cec-10 (ZK973.2) encodes an uncharacterized 865-residue Caenorhabditis elegans protein. It has an N-terminal chromodomain (residues ~49-110) of the kind that in other proteins reads methylated histone lysines, long disordered and compositionally biased regions, and a single recognisable ankyrin repeat (~520-552) inside a larger ankyrin-like region. Sequence-family classifiers (PANTHER PTHR43828, InterPro IPR051642 "SWI6-like") group it with the fungal Swi4/Swi6/Mbp1/Res1/Res2/Cdc10 subunits of the SBF and MBF G1/S transcription complexes. It lacks the KilA-N/APSES DNA-binding domain that defines the DNA-binding subunits of those complexes, and it has only weak pairwise similarity to any of them. Transcriptome data report expression mainly in the germ line. No experimental study of its molecular activity, chromatin binding, localization or loss-of-function phenotype has been published, so its function is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | REMOVE | Summary: IBA from PANTHER node PTN000917496, whose experimental seeds are the fungal SBF/MBF subunits (budding yeast Swi4, Mbp1, Swi6 and three Candida members). These complexes drive G1/S transcription in fungi. CEC-10 is a nematode chromodomain protein with no DNA-binding KilA-N/APSES domain, and nothing links it to the cell cycle. Reason: In fungi, G1/S control through SBF/MBF is a lineage-specific innovation. The DNA-binding subunits came from a viral KilA-N protein at the base of the fungal lineage, and no homologs exist outside fungi. Animals, nematodes included, run G1/S transcription through E2F/DP-Rb. The PTN000917496 IBD is placed deep enough to take in a sporadic metazoan chromodomain/ankyrin lineage that cannot form an MBF/SBF complex: there is no partner DNA-binding subunit, and CEC-10 lacks the KilA-N domain itself. Pairwise similarity between CEC-10 and the six yeast seeds is weak and confined to ankyrin or low-complexity stretches. No cell-cycle phenotype or expression pattern has been reported for cec-10. The process cannot be inherited from this node. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000917496 SUPPORTS SOURCE BUT NOT TARGET Fungal SBF/MBF seeds (budding-yeast Swi4, Mbp1, Swi6; Candida members) genuinely drive G1/S transcription. The node sits above a metazoan chromodomain/ankyrin lineage that has neither the KilA-N DNA-binding subunit nor any evidence of a cell-cycle role. Supporting Evidence: PMID:27162172 We were unable to find any eukaryotic homologs of SBF or Whi5 outside of fungi, with a few exceptions related to DNA viruses that we discuss later. PMID:27162172 SBF and its ancestral animal counterpart E2F file:worm/cec-10/cec-10-bioinformatics/RESULTS.md CEC-10 has no KilA-N / APSES-type HTH DNA-binding domain (IPR003163, IPR018004, PF04383). |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | REMOVE | Summary: contributes_to IBA seeded by the fission yeast MBF subunits Res2 (SPAC22F3.09c), Cdc10 (SPBC336.12c) and Res1 (SPBC725.16). In MBF, Res1/Res2 bind MCB promoter elements through the KilA-N/APSES domain, and Cdc10 contributes to that binding as the non-DNA-binding subunit. Reason: A contributes_to DNA-binding claim requires a complex whose DNA-binding subunit does the binding. Animals have no MBF DNA-binding subunit (KilA-N SBF/MBF proteins are fungal-specific), and CEC-10 itself lacks the KilA-N/APSES domain that Res1, Res2, Mbp1 and Swi4 all carry. There is no complex for CEC-10 to contribute DNA binding to, and no DNA-binding module of its own. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000917496 SUPPORTS SOURCE BUT NOT TARGET Valid for fission-yeast MBF (Res1/Res2 bind DNA via KilA-N, Cdc10 contributes). Not transferable to a nematode protein with no MBF partners and no KilA-N domain. Supporting Evidence: file:worm/cec-10/cec-10-bioinformatics/RESULTS.md All four DNA-binding fungal members tested (S. pombe Res2 and Res1, S. cerevisiae Mbp1 and Swi4) carry this domain at their N terminus. PMID:27162172 SBF/MBF and APSES transcription factors (Asm1, Phd1, Sok2, Efg1, StuA) share a common DNA-binding domain (KilA-N), which is derived from DNA viruses. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IBA GO_REF:0000033 | REMOVE | Summary: IBA seeded by the DNA-binding SBF/MBF subunits Res2 (S. pombe), Swi4 and Mbp1 (S. cerevisiae), all sequence-specific transcription factors that bind DNA through an N-terminal KilA-N/APSES domain. Reason: A DNA-binding transcription factor activity needs a sequence-specific DNA-binding domain. CEC-10 has none: its only recognised domains are a chromodomain and an ankyrin region, and it lacks the KilA-N/APSES domain that confers this activity on every seed. Within the fungal family the activity is not even shared by the non-DNA-binding Swi6/Cdc10 subunits, which PANTHER places in the same subfamily (SF3) as CEC-10. The node assertion is therefore over-propagated to CEC-10 on both lineage and domain-architecture grounds. