ERG20 (YJL167W) encodes farnesyl diphosphate synthase (FPPS) of Saccharomyces cerevisiae, an essential, single-copy member of the FPP/GGPP synthase (polyprenyl synthetase) family that acts as a homodimeric, Mg2+-dependent trans-prenyltransferase. Erg20 catalyses the sequential head-to-tail condensation of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP) to give geranyl diphosphate (GPP; EC 2.5.1.1) and of a second IPP with GPP to give (2E,6E)-farnesyl diphosphate (FPP; EC 2.5.1.10). FPP is the branch-point C15 isoprenoid that feeds ergosterol synthesis (via squalene synthase Erg9) and all essential non-sterol isoprenoids, including dolichols, the hexaprenyl tail of coenzyme Q6 (via Coq1), heme A farnesylation and protein prenylation; no other yeast prenyltransferase can supply this FPP. Erg20 is a soluble cytosolic enzyme that has also been found associated with the ER. Mutations at the chain-length/product-release region (e.g. K197E in erg20-2) cause GPP release and excretion of geraniol, and Erg20 activity can be rate-limiting for ergosterol synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004161 dimethylallyltranstransferase activity | EXP PMID:8096487 Characterization of a lysine-to-glutamic acid mutation in a ... | ACCEPT | Summary: Blanchard & Karst 1993 characterised the erg20-2 (K197E) FPPS mutant that releases GPP-derived geraniol, and UniProt cites this paper for the IPP + DMAPP -> GPP reaction. Core MF (first condensation). Supporting Evidence: PMID:8096487 resulting in a Lys197-->Glu substitution in FPPS which is directly involved in terpenic alcohol formation PMID:8096487 This strain had the unusual property of excreting prenyl alcohols such as geraniol. |
| GO:0004161 dimethylallyltranstransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from FPPS node PTN000162949 (human FDPS, mouse Fdps, Arabidopsis FPS1/FPS2, SGD Erg20). The GPP-forming first condensation is intrinsic to all FPPS enzymes. Correct. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004161 dimethylallyltranstransferase activity | IDA PMID:2681213 Farnesyl diphosphate synthetase. Molecular cloning, sequence... | ACCEPT | Summary: Anderson et al. 1989 cloned ERG20 and showed elevated FPP synthetase activity on over-expression; the FPPS assay comprises both condensations. Correct (abstract-only cache; deferring to curator). Supporting Evidence: PMID:2681213 the 4.5-kilobase EcoRI fragment directed a 2-3-fold over-expression of FPP synthetase activity in transformed yeast cells |
| GO:0004161 dimethylallyltranstransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (RHEA:22408, EC 2.5.1.1). Correct. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004161 dimethylallyltranstransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 assignment of DMAPP + IPP -> GPP to Erg20. Correct reaction. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004161 dimethylallyltranstransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways HEXPPSYN-PWY-2 (hexaprenyl diphosphate biosynthesis) assignment of the GPP-forming step to Erg20. The reaction is correctly attributed; Erg20 supplies the allylic primer that Coq1 extends. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then PMID:19416104 the production of nonsterol molecules, deriving from farnesyl diphosphate (FPP), implicated in N-glycosylation and biosynthesis of heme and ubiquinones |
| GO:0004161 dimethylallyltranstransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY-5123 (trans,trans-FPP biosynthesis) assignment. Correct. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004161 dimethylallyltranstransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-31704 (superpathway of ergosterol biosynthesis) assignment. Correct reaction. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004161 dimethylallyltranstransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-862 (superpathway of ubiquinone biosynthesis) assignment of the GPP-forming step. The MF is correct for Erg20 regardless of the superpathway. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | EXP PMID:8096487 Characterization of a lysine-to-glutamic acid mutation in a ... | ACCEPT | Summary: Blanchard & Karst 1993; erg20 disruption shows Erg20 is the only prenyltransferase able to make FPP. Core MF (second condensation, GPP + IPP -> FPP). Supporting Evidence: PMID:8096487 disruption of ERG20 revealed that in yeast no other prenyl transferase is able to synthesize the FPP molecules required for essential non-sterol metabolites |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from FPPS node PTN000162949 including Erg20 itself, human FDPS, S. pombe Fps1 and plant FPS. Correct. Supporting Evidence: PMID:8096487 disruption of ERG20 revealed that in yeast no other prenyl transferase is able to synthesize the FPP molecules required for essential non-sterol metabolites |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | IDA PMID:2681213 Farnesyl diphosphate synthetase. Molecular cloning, sequence... | ACCEPT | Summary: Anderson et al. 1989; the cloned ERG20 fragment raised FPP synthetase activity in yeast. Core MF. Supporting Evidence: PMID:2681213 the 4.5-kilobase EcoRI fragment directed a 2-3-fold over-expression of FPP synthetase activity in transformed yeast cells |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (RHEA:19361, EC 2.5.1.10). Correct. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt of isopentenyl pyrophosphate with dimethylallyl pyrophosphate, and then |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 assignment of GPP + IPP -> FPP. Correct. