LYS1 (YIR034C, P38998) notes

Pathway context: YeastPathways LYSINE-AMINOAD-PWY-2, final step (EC 1.5.1.7, saccharopine dehydrogenase, NAD+, L-lysine-forming).

• Activity: NAD+-dependent cleavage of saccharopine to lysine + 2-oxoglutarate [UniProt:P38998]; kinetic mechanism of recombinant enzyme PMID:17002315, ordered addition of NAD then saccharopine PMID:17002315. Classical papers PMID:4287986, PMID:4318475 (title-only cache).
• Location: peroxisomal matrix via PTS1/Pex5 PMID:35563734; PMID:28928432. Peroxisomal NAD+ regeneration by Mdh3/Gpd1 shuttles needed; cytosolic Lys1 still works PMID:28928432.
• Pls1 (Ynl097c-b) import requires Lys1 PMID:35563734 -> IMP protein import into peroxisome matrix kept non-core.
• mRNA binding PMID:20844764 -> non-core.
• Decisions: RCA cytosol rows (two pathway diagrams) MODIFY -> peroxisomal matrix GO:0005782. RCA lysine catabolic process (LYSDEGII-PWY) marked over-annotated: reverse reaction possible PMID:35563734 but no yeast evidence of Lys1-dependent lysine degradation found. Protein binding (Rsp5 WW array) REMOVE.
• PTHR11133 PAINT review: PANTHER:PTN000123605 places generic GO:0004753
  on the broad eukaryotic saccharopine-dehydrogenase ancestor, while the
  fungal process nodes are split into PANTHER:PTN000875292 for the NAD(+),
  L-lysine-forming LYS1/lys3 branch and PANTHER:PTN000875327 for the
  reciprocal NADP(+), L-glutamate-forming LYS9/lys9 branch. S. cerevisiae LYS1
  is in PTHR11133:SF23, so the broad GO:0004753 IBA should be narrowed to
  GO:0004754.
• Newer-paper search: Kosir et al. 2026 used acetate-grown pex3 cells for
  peroxisome-deficiency metabolomics and found that lysine trended higher
  without a change in Lys1 abundance PMID:41612055. This adds pathway context
  for peroxisomal substrate/cofactor availability but no new Lys1 activity,
  localization, or annotation change.