tam14 (systematic name SPCC330.20) is a small (70-residue) single-pass endoplasmic reticulum membrane protein of the RAMP4/SERP1 family (Pfam PF06624; InterPro IPR010580, "ER stress-associated"). Its architecture is a short polar/disordered N-terminal segment followed by a single C-terminal transmembrane helix, characteristic of the tail-anchored RAMP4/SERP1 proteins. It is a curated ortholog of human SERP1 (RAMP4) and SERP2 and of budding-yeast Ysy6. In its better-characterized mammalian and budding-yeast orthologs, this family constitutes a small accessory component of the ribosome-associated Sec61 translocon that contacts nascent polypeptides during co-translational translocation and stabilizes newly synthesized membrane proteins during endoplasmic reticulum stress, facilitating their subsequent glycosylation. The corresponding molecular activity, subcellular localization, and biological role of tam14 in fission yeast have not been directly measured; annotations rest on family/orthology inference. tam14 was identified as a novel gene whose transcript levels are altered during meiosis, but no meiotic function has been demonstrated.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Endoplasmic reticulum localization inferred electronically from the InterPro RAMP4/ ER-stress-associated domain (IPR010580). This is consistent with the family assignment and the single C-terminal transmembrane helix, but is more general than the endoplasmic reticulum membrane term that better captures a single-pass RAMP4/SERP1 protein. Reason: Correct in direction and family-supported, but subsumed by the more specific "endoplasmic reticulum membrane" annotations; retained as non-core because the membrane term is the precise location. Supporting Evidence: file:SCHPO/tam14/tam14-deep-research-falcon.md predicted to function as a **small accessory component of the Sec61 translocon** at the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endoplasmic reticulum membrane localization from UniProt Subcellular-Location mapping. This is the electronic counterpart of the ISS annotation below and is well-grounded by the RAMP4/SERP1 family assignment plus the single predicted transmembrane helix (residues 45-65). No direct localization has been shown in S. pombe, but the family/topology basis is strong. Reason: The single-pass, tail-anchored RAMP4/SERP1 architecture localizes to the ER membrane; this is the most specific, best-supported location for tam14 and represents its core cellular component. Supporting Evidence: file:SCHPO/tam14/tam14-deep-research-falcon.md By family inference, tam14 is predicted to localize to the **endoplasmic reticulum membrane** |
| GO:0016020 membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Generic "membrane" localization from Subcellular-Location mapping. This is a high-level parent of the endoplasmic reticulum membrane term and adds no specific information beyond it. Reason: Uninformative parent term redundant with the more specific "endoplasmic reticulum membrane" annotation; the specific term should carry the localization. Supporting Evidence: file:SCHPO/tam14/tam14-deep-research-falcon.md By family inference, tam14 is predicted to localize to the **endoplasmic reticulum membrane** |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular_function placeholder with ND (No Data) evidence, reflecting that no molecular function has been experimentally determined for tam14 in S. pombe. Although the RAMP4/SERP1 family has a described activity (accessory Sec61-translocon component that contacts translocating nascent chains and stabilizes membrane proteins during ER stress), that activity has never been assayed for tam14, and it has no clean, well-scoped GO molecular-function term to which it could be confidently transferred. Reason: The ND molecular_function annotation honestly reflects the current MF-dark state: family membership is clear but the specific in vivo molecular activity of tam14 is unmeasured and not cleanly expressible in GO. No specific MF term is asserted. Supporting Evidence: file:SCHPO/tam14/tam14-deep-research-falcon.md no targeted deletion, localization, or biochemical study has been published specifically for tam14/SPCC330.20 file:SCHPO/tam14/tam14-deep-research-falcon.md rests primarily on **domain and family-level inference** from well-characterized orthologs Knowledge gap: The molecular function of tam14 in S. pombe is undetermined. Whether it acts, like its RAMP4/SERP1 orthologs, as an accessory subunit of the Sec61 translocon that contacts translocating nascent chains and stabilizes newly synthesized membrane proteins during ER stress has never been assayed for the fission-yeast protein. OPEN BIOLOGYONTOLOGY MF_DARK Resolve: Assay tam14-Sec61 association and nascent-chain crosslinking in S. pombe; a separation-of-function