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways HEXPPSYN-PWY-2 assignment of FPP formation, the primer for Coq1. Correct reaction. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY-5123 (trans,trans-FPP biosynthesis). Correct. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-31704 superpathway assignment. Correct reaction. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-862 superpathway assignment. Correct reaction. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0004452 isopentenyl-diphosphate delta-isomerase activity | IDA PMID:7908830 Identification of Cys139 and Glu207 as catalytically importa... | UNDECIDED | Summary: IPP isomerase activity attributed to Erg20 from Street et al. 1994, whose cached abstract describes site-directed mutagenesis (C138, C139, E207) of IPP isomerase, i.e. Idi1, and the same paper supports the IDI1 isomerase annotation. Erg20 is a prenyltransferase of the FPP/GGPP synthase family with no known isomerase activity; this looks like a gene mis-attribution, but the full text is not available, so it is flagged for SGD rather than removed. Supporting Evidence: PMID:7908830 Kinetic studies were conducted with site-directed mutants of IPP isomerase (IPPIase) to evaluate the roles of these amino acids. |
| GO:0004659 prenyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR000092 (polyprenyl synthetase) mapping to the generic prenyltransferase term. Correct but uninformative; the specific activities are known. Proposed replacements: (2E,6E)-farnesyl diphosphate synthase activity Supporting Evidence: PMID:8096487 disruption of ERG20 revealed that in yeast no other prenyl transferase is able to synthesize the FPP molecules required for essential non-sterol metabolites |
| GO:0005737 cytoplasm | IDA PMID:19416104 The YTA7 gene is involved in the regulation of the isoprenoi... | ACCEPT | Summary: Kuranda et al. 2009 (Erg20 two-hybrid partners and Yta7) localisation of Erg20 to the cytoplasm (abstract-only cache; deferring to curator). Consistent with Erg20 being a soluble FPPS. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005773 vacuole | NAS PMID:28904410 Recent Advances in Ergosterol Biosynthesis and Regulation Me... | MARK AS OVER ANNOTATED | Summary: Vacuole NAS from the Hu et al. 2017 review, also echoed in the UniProt function text ("the second module is carried out in the vacuole"). No primary localisation data place Erg20 in the vacuole; direct data and phylogeny place it in the cytosol and ER, so this statement should not be used as a location. Reason: Review-level statement without primary support, at odds with experimental cytosol/ER localisation. Supporting Evidence: file:yeast/ERG20/ERG20-uniprot.txt out in the vacuole and involves the formation of farnesyl diphosphate, PMID:28904410 The biosynthesis of ergosterol can be divided into three modules: mevalonate, farnesyl pyrophosphate (farnesyl-PP) and ergosterol biosynthesis. |
| GO:0005783 endoplasmic reticulum | IDA PMID:19416104 The YTA7 gene is involved in the regulation of the isoprenoi... | ACCEPT | Summary: Kuranda et al. 2009 found Erg20 partners Yta7 at the ER/nucleus and annotated ER association of Erg20 (abstract-only cache; deferring to curator). FPP is consumed by ER enzymes (Erg9, cis-prenyltransferase), so peripheral ER association is plausible; non-core relative to cytosol. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from FPPS node PTN000162949 (human FDPS, mouse Fdps, trypanosome FPPS). FPPS enzymes are soluble cytosolic proteins; correct for Erg20. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 cytosolic compartment. Correct for Erg20. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways HEXPPSYN-PWY-2 cytosolic compartment. Correct for the Erg20 step (Coq1 itself is mitochondrial). Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY-5123 cytosolic compartment. Correct. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-31704 cytosolic compartment. Correct. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-862 cytosolic compartment. Correct for Erg20. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0006696 ergosterol biosynthetic process | IDA PMID:7908830 Identification of Cys139 and Glu207 as catalytically importa... | ACCEPT | Summary: Ergosterol biosynthesis attributed from Street et al. 1994, an IPP isomerase paper (abstract-only); the process is nonetheless correct for Erg20, whose FPP is the direct precursor of squalene and ergosterol, so deferring to the curator. Supporting Evidence: PMID:1779710 The isolation of the functional ERG20 gene allowed us to show that farnesyl diphosphate synthetase could be a rate limiting enzyme in ergosterol biosynthesis in yeast. |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:1779710 Sterol pathway in yeast. Identification and properties of mu... | ACCEPT | Summary: Chambon et al. 1990 isolated erg20 mutants auxotrophic for ergosterol and showed FPPS can be rate-limiting for ergosterol synthesis. Correct. 