Saccharopine dehydrogenase [NAD+, L-lysine-forming] (EC 1.5.1.7) of Saccharomyces cerevisiae. Lys1 catalyses the final step of the fungal alpha-aminoadipate pathway of lysine biosynthesis, the NAD+-dependent cleavage of saccharopine to L-lysine and 2-oxoglutarate. It is a monomeric Rossmann-fold enzyme with an ordered kinetic mechanism (NAD+ binds before saccharopine). Lys1 carries a C-terminal PTS1 and is imported by Pex5 into the peroxisomal matrix, so lysine synthesis is completed inside peroxisomes; NAD+ for the reaction is regenerated there by the Mdh3 and Gpd1 redox shuttles, and Lys1 still supports lysine synthesis when mislocalised to the cytosol. Lys1 abundance in peroxisomes is increased by the small matrix protein Pls1, whose own peroxisomal import depends on Lys1. Lys1 is induced by the Lys14/alpha-aminoadipate semialdehyde system and repressed by lysine, and it has also been detected as an mRNA-binding protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003729 mRNA binding | IDA PMID:20844764 Proteome-wide search reveals unexpected RNA-binding proteins... | KEEP AS NON CORE | Summary: Proteome-wide protein-array screen followed by RIP-chip identified Lys1 as an unexpected RNA-binding protein that co-purified with >1,000 mRNAs, enriched for transcripts of membrane proteins. The data are direct and reproducible for Lys1, but no function for mRNA binding by this peroxisomal enzyme has been established, so it is retained as a non-core, possibly moonlighting, activity. Supporting Evidence: PMID:20844764 Lys1 interacted with >1,000 mRNAs PMID:20844764 Other novel RBPs appear to play dual roles as metabolic enzymes and RNA-binding proteins; Lys1, Gcy1, and Pcs60 encode enzymes that participate in lysine biosynthesis |
| GO:0004753 saccharopine dehydrogenase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT node PTN000123605 spans the saccharopine dehydrogenase family (yeast LYS1, plant and animal AASS SDH domains). Lys1 is a bona fide member and has direct biochemical evidence; the IBA term is the family-level parent of the more precise NAD+, L-lysine-forming activity (GO:0004754) also annotated here. Correct but general. Reason: PTN000123605 is a sound broad saccharopine-dehydrogenase ancestor that spans yeast LYS1, fungal LYS9/lys9 enzymes, plant and animal AASS SDH domains, and other reciprocal family members. The exact NAD(+), L-lysine-forming reaction belongs to the fungal PTHR11133:SF23 branch containing S. cerevisiae LYS1, Candida LYS1, Neurospora lys-4, and S. pombe lys3, so the broad GO:0004753 row is true but subsumed by the accepted exact GO:0004754 activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000123605 Β· PANTHER:PTN000123605 SUPPORTS TRANSFER The PAINT ancestor supports generic saccharopine dehydrogenase activity for the full family, but P38998 is a PTHR11133:SF23 fungal LYS1 member with a target-specific NAD(+), L-lysine-forming GO:0004754 annotation. Supporting Evidence: PMID:17002315 Kinetic data have been measured for the histidine-tagged saccharopine dehydrogenase from Saccharomyces cerevisiae file:yeast/LYS1/LYS1-uniprot.txt Catalyzes the NAD(+)-dependent cleavage of saccharopine to L- file:interpro/panther/PTHR11133/PTHR11133-paint.tsv PTHR11133 PTN000123605 GO:0004753 F IBD false AGI_LocusCode:AT4G33150|FB:FBgn0286198|MGI:MGI:1353573|SGD:S000001473|SGD:S000005333|UniProtKB:P43065|UniProtKB:Q9UDR5 taxon:2759 20260828 file:interpro/panther/PTHR11133/PTHR11133-entries.csv P38998,"Saccharopine dehydrogenase [NAD(+), L-lysine-forming]",protein,559292,Saccharomyces cerevisiae (strain ATCC 204508 / S288c),Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast),LYS1,373,PTHR11133:SF23,"SACCHAROPINE DEHYDROGENASE [NAD(+), L-LYSINE-FORMING]",True |
| GO:0004754 saccharopine dehydrogenase (NAD+, L-lysine-forming) activity | EXP PMID:4287986 Saccharopine, an intermediate of the aminoadipic acid pathwa... | ACCEPT | Summary: Classical purification and characterisation of yeast saccharopine dehydrogenase (Saunders and Broquist 1966); UniProt cites this paper as experimental evidence for the EC 1.5.1.7 reaction. Only the title is cached, but the activity is undisputed for Lys1. Supporting Evidence: PMID:4287986 Saccharopine, an intermediate of the aminoadipic acid pathway of lysine biosynthesis. IV. Saccharopine dehydrogenase. file:yeast/LYS1/LYS1-uniprot.txt Catalyzes the NAD(+)-dependent cleavage of saccharopine to L- |
