Catalytic subunit of dolichol-phosphate-mannose (Dol-P-Man) synthase in fission yeast (EC 2.4.1.83). The soluble, 236-residue GT2-family enzyme transfers mannose from cytosolic GDP-mannose to dolichyl phosphate on the cytoplasmic face of the endoplasmic reticulum, producing Dol-P-Man, the mannosyl donor for lumenal steps of N-glycan precursor assembly, GPI-anchor synthesis and protein O-mannosylation. Like the human enzyme and unlike S. cerevisiae Dpm1, it lacks a C-terminal transmembrane anchor and acts in a heterotrimeric complex with the small membrane subunits dpm2 and dpm3, which tether and stabilise it at the ER membrane. dpm1 is essential, and the null mutant is rescued by either the budding-yeast or the human Dol-P-Man synthase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN002459128) with S. cerevisiae DPM1, human DPM1, mouse Dpm1 and M. tuberculosis Ppm1 among descendants; dpm1 is a canonical member of the DPM1 clade. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Reaction=a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = PMID:9223280 S. cerevisiae DPM1 and its human counterpart both complement the lethal null mutation in S. pombe dpm1(+) |
| GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 2.4.1.83/RHEA:21184 combined IEA mapping; correct for dpm1, whose Dol-P-Man synthase activity is supported by complementation of the lethal null by S. cerevisiae and human DPM1. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Reaction=a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = PMID:9223280 These results show that the protein products of the human and S. pombe Dol- P -Man synthase genes are functionally equivalent to that of S. cerevisiae DPM1 |
| GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS to human DPM1 (O60762), 65% identical and in the same unanchored class; the human cDNA rescues the S. pombe null. Supporting Evidence: PMID:9223280 S. cerevisiae DPM1 and its human counterpart both complement the lethal null mutation in S. pombe dpm1(+) PMID:9223280 the other contains the human, S. pombe, and Caenorhabditis synthases, which lack a hydrophobic COOH-terminal domain |
| GO:0004582 dolichyl-phosphate beta-D-mannosyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS to Pyrococcus furiosus Dol-P-Man synthase (Q8U4M3), the structurally characterised GT2 enzyme; the catalytic residues are conserved, consistent with the activity shown for the S. pombe protein by functional complementation. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Reaction=a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = PMID:9223280 These results show that the protein products of the human and S. pombe Dol- P -Man synthase genes are functionally equivalent to that of S. cerevisiae DPM1 |
| GO:0005737 cytoplasm | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | TOO GENERAL | Summary: ORFeome-wide YFP localisation reported cytoplasmic signal in addition to ER. dpm1 has no transmembrane segment and is held at the cytoplasmic face of the ER by dpm3, so a cytoplasmic signal is plausible but is not the functional site. Reason: Cytoplasm is correct in the broad sense (the ER is part of the cytoplasm and the catalytic subunit faces the cytosol) but ER membrane is the informative location. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. PMID:16280320 A coiled-coil domain near the C terminus of DPM3 was important for tethering DPM1, the catalytic subunit of the enzyme, to the endoplasmic reticulum membrane |
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome-wide YFP screen placed dpm1 at the ER, matching the site of Dol-P-Man synthesis. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0095 ER) for dpm1; correct, though ER membrane (GO:0005789) is more precise. Reason: Organelle-level location kept beside ER membrane (GO:0005789), per the localization carve-out for TOO_GENERAL. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000092441) for ER membrane; dpm1 lacks its own anchor but acts at the ER membrane as part of the DPM synthase complex tethered by dpm3. Supporting Evidence: PMID:16280320 A coiled-coil domain near the C terminus of DPM3 was important for tethering DPM1, the catalytic subunit of the enzyme, to the endoplasmic reticulum membrane file:SCHPO/dpm1/dpm1-uniprot.txt complex composed of dpm1, dpm2 and dpm3. |
| GO:0006488 dolichol-linked oligosaccharide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA (PTN000092440) for dolichol-linked oligosaccharide biosynthesis. Dol-P-Man made by dpm1 is the donor for the lumenal mannosylation steps of LLO assembly; consistent with the S. cerevisiae DPM1 and human DPM1 reviews. Supporting Evidence: PMID:9223280 is a mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of protein PMID:18387370 The sugar transfer from dolichol-phosphate-sugars occurs exclusively on the luminal side of the endoplasmic reticulum and is utilized in all four glycosylation pathways. |
| GO:0006664 glycolipid metabolic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA machine-learning IEA. Dol-P-Man is a glycolipid, so glycolipid metabolism is correct but much less informative than GO:0180047. Reason: Correct general ancestor of the core process. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Reaction=a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = |
| GO:0033185 dolichol-phosphate-mannose synthase complex | ISO GO_REF:0000024 | ACCEPT | Summary: ISO from human DPM1 (O60762), member of the DPM1/DPM2/DPM3 complex. S. pombe has all three subunits and dpm3 complements the mammalian complex, supporting conservation of the complex. Supporting Evidence: PMID:10835346 Schizosaccharomyces pombe has proteins that resemble three human subunits file:SCHPO/dpm1/dpm1-uniprot.txt complex composed of dpm1, dpm2 and dpm3. |
| GO:0046474 glycerophospholipid biosynthetic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA IEA to glycerophospholipid biosynthesis. Dol-P-Man is a polyisoprenoid phosphate sugar, not a glycerophospholipid; the term can only be reached through downstream use of Dol-P-Man in GPI-anchor (phosphatidylinositol) synthesis. Reason: Indirect: dpm1 supplies a donor to GPI mannosyltransferases but does not synthesise glycerophospholipids. Supporting Evidence: PMID:9223280 is a mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of protein |
| GO:0046872 metal ion binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS to P. furiosus Dpm (Q8U4M3), which binds a divalent cation in the active site; cofactor binding supports catalysis rather than being a separate function. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Note=Binds 1 divalent metal cation. |
| GO:0051604 protein maturation | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA IEA to protein maturation. dpm1 makes a lipid-linked sugar donor; any effect on protein maturation is through downstream glycosyltransferases. Reason: Too indirect; Dol-P-Man synthesis, not protein maturation, is what dpm1 does. Supporting Evidence: PMID:9223280 is a mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of protein |
| GO:0180047 dolichol phosphate mannose biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: ISS to P. furiosus Dol-P-Man synthase for dolichol phosphate mannose biosynthesis; this is the process dpm1 directly catalyses, and the PomBase GO-CAM 671ae02600003596 uses the same term. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Reaction=a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = PMID:9223280 These results show that the protein products of the human and S. pombe Dol- P -Man synthase genes are functionally equivalent to that of S. cerevisiae DPM1 |
| GO:1901137 carbohydrate derivative biosynthetic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA IEA to carbohydrate derivative biosynthesis; correct (Dol-P-Man is a carbohydrate derivative) but generic. Reason: Correct general ancestor of GO:0180047. Supporting Evidence: file:SCHPO/dpm1/dpm1-uniprot.txt Reaction=a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = |
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Download this section (compressed HTML)Q: Does S. pombe dpm1 require dpm2 and dpm3 for stability and activity in vivo as the human DPM1 does, given that budding-yeast Dpm1 (single-subunit, anchored) complements the dpm1 null without them?
Experiment: Deplete dpm3 or dpm2 in S. pombe and measure dpm1 protein level, ER-membrane association and microsomal Dol-P-Man synthase activity.
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