SPAC25B8.09 is a soluble methyltransferase type-11 protein found in the nucleus and cytosol. PomBase assigns trans-aconitate methyltransferase activity through curated orthology to budding-yeast Tmt1. This supports a probable small-molecule methyltransferase, while the predominant endogenous substrate and physiological role in fission yeast remain untested. Budding-yeast Tmt1 also methylates 3-isopropylmalate, so trans-aconitate detoxification is not the only plausible metabolic context.
The PomBase target page explicitly labels biological role inferred and provides TMT1/SGD:S000000977 orthology. The downloaded P32643 record verifies that identifier and its experimental sources. PMID:11695919(https://pubmed.ncbi.nlm.nih.gov/11695919/) establishes Tmt1 trans-aconitate methyltransferase activity; PMID:15147181(https://pubmed.ncbi.nlm.nih.gov/15147181/) identifies 3-isopropylmalate as its major endogenous substrate in yeast extracts. The two substrate observations are compatible; neither makes the other reaction false.
Curated orthology is reasonable support for target molecular capability. It does not settle the dominant physiological substrate, conservation of the starvation response, or a universal substrate for PTHR44942. Falcon misses both Tmt1 orthology and the target HDA nucleus/cytosol record. Its blanket “location unknown” is therefore not adopted; nor is absence of a target biochemical paper treated as grounds for erasing a curator-supported localization.
Exact retained output. These are name/location claims, not emitted GO/EC predictions. CNN denotes overlap with existing supported annotation; it does not establish literal membership in the training set.
| Claim type | Verbatim output | Assessment | Evidence and interpretation |
|---|---|---|---|
| name | Methyltransferase type 11 domain-containing protein | CNN | The claim specifies a domain class, not a methyl acceptor. IPR013216/PF08241 directly support that class. The curated Tmt1 orthology makes small-molecule methylation a reasonable additional inference but does not experimentally identify the target substrate. |
PMID:11695919(https://pubmed.ncbi.nlm.nih.gov/11695919/):
We have identified the yeast open reading frame YER175c as the gene encoding the
trans-aconitate methyltransferase of Saccharomyces cerevisiae.
PMID:15147181(https://pubmed.ncbi.nlm.nih.gov/15147181/):
the major
methylated endogenous product of Tmt1 in yeast extracts
The genuine Falcon report is retained with its provider metadata and artifact. Its conclusions were checked against the target record, exact accession and primary sources described above. Scientific uncertainties are recorded as UNC/UNDECIDED findings rather than a request for another reviewer to perform this assessment.
Identity: Q9UTA9 is the canonical, reviewed (Swiss-Prot) full-length product of SPAC25B8.09 (251 aa,
sequence version 1). It is not an isoform, fragment or alternative gene model. It carries the complete
Methyltransf_11 (PF08241) / SAM-dependent MTase superfamily (IPR029063) fold.
Evolutionary placement (new analysis: SPAC25B8.09-bioinformatics/RESULTS-rereview.md,
script compare_sf4_yeast_members.py):
- UniProt places Q9UTA9 in PTHR44942:SF4. The subfamily has two members in each yeast: SPAC25B8.09
and its tandem neighbour SPAC25B8.10 (Q9UTA8), and S. cerevisiae TMT1 (P32643) and CRG1 (P38892).
- The fission-yeast pair is 68% identical (a lineage-specific tandem duplication). Each copy is 25-29%
identical to both TMT1 and CRG1, and TMT1/CRG1 are 36% identical to each other. Pairwise data do not
single out TMT1 as a 1:1 ortholog. This is not a tree, so it is inconclusive on co-orthology.
- The official PANTHER 19.0 per-organism file places Q9UTA9 in PTHR42912:SF95, not PTHR44942:SF4. This
conflict is pinned in interpro/panther/panther-members-overrides.tsv and recorded in the family review
interpro/panther/PTHR44942/PTHR44942-review.yaml. That review lists only TMT1 as the SF4 representative
and treats SPAC25B8.09 as comparative evidence. I do not disagree with that treatment; the open
question is the target's parent family.
- SF4 also contains fungal natural-product O-methyltransferases (ptaH, nsrG, cfoB, pgmE; family entries
CSV), so SF4 membership does not imply one acceptor.
- The IBA (GO:0008168) comes from PTN008676703, a deep node whose donors are E. coli RlmA (P36999),
human TMT1A/METTL7A (Q9H8H3), Mtb Rv2952 (P9WIN3) and P. aeruginosa PA4379 (Q9HW23). These donors span
PTHR43460, PTHR45036 and PTHR42912. Tmt1 is not a donor, and no acceptor-specific term was propagated.
I read that omission as a deliberate PAINT decision.
Annotation decisions (changes vs previous review):
- trans-aconitate 3-methyltransferase activity (ISO from TMT1): ACCEPT -> UNDECIDED. It is plausible, but
orthology and acceptor specificity are unresolved (see above).
- cellular response to amino acid starvation (ISO from TMT1): UNDECIDED -> MARK_AS_OVER_ANNOTATED. On the
donor side this is Gcn4-driven induction plus a Saccharomyces invasive-growth signal (PMID:18092814,
abstract). Induction is expression, not participation, and orthology is unresolved.
- cellular detoxification (ISS from P32643): KEEP_AS_NON_CORE -> MARK_AS_OVER_ANNOTATED. For Tmt1 itself
the detoxification role is a hypothesis ("appears to be"), and its major endogenous substrate is
3-isopropylmalate (PMID:15147181).
- cytoplasm (IEA SubCell): ACCEPT -> MODIFY to cytosol (GO:0005829). This comes from the same
localization study that PomBase curated as cytosol.
- nucleus HDA/IEA and cytosol HDA: ACCEPT (target observation, PMID:16823372).
- methyltransferase activity (IBA): MODIFY -> GO:0008757 (unchanged). GO:0008757 IEA: ACCEPT.
Core function: SAM-dependent methyltransferase activity (GO:0008757) in cytosol and nucleus, with an
unknown acceptor. Description was rewritten to state the paralog pair and the unresolved orthology.
Relative to review next: budding-yeast TMT1 (P32643), the experimentally characterized SF4 member. There is
no review of it in the repo (no genes/yeast/TMT1). Its 1:1 orthology to SPAC25B8.09 is unresolved, so the
relation is recorded as a same-subfamily member. The tandem paralog SPAC25B8.10 (Q9UTA8) is also
unreviewed. No module in modules/ covers this gene or Tmt1.