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. |
| 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. |
| 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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