000010, pqac-00000003) | Kolářová, 2025, unknown venue | 2025 | Not clearly available in retrieved context |
| Expression / stability inference | Yes | DCAF12L2 was reported to show higher steady-state expression than DCAF12 in the tested system; authors suggest weaker autoubiquitination than DCAF12 may explain this difference (pqac-00000010, pqac-00000003) | Kolářová, 2025, unknown venue | 2025 | Not clearly available in retrieved context |
| Disease-target associations (Open Targets) | Yes | Open Targets lists modest associations for DCAF12L2 with glioblastoma multiforme (score 0.2712), restless legs syndrome (0.2438), acquired thrombocytopenia (0.2247), lung adenocarcinoma (0.2232), and prostate adenocarcinoma (0.2141); these are association signals, not proof of causal mechanism (pqac-00000000) | Open Targets platform | Accessed in current session | Platform result; no DOI in context |
| Structural family mechanism from DCAF12: DDB1/CUL4 adaptor architecture | No | Family-level inference only: DCAF12 is a canonical WD40 DCAF substrate receptor within CRL4, forming DDB1-DCAF12-substrate complexes; DDB1 engages WD40 DCAFs and supports substrate recruitment in CRL4 ligases (pqac-00000001, pqac-00000005, pqac-00000006) | Pla-Prats, 2023, EMBO J; Righetto, 2024, PNAS Nexus; Raisch, 2023, Mol Cell Proteomics | Jan/2023; Apr/2024; Oct/2023 | https://doi.org/10.15252/embj.2022112253; https://doi.org/10.1093/pnasnexus/pgae153; https://doi.org/10.1016/j.mcpro.2023.100644 |
| Structural family mechanism from DCAF12: acidic degron recognition | No | Family-level inference only: cryo-EM showed DCAF12 binds CCT5 and MAGEA3 C-terminal di-Glu degrons in a positively charged central WD40 pocket; key DCAF12 residues include Lys91, Lys108, Arg203, Arg256, Arg344; monomeric CCT5, but not assembled TRiC-bound CCT5, is ubiquitinated (pqac-00000001, pqac-00000007, pqac-00000011, pqac-00000012) | Pla-Prats, 2023, EMBO J; Righetto, 2024, PNAS Nexus | Jan/2023; Apr/2024 | https://doi.org/10.15252/embj.2022112253; https://doi.org/10.1093/pnasnexus/pgae153 |
| Methods / assays used for DCAF12L2 evidence | Yes | Evidence base includes affinity purification-mass spectrometry (AP-MS), proteomic interactomics, mutation-impact analysis on substrate interactions, and ubiquitylation analysis of FAM91A1; separate ortholog work used affinity-purification assays for MCMBP/DDB1 binding (pqac-00000009, pqac-00000010) | Onireti, 2022, thesis/unknown venue; Kolářová, 2025, unknown venue | 2022; 2025 | Not clearly available in retrieved context |
| Methods / assays used for family-level mechanism | No | Family-level DCAF12 mechanism established by cryo-EM, TR-FRET, fluorescence polarization peptide binding, NanoBRET in cells, in vitro ubiquitination, BioID/AP-MS, and pulse-SILAC degradation measurements (pqac-00000001, pqac-00000005, pqac-00000006, pqac-00000007) | Pla-Prats, 2023, EMBO J; Righetto, 2024, PNAS Nexus; Raisch, 2023, Mol Cell Proteomics | Jan/2023; Apr/2024; Oct/2023 | https://doi.org/10.15252/embj.2022112253; https://doi.org/10.1093/pnasnexus/pgae153; https://doi.org/10.1016/j.mcpro.2023.100644 |
| Potential application in targeted protein degradation (family-level, not DCAF12L2-specific) | No | DCAF12 structural work suggests its WD40 pocket could be exploited as a small-molecule handle for future PROTAC/degrader design; this is explicitly a DCAF12 family insight and should not be over-interpreted as validated for DCAF12L2 (pqac-00000005) | Righetto, 2024, PNAS Nexus | Apr/2024 | https://doi.org/10.1093/pnasnexus/pgae153 |


*Table: This table summarizes direct versus inferred functional annotation evidence for human DCAF12L2 (Q5VW00), separating sparse target-specific findings from stronger family-level DCAF12 mechanistic data. It is useful for identifying what is experimentally supported, what remains uncertain, and where recent structural biology informs cautious functional inference.*