analysis of the TM helix vs the N-terminal region. Ontology: a molecular-function term for "Sec61 translocon accessory / nascent-chain stabilization" activity would let the family role be expressed. "no targeted deletion, localization, or biochemical study has been published specifically for tam14/SPCC330.20" — file:SCHPO/tam14/tam14-deep-research-falcon.md "Moderate for family-level annotation, low for gene-specific detail" — file:SCHPO/tam14/tam14-deep-research-falcon.md |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Curator sequence-similarity transfer of ER membrane localization from the mammalian ortholog (UniProtKB:Q9R2C1, rat SERP1/RAMP4). Unlike the dubious orthology transfers seen for some fission-yeast orphan genes, this rests on a genuine, curated, reciprocal ortholog relationship (human SERP1/SERP2; S. cerevisiae Ysy6) and on the conserved single-pass tail-anchored topology. It is the best-supported location annotation and duplicates the IEA ER membrane row with stronger (ISS) evidence. Reason: Well-grounded ISS transfer within a real, conserved family; the ER membrane is the core cellular component of tam14. Supporting Evidence: file:SCHPO/tam14/tam14-deep-research-falcon.md By family inference, tam14 is predicted to localize to the **endoplasmic reticulum membrane** |
| GO:0016020 membrane | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Generic "membrane" localization transferred by sequence similarity from the mammalian ortholog. As with the IEA membrane row, this is a high-level parent that is subsumed by the specific endoplasmic reticulum membrane annotation. Reason: Uninformative parent term redundant with "endoplasmic reticulum membrane"; the specific term should carry the localization. Supporting Evidence: file:SCHPO/tam14/tam14-deep-research-falcon.md By family inference, tam14 is predicted to localize to the **endoplasmic reticulum membrane** |
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Download this section (compressed HTML)Q: Does tam14 associate with the Sec61 translocon and contact translocating nascent chains in S. pombe, as its RAMP4/SERP1 orthologs do?
Q: Does the meiotic transcript change reflect a functional meiotic role (e.g. increased ER protein-biogenesis demand during sporulation), or is it an incidental expression change with no phenotype?
Q: Given that S. pombe uses an Ire1/RIDD-based UPR without Hac1/XBP1, is tam14 regulated by, or required for, the fission-yeast ER stress response at all?
Experiment: Affinity-purify tagged tam14 from S. pombe and test co-purification with Sec61 complex subunits; site-specific crosslinking to translocating nascent chains.
Hypothesis: tam14 is an accessory component of the S. pombe Sec61 translocon.
Type: co-immunoprecipitation / crosslinking-MS
Experiment: Phenotype a tam14 deletion (and overexpression) for growth and viability, ER-stress sensitivity (tunicamycin, DTT), and membrane-protein secretion/glycosylation.
Hypothesis: tam14 contributes to ER proteostasis / stress tolerance.
Type: genetics / stress phenotyping
Experiment: GFP-tag tam14 and image localization in vegetative and meiotic/sporulating cells.
Hypothesis: tam14 localizes to the ER membrane and its distribution changes during meiosis.
Type: live-cell fluorescence microscopy
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: No biological process has been established for tam14 in S. pombe. Despite its name (altered transcripts in meiosis), no meiotic — or any other — function has been demonstrated: tam14 was excluded from the deletion-phenotyping set in its discovery study, and no deletion, localization, or biochemical characterization has since been published.
OPEN BIOLOGY BP_DARK
What is known: Firmly established: tam14 is a bona fide, meiotically-regulated protein-coding gene of the conserved RAMP4/SERP1 family; its transcript level changes during a synchronized meiotic program. Undetermined: whether that expression change reflects any meiotic role, and whether tam14 participates (as its orthologs do) in co-translational ER protein biogenesis / ER proteostasis in fission yeast.
Significance: Distinguishing an incidental meiotic expression change from a genuine meiotic or ER-proteostasis role would settle whether the "tam" name reflects biology, and would test whether the conserved RAMP4/SERP1 translocon-accessory role operates in an organism whose UPR is mechanistically divergent (S. pombe lacks Hac1/XBP1 and uses Ire1-dependent RIDD).
What would resolve it: Phenotype a tam14 deletion for growth, ER-stress sensitivity (e.g. tunicamycin/DTT), secretion/glycosylation defects, and sporulation/spore viability; GFP localization across the cell cycle and meiosis; measure tam14-Sec61 association.
Provenance (the field's own admissions):
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