ERG12 (YMR208W; also known as RAR1) encodes mevalonate kinase (EC 2.7.1.36), the GHMP-family kinase that phosphorylates (R)-mevalonate with ATP to form (R)-mevalonate 5-phosphate, the first of three ATP-dependent steps that convert mevalonate to isopentenyl diphosphate (IPP) in the mevalonate pathway. IPP feeds farnesyl diphosphate and thus ergosterol, dolichol, ubiquinone, heme A and protein prenyl groups. Erg12 is the only mevalonate kinase in S. cerevisiae and loss-of-function erg12 mutants are ergosterol auxotrophs. The enzyme is competitively inhibited at the ATP site by farnesyl and geranyl diphosphate, a feedback point on the sterol pathway. Erg12 is a soluble cytosolic protein, with some nuclear GFP signal in genome-wide surveys.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer from rat mevalonate kinase (P17256): GHMP kinases including MVK use Mg2+-ATP. Erg12 has not been shown experimentally to bind Mg2+, but the cofactor requirement is conserved across the mevalonate kinase subfamily and is plausible. Cofactor binding rather than the core activity. Reason: Cofactor-level MF implied by the kinase reaction; retained as non-core. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt Name=Mg(2+); Xref=ChEBI:CHEBI:18420; file:yeast/ERG12/ERG12-uniprot.txt SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase |
| GO:0004496 mevalonate kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the PTHR43290 root mevalonate kinase node PTN000048555, seeded by mouse, rat, human, and S. cerevisiae experimental descendants. Erg12 is the sole S. cerevisiae mevalonate kinase, and the SGD experimental annotation is one of the IBD seeds. Core MF. Supporting Evidence: file:interpro/panther/PTHR43290/PTHR43290-paint.tsv PTHR43290 PTN000048555 GO:0004496 F IBD false PMID:1645230 The nucleotide sequence of the ERG12 gene, encoding mevalonate kinase, from Saccharomyces cerevisiae is presented. file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0004496 mevalonate kinase activity | IDA PMID:1645230 Nucleotide sequence of the ERG12 gene of Saccharomyces cerev... | ACCEPT | Summary: Oulmouden & Karst 1991 sequenced ERG12 and characterised the encoded mevalonate kinase, including feedback sensitivity to farnesyl diphosphate; UniProt cites this paper for the EC 2.7.1.36 reaction and kinetic constants (Km 0.13 mM mevalonate). Core MF. Supporting Evidence: PMID:1645230 The nucleotide sequence of the ERG12 gene, encoding mevalonate kinase, from Saccharomyces cerevisiae is presented. PMID:1645230 we show that mevalonate kinase is not a rate-limiting enzyme; however its sensitivity to FFP could be a key regulatory mechanism in the sterol pathway of yeast file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0004496 mevalonate kinase activity | IDA PMID:16477420 Reduction of background interference in the spectrophotometr... | ACCEPT | Summary: Song 2006 developed a coupled spectrophotometric mevalonate kinase assay using an ERG12-overexpressing strain and measured the activity at wild-type Erg12 levels in yeast extracts. Direct activity measurement supports the core MF. Supporting Evidence: PMID:16477420 A strain of S. cerevisiae over-expressing mevalonate kinase was used to establish conditions for reduction of background interference. PMID:16477420 This method has been successfully applied to S. cerevisiae strains containing a wild type level of mevalonate kinase. |
| GO:0004496 mevalonate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR006205 Mev_gal_kin, RHEA:17065, EC 2.7.1.36). The Rhea reaction is exactly the reaction characterised for Erg12; correct. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0004496 mevalonate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the superpathway of ergosterol biosynthesis (ERGOSTEROL-SYN-PWY-1), which assigns the mevalonate 5-phosphorylation step (EC 2.7.1.36) to Erg12. Correct enzyme-reaction assignment. Supporting Evidence: PMID:1645230 The nucleotide sequence of the ERG12 gene, encoding mevalonate kinase, from Saccharomyces cerevisiae is presented. file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0004496 mevalonate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the mevalonate pathway (IPPSYN-PWY), which assigns (R)-mevalonate + ATP -> (R)-mevalonate 5-phosphate to Erg12. Correct. Supporting Evidence: PMID:1645230 The nucleotide sequence of the ERG12 gene, encoding mevalonate kinase, from Saccharomyces cerevisiae is presented. file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0004496 mevalonate kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from 'mevalonate pathway I' (PWY-922); same EC 2.7.1.36 step assigned to Erg12. Correct. Supporting Evidence: PMID:1645230 The nucleotide sequence of the ERG12 gene, encoding mevalonate kinase, from Saccharomyces cerevisiae is presented. file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO (GHMP kinase N-terminal domain / ATP-binding signature IPR006203/IPR006204/IPR006205). ATP is a substrate of the mevalonate kinase reaction and FPP/GPP inhibit by competing at the ATP site, so ATP binding is real but is subsumed by the kinase activity. Reason: Substrate binding implied by the core kinase MF; non-core. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); file:yeast/ERG12/ERG12-uniprot.txt inhibit mevalonate kinase by binding competitively at the ATP-binding |
| GO:0005524 ATP binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from rat Mvk (P17256) for ATP binding. Correct for Erg12 (ATP is the phosphoryl donor; UniProt notes competitive inhibition at the ATP site) but redundant with the kinase MF. Reason: Substrate binding implied by the core kinase MF; non-core. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); file:yeast/ERG12/ERG12-uniprot.txt inhibit mevalonate kinase by binding competitively at the ATP-binding |
