BTS1 encodes geranylgeranyl diphosphate (GGPP) synthase, a type III trans-prenyltransferase of the FPP/GGPP synthase family (PTHR12001). It adds one isopentenyl diphosphate to (2E,6E)-farnesyl diphosphate to form (2E,6E,10E)-GGPP (EC 2.5.1.29), using Mg2+-coordinated aspartate-rich motifs; Km values are reported for FPP (3.2 uM) and IPP (0.8 uM). GGPP is the lipid donor for the type I and type II protein geranylgeranyltransferases, which modify Rho and Rab GTPases such as Ypt1 and Sec4 and so anchor them to membranes. BTS1 was isolated as a multicopy suppressor of bet2-1, a mutation in the beta subunit of Rab geranylgeranyltransferase, and suppresses it by enlarging the cellular GGPP pool. BTS1 is not essential, but its disruption reduces geranylgeranylation of many proteins and makes cells cold-sensitive. Crystal structures of yeast GGPPS with bisphosphonates show separate FPP, IPP and GGPP product binding sites. The upstream FPP is made by the essential FPP synthase Erg20p.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004161 dimethylallyltranstransferase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: IEA from RHEA:22408/EC 2.5.1.1 (DMAPP + IPP -> GPP), propagated from a UniProt catalytic-activity line that has no yeast-specific evidence attached. Bts1p is a type III (fungal/animal) GGPP synthase whose characterised substrates are FPP and IPP; the FPP-binding site is seen in its crystal structures and kinetic constants are reported for FPP and IPP only. In yeast, DMAPP->GPP->FPP is catalysed by the essential FPP synthase Erg20p, and there is no experimental evidence that Bts1p contributes to GPP or FPP production in vivo. Reason: No evidence that Bts1p synthesises geranyl diphosphate; the physiological GGPP synthase reaction uses FPP as the allylic primer. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt KM=3.2 uM for farnesyl diphosphate; PMID:17535895 Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. |
| GO:0004311 geranylgeranyl diphosphate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000243244 (GGPP synthase clade of PTHR12001, including human GGPS1 and BTS1 itself as experimental sources). Bts1p is the yeast GGPPS; correct. Supporting Evidence: PMID:7665600 This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. |
| GO:0004311 geranylgeranyl diphosphate synthase activity | IDA PMID:23493556 Prediction of function for the polyprenyl transferase subgro... | ACCEPT | Summary: Wallrapp et al. (EFI) analysed the polyprenyl transferase subgroup of the isoprenoid synthase superfamily and assayed product chain length for many members; the cached text does not name BTS1 explicitly, so the yeast-specific result is presumably in the supplementary data. Consistent with established Bts1p GGPPS activity; accepted. Supporting Evidence: PMID:23493556 Beginning with DMAPP, a series of polyprenyl diphosphates with C 10 (geranyl diphosphate, GPP), C 15 (farnesyl diphosphate, FPP), C 20 (geranylgeranyl diphosphate, GGPP) |
| GO:0004311 geranylgeranyl diphosphate synthase activity | IDA PMID:7665600 BTS1 encodes a geranylgeranyl diphosphate synthase in Saccha... | ACCEPT | Summary: Jiang et al. identified BTS1 as a multicopy suppressor of bet2-1 and showed it encodes geranylgeranyl diphosphate synthase (enzymatic data in the full text; UniProt cites this paper as evidence for the EC 2.5.1.29 reaction). Core activity. Supporting Evidence: PMID:7665600 This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0004311 geranylgeranyl diphosphate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA00096937, RHEA:17653, EC 2.5.1.29). Correct and experimentally supported for Bts1p. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0004311 geranylgeranyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from HEXPPSYN-PWY-2 (hexaprenyl diphosphate biosynthesis): FPP + IPP -> GGPP (EC 2.5.1.29). The reaction assignment is correct for Bts1p, even though the pathway context (hexaprenyl diphosphate/ubiquinone) is questionable (see the BP rows). Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0004311 geranylgeranyl diphosphate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from PWY3O-862 (superpathway of ubiquinone biosynthesis): FPP + IPP -> GGPP (EC 2.5.1.29). The reaction assignment is correct for Bts1p, even though the pathway context (hexaprenyl diphosphate/ubiquinone) is questionable (see the BP rows). Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: IEA from RHEA:19361/EC 2.5.1.10 (GPP + IPP -> FPP), from a UniProt catalytic-activity line without experimental evidence. Bts1p is a type III (fungal/animal) GGPP synthase whose characterised substrates are FPP and IPP; the FPP-binding site is seen in its crystal structures and kinetic constants are reported for FPP and IPP only. In yeast, DMAPP->GPP->FPP is catalysed by the essential FPP synthase Erg20p, and there is no experimental evidence that Bts1p contributes to GPP or FPP production in vivo. Reason: FPP synthesis in yeast is the role of Erg20p; Bts1p uses FPP rather than making it. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt KM=3.2 uM for farnesyl diphosphate; PMID:17535895 Our results on GGPPS (10 structures) show that there are three bisphosphonate-binding sites, consisting of FPP or isopentenyl diphosphate substrate-binding sites together with a GGPP product- or inhibitor-binding site. |
