erg28 (SPBC337.09) encodes the Schizosaccharomyces pombe ortholog of Erg28, a small (136 aa) non-catalytic multi-pass ER-membrane protein conserved from yeast to humans (human ERG28/C14orf1). By homology with budding-yeast Erg28 it is the scaffold of the sterol C-4 demethylation complex, tethering the C-4 methylsterol oxidase erg25, the decarboxylating dehydrogenase erg26 and the 3-keto reductase erg27 to the ER membrane and to each other so that both C-4 methyl groups are removed efficiently during ergosterol synthesis. Its role in fission yeast is inferred from orthology; no S. pombe erg28 mutant phenotype or interaction data are in the annotation record.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP localisation (Matsuyama et al. 2006) placed Erg28 in the ER. Consistent with the ER-membrane scaffold role. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ER from PTN000397028 (S. cerevisiae ERG28, Arabidopsis ERG28). Consistent with the S. pombe HDA. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to file:SCHPO/erg28/erg28-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305}; |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping of the curated ER membrane location (multi-pass membrane protein). Correct and the most specific location. Supporting Evidence: file:SCHPO/erg28/erg28-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305}; |
| GO:0005789 endoplasmic reticulum membrane | ISS PMID:11160377 A novel gene conserved from yeast to humans is involved in s... | ACCEPT | Summary: PomBase ISS from S. cerevisiae Erg28 (P40030), cited to Gachotte et al. 2001, which identified the S. pombe ortholog and proposed an ER tethering role. Budding-yeast Erg28 is an ER-membrane protein; transfer to the ortholog is sound. Supporting Evidence: PMID:11160377 ERG28 was also found in Schizosaccharomyces pombe and Arabidopsis as well as humans PMID:11160377 We speculate that the role of the Erg28 protein (Erg28p) may be either to tether Erg26p and Erg27p to the endoplasmic reticulum or to facilitate interaction between these proteins. |
| GO:0006696 ergosterol biosynthetic process | ISS PMID:11160377 A novel gene conserved from yeast to humans is involved in s... | ACCEPT | Summary: ISS from S. cerevisiae ERG28, whose deletion causes a C-4 demethylation lesion with accumulation of 3-keto and carboxylic acid sterols. Erg28 contributes the structural scaffolding that the C-4 demethylation enzymes depend on, which meets the bar for participation in the process. Supporting Evidence: PMID:11160377 indicates a lesion in sterol C-4 demethylation PMID:11160377 ERG28 was also found in Schizosaccharomyces pombe and Arabidopsis as well as humans |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO membrane from the Erg28 family signature (IPR005352). Correct but uninformative; the specific location is the ER membrane. Reason: Generic parent; ER membrane is supported. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:SCHPO/erg28/erg28-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305}; |
| GO:0016126 sterol biosynthetic process | IEA GO_REF:0000041 | TOO GENERAL | Summary: UniPathway ergosterol biosynthesis mapping to sterol biosynthetic process; correct general parent of GO:0006696. Supporting Evidence: file:SCHPO/erg28/erg28-uniprot.txt PATHWAY: Steroid metabolism; ergosterol biosynthesis. |
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA protein-macromolecule adaptor activity from PTN000397028; the experimental basis is the budding-yeast Erg28 scaffold that binds Erg25, Erg26, Erg27 and Erg6. This is the best available MF for a non-catalytic scaffold, and matches the PomBase GO-CAM activity for erg28. Supporting Evidence: file:SCHPO/erg28/erg28-uniprot.txt has a role as a scaffold to help anchor the catalytic components of the file:SCHPO/erg28/erg28-uniprot.txt Erg28 acts as a scaffold to tether erg27 and other 4,4-demethylation- |
| GO:0043495 protein-membrane adaptor activity | ISO GO_REF:0000024 | KEEP AS NON CORE | Summary: ISO from SGD ERG28 protein-membrane adaptor activity: Erg28 anchors the C-4 demethylation enzymes to the ER membrane. Correct description of the anchoring aspect, but the core scaffold function (bringing the enzymes together) is better captured by GO:0030674. Reason: Captures ER anchoring; the enzyme-tethering adaptor term is the core MF. Supporting Evidence: file:SCHPO/erg28/erg28-uniprot.txt has a role as a scaffold to help anchor the catalytic components of the PMID:11160377 We speculate that the role of the Erg28 protein (Erg28p) may be either to tether Erg26p and Erg27p to the endoplasmic reticulum or to facilitate interaction between these proteins. |
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Download this section (compressed HTML)Q: Does S. pombe erg28 deletion cause the C-4 demethylation block (3-keto and 4-carboxy sterol accumulation) seen in budding yeast, and is erg28 required for ER retention of erg25/erg26/erg27?
Q: In the PomBase GO-CAM erg28 is linked to erg25, erg26 and erg27 by 'directly provides input for'; would 'directly positively regulates' or a has-part/complex representation better model a scaffold?
Experiment: Co-immunoprecipitation / split-ubiquitin tests of erg28 with erg25, erg26, erg27 and erg6, and GC-MS sterol profiling of erg28 deletion cells.
Hypothesis: Fission-yeast Erg28 scaffolds the C-4 demethylation enzymes as in S. cerevisiae.
Type: protein interaction / sterol profiling
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