L-aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase Lys5 of Saccharomyces cerevisiae, a small (31 kDa) Sfp/AcpS-superfamily 4'-phosphopantetheinyl transferase (EC 2.7.8.7). Lys5 transfers the 4'-phosphopantetheine moiety of coenzyme A onto Ser880 in the peptidyl-carrier domain of the aminoadipate reductase Lys2, converting apo-Lys2 into the active holo-enzyme. Lys5 and Lys2 form a two-component system: without Lys5, Lys2 cannot load aminoadipate onto its PCP arm and the reduction of L-2-aminoadipate to the 6-semialdehyde in lysine biosynthesis does not occur, so lys5 mutants are lysine auxotrophs with the same aminoadipate-utilisation phenotype as lys2 mutants. Lys5 is a low-abundance cytosolic protein.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro (4'-phosphopantetheinyl transferase superfamily, ACPS domain) mapping to magnesium ion binding. PPTases of this superfamily use Mg2+ to coordinate the CoA pyrophosphate; plausible for Lys5 but not measured. A cofactor property only. Supporting Evidence: file:yeast/LYS5/LYS5-uniprot.txt SIMILARITY: Belongs to the P-Pant transferase superfamily. AcpS family. |
| GO:0005737 cytoplasm | TAS PMID:3928261 alpha-Aminoadipate pathway for the biosynthesis of lysine in... | MODIFY | Summary: Review of the yeast alpha-aminoadipate pathway listing the aminoadipate reductase system (Lys2 with Lys5) among the cytosolic steps. Cytosol, as asserted by the current PAINT IBA, is the more precise compartment. Reason: Bhattacharjee's pathway review describes the Lys2/Lys5 aminoadipate reductase system as one of the cytosolic lysine-biosynthesis steps, so the broad cytoplasm row should be replaced by GO:0005829 cytosol. Proposed replacements: cytosol Supporting Evidence: PMID:3928261 Five of the lysine enzymes are localized in mitochondria and three in cytosol. PMID:3928261 two unlinked gene functions required for each of AA reductase (LYS2 and LYS5) |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of cytosolic activity for the eukaryotic Sfp-type PPTase clade. Lys5 modifies the cytosolic enzyme Lys2, so cytosol is the expected site of action. Supporting Evidence: PMID:3928261 Five of the lysine enzymes are localized in mitochondria and three in cytosol. PMID:10320345 These results identify the Lys5/Lys2 pair as a two-component system in which Lys5 covalently primes Lys2, allowing alpha-aminoadipate reductase activity by holo-Lys2 with catalytic cycles of autoaminoacylation and reductive cleavage. |
| GO:0008897 holo-[acyl-carrier-protein] synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of 4'-phosphopantetheinyl transferase activity. The GO term definition explicitly covers peptidyl-carrier proteins and cites the Lys5 paper; it is the correct term for Lys5's transfer of phosphopantetheine from CoA to the Lys2 PCP domain. Supporting Evidence: PMID:10320345 Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis. PMID:10320345 The apo-PCP fragment was covalently modified to phosphopantetheinylated holo-PCP by pure Lys5 and CoASH |
| GO:0008897 holo-[acyl-carrier-protein] synthase activity | IDA PMID:10320345 Lysine biosynthesis in Saccharomyces cerevisiae: mechanism o... | ACCEPT | Summary: Purified Lys5 transferred 4'-phosphopantetheine from CoA to Ser880 of the Lys2 PCP fragment (Km about 1 uM for both PCP and CoA), converting apo-Lys2 to the active holo form. Direct demonstration of the core activity. Supporting Evidence: PMID:10320345 Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis. PMID:10320345 The apo-PCP fragment was covalently modified to phosphopantetheinylated holo-PCP by pure Lys5 and CoASH |
| GO:0008897 holo-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro ACPS/EC 2.7.8.7) consistent with the experimentally shown activity. Supporting Evidence: PMID:10320345 Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis. |
| GO:0009085 L-lysine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of lysine biosynthesis for the fungal Lys5 clade. Lys5 does part of the work of the pathway by installing the phosphopantetheine prosthetic group without which the Lys2 aminoadipate reductase step cannot occur; in effect it is a dedicated activating subunit of the reductase system. Supporting Evidence: PMID:10320345 These results identify the Lys5/Lys2 pair as a two-component system in which Lys5 covalently primes Lys2, allowing alpha-aminoadipate reductase activity by holo-Lys2 with catalytic cycles of autoaminoacylation and reductive cleavage. |
| GO:0009085 L-lysine biosynthetic process | IMP PMID:3921525 alpha-Aminoadipate as a primary nitrogen source for Saccharo... | ACCEPT | Summary: lys5 mutants, like lys2 mutants, are lysine auxotrophs blocked at the aminoadipate reductase step and can therefore use alpha-aminoadipate as a nitrogen source, the property used to select them. Supporting Evidence: PMID:3921525 lys2 and lys5 mutants contain blocks leading to the formation of this intermediate PMID:3921525 In contrast to wild-type strains of the yeast Saccharomyces cerevisiae, lys2 and lys5 mutants are able to utilize alpha-aminoadipate as a primary source of nitrogen. |
| GO:0051604 protein maturation | IBA GO_REF:0000033 | MODIFY | Summary: PAINT inference of protein maturation for the PPTase family. Lys5 performs the post-translational conversion of apo-Lys2 to its functional holo form, which fits the definition of protein maturation. The more specific process, protein phosphopantetheinylation (GO:0018215), is proposed as a new annotation. Reason: The PAINT protein-maturation inference is biologically sound for Lys5-mediated carrier-domain activation, but GO:0051604 groups many unrelated routes to protein maturation. Protein phosphopantetheinylation is the specific process executed by Lys5 and is already proposed here as GO:0018215. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000259224 · PTN000259224 SUPPORTS TRANSFER The PAINT node placement on the eukaryotic SF10 PPTase clade is sound; only the inherited process term is less specific than Lys5-catalyzed phosphopantetheinylation. Proposed replacements: protein phosphopantetheinylation Supporting Evidence: PMID:10320345 Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis. PMID:10320345 The apo-PCP fragment was covalently modified to phosphopantetheinylated holo-PCP by pure Lys5 and CoASH |
| GO:0018215 protein phosphopantetheinylation | IDA PMID:10320345 Lysine biosynthesis in Saccharomyces cerevisiae: mechanism o... | NEW | Summary: Proposed new annotation. Lys5 is the enzyme that catalyses phosphopantetheinylation of Lys2 Ser880, so it performs this protein-modification process itself. Reason: Lys5 performs the modification step (transfer of 4'-phosphopantetheine from CoA to the PCP serine), so this passes the 'who performs the step' test. Comparator check: Candida albicans LYS5 (Q59N08, CGD IDA/IGI) and Arabidopsis PPT (TAIR IDA) carry GO:0018215; S. cerevisiae LYS5 lacks it. GO:0018215 is a protein modification process and is not an ancestor or descendant of the existing protein maturation (GO:0051604) annotation. Supporting Evidence: PMID:10320345 Here, we show that the 31-kDa Lys5 is a specific posttranslational modification catalyst, using coenzyme A (CoASH) as a cosubstrate to phosphopantetheinylate Ser880 of the 155-kDa Lys2 and activate it for catalysis. PMID:10320345 The apo-PCP fragment was covalently modified to phosphopantetheinylated holo-PCP by pure Lys5 and CoASH |
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