| GO:0004659 prenyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from IPR000092 (polyprenyl synthetase) to the generic prenyltransferase activity. Correct but uninformative; the specific activity is GGPP synthase. Reason: GO:0004311 geranylgeranyl diphosphate synthase activity is the precise, experimentally supported activity. Proposed replacements: geranylgeranyl diphosphate synthase activity Supporting Evidence: PMID:7665600 This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (Cytoplasm, by similarity). GGPP produced by Bts1p is used by the cytosolic geranylgeranyltransferases I and II, and the enzyme has no targeting signal; cytoplasm is the expected location. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. PMID:7665600 Our findings imply that BTS1 suppresses the bet2-1 mutant by increasing the intracellular pool of geranylgeranyl diphosphate. |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: Huh et al. GFP survey (HDA) scored Bts1p-GFP in mitochondria; GOA carries both located_in and is_active_in (is_active_in) from this single high-throughput observation. Bts1p function (supply of GGPP for protein geranylgeranylation of Rab/Rho GTPases) is cytosolic and no mitochondrial GGPP requirement has been shown, so the mitochondrial signal is retained only as an observed, non-core location; the is_active_in qualifier is stronger than a GFP image supports. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: Huh et al. GFP survey (HDA) scored Bts1p-GFP in mitochondria; GOA carries both located_in and is_active_in (located_in) from this single high-throughput observation. Bts1p function (supply of GGPP for protein geranylgeranylation of Rab/Rho GTPases) is cytosolic and no mitochondrial GGPP requirement has been shown, so the mitochondrial signal is retained only as an observed, non-core location; the is_active_in qualifier is stronger than a GFP image supports. 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 cytosolic location from PWY3O-862 (superpathway of ubiquinone biosynthesis). Consistent with the cytoplasmic location of Bts1p and with use of its product by cytosolic protein geranylgeranyltransferases. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA from HEXPPSYN-PWY-2 (hexaprenyl diphosphate biosynthesis), which places the Bts1p GGPPS reaction upstream of Coq1p hexaprenyl diphosphate synthase. There is no evidence that bts1 mutants are coenzyme Q deficient (they are viable, cold-sensitive and defective in protein geranylgeranylation), and the allylic primer used by Coq1p in vivo is not established; FPP from Erg20p is generally considered the primer for long-chain trans-prenyl synthases. Even if GGPP were a primer, Bts1p would be supplying a precursor rather than performing a step of ubiquinone synthesis. Superpathway inflation. Reason: Bts1p performs no step of ubiquinone biosynthesis; its established process is geranylgeranyl diphosphate biosynthesis (GO:0033386). Supporting Evidence: PMID:7665600 BTS1 is not essential for the vegetative growth of cells; however, disrupting it impedes the geranylgeranylation of many cellular proteins and renders cells cold sensitive for growth. |
| GO:0006744 ubiquinone biosynthetic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA from PWY3O-862 (superpathway of ubiquinone biosynthesis), which places the Bts1p GGPPS reaction upstream of Coq1p hexaprenyl diphosphate synthase. There is no evidence that bts1 mutants are coenzyme Q deficient (they are viable, cold-sensitive and defective in protein geranylgeranylation), and the allylic primer used by Coq1p in vivo is not established; FPP from Erg20p is generally considered the primer for long-chain trans-prenyl synthases. Even if GGPP were a primer, Bts1p would be supplying a precursor rather than performing a step of ubiquinone synthesis. Superpathway inflation. Reason: Bts1p performs no step of ubiquinone biosynthesis; its established process is geranylgeranyl diphosphate biosynthesis (GO:0033386). Supporting Evidence: PMID:7665600 BTS1 is not essential for the vegetative growth of cells; however, disrupting it impedes the geranylgeranylation of many cellular proteins and renders cells cold sensitive for growth. |