| GO:0004754 saccharopine dehydrogenase (NAD+, L-lysine-forming) activity | EXP PMID:4318475 A kinetic study of saccharopine dehydrogenase reaction. | ACCEPT | Summary: Kinetic study of the yeast saccharopine dehydrogenase reaction (Fujioka and Nakatani 1970), source of the UniProt Km values for NADH, NAD+, saccharopine, 2-oxoglutarate and lysine. Supports the lysine-forming saccharopine dehydrogenase activity of Lys1. Supporting Evidence: PMID:4318475 A kinetic study of saccharopine dehydrogenase reaction. file:yeast/LYS1/LYS1-uniprot.txt Catalyzes the NAD(+)-dependent cleavage of saccharopine to L- |
| GO:0004754 saccharopine dehydrogenase (NAD+, L-lysine-forming) activity | IDA PMID:17002315 Overall kinetic mechanism of saccharopine dehydrogenase from... | ACCEPT | Summary: Recombinant His-tagged Lys1 was assayed in both directions; NAD+ binds first, followed by saccharopine, in the physiological (lysine-forming) direction. Direct demonstration of the core catalytic activity. Supporting Evidence: PMID:17002315 Kinetic data have been measured for the histidine-tagged saccharopine dehydrogenase from Saccharomyces cerevisiae file:yeast/LYS1/LYS1-uniprot.txt Catalyzes the NAD(+)-dependent cleavage of saccharopine to L- |
| GO:0004754 saccharopine dehydrogenase (NAD+, L-lysine-forming) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from InterPro IPR027281 (lysine-forming SDH), Rhea:12440 and EC 1.5.1.7; all three mappings match the experimentally characterised reaction of Lys1. Supporting Evidence: PMID:17002315 Kinetic data have been measured for the histidine-tagged saccharopine dehydrogenase from Saccharomyces cerevisiae file:yeast/LYS1/LYS1-uniprot.txt Catalyzes the NAD(+)-dependent cleavage of saccharopine to L- |
| GO:0004754 saccharopine dehydrogenase (NAD+, L-lysine-forming) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways LYSINE-AMINOAD-PWY-2 (lysine biosynthesis via aminoadipate) assigns the final step, saccharopine -> L-lysine + 2-oxoglutarate, to Lys1. Correct. Supporting Evidence: PMID:17002315 Kinetic data have been measured for the histidine-tagged saccharopine dehydrogenase from Saccharomyces cerevisiae file:yeast/LYS1/LYS1-uniprot.txt Catalyzes the NAD(+)-dependent cleavage of saccharopine to L- |
| GO:0005515 protein binding | IPI PMID:16606443 Comparative analysis of Saccharomyces cerevisiae WW domains ... | REMOVE | Summary: Lys1 was one of 207 proteins that bound yeast WW domains (with/from Rsp5, P39940) on protein microarrays. This likely reflects a PY-motif interaction with the Rsp5 ubiquitin ligase, but 'protein binding' conveys nothing about Lys1 function and no consequence for Lys1 has been shown. Removal reflects the uninformative term, not doubt that the interaction occurs. Supporting Evidence: PMID:16606443 We used protein microarray technology to generate a protein interaction map for 12 of the 13 WW domains present in proteins of the yeast S. cerevisiae. |
| GO:0005737 cytoplasm | HDA PMID:11914276 Subcellular localization of the yeast proteome. | TOO GENERAL | Summary: Genome-wide immunolocalisation (Kumar et al. 2002) called Lys1 cytoplasmic. In GO the peroxisome is part of the cytoplasm, so this is true but imprecise; the specific site is the peroxisomal matrix. Supporting Evidence: PMID:11914276 By high-throughput immunolocalization of tagged gene products, we have determined the subcellular localization of 2744 yeast proteins. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT inference of cytoplasmic activity for the saccharopine dehydrogenase family. For yeast Lys1 the active pool is in the peroxisomal matrix (PTS1/Pex5-dependent), which lies within the GO cytoplasm, so the IBA is not wrong but less informative than peroxisome. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000123605 Β· PANTHER:PTN000123605 SUPPORTS TRANSFER The PAINT ancestor supports broad cytoplasm for the full saccharopine dehydrogenase family, but P38998 has a target-specific peroxisome and peroxisomal matrix localization. Supporting Evidence: PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. PMID:35563734 the last step of lysine biosynthesis occurs in peroxisomes by the saccharopine dehydrogenase enzyme, Lys1 (Lysine requiring 1) [50], which possesses a PTS1 motif with high affinity to Pex5 [51]. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA machine-learning location. Accurate only in the broad sense that peroxisomes are cytoplasmic organelles; the specific location of Lys1 is the peroxisome. Supporting Evidence: PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. PMID:35563734 the last step of lysine biosynthesis occurs in peroxisomes by the saccharopine dehydrogenase enzyme, Lys1 (Lysine requiring 1) [50], which possesses a PTS1 motif with high affinity to Pex5 [51]. |
| GO:0005777 peroxisome | EXP PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: The SWAT N-terminal GFP library was crossed with a Pex3-mCherry peroxisomal marker to find peroxisomal proteins whose PTS1 is masked by C-terminal tags; Lys1 (C-terminal PTS1) was among the newly visualised peroxisomal proteins (supplementary data). Supporting Evidence: PMID:26928762 To uncover new peroxisomal proteins we mated a strain expressing the peroxisomal marker, Pex3-mCherry, with the haploid SWAT-GFP and SWAT-SP-GFP libraries PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. |
| GO:0005777 peroxisome | EXP PMID:28928432 Two NAD-linked redox shuttles maintain the peroxisomal redox... | ACCEPT | Summary: GFP-Lys1p colocalises with a peroxisomal matrix marker; C-terminal tagging that masks the PTS1 relocates Lys1 to the cytosol. This paper also shows that peroxisomal NAD+ regeneration (Mdh3/Gpd1 shuttles) is needed for Lys1 function in peroxisomes. Supporting Evidence: PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. PMID:35563734 the last step of lysine biosynthesis occurs in peroxisomes by the saccharopine dehydrogenase enzyme, Lys1 (Lysine requiring 1) [50], which possesses a PTS1 motif with high affinity to Pex5 [51]. PMID:28928432 Firstly, by mislocalising Lys1p to the cytosol in mdh3/gpd1Ξ cells, lysine biosynthesis is restored |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location (Peroxisome, experimentally supported by PMID:26928762 and PMID:28928432) mapped to GO. Correct. Supporting Evidence: PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. PMID:35563734 the last step of lysine biosynthesis occurs in peroxisomes by the saccharopine dehydrogenase enzyme, Lys1 (Lysine requiring 1) [50], which possesses a PTS1 motif with high affinity to Pex5 [51]. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: RCA from the YeastPathways lysine degradation diagram assigns cytosol to Lys1 by default. Native Lys1 carries a PTS1 and is imported into the peroxisomal matrix via Pex5; it is cytosolic only when the PTS1 is masked or peroxisome import fails. The location should be the peroxisomal matrix. Proposed replacements: peroxisomal matrix Supporting Evidence: PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. PMID:35563734 the last step of lysine biosynthesis occurs in peroxisomes by the saccharopine dehydrogenase enzyme, Lys1 (Lysine requiring 1) [50], which possesses a PTS1 motif with high affinity to Pex5 [51]. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: RCA from YeastPathways LYSINE-AMINOAD-PWY-2 assigns cytosol to every pathway enzyme. For Lys1 this is incorrect for the wild-type protein: the last step of lysine biosynthesis occurs in the peroxisomal matrix (PTS1/Pex5-dependent import). Replace with peroxisomal matrix. Proposed replacements: peroxisomal matrix Supporting Evidence: PMID:28928432 Indeed GFP-Lys1p localises to peroxisomes but GFP-Lys12p does not. PMID:35563734 the last step of lysine biosynthesis occurs in peroxisomes by the saccharopine dehydrogenase enzyme, Lys1 (Lysine requiring 1) [50], which possesses a PTS1 motif with high affinity to Pex5 [51]. |