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH WRONG ORTHOLOG OR PARALOG Sources checked: PANTHER:PTN000917496 SUPPORTS SOURCE BUT NOT TARGET Activity is real for the KilA-N-containing seeds (Res2, Swi4, Mbp1). It is absent from the domain architecture of CEC-10 and even from its fungal SF3 neighbours Swi6/Cdc10. Supporting Evidence: file:worm/cec-10/cec-10-bioinformatics/RESULTS.md CEC-10 has no KilA-N / APSES-type HTH DNA-binding domain (IPR003163, IPR018004, PF04383). UniProtKB:Q9N4L7 PANTHER; PTHR43828:SF3; CHROMO DOMAIN-CONTAINING PROTEIN; 1. |
| GO:0005634 nucleus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning prediction of nuclear localization. CEC-10 has a canonical chromodomain (PROSITE PS50013, SMART SM00298). In characterised proteins this module binds methylated histone tails, so a nuclear (chromatin) location is plausible. CEC-10 localization has not been tested. Reason: Nuclear localization fits the domain architecture: a chromodomain, as in the related C. elegans chromodomain protein CEC-4, which reads methylated H3K9 at the nuclear periphery. Nothing contradicts it, so the term is kept. It is a broad prediction and not evidence of any specific function, so it is not treated as core. The ARBA rule itself is not cited as support. Supporting Evidence: UniProtKB:Q9N4L7 SMART; SM00298; CHROMO; 1. PMID:26607792 CEC-4 binds preferentially mono-, di-, or tri-methylated H3K9 and localizes at the nuclear envelope independently of H3K9 methylation and nuclear lamin. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA whose only gene-level donor is budding-yeast Swi6 (SGD:S000004172). Swi6 is exported to the cytoplasm in a cell-cycle-regulated manner as part of SBF/MBF control. Reason: The cytoplasmic pool of yeast Swi6 reflects regulated nuclear export of an SBF/MBF cofactor. That fungal regulatory mechanism does not transfer to CEC-10, which has no SBF/MBF partners. Nothing directly contradicts a cytoplasmic presence of CEC-10, but the only basis for the row is the over-deep MBF node, and the chromodomain points to a nuclear rather than a cytoplasmic site of action. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000917496 SUPPORTS SOURCE BUT NOT TARGET Rests on yeast Swi6 shuttling, a regulatory feature of fungal SBF/MBF that does not carry over to a nematode chromodomain protein. Supporting Evidence: PMID:27162172 We were unable to find any eukaryotic homologs of SBF or Whi5 outside of fungi, with a few exceptions related to DNA viruses that we discuss later. |
| GO:0030907 MBF transcription complex | IBA GO_REF:0000033 | REMOVE | Summary: IBA placing CEC-10 in the MBF complex, seeded by fission yeast Res2, Cdc10 and Res1 and budding yeast Mbp1 and Swi6. MBF is a fungal G1/S transcription complex formed by a KilA-N DNA-binding subunit (Mbp1, Res1/Res2) and the Swi6/Cdc10 cofactor. Wei et al. 2020 (rate-ratio screen) flagged this annotation, and the related SBF transcription complex IBA, as likely misannotations for this protein. Reason: Animals cannot assemble MBF: its DNA-binding subunits are fungal-specific, derived from a viral KilA-N protein, and C. elegans has no KilA-N protein in this family. CEC-10 sits in the same PANTHER subfamily as Swi6/Cdc10 (SF3), which explains the propagation. It shares only weak, mostly ankyrin-region and low-complexity similarity with them, and it carries an N-terminal chromodomain absent from every fungal member. The PTN000917496 IBD is placed above a metazoan branch that cannot hold the complex: a lineage/taxon mismatch caused by node depth. The Wei et al. flag stands. The better fix is an IRD on the metazoan branch below PTN000917496, or a Fungi-only taxon constraint on GO:0030907. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000917496 SUPPORTS SOURCE BUT NOT TARGET MBF membership is experimentally solid for the fission-yeast (Res1, Res2, Cdc10) and budding-yeast (Mbp1, Swi6) seeds. The node is too deep for the metazoan branch carrying CEC-10, which has no MBF partners. Supporting Evidence: PMID:27162172 The emergence of the new fungal regulators SBF, which includes the large APSES family, and Whi5 is abrupt and occurs near the split of basal fungi from metazoans PMID:32470107 Importantly, 56% of the misannotations are 'Inferred from Biological aspect of Ancestor (IBA)' file:worm/cec-10/cec-10-bioinformatics/RESULTS.md Pairwise alignment gives no evidence that CEC-10 is an ortholog of any MBF or SBF subunit. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | REMOVE | Summary: IBA seeded by the fungal SBF/MBF subunits (S. pombe Res2, Cdc10, Res1; S. cerevisiae Swi4, Mbp1, Swi6; Candida and Aspergillus nidulans members), all of which activate G1/S gene transcription. Reason: Transcriptional activation by the seeds depends on SBF/MBF assembly at MCB/SCB promoter elements. As argued for the MBF complex row, that machinery does not exist in animals, and CEC-10 has no DNA-binding domain. A chromodomain protein might well influence transcription through chromatin, but no data address whether CEC-10 does, or in which direction. The inherited activator role is unsupported. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000917496 SUPPORTS SOURCE BUT NOT TARGET Activation of G1/S genes by fungal SBF/MBF is well established. The node is too deep to pass it to a metazoan chromodomain protein. Supporting Evidence: PMID:27162172 We were unable to find any eukaryotic homologs of SBF or Whi5 outside of fungi, with a few exceptions related to DNA viruses that we discuss later. file:worm/cec-10/cec-10-bioinformatics/RESULTS.md CEC-10 has no KilA-N / APSES-type HTH DNA-binding domain (IPR003163, IPR018004, PF04383). |
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Download this section (compressed HTML)Q: Should a negative (IRD) annotation be placed on the metazoan branch below PANTHER PTN000917496, or a Fungi-only taxon constraint be added to GO:0030907 MBF transcription complex and GO:0033309 SBF transcription complex, so that sporadic animal PTHR43828 members such as CEC-10 stop inheriting MBF/SBF terms?
Q: Is CEC-10 a true descendant of an ancestral Swi6/Cdc10-like protein, or was it pulled into PTHR43828:SF3 by ankyrin-repeat similarity alone? A tree built only on the conserved ankyrin and C-terminal regions would show whether the subfamily assignment is sound.
Q: Does the CEC-10 chromodomain retain the aromatic cage needed to bind methyl-lysine?
Experiment: Test binding of the recombinant CEC-10 chromodomain (residues ~40-120) to a panel of methylated histone H3 and H4 tail peptides (H3K9me1/2/3, H3K27me3, H3K36me3, H4K20me), with CEC-4 as a positive control.
Hypothesis: The CEC-10 chromodomain is a methyl-lysine reader, which would place CEC-10 in chromatin regulation rather than in a cell-cycle transcription complex.
Experiment: Generate an endogenously tagged CEC-10 allele and a CRISPR null, then examine germline localization, brood size, the mortal germline phenotype over generations, and germline transgene silencing.
Hypothesis: CEC-10 acts on germline chromatin, and its loss affects germline heterochromatin or silencing.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular activity of CEC-10 is unknown. Specifically, it is untested whether its chromodomain binds methylated histone lysines (and which: H3K9me, H3K27me or other), and what, if anything, its ankyrin region binds.
OPEN BIOLOGY WHOLLY_DARK
What is known: It is established only that CEC-10 has a canonical chromodomain (PROSITE/SMART matches), long disordered regions and an ankyrin-like region, and that it lacks a sequence-specific DNA-binding domain. The related C. elegans chromodomain protein CEC-4 reads methylated H3K9, but no binding, localization or interaction data exist for CEC-10.
Significance: Without a defined activity, the only GO annotations CEC-10 carries are inherited from a fungal cell-cycle complex that animals lack, so it is effectively unannotated.
What would resolve it: Peptide-array or isothermal titration binding of the recombinant chromodomain to modified histone tail peptides, tagged-allele localization in the germ line, and IP-mass spectrometry for partners.
Provenance (the field's own admissions):
Gap: The biological role of cec-10 is unknown; no loss-of-function phenotype has been reported, despite predominantly germline expression.
OPEN BIOLOGY BP_DARK
What is known: Expression is reported mainly in the germ line (Bgee). No genetic or phenotypic study of cec-10 has been published.
Significance: Germline chromodomain proteins in C. elegans often act in heterochromatin maintenance or small-RNA pathways; whether cec-10 belongs to either is open.
What would resolve it: CRISPR deletion of cec-10 with brood-size, mortal-germline (multigenerational) and transgene-silencing assays, plus H3K9me ChIP in mutant germlines.
Provenance (the field's own admissions):
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