dca7 (systematic name SPBC17D11.08) is an uncharacterized WD40 repeat-containing protein of the fission yeast Schizosaccharomyces pombe. Its sequence comprises multiple WD40 repeats predicted to fold into a beta-propeller and it carries the DCAF7-like domain signature (InterPro IPR045159), identifying it as the fission yeast ortholog of the animal DCAF7/WDR68/HAN11 protein and of S. cerevisiae YPL247C; it is a predominantly single-copy protein conserved across fungi and metazoa. The protein has no recognizable catalytic, transmembrane, or signal domain, consistent with a non-enzymatic scaffold/adaptor architecture. In a genome-wide GFP-tagging survey the protein was localized to the cytoplasm and the Golgi apparatus, and it is phosphorylated on serine residues. Its biological role has not been experimentally determined in S. pombe; deletion of the gene is viable. A proteome-wide binary two-hybrid screen detected an interaction with the Yak/DYRK-family kinase Ppk15, suggesting a candidate conserved partnership but not yet establishing a molecular function, scaffolding mechanism, or downstream process. Animal orthologs act as WD40 scaffolds/adaptors for DYRK-family kinases. A proposed CUL4-DDB1 (CRL4) substrate-receptor role remains unverified even for human DCAF7 and has not been demonstrated in fission yeast.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred (IBA) nuclear localization propagated within PANTHER family PTHR19919 (DCAF7/WDR68). Animal DCAF7 is nucleocytoplasmic and its nuclear pool is functionally important, so a nuclear location is phylogenetically plausible, and PomBase independently carries this cellular component. However, the one direct S. pombe localization dataset (PMID:16823372) reported cytoplasm and Golgi, not nucleus, so this remains an inference. Retained as a plausible, non-core localization annotation; it does not describe a molecular function. Reason: IBA localization consistent with the family and independently curated by PomBase, but it is a location rather than a core function and is not directly demonstrated in S. pombe. Supporting Evidence: file:SCHPO/dca7/dca7-deep-research-falcon.md DCAF7/WDR68 localizes to both the nucleus and cytoplasm, with its distribution regulated by its kinase binding partners. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasmic localization mapped by UniProt from the Subcellular Location vocabulary. It is underpinned by an experimental S. pombe datum: the genome-wide GFP/YFP localization survey (PMID:16823372), recorded in UniProt as "Cytoplasm {ECO:0000269|PubMed:16823372}". A well-supported localization, but a location rather than a molecular function. Reason: Localization is experimentally supported (via UniProt ECO:0000269|PubMed:16823372) but is non-core; it does not describe what the protein does. Supporting Evidence: UniProt:O74763 Cytoplasm {ECO:0000269|PubMed:16823372} |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Golgi localization mapped by UniProt from the Subcellular Location vocabulary, derived from the same single high-throughput GFP/YFP survey (PMID:16823372; UniProt "Golgi apparatus {ECO:0000269|PubMed:16823372}"). A WD40 scaffold/adaptor is not an obvious Golgi resident and this single-method observation may reflect a minor or secondary pool; it should be treated with caution and is not corroborated by any interaction or functional evidence. Reason: Retained because it derives from an experimental localization dataset, but flagged as weakly supported (single high-throughput method, no corroboration) and non-core. Supporting Evidence: UniProt:O74763 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular_function term with the ND ("No biological Data") evidence code, the PomBase convention for a gene whose molecular function has not been experimentally determined. PomBase also curates a Dca7-Ppk15 binary two-hybrid interaction from the proteome-wide FissionNet screen (PMID:26771498), but retains this ND annotation rather than assigning a binding function. Because the individual pair lacks targeted validation or a functional assay, that high-throughput edge is treated as a hypothesis lead rather than grounds to overrule the curator's ND call. Reason: ND remains the appropriate curated state: a single proteome-wide Y2H edge suggests a possible kinase partnership but does not establish the primary molecular function or a Dca7-dependent scaffolding mechanism. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological_process term with the ND evidence code, indicating that no biological process has been experimentally assigned to dca7 in S. pombe. Deletion is viable and only broad, non-specific stress-screen phenotypes are recorded, so no defensible specific BP annotation can be made. Retained as the honest placeholder marking a genuine biological-process knowledge gap. Reason: ND correctly encodes that the biological process of this dark gene is unknown; it is not a substantive term to replace or remove. |
| GO:0080008 Cul4-RING E3 ubiquitin ligase complex | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Complex membership inferred by sequence similarity (ISS) from human DCAF7 (UniProt P61962). This is a legitimate curator transfer from an ortholog, so it is not treated as a paralog error. However, the primary DCAF7 adaptor study explicitly describes the CRL4 substrate-receptor role as deduced and not experimentally verified (PMID:27307198), and no S. pombe evidence places Dca7 with Pcu4/Ddb1. The annotation therefore expresses a plausible family association more strongly than the available evidence warrants. Reason: The orthology is sound, but the asserted complex membership lacks local evidence and depends on an unverified mechanistic interpretation of the human ortholog. Retain for curator review rather than REMOVE, while marking the claim as over-annotated. Supporting Evidence: PMID:27307198 However, this role of DCAF7 has not yet been experimentally verified. |
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Download this section (compressed HTML)Q: Does the high-throughput Dca7-Ppk15 Y2H interaction reproduce by reciprocal co-IP or proximity labeling at native expression, and does Dca7 alter Ppk15 localization, stability, substrate recruitment, or phosphorylation output?