| GO:0009085 L-lysine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Lysine biosynthesis via the alpha-aminoadipate pathway; Lys1 catalyses its final step. PTN000875292 is the fungal LYS1/lys3 PAINT node, separate from the LYS9/lys9 biosynthetic node and from the animal/plant lysine-catabolic AASS branches. Supporting Evidence: file:yeast/LYS1/LYS1-uniprot.txt (AAA) pathway for lysine biosynthesis. PMID:28928432 Saccharopine dehydrogenase, encoded by the LYS1 gene, requires NAD+ for the production of lysine. |
| GO:0009085 L-lysine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: IEA from InterPro/UniPathway mapping (L-lysine biosynthesis via AAA pathway, step 3/3 of the fungal route). Correct for Lys1. Supporting Evidence: file:yeast/LYS1/LYS1-uniprot.txt (AAA) pathway for lysine biosynthesis. PMID:28928432 Saccharopine dehydrogenase, encoded by the LYS1 gene, requires NAD+ for the production of lysine. |
| GO:0009085 L-lysine biosynthetic process | IMP PMID:17247984 Chromosome Mapping in Saccharomyces: Centromere-Linked Genes... | ACCEPT | Summary: Hawthorne and Mortimer (1960) mapped lys1 as a centromere-linked lysine auxotrophic locus; lys1 mutants require lysine. Only the title is cached; the auxotrophy is the classical genetic definition of LYS1. Supporting Evidence: PMID:17247984 Chromosome Mapping in Saccharomyces: Centromere-Linked Genes. file:yeast/LYS1/LYS1-uniprot.txt (AAA) pathway for lysine biosynthesis. PMID:28928432 Saccharopine dehydrogenase, encoded by the LYS1 gene, requires NAD+ for the production of lysine. |
| GO:0009085 L-lysine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways LYSINE-AMINOAD-PWY-2; Lys1 performs the final saccharopine -> lysine step. Correct. Supporting Evidence: file:yeast/LYS1/LYS1-uniprot.txt (AAA) pathway for lysine biosynthesis. PMID:28928432 Saccharopine dehydrogenase, encoded by the LYS1 gene, requires NAD+ for the production of lysine. |
| GO:0016558 protein import into peroxisome matrix | IMP PMID:35563734 Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulati... | KEEP AS NON CORE | Summary: Peroxisomal import of the PTS1-lacking matrix protein Pls1 (Ynl097c-b) requires Lys1: in lys1 deletion cells Pls1 is not peroxisomal, and Lys1 overexpression drives Pls1 into peroxisomes, consistent with Pls1 piggy-backing on PTS1-bearing Lys1. The acts_upstream_of_or_within qualifier is appropriate; this is a cargo-specific consequence of the Lys1-Pls1 relationship, not a general role in peroxisomal import. Supporting Evidence: PMID:35563734 Indeed, in LYS1-deleted cells, Ynl097c-b did not localize to peroxisomes in neither control nor lysine-deprived media PMID:35563734 Indeed, when we overexpressed Lys1, Ynl097c-b was localized to peroxisomes regardless of the media |
| GO:0019477 L-lysine catabolic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: Generated from the YeastPathways lysine degradation diagram (LYSDEGII-PWY), which uses the reverse saccharopine dehydrogenase reaction (lysine + 2-oxoglutarate -> saccharopine). Lys1 can catalyse the reverse reaction in vitro, but the experimentally characterised physiological role of Lys1 is the lysine-forming direction, and no S. cerevisiae evidence reviewed here shows Lys1-dependent lysine catabolism. Lysine degradation via saccharopine is the role of the bifunctional AASS-type enzymes in plants and animals. Supporting Evidence: PMID:35563734 Lys1 can convert saccharopine to lysine or the reverse reaction depending on the local pH in the active site PMID:17002315 suggesting the ordered addition of nicotinamide adenine dinucleotide (NAD) followed by saccharopine in the physiologic reaction direction |
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Download this section (compressed HTML)Q: Does Lys1 contribute to lysine catabolism in S. cerevisiae under any condition (e.g. lysine excess), or is the reverse saccharopine-forming reaction physiologically irrelevant in this yeast?
Q: Is the mRNA binding of Lys1 (>1,000 transcripts, enriched for membrane-protein mRNAs) functionally relevant, and does it occur in the cytosol before peroxisomal import?
Saccharopine dehydrogenase (NAD+, L-lysine-forming); catalyzes the conversion of saccharopine to L-lysine, which is the final step in the lysine biosynthesis pathway; contains mRNA binding activity; required for targeting of Pls1p to the peroxisomal matrix in the absence of lysine
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