PPN1 notes

2026-11-06

• Fetched the S. cerevisiae PPN1 review seed with just fetch-gene yeast PPN1 --uniprot-id Q04119; symbol lookup timed out twice, but the reviewed UniProt accession fetched cleanly.
• The default Falcon deep-research provider was unavailable in this checkout: just deep-research yeast PPN1 --provider falcon reported that only claude_code was configured. I therefore used the cached GOA publications, UniProt record, PANTHER PAINT slice and manual publication search for this pass.
• The GOA molecular-function rows are well supported. Sethuraman et al. cloned PPN1, matched purified Ppn1 peptides to YDR452W, showed a 25-fold activity increase on overexpression and loss of Ppn1 activity after PPN1 disruption PMID:11447286. Shi and Kornberg purified mature, proteolytically processed Ppn1 and confirmed long-chain polyphosphate cleavage by the homogeneous enzyme PMID:15792812. Andreeva et al. later compared purified yeast Ppn1, Ppn2, Ppx1 and Ddp1 and found that Ppn1 has both high exopolyphosphatase activity and endopolyphosphatase activity PMID:31175919.
• The older cytosolic exopolyphosphatase study PMID:15170373 purified the high-molecular-mass activity before it had been assigned to a gene. The follow-up paper identifies the high-molecular-mass cytosolic exopolyphosphatase as a PPN1 gene product PMID:17009950, so the 2004 GOA row can be accepted with the 2006 assignment as additional evidence.
• Gerasimaitė et al. purified recombinant Ppn1 and showed the same enzyme can be biased toward terminal phosphate release by Co2+ or internal polyP fragmentation by Mg2+, with additional ADP/arginine/ATP modulation of the Mg2+-dependent endopolyphosphatase mode PMID:25742176. The in vitro switch sharpens the remaining question to whether these cation/metabolite regimes occur in native vacuolar and cytosolic Ppn1 pools in vivo.
• Reggiori and Pelham treat Phm5/Ppn1 as a membrane cargo protein sorted into multivesicular-body internal vesicles en route to the vacuole, with ubiquitination of the cytosolic tail controlling whether it reaches the vacuolar interior or accumulates on the vacuolar membrane PMID:11566881. I kept the fungal-type vacuole membrane rows as non-core and represented the main catalytic site at GO:0000324 fungal-type vacuole.
• The nuclear annotation is the only unresolved row. The cached record for PMID:16862600 is abstract-only; it states that PPN1 inactivation eliminates the nuclear exopolyphosphatase activity, but the abstract does not prove that Ppn1 protein enters nuclei rather than controlling the nuclear activity indirectly.
• PAINT PTN000818947 is a compact fungal PPN1 node. It carries IBD rows for GO:0000298 endopolyphosphatase activity, GO:0004309 exopolyphosphatase activity, GO:0000324 fungal-type vacuole and GO:0006798 polyphosphate catabolic process, and 2026 IRDs prune the metazoan GO:0008081 phosphoric diester hydrolase activity and GO:0005576 extracellular region assertions at the fungal node. The WITH/FROM self-seed SGD:S000002860 is the experimental grounding used to place the IBD, not circular evidence. The second seed, CGD:CAL0000182615, is a Candida albicans identifier rather than the C. glabrata CANGA/PPN1 member.
• A newer 2025 systematic engineering study found that deleting PPN1 increases cellular polyphosphate, chose ppn1 as the starting deletion because it improved chain length and cellular polyP, and got the highest intracellular polyP in a ppn1 vip1 double mutant PMID:40291979. This is modern in vivo support for Ppn1 as a polyP catabolic enzyme, but it does not change the term choices.
• A 2025 FRET assay paper uses known vacuolar PPN1, vacuolar PPN2 and cytosolic DDP1 biology as background, then finds an additional Mn2+-dependent endopolyphosphatase activity in a quadruple yeast mutant PMID:40607052. It does not refute the PPN1 assignments and suggests the PPN1 family is not the last unidentified yeast endopolyphosphatase activity.
• The SGD hand-written description fetched from Alliance summarizes the dual endo/exopolyphosphatase biology and vacuolar/cytosolic/nuclear localization. Its "homodimer" statement conflicts with the UniProt SUBUNIT line that curates Ppn1 as a homotetramer from PMID:15792812; the review records this as a structured source_defects query for SGD to check.