Spermidine synthase (putrescine aminopropyltransferase, EC 2.5.1.16) of Saccharomyces cerevisiae, a member of the spermidine/spermine synthase family that transfers the aminopropyl group of decarboxylated S-adenosylmethionine to putrescine, forming spermidine and 5'-methylthioadenosine. Spe3 is the only spermidine synthase in yeast: spe3 null mutants lack spermidine synthase activity and have an absolute requirement for spermidine (or high spermine), which is needed for hypusine modification of eIF5A and growth. Spermidine is further converted to spermine by Spe4, with which Spe3 interacts. Spe3 is a cytosolic enzyme; its MTA product feeds the methionine salvage pathway. Spermidine made by Spe3p is also the precursor of spermine, which the polyamine oxidase Fms1p converts to the beta-alanine used for pantothenic acid and coenzyme A synthesis; spe3 mutants therefore require beta-alanine or pantothenate.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR001045 (spermidine/spermine synthase family) mapping to root catalytic activity. Reason: Replace with the specific aminopropyltransferase activity. Proposed replacements: spermidine synthase activity |
| GO:0004766 spermidine synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for spermidine synthase activity; Spe3 is the canonical spermidine synthase with its own IMP. Supporting Evidence: file:yeast/SPE3/SPE3-uniprot.txt Reaction=S-adenosyl 3-(methylsulfanyl)propylamine + putrescine = S- PMID:9073064 The deduced amino acid sequence has a high similarity to mammalian spermidine synthases, and has putative S-adenosylmethionine binding motifs. |
| GO:0004766 spermidine synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:12721/EC 2.5.1.16; correct. Supporting Evidence: file:yeast/SPE3/SPE3-uniprot.txt Reaction=S-adenosyl 3-(methylsulfanyl)propylamine + putrescine = S- |
| GO:0004766 spermidine synthase activity | IMP PMID:9073064 Spermidine biosynthesis in Saccharomyces cerevisae: polyamin... | ACCEPT | Summary: SGD IMP (Hamasaki-Katagiri 1997): spe3 null mutant has no spermidine synthase activity. Supporting Evidence: PMID:9073064 To investigate the effect of total loss of the SPE3 gene, we constructed a null mutant of this gene, spe3delta, which has no spermidine synthase activity and has an absolute requirement for spermidine or spermine for the growth. |
| GO:0004766 spermidine synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (BSUBPOLYAMSYN-PWY spermidine biosynthesis I); correct. |
| GO:0004766 spermidine synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (POLYAMSYN-YEAST-PWY); correct. |
| GO:0004766 spermidine synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-351 superpathway of methionine salvage) for the spermidine synthase reaction; activity assignment correct. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: High-throughput interaction between Spe3 and Spe4 (spermine synthase), detected in the Gavin 2006 TAP-MS complex survey. A Spe3-Spe4 association is biologically plausible (sequential aminopropyltransferases sharing dcAdoMet; plant SPDS/SPMS form hetero-complexes), but 'protein binding' does not describe the activity of either enzyme. Reason: Reproducible across three independent screens (AP-MS, Y2H, interactome) and biologically plausible, but bare protein binding carries no functional information; removal does not imply the interaction is false. A confirmed Spe3-Spe4 complex would be better captured as a complex term. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | REMOVE | Summary: High-throughput interaction between Spe3 and Spe4 (spermine synthase), detected in the Yu 2008 binary Y2H map. A Spe3-Spe4 association is biologically plausible (sequential aminopropyltransferases sharing dcAdoMet; plant SPDS/SPMS form hetero-complexes), but 'protein binding' does not describe the activity of either enzyme. Reason: Reproducible, plausible pathway-partner interaction, but bare protein binding is uninformative; removal does not imply the interaction is false. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: High-throughput interaction between Spe3 and Spe4 (spermine synthase), detected in the Michaelis 2023 yeast interactome. A Spe3-Spe4 association is biologically plausible (sequential aminopropyltransferases sharing dcAdoMet; plant SPDS/SPMS form hetero-complexes), but 'protein binding' does not describe the activity of either enzyme. Reason: Reproducible, plausible pathway-partner interaction, but bare protein binding is uninformative; removal does not imply the interaction is false. |
| GO:0005634 nucleus | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: Huh 2003 GFP survey: nuclear signal; no nuclear role known. Reason: High-throughput localization, non-core. 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 2003 GFP survey: cytoplasm. Supporting Evidence: 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: PAINT IBA cytosol (is_active_in); consistent. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA cytosol (BSUBPOLYAMSYN-PWY). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA cytosol (POLYAMSYN-YEAST-PWY). |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA cytosol (PWY3O-351). |
| GO:0006595 polyamine metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro IPR030668 mapping to polyamine metabolic process; correct but general. |
| GO:0006596 polyamine biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning IEA for polyamine biosynthetic process; correct parent of spermidine biosynthesis. |
| GO:0006596 polyamine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (POLYAMSYN-YEAST-PWY) polyamine biosynthesis; correct. |
| GO:0008295 spermidine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA spermidine biosynthetic process; core. Supporting Evidence: PMID:9073064 To investigate the effect of total loss of the SPE3 gene, we constructed a null mutant of this gene, spe3delta, which has no spermidine synthase activity and has an absolute requirement for spermidine or spermine for the growth. |
| GO:0008295 spermidine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00248 mapping (spermidine biosynthesis); correct. |
| GO:0008295 spermidine biosynthetic process | IMP PMID:9073064 Spermidine biosynthesis in Saccharomyces cerevisae: polyamin... | ACCEPT | Summary: SGD IMP (Hamasaki-Katagiri 1997): spe3 mutant requires spermidine. Supporting Evidence: PMID:9073064 To investigate the effect of total loss of the SPE3 gene, we constructed a null mutant of this gene, spe3delta, which has no spermidine synthase activity and has an absolute requirement for spermidine or spermine for the growth. |
| GO:0008295 spermidine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (BSUBPOLYAMSYN-PWY); correct. |
| GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for 'transferase activity, transferring alkyl or aryl (other than methyl) groups'; correct parent of the aminopropyltransferase activity. Reason: Use the specific activity. Proposed replacements: spermidine synthase activity |
| GO:0071267 L-methionine salvage | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: YeastPathways RCA inherited from the 'superpathway of methionine salvage' (PWY3O-351), which chains polyamine synthesis to MTA salvage. Spe3 produces MTA as a co-product of spermidine synthesis but performs no step that regenerates methionine; the salvage steps are catalysed by Meu1, Mri1, Mde1, Utr4, Adi1 and the transaminases. Reason: Superpathway inflation: generating the salvage substrate is not participating in methionine salvage. |
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Spermidine synthase; involved in biosynthesis of spermidine and also in biosynthesis of pantothenic acid; spermidine is required for growth of wild-type cells
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