DCAF17

Summary: DCAF17 associates with cullin-containing DDB1 complexes.

Reason: The recovered human 293T study identifies DCAF17 by seven peptides in DDB1 affinity purification (Figure 1C) and validates GST-DCAF17 association in Figure 1E lane 10. GO:0097602 refines the CUL4A/CUL4B partner class; it does not cover DDB1 (Q16531), which is not a cullin. DDB1 association remains an independently supported part of this source assertion. No suitable DDB1-specific binding descendant was established by the bounded GO search, so no additional replacement is asserted. These cell-lysate experiments do not establish a purified binary interface or a DCAF17 substrate-recruitment mechanism.

Proposed replacements: cullin family protein binding

Summary: Human Protein Atlas immunofluorescence supports nucleoplasmic localization of DCAF17.

Reason: The actual HPA record for ENSG00000115827/Q5H9S7 reports nucleoplasm as the main subcellular location and rates the immunofluorescence evidence Supported. The record lists antibodies HPA053339 and HPA055040. This matches the current GO definition, which excludes the nucleolus; the nucleolar observation from a separate study should therefore be retained as a distinct localization context. The HPA record does not resolve which of the two official protein products generates the signal. Antibody images were not independently inspected.

Summary: The Reactome NEDD8-transfer event includes DCAF17 in its nucleoplasmic CRL4 complex.

Reason: The actual event R-HSA-8952638 reaches DCAF17 through its input complex 8952580, CRL4 complex 8955268/976149, DCAF set 976118 and protein entity 8863278, whose reference is Q5H9S7. That protein entity is explicitly assigned to nucleoplasm, independently consistent with the HPA localization. The event describes UBE2M transferring NEDD8 to cullins; DCAF17's membership does not establish that DCAF17 catalyzes NEDD8 transfer. Reactome explicitly notes that these CRL4 complexes are depicted in the nucleus because many targets are nuclear, while cytoplasmic targets also exist.

Summary: The Reactome UBE2M-binding event contains the nucleoplasmic DCAF17 complex member.

Reason: Event R-HSA-8952639 includes CRL4 complex 8955268, with a literal containment path through 976149 and DCAF set 976118 to DCAF17 entity 8863278 and Q5H9S7. The entity's compartment is nucleoplasm and its modeled sequence spans residues 1–520. The localization is compatible with the separate HPA observation; the model does not establish that DCAF17 itself binds UBE2M or that the 240-residue product has the same localization. The event's reported recruitment mechanism concerns UBE2M, cullins and DCUN1D proteins.

Summary: DCAF17 is a modeled nucleoplasmic CRL4 member in the CAND1-binding event.

Reason: Event R-HSA-8955245 contains the CRL4 input 976149 and the CAND1-bound output 8955244. The CRL4 complex includes DCAF set 976118, with literal member DCAF17 8863278/Q5H9S7 in nucleoplasm. This source supports the modeled compartment, corroborated by HPA immunofluorescence. It does not identify DCAF17 as the CAND1 binding interface or establish a DCAF17-specific exchange reaction; the event describes CAND1 binding the cullin scaffold.

Summary: The COMMD/CAND1 exchange model includes nucleoplasmic DCAF17 through the CRL4 DCAF set.

Reason: Event R-HSA-8955285 connects both the CAND1-bound input 8955244 and CRL4 output 8955268 to complex 976149, DCAF set 976118 and DCAF17 entity 8863278/Q5H9S7. That entity is assigned to nucleoplasm, consistent with the independent HPA observation. The source describes COMMD proteins and CCDC22 displacing CAND1; it does not demonstrate that DCAF17 itself performs the displacement or identify its ubiquitination substrate.

Summary: The COP9 deneddylation event retains DCAF17 as a nucleoplasmic CRL4 complex member.

Reason: The input and output complexes of R-HSA-8956045 contain the DCAF set 976118 and its literal DCAF17 member 8863278/Q5H9S7, explicitly located in nucleoplasm. The modeled compartment is independently consistent with HPA localization. The catalytic activity belongs to the COP9 signalosome, not DCAF17; this cellular-component annotation does not assign deneddylase activity or a specific ubiquitination substrate to DCAF17.

Summary: Both major DCAF17 products localize to nucleoli in the tested human cells.

Reason: PMID:19026396 reports untagged 520-aa beta and 240-aa alpha products in HEK293 nucleoli and endogenous C2orf37/B23 colocalization in lymphoblasts. The shared antibody epitope, peptide competition, Methods and Figure 4 support this location. GFP-fusion aggregation was treated by the authors as an artifact; it is not the positive localization assay. The experimental product architecture matches the official long product and its 281–520 short product.

