ERG8 (YMR220W) encodes phosphomevalonate kinase (EC 2.7.4.2), which phosphorylates (R)-mevalonate 5-phosphate with ATP to give (R)-mevalonate 5-diphosphate, the second of three ATP-dependent steps that convert mevalonate to isopentenyl diphosphate. Erg8 belongs to the GHMP kinase superfamily (fungal/plant-type PMK) and is unrelated in sequence to the animal PMVK enzyme. ERG8 is essential; thermosensitive erg8 alleles cause ergosterol auxotrophy and loss of PMK activity. Erg8 is a low-abundance soluble cytoplasmic protein, with some nuclear GFP signal in genome-wide surveys.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004631 phosphomevalonate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the fungal/plant-type (GHMP) phosphomevalonate kinase node PTN001274235 (Arabidopsis AT1G31910 and yeast ERG8). This ERG8-type PMK is unrelated to the animal nucleoside-monophosphate-kinase-type PMVK, so the node correctly excludes animals. Core MF. Supporting Evidence: PMID:1846667 Expression of the ERG8 gene in S. cerevisiae from the galactose-inducible galactokinase (GAL1) promoter resulted in 1,000-fold-elevated levels of phosphomevalonate kinase enzyme activity. file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0004631 phosphomevalonate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR016005 Erg8, RHEA:16341, EC 2.7.4.2). Correct. Supporting Evidence: file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0004631 phosphomevalonate kinase activity | IMP PMID:1846667 Cloning and characterization of ERG8, an essential gene of S... | ACCEPT | Summary: Tsay & Robinson 1991: the erg8-1 ts mutant is defective in phosphomevalonate kinase, cloned ERG8 complements it, and GAL1-driven ERG8 raises PMK activity ~1000-fold. Core MF. Supporting Evidence: PMID:1846667 Saccharomyces cerevisiae strains that contain the ery8-1 mutation are temperature sensitive for growth due to a defect in phosphomevalonate kinase, an enzyme of isoprene and ergosterol biosynthesis. PMID:1846667 Expression of the ERG8 gene in S. cerevisiae from the galactose-inducible galactokinase (GAL1) promoter resulted in 1,000-fold-elevated levels of phosphomevalonate kinase enzyme activity. |
| GO:0004631 phosphomevalonate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ERGOSTEROL-SYN-PWY-1) assigns (R)-mevalonate 5-phosphate + ATP -> (R)-mevalonate diphosphate (EC 2.7.4.2) to Erg8. Correct. Supporting Evidence: PMID:1846667 Expression of the ERG8 gene in S. cerevisiae from the galactose-inducible galactokinase (GAL1) promoter resulted in 1,000-fold-elevated levels of phosphomevalonate kinase enzyme activity. file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0004631 phosphomevalonate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY), same PMK step. Correct. Supporting Evidence: PMID:1846667 Expression of the ERG8 gene in S. cerevisiae from the galactose-inducible galactokinase (GAL1) promoter resulted in 1,000-fold-elevated levels of phosphomevalonate kinase enzyme activity. file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0004631 phosphomevalonate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-922), same PMK step. Correct. Supporting Evidence: PMID:1846667 Expression of the ERG8 gene in S. cerevisiae from the galactose-inducible galactokinase (GAL1) promoter resulted in 1,000-fold-elevated levels of phosphomevalonate kinase enzyme activity. file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO from GHMP kinase ATP-binding/N-terminal domain signatures. ATP is the phosphoryl donor of the PMK reaction and Tsay & Robinson noted a putative ATP-binding motif, so the term is correct but implied by the kinase MF. Reason: Substrate binding implied by core MF. Supporting Evidence: PMID:1846667 putative ATP-binding domain present in many kinases file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0005634 nucleus | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: Huh et al. 2003 genome-wide GFP scored Erg8 in cytoplasm and nucleus. Erg8 is a very low-abundance protein and no nuclear role is known. Reason: High-throughput localisation with no known nuclear function. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. 2003 GFP: cytoplasmic Erg8, consistent with the soluble protein observed on overexpression. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:1846667 Overproduction of a soluble protein with the predicted 48-kDa size for phosphomevalonate kinase was also observed in the yeast cells. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell (SL-0086 Cytoplasm). Correct. Supporting Evidence: file:yeast/ERG8/ERG8-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:1846667}. |
