Homocitrate synthase isozyme Lys21 (EC 2.3.3.14) of Saccharomyces cerevisiae, paralog of Lys20 in the alpha-isopropylmalate synthase/homocitrate synthase family. It condenses acetyl-CoA and 2-oxoglutarate to homocitrate, the first step of the alpha-aminoadipate pathway of lysine biosynthesis. Lys21 is strongly and allosterically inhibited by lysine (Ki about 0.05 mM), which also induces positive cooperativity for 2-oxoglutarate. During respiratory (ethanol) growth Lys21 supplies most of the homocitrate, whereas on glucose Lys20 and Lys21 are redundant. Although historically called the 'mitochondrial' isozyme, Lys21 has been localised experimentally to the nucleus, together with Lys20.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro (HMGL-like/DRE-TIM barrel) mapping to the root term catalytic activity. Uninformative; Lys21 has experimentally established homocitrate synthase activity. Proposed replacements: homocitrate synthase activity Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. PMID:18524920 lysine is a strong allosteric inhibitor of Lys21p |
| GO:0004410 homocitrate synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference for the fungal LYS20/LYS21 homocitrate synthase subfamily; Lys21 has its own biochemical evidence. Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. PMID:18524920 lysine is a strong allosteric inhibitor of Lys21p |
| GO:0004410 homocitrate synthase activity | IDA PMID:10103047 In Saccharomyces cerevisae, feedback inhibition of homocitra... | ACCEPT | Summary: Feller et al. characterised the two homocitrate synthase isozymes encoded by LYS20 and LYS21, including their different lysine sensitivities and feedback-resistant (fbr) alleles of each gene that desensitise the activity to lysine. Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. |
| GO:0004410 homocitrate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro/Rhea:12929/EC 2.3.3.14) matching the characterised activity. Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. PMID:18524920 lysine is a strong allosteric inhibitor of Lys21p |
| GO:0004410 homocitrate synthase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer from a characterised homocitrate synthase (UniProt cites O87198). Correct and consistent with direct yeast data. Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. PMID:18524920 lysine is a strong allosteric inhibitor of Lys21p |
| GO:0004410 homocitrate synthase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways LYSINE-AMINOAD-PWY-2 assigns the homocitrate synthase step to Lys21 as well as Lys20. Correct. Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. PMID:18524920 lysine is a strong allosteric inhibitor of Lys21p |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: The genome-wide in vivo PCA screen detected an interaction between Lys21 and its paralog Lys20 (with/from P48570). Mixed Lys20/Lys21 homocitrate synthase oligomers are plausible, as the isozymes are co-expressed and co-localised in the nucleus, but 'protein binding' conveys no functional information and no consequence of the interaction has been shown. Removal reflects the uninformative term, not doubt about the interaction. Supporting Evidence: PMID:18467557 We have performed a genome-wide in vivo screen for protein-protein interactions in Saccharomyces cerevisiae by means of a protein-fragment complementation assay (PCA). |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Proteome-wide affinity enrichment-mass spectrometry detected an interaction between Lys21 and its paralog Lys20 (with/from P48570). Mixed Lys20/Lys21 homocitrate synthase oligomers are plausible, as the isozymes are co-expressed and co-localised in the nucleus, but 'protein binding' conveys no functional information and no consequence of the interaction has been shown. Removal reflects the uninformative term, not doubt about the interaction. Supporting Evidence: PMID:37968396 Affinity purification coupled to mass spectrometry is an ideal tool for such mapping |
| GO:0005634 nucleus | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: High-throughput immunolocalisation called Lys21 nuclear, consistent with the targeted studies. Supporting Evidence: PMID:11914276 By high-throughput immunolocalization of tagged gene products, we have determined the subcellular localization of 2744 yeast proteins. PMID:9099739 Cell fractionation studies localize the 47- and 49-kDa proteins to the nucleus. |
| GO:0005634 nucleus | IDA PMID:9099739 Homocitrate synthase is located in the nucleus in the yeast ... | ACCEPT | Summary: Lys21 (YDL131w, 49 kDa) was identified by monoclonal antibodies against nuclear proteins and localised to the nucleus by immunofluorescence and fractionation. Supporting Evidence: PMID:9099739 Cell fractionation studies localize the 47- and 49-kDa proteins to the nucleus. PMID:9099739 corresponding to YDL182w (LYS20) and YDL131w in the Saccharomyces genome data base |
