Spermine synthase (spermidine aminopropyltransferase, EC 2.5.1.22) of Saccharomyces cerevisiae, a paralogue of spermidine synthase Spe3 in the spermidine/spermine synthase family. Spe4 transfers the aminopropyl group of decarboxylated S-adenosylmethionine to spermidine, forming spermine and 5'-methylthioadenosine. spe4 deletion mutants contain no spermine and no spermine synthase activity yet grow normally, showing that spermine is dispensable in yeast, in contrast to the essential spermidine made by Spe3. Spe4 is cytosolic and interacts with Spe3 in high-throughput screens. Spermine is also the precursor of the beta-alanine used for pantothenic acid and coenzyme A synthesis: the amine oxidase Fms1 degrades it to beta-alanine, so spe4 mutants are beta-alanine auxotrophs on minimal medium.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR001045 mapping to root catalytic activity. Reason: Replace with the specific spermine synthase activity. Proposed replacements: spermine synthase activity |
| GO:0004766 spermidine synthase activity | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA from the spermidine synthase node (PTN000168362). Spe4 is the yeast spermine synthase, a paralogue of Spe3 that sits in the same PANTHER family. Genetic evidence argues against spermidine synthase activity for Spe4: spe3 null cells, which retain SPE4, have no detectable spermidine synthase activity and are spermidine auxotrophs. Spe4 therefore uses spermidine as acceptor rather than producing it. Reason: Paralogue over-propagation: target-specific genetic evidence (spe3 null has no spermidine synthase activity despite intact SPE4) shows Spe4 lacks this function; its activity is spermine synthase. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000168362 · PTN000168362 SUPPORTS SOURCE BUT NOT TARGET Spermidine synthase node; Spe4 is a fungal spermine synthase paralogue of Spe3 within this family. SGD:S000006273 · SPE3 SUPPORTS SOURCE BUT NOT TARGET Yeast spermidine synthase paralogue; spe3 null lacks spermidine synthase activity despite intact SPE4. 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. file:yeast/SPE4/SPE4-uniprot.txt Reaction=S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = |
| 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, plausible pathway-partner interaction, but bare protein binding is uninformative; removal does not imply the interaction is false. |
| 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: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); aminopropyltransferases are cytosolic. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA cytosol (ARGSPECAT-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 IEA polyamine biosynthetic process; correct parent of spermine biosynthesis. |
| GO:0006596 polyamine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (POLYAMSYN-YEAST-PWY) polyamine biosynthesis; correct. |
| GO:0006597 spermine biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway UPA00249 mapping (spermine biosynthesis); correct. |
| GO:0006597 spermine biosynthetic process | IMP PMID:9573363 Spermine is not essential for growth of Saccharomyces cerevi... | ACCEPT | Summary: SGD IMP (Hamasaki-Katagiri 1998): spe4 deletion abolishes spermine and spermine synthase activity. Supporting Evidence: PMID:9573363 This mutant has neither spermine nor spermine synthase activity. |
| GO:0006597 spermine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ARGSPECAT-PWY spermine biosynthesis); correct. |
| GO:0008295 spermidine biosynthetic process | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA from the spermidine synthase node (PTN000168362). Spe4 is the yeast spermine synthase, a paralogue of Spe3 that sits in the same PANTHER family. Genetic evidence argues against spermidine synthase activity for Spe4: spe3 null cells, which retain SPE4, have no detectable spermidine synthase activity and are spermidine auxotrophs. Spe4 therefore uses spermidine as acceptor rather than producing it. Spermidine biosynthesis is likewise attributable to Spe3 alone. Reason: Paralogue over-propagation; Spe4 consumes rather than synthesises spermidine. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN000168362 · PTN000168362 SUPPORTS SOURCE BUT NOT TARGET Spermidine synthase node; Spe4 is a fungal spermine synthase paralogue of Spe3 within this family. SGD:S000006273 · SPE3 SUPPORTS SOURCE BUT NOT TARGET Yeast spermidine synthase paralogue; spe3 null lacks spermidine synthase activity despite intact SPE4. 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. PMID:9573363 This mutant has neither spermine nor spermine synthase activity. |
| GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA for alkyl/aryl transferase activity; correct parent of aminopropyltransferase activity. Reason: Use the specific activity. Proposed replacements: spermine synthase activity |
| GO:0016768 spermine synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via RHEA:19973/EC 2.5.1.22; correct core activity. Supporting Evidence: file:yeast/SPE4/SPE4-uniprot.txt Reaction=S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = |
| GO:0016768 spermine synthase activity | IMP PMID:9573363 Spermine is not essential for growth of Saccharomyces cerevi... | ACCEPT | Summary: SGD IMP (Hamasaki-Katagiri 1998): spe4 mutant lacks spermine synthase activity. Supporting Evidence: PMID:9573363 This mutant has neither spermine nor spermine synthase activity. |
| GO:0016768 spermine synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (ARGSPECAT-PWY) spermine synthase step; correct. |
| GO:0016768 spermine synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (POLYAMSYN-YEAST-PWY); correct. |
| GO:0016768 spermine synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-351) for the spermine synthase reaction; activity assignment correct. |
| 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. Spe4 produces MTA as a co-product of spermine 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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Download this section (compressed HTML)Q: Does Spe4 have any residual putrescine aminopropyltransferase activity in vitro, and is the PAINT spermidine-synthase node placement correct for the fungal spermine synthase clade?
Q: What physiological role does spermine play in yeast given that spe4 mutants grow normally?
Spermine synthase; required for the biosynthesis of spermine and also involved in biosynthesis of pantothenic acid
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