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. PMID:1779710 The isolation of the functional ERG20 gene allowed us to show that farnesyl diphosphate synthetase could be a rate limiting enzyme in ergosterol biosynthesis in yeast. |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways ERGOSTEROL-SYN-PWY-1 membership. Correct. Supporting Evidence: PMID:1779710 The isolation of the functional ERG20 gene allowed us to show that farnesyl diphosphate synthetase could be a rate limiting enzyme in ergosterol biosynthesis in yeast. |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-31704 membership. Correct. Supporting Evidence: PMID:1779710 The isolation of the functional ERG20 gene allowed us to show that farnesyl diphosphate synthetase could be a rate limiting enzyme in ergosterol biosynthesis in yeast. |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways HEXPPSYN-PWY-2 places Erg20's GPP/FPP formation in hexaprenyl diphosphate (and hence ubiquinone) biosynthesis. Erg20 makes the general isoprenoid branch-point FPP that also feeds sterols, dolichols, heme A and prenylation; Coq1 performs the CoQ-specific chain elongation. Annotating the general precursor supplier to each downstream product is superpathway inflation. Reason: FPP supply is upstream and shared; the FPP-biosynthesis term already captures Erg20's role. Supporting Evidence: PMID:2681213 Farnesyl diphosphate (FPP) synthetase is a key enzyme in isoprenoid biosynthesis which supplies C15 precursors for several classes of essential metabolites including sterols, dolichols, and ubiquinones. PMID:19416104 the production of nonsterol molecules, deriving from farnesyl diphosphate (FPP), implicated in N-glycosylation and biosynthesis of heme and ubiquinones |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways PWY3O-862 (superpathway of ubiquinone biosynthesis) inheritance. Same reasoning; Erg20 is a shared isoprenoid precursor enzyme, not a CoQ pathway enzyme. Reason: Superpathway-inherited process; general precursor supply. Supporting Evidence: PMID:2681213 Farnesyl diphosphate (FPP) synthetase is a key enzyme in isoprenoid biosynthesis which supplies C15 precursors for several classes of essential metabolites including sterols, dolichols, and ubiquinones. |
| GO:0008299 isoprenoid biosynthetic process | IDA PMID:2681213 Farnesyl diphosphate synthetase. Molecular cloning, sequence... | TOO GENERAL | Summary: Anderson et al. 1989; FPPS is a key isoprenoid enzyme. Correct, general parent of the FPP term. Supporting Evidence: PMID:2681213 Farnesyl diphosphate (FPP) synthetase is a key enzyme in isoprenoid biosynthesis which supplies C15 precursors for several classes of essential metabolites including sterols, dolichols, and ubiquinones. PMID:2681213 the 4.5-kilobase EcoRI fragment directed a 2-3-fold over-expression of FPP synthetase activity in transformed yeast cells |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro IPR000092/IPR039702 mapping. Correct, general. Supporting Evidence: PMID:2681213 Farnesyl diphosphate (FPP) synthetase is a key enzyme in isoprenoid biosynthesis which supplies C15 precursors for several classes of essential metabolites including sterols, dolichols, and ubiquinones. |
| GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR039702 (FPS1-like) mapping to a high-level transferase class. Correct but uninformative. Proposed replacements: (2E,6E)-farnesyl diphosphate synthase activity Supporting Evidence: PMID:8096487 disruption of ERG20 revealed that in yeast no other prenyl transferase is able to synthesize the FPP molecules required for essential non-sterol metabolites |
| GO:0033384 geranyl diphosphate biosynthetic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: UniPathway UPA00259 mapping. Erg20 does form GPP, mostly as an enzyme-bound intermediate that is extended to FPP; free GPP release is minor in wild type (raised by the K197E erg20-2 mutation). Correct but secondary to FPP biosynthesis. Supporting Evidence: PMID:8096487 resulting in a Lys197-->Glu substitution in FPPS which is directly involved in terpenic alcohol formation PMID:8096487 This strain had the unusual property of excreting prenyl alcohols such as geraniol. |
| GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from FPPS node PTN000162949. Correct; core process. Supporting Evidence: PMID:8096487 disruption of ERG20 revealed that in yeast no other prenyl transferase is able to synthesize the FPP molecules required for essential non-sterol metabolites |
| GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process | IDA PMID:2681213 Farnesyl diphosphate synthetase. Molecular cloning, sequence... | ACCEPT | Summary: Anderson et al. 1989; FPP synthetase activity of cloned ERG20. Core process. Supporting Evidence: PMID:2681213 the 4.5-kilobase EcoRI fragment directed a 2-3-fold over-expression of FPP synthetase activity in transformed yeast cells |
| GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00260 mapping. Correct. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
| GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY-5123 (trans,trans-FPP biosynthesis) membership. Correct. Supporting Evidence: PMID:19416104 FPP formed from mevalonate in a reaction catalyzed by FPP synthase (Erg20p). |
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Download this section (compressed HTML)Q: The ERG20 IDA to IPP isomerase activity (GO:0004452) and ergosterol biosynthesis cite PMID:7908830, an Idi1 mutagenesis paper; should SGD move these to IDI1?
Q: Is there primary evidence for a vacuolar location of the yeast mevalonate/FPP module (Erg20, Idi1), as stated in the Hu et al. 2017 review and UniProt, or should those NAS annotations be retired?
Experiment: Re-examine Erg20 localisation (endogenous tag, fractionation) under respiratory and sterol-limited conditions to test the reported ER association and any vacuolar pool.
Farnesyl pyrophosphate synthetase; has both dimethylallyltranstransferase and geranyltranstransferase activities; catalyzes the formation of C15 farnesyl pyrophosphate units for isoprenoid and sterol biosynthesis
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