ftm3 (SPAC750.04c) is a small (146-residue, ~17 kDa) membrane protein of the Schizosaccharomyces pombe Ftm ("sub-telomeric 5Tm") protein family, a lineage-specific family encoded in the sub-telomeric regions of the fission-yeast genome (paralogs ftm1, ftm2, ftm4, ftm5, ftm6 and ftm7). It belongs to the UPF0742 family and carries the Pombe_5TM domain (Pfam PF09437, InterPro IPR018291, "Pombe specific 5TM protein"), a domain of unknown function essentially restricted to Schizosaccharomyces. The protein is predicted to be membrane-integral (at least one transmembrane helix) and, by similarity to its experimentally localized paralog ftm2, is assigned to the cytoplasm and the nuclear/nuclear-envelope membrane, where the family shows cytoplasmic puncta and nuclear-rim staining. No molecular activity, substrate, ligand or interaction partner has been established for ftm3 or any Ftm-family member; its biological role is undetermined, and it is classified as a conserved protein of unknown function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation mapping the UniProtKB/Swiss-Prot subcellular-location "Cytoplasm" to GO via GO_REF:0000044. It restates the same location that is assigned to ftm3 by ISS from its paralog ftm2. Localization is a defensible, conservative call for this otherwise uncharacterized protein, but it is not a core function. Reason: Consistent with the UniProt SubCell location and with the ISS cytoplasm annotation below; redundant electronic restatement, retained as supporting localization evidence rather than a core function. Supporting Evidence: UniProt:P0CU06 SUBCELLULAR LOCATION: Cytoplasm |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic annotation mapping the UniProtKB/Swiss-Prot subcellular-location "Nucleus membrane" to GO via GO_REF:0000044. It restates the nuclear-envelope localization assigned to ftm3 by ISS from paralog ftm2 (cytoplasmic dots and the nuclear envelope). Not a core function. Reason: Consistent with the UniProt SubCell "Nucleus membrane" location and with the ISS nuclear-membrane annotation below; redundant electronic restatement retained as supporting localization evidence. Supporting Evidence: UniProt:P0CU06 C:nuclear membrane |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular_function term with the ND (No biological Data available) evidence code, assigned by PomBase. The molecular function of ftm3 is genuinely unknown: the protein belongs to the UPF0742 / Pombe_5TM family, a Schizosaccharomyces-specific domain of unknown function with no established catalytic, transport, or binding activity, and no functional literature exists for ftm3 or any Ftm paralog. Reason: The ND placeholder is the correct, honest representation for a conserved protein of unknown molecular function. No specific MF term is warranted from current evidence, and 'protein binding' would be uninformative and unsupported. The gene's search record (notes) finds no study of ftm3 in S. pombe that identifies a molecular function. Supporting Evidence: file:SCHPO/ftm3/ftm3-notes.md **Molecular function**: unknown. No enzymatic activity, no ligand/substrate, no binding partner |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological_process term with the ND evidence code, assigned by PomBase. No biological process is experimentally attributed to ftm3. A high-throughput expression change under glucose availability exists at PomBase (GO:0042149, RNA-level), but it is a transcript-abundance observation, is not part of the GOA set reviewed here, and does not establish a functional role. Reason: ND correctly records that the biological process of ftm3 is unknown; no process term is supported by current evidence. Possibly stale: the 2026-11-06 ND citation pass found literature on this gene in this species that may identify a biological process; see ftm3-notes.md, section "ND literature-search citations (2026-11-06)". A curator should check it before this ACCEPT stands. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cytoplasmic localization transferred to ftm3 by curator sequence-similarity judgment (GO_REF:0000024) with:UniProtKB:P0CU07, i.e. from the paralog ftm2 (SPAC977.02), whose cytoplasm/nuclear-membrane localization was determined experimentally in the genome-wide YFP ORFeome study (PMID:16823372). A reasonable localization inference for a close paralog, but localization is not a core function and is by-similarity for ftm3 itself. Reason: Grounded in experimental localization of a close paralog via a reliable genome-wide study; defensible as supporting localization evidence but not a core molecular/biological function. Supporting Evidence: UniProt:P0CU06 SUBCELLULAR LOCATION: Cytoplasm |
| GO:0031965 nuclear membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nuclear-membrane localization transferred to ftm3 by curator sequence-similarity judgment (GO_REF:0000024) with:UniProtKB:P0CU07 (paralog ftm2), whose nuclear-envelope localization was experimentally determined (PMID:16823372). The UniProt note records localization to cytoplasmic dots and the nuclear envelope. Localization inference, not a core function. Reason: Consistent with the paralog's experimental nuclear-envelope localization; retained as supporting localization evidence rather than a core function. Supporting Evidence: UniProt:P0CU06 C:nuclear membrane |
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Download this section (compressed HTML)Q: Does the Ftm / UPF0742 / Pombe_5TM family have a coherent shared molecular function, or are these rapidly-evolving sub-telomeric genes of low or conditional function?