Summary: Mouse Dcaf17 loss disrupts sperm development, supporting a contextual spermatogenesis role.

Reason: The original study deletes mouse Dcaf17 exon 4 and verifies the resulting frameshift. Mutant males are infertile and produce fewer, poorly motile, morphologically abnormal sperm; histology, alpha-tubulin staining and electron microscopy identify particularly severe post-meiotic defects in nuclear shaping, manchette organization and acrosome development. These are positive source-specific observations supporting the existing broad spermatogenesis association. They are mouse loss-of-function experiments, not direct assays of either human protein product or proof that DCAF17 is a microtubule structural component. The proposed connection to CUL4-dependent protein homeostasis is explicitly speculative in the Discussion and does not identify a DCAF17 substrate or performed ubiquitination step. The published correction concerns author indexing only.

Summary: Predicted membrane topology is not experimentally reconciled with nucleolar localization.

Reason: The official long product has two hydrophobic helices predicted at residues 186–206 and 222–242 (ECO:0000255), whereas the 240-residue product lacks both. UniProt explicitly flags a conflict between the predicted transmembrane regions and the experimental nucleolar localization. PMID:19026396 shows nucleolar localization of untagged products and endogenous protein; it does not resolve membrane insertion, topology, or partitioning of the long product between pools. The membrane annotation is therefore uncertain because these positive sequence and localization observations remain unreconciled, rather than because the paper is inaccessible. The literal mapping and product distinction are retained.

Summary: CUL4 association supports a candidate ubiquitination role, but the performed DCAF17 step remains unresolved.

Reason: IPR031620 genuinely matches the human protein and maps to protein ubiquitination, while its description proposes substrate-receptor activity. PMID:16949367 demonstrates DCAF17 association; the substrate-turnover and replication experiments concern DCAF2/Cdt2. A noncatalytic structural or substrate-recruitment contribution would qualify as participation, but the DCAF17 experiments do not identify the substrate, interface, or assembly contribution by which DCAF17 performs a ubiquitination step. Positive membership in curator-inferred CUL4 complexes establishes association without resolving that mechanistic role. Mouse knockout transcriptome changes and increased bulk ubiquitin in the 2025 proteome abstract likewise do not identify the performed DCAF17 step. Retain genuine functional uncertainty, without treating a catalytic assay as mandatory or asserting that DCAF17 cannot participate.

Summary: DCAF17 is supported as a member of CUL4A-DDB1-associated assemblies.

Reason: PMID:16949367 Figure 1E lane 10 supports DCAF17 association with CUL4A and DDB1 in transfected human 293T cell lysates, following the DDB1 affinity-purification identification in Figure 1C. CPX-2415 separately records the DCAF17/DDB1/RBX1/CUL4A complex as curator-inferred. The cellular-component assertion does not assign the complex catalytic activity or a proven substrate-receptor mechanism to DCAF17 itself.

Summary: DCAF17 is supported as a member of CUL4B-DDB1-associated assemblies.

Reason: The actual Figure 1E lane 10 includes a CUL4B-level signal in the GST-DCAF17 cell-lysate association experiment, and CPX-2416 records the DCAF17/DDB1/RBX1/CUL4B assembly as curator-inferred. This supports the existing positive membership alongside the CUL4A assertion. Unquantified relative band intensity does not establish a biologically distinct core-versus-contextual role. Both assemblies are represented by the single generic CUL4 core; neither a purified stoichiometric complex nor a distinct CUL4B-dependent DCAF17 substrate mechanism is claimed.

Summary: The inherited Cul4 complex assertion is experimentally grounded on DCAF17 itself.

Reason: The actual PTHR14815 tree places human Q5H9S7 at PTN002495134 beneath the Eumetazoa node PTN001028294. The literal IBD assigns GO:0080008 at that ancestral node with Q5H9S7 as experimental descendant support; the current human IDA annotation from PMID:16949367 supplies the positive grounding. The 15-node target path and target sequence in the alignment are intact. Self inclusion is legitimate and is not circular. Complex inheritance does not independently establish substrate specificity or E3 catalytic activity.

Summary: The original study directly supports association with Cul4-DDB1 complexes.

Reason: DCAF17 is identified in human DDB1 affinity purification and tested with DDB1/CUL4A/CUL4B in Figure 1E lane 10. This supports the existing broad complex membership. The interaction preparation and curator-defined assembly do not show that DCAF17 alone catalyzes ubiquitination or recognizes any particular substrate.