| GO:0008299 isoprenoid biosynthetic process | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from PTN000243362 (the broad trans-prenyl diphosphate synthase node of PTHR12001). GGPP synthesis is an isoprenoid biosynthetic process; correct but general (GO:0033386 is more specific). Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO mapping from IPR000092 (polyprenyl synthetase). Correct but general; GO:0033386 is the specific process. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0016114 terpenoid biosynthetic process | IDA PMID:7665600 BTS1 encodes a geranylgeranyl diphosphate synthase in Saccha... | MODIFY | Summary: IDA annotation from Jiang et al. 1995: Bts1p synthesises GGPP and its disruption impairs protein geranylgeranylation. The essence (Bts1p makes a C20 isoprenoid) is right, but the specific process term is geranylgeranyl diphosphate biosynthesis; "terpenoid biosynthetic process" is broad. Reason: GO:0033386 geranylgeranyl diphosphate biosynthetic process precisely describes the product made by Bts1p. Proposed replacements: geranylgeranyl diphosphate biosynthetic process Supporting Evidence: PMID:7665600 This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. PMID:7665600 BTS1 is not essential for the vegetative growth of cells; however, disrupting it impedes the geranylgeranylation of many cellular proteins and renders cells cold sensitive for growth. |
| GO:0016114 terpenoid biosynthetic process | IMP PMID:7665600 BTS1 encodes a geranylgeranyl diphosphate synthase in Saccha... | MODIFY | Summary: IMP annotation from Jiang et al. 1995: Bts1p synthesises GGPP and its disruption impairs protein geranylgeranylation. The essence (Bts1p makes a C20 isoprenoid) is right, but the specific process term is geranylgeranyl diphosphate biosynthesis; "terpenoid biosynthetic process" is broad. Reason: GO:0033386 geranylgeranyl diphosphate biosynthetic process precisely describes the product made by Bts1p. Proposed replacements: geranylgeranyl diphosphate biosynthetic process Supporting Evidence: PMID:7665600 This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. PMID:7665600 BTS1 is not essential for the vegetative growth of cells; however, disrupting it impedes the geranylgeranylation of many cellular proteins and renders cells cold sensitive for growth. |
| GO:0033384 geranyl diphosphate biosynthetic process | IEA GO_REF:0000041 | MARK AS OVER ANNOTATED | Summary: UniPathway UPA00259 (geranyl diphosphate biosynthesis) mapping, derived from the UniProt pathway line that accompanies the unsupported EC 2.5.1.1 reaction. Bts1p is a type III (fungal/animal) GGPP synthase whose characterised substrates are FPP and IPP; the FPP-binding site is seen in its crystal structures and kinetic constants are reported for FPP and IPP only. In yeast, DMAPP->GPP->FPP is catalysed by the essential FPP synthase Erg20p, and there is no experimental evidence that Bts1p contributes to GPP or FPP production in vivo. Reason: No experimental support that Bts1p makes geranyl diphosphate. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt KM=3.2 uM for farnesyl diphosphate; |
| GO:0033386 geranylgeranyl diphosphate biosynthetic process | IDA PMID:23493556 Prediction of function for the polyprenyl transferase subgro... | ACCEPT | Summary: Wallrapp et al. (EFI polyprenyl transferase survey) is credited by SGD with direct evidence that Bts1p produces GGPP. Correct; core process. Supporting Evidence: PMID:23493556 Beginning with DMAPP, a series of polyprenyl diphosphates with C 10 (geranyl diphosphate, GPP), C 15 (farnesyl diphosphate, FPP), C 20 (geranylgeranyl diphosphate, GGPP) PMID:7665600 This suppressor gene, called BTS1, encodes the yeast geranylgeranyl diphosphate synthase. |
| GO:0033386 geranylgeranyl diphosphate biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00389 (geranylgeranyl diphosphate biosynthesis from FPP and IPP) mapping. Correct core process for Bts1p. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E,6E)-farnesyl diphosphate = |
| GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process | IEA GO_REF:0000041 | MARK AS OVER ANNOTATED | Summary: UniPathway UPA00260 (farnesyl diphosphate biosynthesis) mapping from the UniProt pathway line tied to the unsupported EC 2.5.1.10 reaction. Bts1p is a type III (fungal/animal) GGPP synthase whose characterised substrates are FPP and IPP; the FPP-binding site is seen in its crystal structures and kinetic constants are reported for FPP and IPP only. In yeast, DMAPP->GPP->FPP is catalysed by the essential FPP synthase Erg20p, and there is no experimental evidence that Bts1p contributes to GPP or FPP production in vivo. Reason: FPP is the substrate of Bts1p, not its product; FPP biosynthesis is carried out by Erg20p. Supporting Evidence: file:yeast/BTS1/BTS1-uniprot.txt KM=3.2 uM for farnesyl diphosphate; |
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Download this section (compressed HTML)Q: Does Bts1p-derived GGPP contribute to any mitochondrial process (e.g. as a primer for Coq1p hexaprenyl diphosphate synthesis), or is the GFP-based mitochondrial localisation an artefact?
Q: Is the cold-sensitive growth of bts1 null cells solely due to under-geranylgeranylation of Rab/Rho GTPases?
Experiment: Measure CoQ6 content and 13C-IPP incorporation into CoQ6 in bts1 null versus wild-type cells (with and without ERG20 knockdown) by LC-MS/MS.
Hypothesis: Bts1p does not contribute to coenzyme Q6 side-chain synthesis
Type: lipidomics / isotope labelling
Geranylgeranyl diphosphate synthase (GGPPS); increases the intracellular pool of geranylgeranyl diphosphate, suppressor of bet2 mutation that causes defective geranylgeranylation of small GTP-binding proteins that mediate vesicular traffic
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