Annotation inferences using phylogenetic trees
The DNA sequence of the human X chromosome
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Provides the genomic DNA sequence of the human X chromosome, establishing the chromosomal location and gene structure of DCAF12L2 at Xq25.
"...The DNA sequence of the human X chromosome..."
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)
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Provides full-length cDNA sequence for DCAF12L2 from brain tissue, confirming that the gene is transcribed.
"...The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)..."
A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1
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Identifies 18 DCAFs (DDB1- and CUL4-associated factors), showing that WD40-containing DCAFs interact with DDB1 via a conserved WDXR motif. Establishes the general framework for DCAF substrate receptor function in CRL4 complexes.
"...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..."
Probing the CRL4-DCAF12 interactions with MAGEA3 and CCT5 di-Glu C-terminal degrons
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Resolves the 3.17A cryo-EM structure of DDB1-DCAF12-MAGEA3 complex. Demonstrates that DCAF12 (the parent gene) uses its WD40 beta-propeller to recognize C-terminal diglutamate degrons. This characterizes the parent gene function, not DCAF12L2 itself.
"...Damaged DNA-binding protein-1 (DDB1)- and CUL4-associated factor 12 (DCAF12) serves as the substrate recognition component within the Cullin4-RING E3 ligase (CRL4) complex, capable of identifying C-terminal double-glutamic acid degrons to promote the degradation of specific substrates through the ubiquitin proteasome system. Melanoma-associated antigen 3 (MAGEA3) and T-complex protein..."
Recognition of the CCT5 di-Glu degron by CRL4(DCAF12) is dependent on TRiC assembly
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Provides 2.8 A cryo-EM structure of DDB1-DCAF12-CCT5 complex; DCAF12 binds the CCT5 di-Glu degron in the WD40 central pocket and selectively ubiquitinates monomeric CCT5 but not TRiC-assembled CCT5, establishing an assembly-quality-control mechanism for the parent gene DCAF12 family.
"Pla-Prats et al. (EMBO Journal; publication date **Jan 2023**; https://doi.org/10.15252/embj.2022112253) report a **2.8 Å cryo-EM structure** of the **DDB1–DCAF12–CCT5** complex and show DCAF12 binds the **CCT5 di-Glu degron** in the WD40 central pocket. Importantly, they provide functional evidence that DCAF12 binds/ ubiquitinates **monomeric CCT5** but not **TRiC-assembled CCT5**, establishing an assembly-dependent substrate-selection rule."
Pulse-SILAC and Interactomics Reveal Distinct DDB1-CUL4-Associated Factors, Cellular Functions, and Protein Substrates
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Systematic BioID/AP-MS and pulse-SILAC mapping of DCAF-DDB1 interactomes and substrate degradation effects across the DCAF family, providing methodology applicable to mapping DCAF12L2 substrates and CRL4 engagement.
"Raisch et al. (Molecular & Cellular Proteomics; publication date **Oct 2023**; https://doi.org/10.1016/j.mcpro.2023.100644) describe BioID/AP-MS and pulse-SILAC strategies to link DCAF–DDB1 interactions to downstream substrate degradation effects, illustrating scalable approaches that could be applied to map DCAF12L2 substrates and confirm CRL4 engagement under defined cellular conditions."
Falcon deep-research report on DCAF12L2 (Edison Scientific Literature, 2026-05-29)
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Reports proteomics-level identification of MEKK4 and the WDR11/FAM91A1 complex as candidate CRL4^DCAF12L2 substrates, and notes cancer-associated mutations P334L, R335C/H, and ~residue 337 in the WD40 region that block substrate binding (Onireti thesis 2022, not peer-reviewed and not independently corroborated in the retrieved corpus).
"A proteomics-focused source reports DCAF12L2 as a **CRL4 substrate receptor (CRL4^DCAF12L2)** and describes **affinity purification–mass spectrometry (AP-MS)** evidence identifying **MEKK4** and the **WDR11 complex** as two independent substrate contexts; it further reports that **CRL4^DCAF12L2 mediates ubiquitylation of FAM91A1**, a component of the WDR11 complex."
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Reports contradictory negative evidence from a 2025 ortholog-testing study: no detectable DCAF12L2 binding to MCMBP and no significant DDB1 binding to DCAF12L2 in affinity assays, leaving functional CRL4 assembly for DCAF12L2 unresolved.
"A separate experimental source (2025) tested DCAF12L2 (and DCAF12L1) for interaction with **MCMBP** (a known DCAF12 substrate in that research program) and found **no detectable binding**, consistent with prior work that neither DCAF12L1 nor DCAF12L2 binds the same **C-terminal acidic end** degron as DCAF12. The authors also report **no significant binding of DDB1** to DCAF12L1 or DCAF12L2 in their assays, concluding it remains unclear whether these paralogs can assemble a fully functional CRL4 complex under those conditions."
Manual DCAF12L2 curation notes
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Records the conservative curation boundary for DCAF12L2: the gene is a Tdark DCAF12-family protein with indirect CRL4/substrate-adaptor support, but no direct biochemical paper, validated DDB1/CUL4 interaction, or confirmed substrate.
"There is no direct DCAF12L2 biochemical paper, no validated DDB1/CUL4 binding experiment, and no confirmed DCAF12L2 substrate."
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Summarizes the DCAF12L2-specific experimental unknowns that define this gene as functionally dark despite family-level DCAF12 inference.
"No direct experimental characterization of DCAF12L2 protein function exists"
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Notes the reproductive-expression clue that motivates, but does not resolve, a possible DCAF12L2 role in male germ-cell biology.
"It is enriched in testis/epididymis"