| 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 survey scored Erg12-GFP in cytoplasm and nucleus. No nuclear function of mevalonate kinase is known; the historical RAR1 (plasmid-stability) phenotype is not evidence of a nuclear role of the enzyme. Reason: High-throughput localisation without a 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. | MODIFY | Summary: Huh et al. 2003 GFP survey detected Erg12 in cytoplasm and nucleus. The cytoplasmic signal is consistent with soluble cytosolic mevalonate kinase, but cytosol is the more precise accepted location from SWAT, PAINT, UniProtKB-SubCell, and YeastPathways rows. Reason: Cytosol is the more specific supported compartment and is already asserted for Erg12. Proposed replacements: cytosol Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO cytoplasm from the mevalonate/galactokinase family signature IPR006205. The broad compartment is biologically consistent with soluble Erg12, but the PAINT, UniProtKB-SubCell, SWAT, and pathway rows already place the enzyme in the more precise cytosol. Reason: Cytosol is the more specific supported compartment and is already asserted for Erg12. Proposed replacements: cytosol Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: SWAT N-terminal GFP library (Yofe et al. 2016) scored Erg12 as cytosolic. Consistent with UniProt and with the soluble nature of the enzyme. Supporting Evidence: PMID:26928762 we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT cytosol inference from the PTHR43290 root mevalonate-kinase node PTN000048555. The IBA agrees with yeast GFP evidence and UniProtKB-SubCell placement of the soluble mevalonate kinase in the cytosol. Supporting Evidence: file:interpro/panther/PTHR43290/PTHR43290-paint.tsv PTHR43290 PTN000048555 GO:0005829 C IBD false file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol PMID:26928762 we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping (SL-0091 Cytoplasm, cytosol). Correct. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ERGOSTEROL-SYN-PWY-1) places the mevalonate kinase step in the cytosol. Correct; agrees with GFP data. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol PMID:26928762 we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY) cytosolic mevalonate kinase step. Correct. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol PMID:26928762 we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-922) cytosolic mevalonate kinase step. Correct. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol PMID:26928762 we constructed and investigated a library of ∼1,800 strains carrying SWAT-GFP modules at the amino termini of endomembrane proteins |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from fungal node PTN000825284, seeded by S. cerevisiae ERG12 and restricted to Fungi (taxon:4751). Erg12 supplies mevalonate-pathway IPP for farnesyl diphosphate and downstream ergosterol synthesis, and erg12 mutants are ergosterol auxotrophs. Supporting Evidence: file:interpro/panther/PTHR43290/PTHR43290-paint.tsv PTHR43290 PTN000825284 GO:0006696 P IBD false 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 | IDA PMID:1645230 Nucleotide sequence of the ERG12 gene of Saccharomyces cerev... | ACCEPT | Summary: Oulmouden & Karst 1991: Erg12 kinase activity and its FPP sensitivity as a regulatory point in the sterol pathway. Erg12 catalyses an upstream step of ergosterol synthesis; accept as the downstream end-product pathway. Supporting Evidence: PMID:1645230 we show that mevalonate kinase is not a rate-limiting enzyme; however its sensitivity to FFP could be a key regulatory mechanism in the sterol pathway of yeast |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:200835 Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants... | ACCEPT | Summary: Karst & Lacroute 1977 isolated thermosensitive ergosterol auxotrophs lacking mevalonate kinase (erg12). 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; Erg12 catalyses a step of that superpathway. Accept. Supporting Evidence: PMID:200835 Thermosensitive mutants, auxotrophic for ergosterol synthesis, have been isolated file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO isoprenoid-biosynthesis mapping from the mevalonate/galactokinase signature. True for Erg12 but too broad because the review keeps the specific GO:0019287 IPP-biosynthesis rows. Reason: The accepted GO:0019287 mevalonate-pathway IPP biosynthesis rows entail this broad parent; the InterPro2GO parent adds no distinct biological role. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: |
| GO:0008299 isoprenoid biosynthetic process | RCA GO_REF:0000123 | TOO GENERAL | Summary: YeastPathways RCA from IPPSYN-PWY. True for Erg12 but too broad because the review keeps the specific GO:0019287 IPP-biosynthesis rows from the same mevalonate pathway. Reason: The accepted GO:0019287 mevalonate-pathway IPP biosynthesis rows entail this broad parent; this RCA parent adds no distinct biological role. Supporting Evidence: file:yeast/ERG12/ERG12-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from the PTHR43290 root node PTN000048555. Erg12 directly phosphorylates mevalonate in step 1 of IPP biosynthesis from mevalonate. Core BP. Supporting Evidence: file:interpro/panther/PTHR43290/PTHR43290-paint.tsv PTHR43290 PTN000048555 GO:0019287 P IBD false file:yeast/ERG12/ERG12-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: file:yeast/ERG12/ERG12-uniprot.txt Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+); |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00057 mapping (isopentenyl diphosphate biosynthesis via mevalonate pathway). Correct core BP. Supporting Evidence: file:yeast/ERG12/ERG12-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: erg12 mutants lack mevalonate kinase and are ergosterol auxotrophs, placing Erg12 in the early (mevalonate) part of the pathway. Core BP. Supporting Evidence: PMID:200835 phosphomevalonic kinase (erg 8), mevalonic kinase (erg12) |
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Mevalonate kinase; acts in the biosynthesis of isoprenoids and sterols, including ergosterol, from mevalonate; human MVK functionally complements the lethality of the erg12 null mutation
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