PTM1 (YKL039W) is a polytopic integral membrane protein of the budding yeast secretory pathway. It has the architecture characteristic of the GOST/LUSTR (GOLD-domain seven-transmembrane, also called Lung Seven TransMembrane) protein family: a cleavable N-terminal signal peptide, a large lumenal N-terminal β-sandwich domain, and a GPCR-like bundle of seven transmembrane helices, ending in a cytoplasmic, disordered, acidic and phosphorylated C-terminal tail. The lumenal domain carries a predicted N-glycosylation site. PTM1 localizes to the Golgi apparatus membrane and the early endosome membrane, and co-purifies with the late-Golgi/endosomal SNARE Tlg2. It is the fungal representative of the family that in animals includes GPR107, GPR108, TMEM87A/TMEM87B, GPR180 and Wntless (WLS); yeast additionally has a whole-genome-duplication paralog, YHL017W. Members of this family are Golgi/endosome-resident proteins broadly associated with membrane-protein trafficking through the secretory and endosomal system, and are thought to act as trafficking chaperones for membrane-associated or hydrophobic cargo rather than as signalling GPCRs, but no molecular function, substrate or ligand has been established for PTM1, and its precise cellular role remains undefined.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi localization is supported both by phylogenetic inference from the GOST/LUSTR family (which is broadly Golgi/endosome-resident) and by direct experimental co-purification of PTM1 with the yeast late-Golgi compartment. Reason: Consistent with the experimental subcellular localization (PMID:16107716, copurification with the Tlg2 late-Golgi/endosome compartment) and with family-wide Golgi localization. Under the root organelle policy (projects/ORGANELLES.md), GO:0005794 (Golgi apparatus) is retained alongside the specific sub-compartment annotation GO:0000139 (Golgi membrane). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000477279 · PANTHER:PTN000477279 SUPPORTS TRANSFER Broad GOST/LUSTR-family node with Golgi-localization support across plant, mouse, and human descendants; PTM1 retains the conserved GOLD-domain/7TM architecture and has independent yeast late-Golgi co-purification evidence. UniProtKB:Q8NBN3 · TMEM87A SUPPORTS TRANSFER Human GOST-family ortholog/paralog experimentally localized to the Golgi apparatus (PMID:36373655). UniProtKB:Q9NPR9 · GPR108 SUPPORTS TRANSFER Human GOST-family member localized to the Golgi apparatus. Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins file:yeast/PTM1/PTM1-deep-research-sgd.md copurifies with late Golgi vesicles containing the v-SNARE Tlg2p |
| GO:0016020 membrane | IBA GO_REF:0000033 | MODIFY | Summary: PTM1 is a seven-transmembrane integral membrane protein of the Golgi and early endosome membranes, so the generic parent term GO:0016020 (membrane) is true but less specific than the compartment membrane terms already annotated on the gene. Reason: Unlike root organelle terms, generic GO:0016020 (membrane) follows the standard refinement rule (AGENTS.md): a true but overly general parent term is refined with MODIFY to the specific supported descendants GO:0000139 (Golgi membrane) and GO:0031901 (early endosome membrane), both of which are already accepted on PTM1 based on immunoisolation of Tlg2p-positive late-Golgi/endosomal vesicles (PMID:16107716). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000477279 · PANTHER:PTN000477279 SUPPORTS TRANSFER Broad GOST/LUSTR-family node where membrane localization follows from the conserved seven-transmembrane architecture, but GO:0016020 stops at the generic parent rather than the specific Golgi and early endosome membrane compartments (GO:0000139, GO:0031901). UniProtKB:Q8NBN3 · TMEM87A SUPPORTS TRANSFER Human GOST-family 7TM integral membrane protein localized to the Golgi membrane. UniProtKB:Q9NPR9 · GPR108 SUPPORTS TRANSFER Human GOST-family 7TM integral membrane protein of the Golgi/endosomal system. Proposed replacements: Golgi membrane early endosome membrane Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins |
| GO:0042147 retrograde transport, endosome to Golgi | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Transferred by phylogenetic inference at PANTHER node PTN000477361 from mammalian GOST-family homologs TMEM87A and TMEM87B. This process is biologically compatible with PTM1's co-purification with Tlg2p-containing late-Golgi/early-endosome vesicles, though no direct trafficking assay in yeast has yet defined PTM1's cargo or retrograde transport requirement. Reason: Reasonable, localization-compatible phylogenetic inference from mammalian TMEM87A/TMEM87B, consistent with PTM1's residence in Tlg2p-positive late-Golgi/endosomal membranes (where Tlg2p mediates endosome-to-Golgi traffic), though the comparative GOST-family trafficking statement in PMID:36373655 is hypothesis-level and no direct functional assay in yeast has yet tested PTM1; kept as a plausible non-core process context. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000477361 · PANTHER:PTN000477361 SUPPORTS TRANSFER TMEM87/PTM1 subfamily node; PTM1 shares the conserved GOLD-domain/7TM architecture and late-Golgi/endosome localization, making endosome-to-Golgi retrograde transport a biologically plausible non-core process inference pending direct yeast genetic/trafficking characterization. UniProtKB:Q8NBN3 · TMEM87A SUPPORTS TRANSFER Human TMEM87A shown to participate in endosome-to-trans-Golgi network retrograde transport. UniProtKB:Q96K49 · TMEM87B SUPPORTS TRANSFER Human TMEM87B paralog acting redundantly with TMEM87A in endosome-to-TGN retrograde transport. Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins PMID:36373655 structurally homologous GOST proteins could serve a common role in trafficking |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Specific, experimentally-grounded localization derived from the UniProt Swiss-Prot subcellular-location mapping (Golgi apparatus membrane; multi-pass), which itself rests on PMID:16107716. Reason: Precise and correct localization for a multi-pass Golgi membrane protein; core localization. Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins |
| GO:0005829 cytosol | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Assigned by automated logical inference from the retrograde-transport process term (with/from GO:0042147), not from evidence that PTM1 is a soluble cytosolic protein. PTM1 is a polytopic integral membrane protein; only its C-terminal tail faces the cytoplasm. Reason: Misleading as a cellular-component assignment for an integral membrane protein; it is an artefact of inter-ontology logical inference from the BP term rather than a bona fide localization. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR009637, GPR107/GPR108-like) infers integral-membrane localization, which is true but less specific than the Golgi-membrane and early-endosome-membrane annotations already carried by the gene. Reason: Unlike root organelle terms, generic GO:0016020 (membrane) follows the standard refinement rule (AGENTS.md): a true but overly general parent term is refined with MODIFY to the specific supported descendants GO:0000139 (Golgi membrane) and GO:0031901 (early endosome membrane), both already accepted on PTM1. Proposed replacements: Golgi membrane early endosome membrane Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins |
| GO:0031901 early endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Secondary localization from the UniProt subcellular-location mapping, grounded in the PMID:16107716 co-purification with the late-Golgi/endosome (Tlg2) compartment. Reason: Experimentally grounded secondary localization; correct and specific. Non-core relative to the primary Golgi localization. Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular-function term with the ND (no biological data) evidence code. This is an honest reflection of the state of knowledge: no molecular function, enzymatic activity, ligand or transported substrate has been established for PTM1, and the wider GOST family's molecular function is itself unresolved. Reason: Appropriate ND annotation for a gene whose molecular function is genuinely unknown; retaining it correctly signals the molecular-function knowledge gap. The gene's search record (PTM1-notes.md) finds no study demonstrating an enzymatic, ligand-binding, transporter or channel activity for PTM1. Supporting Evidence: file:yeast/PTM1/PTM1-notes.md No enzymatic activity; no demonstrated ligand, transporter |
| GO:0005575 cellular_component | ND GO_REF:0000015 | REMOVE | Summary: Root cellular-component ND annotation. It is now superseded by the specific, experimentally-grounded Golgi-membrane and early-endosome-membrane annotations. Reason: No longer reflects the state of knowledge now that specific compartment localizations are annotated; should not be treated as core. (An ND root annotation that specific evidence has overtaken.) NO_DATA re-check: Re-checked 2026-10-31 against core_functions; immunoisolation of S. cerevisiae Golgi compartments (PMID:16107716) localizes PTM1. The earlier MARK_AS_OVER_ANNOTATED is not used on an ND row, so the stale ND is removed. Supporting Evidence: PMID:16107716 we immunoisolated vesicles carrying either of the SNAREs Sed5 or Tlg2, the markers of the early and late Golgi compartments, respectively, and analyzed the membrane proteins file:yeast/PTM1/PTM1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:16107716} |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological-process ND annotation, reflecting that the specific biological role of PTM1 in yeast has not been experimentally determined. A more specific (though still inferred) BP annotation exists via the IBA endosome-to-Golgi-retrograde-transport term. Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the biological process is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: KEEP_AS_NON_CORE. The gene's search record (PTM1-notes.md) finds no study of yeast PTM1 that establishes a biological process, only a family- and localization-based presumption. Supporting Evidence: file:yeast/PTM1/PTM1-notes.md **Biological process**: unknown beyond a presumed role in secretory-pathway / Golgi |
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Download this section (compressed HTML)Q: Does PTM1 function as a cargo-binding trafficking chaperone for a specific membrane protein or lipid in the yeast Golgi/endosome system, analogous to how Wntless chaperones lipidated Wnt in animals?