Q: Does Dca7 physically associate with the S. pombe Cul4 (Pcu4)/Ddb1 machinery, or is the ISS-transferred CUL4-RING E3 ubiquitin ligase complex membership not realized in fission yeast?
Q: Is the Golgi localization observed in the genome-wide GFP survey a genuine steady-state pool or a tagging/overexpression artifact, given that a WD40 scaffold has no obvious Golgi role?
Experiment: Affinity purification of a functional epitope-tagged Dca7 from S. pombe followed by mass spectrometry to define its in vivo interactome, with reciprocal tagging/co-IP validation of the top hits and comparison against candidate DYRK/Yak kinases and Cul4/Ddb1 subunits.
Hypothesis: Dca7 forms a native complex with the Yak/DYRK-family kinase Ppk15 and is required for a measurable aspect of Ppk15 localization, stability, substrate recruitment, or signaling.
Type: affinity purification-mass spectrometry (AP-MS) interactome mapping
Experiment: Systematic phenotypic profiling of a dca7 deletion strain (growth, stress panels, quiescence survival, and transcriptome/RNA-seq) alongside a WD40 propeller-surface point mutant to test whether phenotypes depend on the protein-binding surface, and epistasis analysis with candidate kinase and Cul4/Ddb1 partners.
Hypothesis: Dca7 contributes to a specific biological process (e.g. gene expression or a stress pathway) despite being non-essential.
Type: reverse-genetics phenotyping, transcriptomics, and epistasis analysis
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular function of S. pombe dca7 (SPBC17D11.08) is undetermined: it is not known whether its WD40 beta-propeller merely binds Ppk15 or acts as a functional kinase scaffold, whether it is a ubiquitin-ligase substrate receptor, or how either interaction affects a downstream pathway. The Dca7-Ppk15 Y2H edge is a specific interaction lead, but PomBase retains MF as ND and the pair has no targeted validation or functional assay.
OPEN BIOLOGY MF_DARK
What is known: Firmly established: the protein exists, is a phosphorylated WD40-repeat protein with a DCAF7-like domain (InterPro IPR045159), is conserved one-to-one across fungi and metazoa, localizes to the cytoplasm and Golgi in a genome-wide GFP survey, and its deletion is viable. PomBase records a high-throughput Dca7-Ppk15 binary Y2H interaction, and Ppk15 is a Yak/DYRK-family kinase. Animal DCAF7/WDR68 is a catalytically inactive adaptor for DYRK-family kinases. What remains unknown is whether the S. pombe interaction occurs in native cells and whether Dca7 changes Ppk15 localization, stability, or signaling output.
Significance: dca7 belongs to a deeply conserved, single-copy protein family with important roles in animal signaling and development (DYRK1A/HIPK2 regulation, transcription, DNA-repair protein turnover). A defined fission-yeast function would clarify the ancestral, pre-metazoan role of the DCAF7/WDR68 scaffold and whether the DYRK-partner or CUL4-receptor role is the conserved core.
What would resolve it: Affinity purification-mass spectrometry of tagged Dca7 to identify its fission-yeast interactome (testing for association with a DYRK/Yak-family kinase and/or with Cul4/Ddb1); reciprocal tagging of candidate partners; and phenotypic profiling of a dca7 deletion under conditions where DCAF7-family functions are relevant (stress signaling, DNA damage).
Provenance (the field's own admissions):
Gap: The biological process dca7 participates in within S. pombe is unknown. PomBase records the biological process as ND, deletion is viable, and only broad, non-specific high-throughput stress-resistance/sensitivity and quiescence-survival phenotypes are catalogued, none of which pin the gene to a specific pathway.
OPEN BIOLOGY BP_DARK
What is known: Established: dca7 deletion is viable and the gene appears in numerous genome-wide phospho/phenomic datasets, and it has high-throughput physical-interaction hits (with the chromatin remodeler fft3 by affinity capture-MS, and with the kinase ppk15 by two-hybrid). Unknown: whether any of these reflect a real, dedicated biological role, and what pathway dca7 belongs to.
Significance: Assigning a biological process would move dca7 out of the fission-yeast "conserved unknown" set and could reveal whether the DCAF7/WDR68 scaffold has a conserved role in a specific pathway (e.g. gene expression, as suggested by the PomBase product line) predating its elaboration in animals.
What would resolve it: Directed phenotyping of a dca7 deletion (and of a WD40-surface point mutant) in the processes where orthologs act, combined with epistasis against candidate kinase or Cul4/Ddb1 partners; transcriptome analysis to test the "implicated in gene expression" hypothesis.
Provenance (the field's own admissions):
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