| GO:0005634 nucleus | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of nuclear location; matches two independent experimental studies. Supporting Evidence: PMID:9099739 Cell fractionation studies localize the 47- and 49-kDa proteins to the nucleus. PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Derived from the UniProt subcellular location 'Mitochondrion', which UniProt itself marks as inferred by curator (ECO:0000305) and which matches the historical name 'mitochondrial homocitrate synthase' from early fractionation of HCS activity. Two independent targeted studies place Lys21 in the nucleus, and unlike Lys20 it was not detected in the large mitochondrial proteome datasets annotated in GOA. The mitochondrial assignment is not supported by direct evidence for Lys21. Supporting Evidence: PMID:9099739 Cell fractionation studies localize the 47- and 49-kDa proteins to the nucleus. PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. file:yeast/LYS21/LYS21-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000305}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: Pathway-diagram default location from YeastPathways. A cytosolic pool of Lys21 is possible, but the experimentally established location is the nucleus. Supporting Evidence: PMID:9099739 Cell fractionation studies localize the 47- and 49-kDa proteins to the nucleus. PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | KEEP AS NON CORE | Summary: Predicted zinc-binding protein in a bioinformatic census of the yeast zinc proteome. Homocitrate synthases have an active-site divalent metal (UniProt lists Mg2+/Mn2+ by similarity); the physiological metal of Lys21 is not established. Plausible cofactor property, not a core function. Supporting Evidence: PMID:30358795 The yeast zinc proteome of 582 known or potential zinc-binding proteins was identified using a bioinformatics analysis that combined global domain searches with local motif searches. |
| GO:0009085 L-lysine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference for the homocitrate synthase clade. Lys21 catalyses the first step of lysine biosynthesis and is the dominant isozyme on non-fermentable carbon. Supporting Evidence: PMID:18524920 Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. |
| GO:0009085 L-lysine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/UniPathway mapping to lysine biosynthesis. Correct. Supporting Evidence: PMID:18524920 Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. |
| GO:0009085 L-lysine biosynthetic process | IGI PMID:18524920 Specialization of the paralogue LYS21 determines lysine bios... | ACCEPT | Summary: Genetic interaction with LYS20 (with/from S000002341): Quezada et al. compared single and double mutants and concluded that the two isozymes play redundant roles in lysine synthesis under fermentative growth. Supporting Evidence: PMID:18524920 Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. |
| GO:0009085 L-lysine biosynthetic process | IMP PMID:18524920 Specialization of the paralogue LYS21 determines lysine bios... | ACCEPT | Summary: Mutant analysis showed that during growth on ethanol homocitrate is made mainly through Lys21p, so loss of LYS21 compromises lysine synthesis under respiratory conditions. Supporting Evidence: PMID:18524920 Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. |
| GO:0009085 L-lysine biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways LYSINE-AMINOAD-PWY-2; Lys21 catalyses step 1. Correct. Supporting Evidence: PMID:18524920 Our results show that during growth on ethanol, homocitrate is mainly synthesized through Lys21p, while under fermentative metabolism, Lys20p and Lys21p play redundant roles. |
| GO:0046912 acyltransferase activity, acyl groups converted into alkyl on transfer | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to the EC 2.3.3 parent class. Correct but general; replace with the experimentally supported child, homocitrate synthase activity. Proposed replacements: homocitrate synthase activity Supporting Evidence: PMID:10103047 demonstrate that Saccharomyces cerevisiae possesses two genes, LYS20 and LYS21, encoding two homocitrate synthase isoenzymes which are located in the nucleus. PMID:10103047 Each isoform is inhibited by lysine with a different sensitivity. PMID:18524920 lysine is a strong allosteric inhibitor of Lys21p |
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Homocitrate synthase isozyme; catalyzes the condensation of acetyl-CoA and alpha-ketoglutarate to form homocitrate, which is the first step in the lysine biosynthesis pathway; LYS21 has a paralog, LYS20, that arose from the whole genome duplication
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