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 Ξ²-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. This is a well-supported 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:0016020 membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PTM1 is an integral, multi-pass (seven-transmembrane) membrane protein, so "membrane" is factually correct but uninformative given the more specific Golgi-membrane and early-endosome-membrane annotations. Reason: True but shallow parent term; the specific compartment (Golgi/endosome membrane) annotations are more informative. Retain as non-core. |
| GO:0042147 retrograde transport, endosome to Golgi | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The only biological-process annotation with specific content. Transferred by phylogenetic inference from mammalian orthologs (with/from GPR108/TMEM87B). Compatible with PTM1's late-Golgi/endosome localization, but there is no direct yeast experimental evidence that PTM1 mediates endosome-to-Golgi retrograde transport, and PTM1 sits in a distinct PANTHER subfamily (SF1) from the mammalian members the annotation derives from. Reason: Reasonable, localization-compatible phylogenetic inference, but unverified for yeast and subfamily-diverged; keep as a plausible process context rather than an established core function. Not removed, per guidance that IBA process inferences compatible with localization should not be second-guessed away. |
| 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 | KEEP AS NON CORE | Summary: InterPro2GO (IPR009637, GPR107/GPR108-like) correctly infers integral-membrane status. Redundant with the IBA membrane term and uninformative relative to the Golgi/endosome-membrane annotations. Reason: Correct but shallow parent; retain as non-core supporting the integral membrane nature. |
| 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. |
| GO:0005575 cellular_component | ND GO_REF:0000015 | MARK AS OVER ANNOTATED | 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.) |
| GO:0008150 biological_process | ND GO_REF:0000015 | KEEP AS NON CORE | 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: Honestly reflects the limited process-level knowledge; retained as non-core given the only specific BP term is an unverified phylogenetic inference. |
Loading supporting contentβ¦
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 ptm1Ξ 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) β does it regulate localization, turnover, or interaction with trafficking machinery?
Experiment: Construct ptm1Ξ, yhl017wΞ, and the ptm1Ξ yhl017wΞ 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 ptm1Ξ (and ptm1Ξ yhl017wΞ) 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 β 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 β a cleavable signal peptide, a lumenal N-terminal GOLD-like Ξ²-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 ptm1Ξ 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 ptm1Ξ yhl017wΞ double mutant) would anchor PTM1 to a specific trafficking step and enable targeted mechanistic study.
Provenance (the field's own admissions):
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)