Q: Is the apparent lack of a ptm1Δ phenotype due to functional redundancy with the whole-genome-duplication paralog YHL017W?
Q: What is the functional significance of the phosphorylation of PTM1's cytoplasmic acidic tail (Ser480/Thr483/Thr498) — does it regulate localization, turnover, or interaction with trafficking machinery?
Experiment: Construct ptm1Δ, yhl017wΔ, and the ptm1Δ yhl017wΔ double mutant and assay for synthetic growth, secretion, glycosylation, and Golgi/endosome morphology defects, including sensitivity to cell-wall stressors (calcofluor white, Congo red) and trafficking-pathway perturbations.
Hypothesis: PTM1 acts redundantly with YHL017W in a Golgi/endosome membrane-trafficking step, so single deletions have little phenotype.
Type: genetic epistasis / phenotypic profiling
Experiment: Affinity-purify functionally-tagged PTM1 from yeast membranes under mild detergent conditions and identify co-purifying proteins and lipids by mass spectrometry; validate candidate cargoes by testing their localization, stability, or trafficking in ptm1Δ (and ptm1Δ yhl017wΔ) cells.
Hypothesis: PTM1 binds and traffics a specific membrane-associated or lipidated cargo.
Type: affinity purification-mass spectrometry / cargo-dependency assay
Experiment: Purify recombinant PTM1 (or its 7TM domain), determine its structure by cryo-EM, and use lipidomics/native mass spectrometry to identify co-purifying lipids occupying the predicted 7TM cavity.
Hypothesis: The conserved hydrophobic 7TM cavity of PTM1 (as seen in TMEM87A/WLS) binds a lipid or lipidated peptide.
Type: structural biology / native MS lipidomics
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The molecular function of PTM1 is unknown: no enzymatic activity, transported substrate, bound ligand, or channel/receptor activity has been demonstrated, and it is not known whether PTM1 acts as a cargo-binding trafficking chaperone (the leading family hypothesis), a scaffolding/adaptor protein, or something else.
OPEN BIOLOGY MF_DARK
What is known: The protein's domain architecture is firmly established — a cleavable signal peptide, a lumenal N-terminal GOLD-like β-sandwich domain, seven transmembrane helices (GOST_TM / GPR107-GPR108-like fold), and a cytoplasmic acidic tail. For the wider family, structures of TMEM87A and WLS reveal a large hydrophobic 7TM cavity, and WLS is shown to chaperone lipidated Wnt, motivating (but not proving) a lipid/hydrophobic-cargo-binding role for the family.
Significance: PTM1 is the yeast entry point to a conserved, medically relevant but mechanistically enigmatic family (GPR107 in toxin trafficking, GPR108 in AAV transduction, WLS in Wnt secretion); a defined molecular activity in the tractable yeast system would illuminate the whole family.
Provenance (the field's own admissions):
Gap: The physiological cargo(es) or interacting client(s) of PTM1 that would define its trafficking role are unidentified; it is unknown which membrane proteins or lipids, if any, depend on PTM1 for their transport, sorting, or retention within the Golgi/endosome system.
OPEN BIOLOGY MF_DARK
What is known: PTM1 co-purifies with the late-Golgi/endosomal Tlg2 compartment, and BioGRID records physical/genetic interactions, but no PTM1-dependent cargo has been functionally established. In the paralogous family, WLS has a defined client (Wnt), setting a template for the kind of client relationship sought.
Significance: Identifying a PTM1-dependent cargo would convert the family-level "trafficking chaperone" hypothesis into a testable, yeast-defined mechanism.
Provenance (the field's own admissions):
Gap: The biological process PTM1 participates in, and its loss-of-function phenotype, are undefined. No clear phenotype has been reported for the ptm1Δ single mutant, and it is unknown whether the whole-genome-duplication paralog YHL017W provides functional redundancy that masks a phenotype.
OPEN BIOLOGY BP_DARK
What is known: Localization to the Golgi/endosome network and an IBA-inferred (unverified in yeast) association with endosome-to-Golgi retrograde transport delimit the plausible process space. PTM1 has a WGD ohnolog, YHL017W, in the same PANTHER subfamily (PTHR21229:SF1), a classic setup for genetic buffering.
Significance: A defined phenotype (ideally in a ptm1Δ yhl017wΔ double mutant) would anchor PTM1 to a specific trafficking step and enable targeted mechanistic study.
Provenance (the field's own admissions):
Protein of unknown function; copurifies with late Golgi vesicles containing the v-SNARE Tlg2p; PTM1 has a paralog, YHL017W, that arose from the whole genome duplication
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