Q: Is ftm3 functionally redundant with its paralogs, such that a phenotype only emerges in combinatorial ftm-family deletions?
Experiment: Construct single and combinatorial ftm-family deletion strains (ftm1-ftm7) and screen for growth, morphology, and stress/metabolic phenotypes (including glucose limitation) to detect redundant or conditional functions.
Experiment: Determine ftm3's direct subcellular localization (endogenous fluorescent tagging) and experimental membrane topology, and identify physical interaction partners (affinity purification-MS) to generate function hypotheses.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular function of ftm3 is completely unknown. No catalytic activity, transporter/channel activity, ligand, substrate, or biochemical activity has been demonstrated or is predictable for the protein.
OPEN BIOLOGY MF_DARK
What is known: What is established is family and domain membership only: ftm3 belongs to the UPF0742 family and carries the Pombe_5TM domain (Pfam PF09437 / InterPro IPR018291, "Pombe specific 5TM protein"). This is a domain of unknown function with no functional annotation, essentially restricted to Schizosaccharomyces, so no cross-species orthology provides a functional hypothesis. PomBase records the molecular function as ND ("No biological Data").
Significance: ftm3 is one of a lineage-specific, sub-telomeric family (ftm1-ftm7) of fission-yeast proteins with no assigned activity; establishing even the biochemical class (e.g. transporter, receptor, structural membrane protein) would open the whole family.
What would resolve it: Biochemical characterization of purified/tagged ftm3 (or a family member), structure determination or confident structure-based fold/activity assignment, and assays guided by its membrane topology (e.g. transport/channel assays) to test candidate activities.
Provenance (the field's own admissions):
Gap: The biological process and cellular role of ftm3 are unknown. It is undetermined which pathway or process the protein participates in, and no loss-of-function phenotype has been reported for an ftm3 deletion.
OPEN BIOLOGY BP_DARK
What is known: ftm3 is expressed during vegetative growth and its transcript level changes with glucose availability (PomBase high-throughput expression annotation, GO:0042149, derived from RNA-seq), and the closely related paralog ftm2 is dispensable (ftm2delta viable with normal morphology). These are correlative/genetic observations only; PomBase records the biological process for ftm3 as ND.
Significance: Determining the process (e.g. a membrane/nuclear-envelope function, a stress or metabolic response, or a redundant/conditionally-required role) would move the Ftm family out of the conserved-unknown set.
What would resolve it: Phenotypic profiling of single and combinatorial ftm-family deletions across stress and metabolic conditions (including glucose limitation), genetic-interaction mapping, and identification of physical interaction partners.
Provenance (the field's own admissions):
Gap: ftm3's own subcellular localization and membrane topology have not been measured directly. Its cytoplasm/nuclear-membrane assignment is inferred entirely by similarity from the paralog ftm2, and although the family is named "5TM", the UniProt feature table annotates only a single predicted transmembrane helix, so the true topology is unresolved.
OPEN BIOLOGYCURATION CC_DARK
What is known: The paralog ftm2 (P0CU07/SPAC977.02) was experimentally localized to the cytoplasm and nuclear membrane (cytoplasmic dots and the nuclear envelope) in a genome-wide YFP study (PMID:16823372), and ftm3's GO localization is transferred from it by ISS (with:UniProtKB:P0CU07). No direct ftm3 localization or topology experiment is on record.
Significance: Confirming ftm3's localization and topology directly (rather than by paralog transfer) would validate the propagated annotations and constrain candidate functions (e.g. nuclear-envelope vs general-membrane roles).
What would resolve it: Fluorescent tagging and imaging of ftm3 in S. pombe, and experimental membrane-topology mapping to resolve the transmembrane-helix count implied by the "5TM" family name.
Provenance (the field's own admissions):
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