| GO:0005773 vacuole | NAS PMID:28904410 Recent Advances in Ergosterol Biosynthesis and Regulation Me... | REMOVE | Summary: NAS from the Hu et al. 2017 review, whose body text states that the six reactions from mevalonate to FPP (Erg12, Erg8, Erg19, Idi1, Erg20) are carried out in vacuoles (a statement UniProt has also propagated into its FUNCTION text). No primary data place Erg8 in the vacuole: Erg8 is a soluble cytoplasmic protein by GFP and fractionation, has no signal peptide or vacuolar sorting signal, and the pathway enzymes upstream and downstream are cytosolic or ER-bound. Reason: Unsupported review statement contradicted by primary localisation data. Supporting Evidence: PMID:28904410 The biosynthesis of ergosterol can be divided into three modules: mevalonate, farnesyl pyrophosphate (farnesyl-PP) and ergosterol biosynthesis. PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:1846667 Overproduction of a soluble protein with the predicted 48-kDa size for phosphomevalonate kinase was also observed in the yeast cells. |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | REMOVE | Summary: IBA (is_active_in peroxisome) from a plant sub-node (PTN000781523) seeded only by Arabidopsis PMK AT1G31910, which carries a PTS1 and is peroxisomal in plants. Yeast Erg8 ends in ...ETYLDK with no PTS1 and is cytoplasmic in GFP surveys; the peroxisomal location is a plant-lineage property that should not be inherited by fungal Erg8. Reason: Lineage-specific (plant) localisation over-propagated; contradicted by yeast localisation data and absence of a PTS1. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000781523 · PTN000781523 SUPPORTS SOURCE BUT NOT TARGET Peroxisomal PMK is supported for Arabidopsis AT1G31910 (PTS1-bearing) but yeast Erg8 lacks a PTS1 and is cytoplasmic. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories file:yeast/ERG8/ERG8-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:1846667}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ERGOSTEROL-SYN-PWY-1) places the PMK step in the cytosol. Consistent with GFP and with the soluble protein. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:1846667 Overproduction of a soluble protein with the predicted 48-kDa size for phosphomevalonate kinase was also observed in the yeast cells. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY), cytosolic PMK step. Accept. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:1846667 Overproduction of a soluble protein with the predicted 48-kDa size for phosphomevalonate kinase was also observed in the yeast cells. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-922), cytosolic PMK step. Accept. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:1846667 Overproduction of a soluble protein with the predicted 48-kDa size for phosphomevalonate kinase was also observed in the yeast cells. |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from a fungal node (PTN001274236) seeded by yeast ERG8. Accept. Supporting Evidence: PMID:1846667 Saccharomyces cerevisiae strains that contain the ery8-1 mutation are temperature sensitive for growth due to a defect in phosphomevalonate kinase, an enzyme of isoprene and ergosterol biosynthesis. PMID:200835 phosphomevalonic kinase (erg 8), mevalonic kinase (erg12) |
| GO:0006696 ergosterol biosynthetic process | IDA PMID:1846667 Cloning and characterization of ERG8, an essential gene of S... | ACCEPT | Summary: Tsay & Robinson 1991 describe PMK as an enzyme of isoprene and ergosterol biosynthesis, with ERG8 essential. Accept. Supporting Evidence: PMID:1846667 Saccharomyces cerevisiae strains that contain the ery8-1 mutation are temperature sensitive for growth due to a defect in phosphomevalonate kinase, an enzyme of isoprene and ergosterol biosynthesis. PMID:1846667 Disruption of the chromosomal ERG8 coding region by integration of URA3 or HIS3 marker fragments was lethal in haploid cells, indicating that this gene is essential. |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:200835 Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants... | ACCEPT | Summary: Karst & Lacroute 1977: erg8 thermosensitive ergosterol auxotrophs lack phosphomevalonate kinase. Accept. Supporting Evidence: PMID:200835 Thermosensitive mutants, auxotrophic for ergosterol synthesis, have been isolated PMID:200835 phosphomevalonic kinase (erg 8), mevalonic kinase (erg12) |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the ergosterol superpathway. Accept. Supporting Evidence: PMID:1846667 Saccharomyces cerevisiae strains that contain the ery8-1 mutation are temperature sensitive for growth due to a defect in phosphomevalonate kinase, an enzyme of isoprene and ergosterol biosynthesis. |
| GO:0008299 isoprenoid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY) isoprenoid biosynthetic process; correct but general parent of GO:0019287. Supporting Evidence: file:yeast/ERG8/ERG8-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001274235 (Arabidopsis PMK, yeast ERG8). Erg8 performs step 2/3 of IPP formation from mevalonate. Core BP. Supporting Evidence: file:yeast/ERG8/ERG8-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: file:yeast/ERG8/ERG8-uniprot.txt Reaction=(R)-5-phosphomevalonate + ATP = (R)-5-diphosphomevalonate + |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00057 mapping. Correct core BP. Supporting Evidence: file:yeast/ERG8/ERG8-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IMP PMID:200835 Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants... | ACCEPT | Summary: Karst & Lacroute 1977: erg8 mutants lacking PMK define an early mevalonate-pathway step. Core BP. Supporting Evidence: PMID:200835 phosphomevalonic kinase (erg 8), mevalonic kinase (erg12) |
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