MVD1 (YNR043W; also known as ERG19) encodes diphosphomevalonate decarboxylase (mevalonate pyrophosphate decarboxylase, EC 4.1.1.33), a homodimeric GHMP-fold enzyme that uses ATP to phosphorylate and decarboxylate (R)-mevalonate 5-diphosphate, releasing isopentenyl diphosphate (IPP), CO2, ADP and phosphate. This is the last step of the mevalonate pathway and produces the C5 building block of all isoprenoids, including ergosterol, dolichol, ubiquinone and prenyl groups. Asp302 is essential for catalysis and Lys18 contributes to ATP binding. MVD1 is essential for viability; erg19 mutants are ergosterol auxotrophs, and elevated Mvd1 expression lowers steady-state sterol levels. Mvd1 is a soluble cytosolic enzyme.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004163 diphosphomevalonate decarboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the diphosphomevalonate decarboxylase node PTN000104601 (Arabidopsis MVD1/2, C. albicans, mouse, rat, human MVD P53602, yeast MVD1). Mvd1 is the sole MDD in yeast. Core MF. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + |
| GO:0004163 diphosphomevalonate decarboxylase activity | IDA PMID:15169949 Identification of active site residues in mevalonate diphosp... | ACCEPT | Summary: Krepkiy & Miziorko 2004 purified recombinant yeast MDD and measured its activity, identifying Asp302 as catalytic. Direct assay; core MF. Supporting Evidence: PMID:15169949 This report documents the optimized conditions for expression and isolation of substantial amounts of recombinant his-tagged yeast MDD. PMID:15169949 support assignment of a crucial catalytic role to Asp 302 |
| GO:0004163 diphosphomevalonate decarboxylase activity | IDA PMID:8626466 Molecular cloning and expression of the cDNAs encoding human... | ACCEPT | Summary: Toth & Huwyler 1996 cloned and expressed the yeast MDD cDNA alongside the human enzyme; UniProt cites this work for the EC 4.1.1.33 reaction. Core MF. Supporting Evidence: PMID:8626466 We also cloned and expressed the yeast homolog using the human enzyme's similarity to a previously unidentified and incomplete genomic sequence. file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + |
| GO:0004163 diphosphomevalonate decarboxylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR029765, RHEA:23732, EC 4.1.1.33). Correct. Supporting Evidence: file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + |
| GO:0004163 diphosphomevalonate decarboxylase activity | IMP PMID:15169949 Identification of active site residues in mevalonate diphosp... | ACCEPT | Summary: IMP: D302A/D302N and K18M mutants of yeast MDD lose 10^3-10^5-fold kcat or 30-fold activity while retaining ATP binding, showing the activity resides in the Mvd1 active site. Core MF. Supporting Evidence: PMID:15169949 support assignment of a crucial catalytic role to Asp 302 PMID:15169949 A 30-fold decrease in activity and a 16-fold inflation of the K(m) for ATP is documented for the K18M mutant |
| GO:0004163 diphosphomevalonate decarboxylase activity | IMP PMID:1779710 Sterol pathway in yeast. Identification and properties of mu... | ACCEPT | Summary: Chambon et al. 1991 isolated erg19 ergosterol auxotrophs blocked in mevalonate diphosphate decarboxylase. Core MF. Supporting Evidence: PMID:1779710 Yeast mutant strains auxotrophic for ergosterol and blocked in mevalonate diphosphate decarboxylase (erg19) and farnesyl diphosphate (FPP) synthetase (erg20) were isolated. |
| GO:0004163 diphosphomevalonate decarboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ERGOSTEROL-SYN-PWY-1) assigns mevalonate diphosphate + ATP -> IPP + CO2 + ADP + Pi (EC 4.1.1.33) to Mvd1. Correct. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + |
| GO:0004163 diphosphomevalonate decarboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY), same MDD step. Correct. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + |
| GO:0004163 diphosphomevalonate decarboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-922), same MDD step. Correct. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Huh et al. 2003 GFP: cytoplasmic Mvd1. Consistent with a soluble homodimeric enzyme. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| 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 assigns the mevalonate-to-FPP module (Erg12, Erg8, Erg19, Idi1, Erg20) to vacuoles (a statement also propagated into UniProt FUNCTION text). No primary data place Mvd1 in the vacuole: GFP shows it is cytoplasmic, it is soluble and has no vacuolar sorting signal. 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 |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cytosol (is_active_in) from PTN000104601 (mouse Mvd, human MVD). Consistent with yeast GFP data. Accept. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO cytosol from the MDD family signature IPR029765. Correct for Mvd1. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ERGOSTEROL-SYN-PWY-1) cytosolic MDD step. Accept. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY) cytosolic MDD step. Accept. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY-922) cytosolic MDD step. Accept. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0006696 ergosterol biosynthetic process | IDA PMID:8626466 Molecular cloning and expression of the cDNAs encoding human... | ACCEPT | Summary: IDA from Toth & Huwyler 1996 (expression of active yeast MDD). MDD produces IPP for ergosterol; accept the end-product pathway, which is also supported by erg19 ergosterol auxotrophy. Supporting Evidence: PMID:8626466 We also cloned and expressed the yeast homolog using the human enzyme's similarity to a previously unidentified and incomplete genomic sequence. PMID:1779710 Yeast mutant strains auxotrophic for ergosterol and blocked in mevalonate diphosphate decarboxylase (erg19) and farnesyl diphosphate (FPP) synthetase (erg20) were isolated. |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from the ergosterol superpathway. Accept. Supporting Evidence: PMID:1779710 Yeast mutant strains auxotrophic for ergosterol and blocked in mevalonate diphosphate decarboxylase (erg19) and farnesyl diphosphate (FPP) synthetase (erg20) were isolated. |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR005935 Mev_decarb) isoprenoid biosynthetic process. Correct; general parent of GO:0019287. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. |
| GO:0008299 isoprenoid biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (IPPSYN-PWY) isoprenoid biosynthetic process. Correct but general. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. |
| GO:0016126 sterol biosynthetic process | IMP PMID:9244250 The Saccharomyces cerevisiae mevalonate diphosphate decarbox... | ACCEPT | Summary: Berges et al. 1997: ERG19 is essential, a ts allele is explained by a single Leu-to-Pro change, and ERG19 overexpression lowers steady-state sterol levels. Sterol biosynthesis is correct (parent of ergosterol biosynthesis). Supporting Evidence: PMID:9244250 the ERG19 gene, which was shown to be an essential gene for yeast, was disrupted PMID:9244250 a high level of expression of the wild-type ERG19 gene led to a lower sterol steady-state accumulation compared to that of a wild-type strain |
| GO:0016831 carboxy-lyase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR005935) generic carboxy-lyase activity. The specific, experimentally established activity is diphosphomevalonate decarboxylase activity (GO:0004163), a descendant of this term. Proposed replacements: diphosphomevalonate decarboxylase activity Supporting Evidence: file:yeast/MVD1/MVD1-uniprot.txt Reaction=(R)-5-diphosphomevalonate + ATP = isopentenyl diphosphate + PMID:15169949 This report documents the optimized conditions for expression and isolation of substantial amounts of recombinant his-tagged yeast MDD. |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000104601 (Arabidopsis, C. albicans, mouse, rat). Mvd1 performs step 3/3, the ATP-dependent decarboxylation that yields IPP. Core BP. Supporting Evidence: PMID:9244250 The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. file:yeast/MVD1/MVD1-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: |
| GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR029765, UniPathway UPA00057). Correct core BP. Supporting Evidence: file:yeast/MVD1/MVD1-uniprot.txt via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: |
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Download this section (compressed HTML)Mevalonate pyrophosphate decarboxylase; essential enzyme involved in the biosynthesis of isoprenoids and sterols, including ergosterol; acts as a homodimer
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