PAC1 (S. cerevisiae, P39946) review notes

2026-09-27 initial review (claude-code)

Context: yeast LIS1 ortholog, comparative member of modules/nucleokinesis.yaml (human PAFAH1B1 reviewed).

Key evidence
- Pac1 in dynein/dynactin pathway; required for MT sliding along bud cortex and spindle movement; at MT plus ends; targets dynein to plus ends PMID:12566428. Commentary PMID:12566423.
- Ndl1 needed for efficient Pac1 plus-end targeting; Pac1-Ndl1 co-IP PMID:15965467.
- Lis1 binds motor at AAA ring/stalk interface; "clutch" PMID:22939623; structure and yeast mutants PMID:34994688.
- Stabilizes uninhibited dynein PMID:32341548; Num1 relieves Pac1-mediated inhibition at cortex PMID:26483554.
- Motor domain targets dynein to plus ends in Pac1-dependent manner PMID:19185494.
- Falcon deep research (PAC1-deep-research-falcon.md) consistent: non-catalytic dimeric dynein regulator; used as supporting text for dynein complex binding and core function.

Decisions
- NEW GO:0140659 cytoskeletal motor regulator activity (IDA PMID:22939623), NEW GO:0035371 microtubule plus-end.
- Core BPs: nuclear migration along MT (IMP), spindle orientation (IEA accepted), microtubule sliding (IEA accepted; directly supported in yeast).
- Nucleus IDA (PMID:15965467) and IEA: KEEP_AS_NON_CORE - no explicit statement in cached text, but SGD and UniProt both extracted it from this paper (likely IF figures); no nuclear function known.
- Spindle pole IEA: UNDECIDED - Pac1 required for dynein SPB localization, Pac1 itself not shown at SPB in cached papers.
- Protein binding rows (Kel1, Nnf1, Rsc4; large-scale screens) removed as uninformative.
- Identical protein binding (dimerization) kept non-core.
- MT plus-end binding IDA kept non-core (localization evidence; partly Ndl1/Bik1-dependent).

2026-09-28 IBA/new-literature re-review

• Current PAC1 GOA has two GO_REF:0000033 IBA rows, both for cellular-component
  localization. PANTHER:PTN008687761 transfers GO:0005737 cytoplasm; this is broad but
  correct for cytoplasmic Pac1/LIS1. PANTHER:PTN002891245 transfers
  GO:0015630 microtubule cytoskeleton; this is also correct and includes the direct
  yeast Pac1 plus-end localization evidence as a PAINT descendant source, which is expected
  rather than circular.
• No IBA rows currently assert Pac1's direct dynein-regulator molecular activity; the review
  should keep the proposed GO:0140659 cytoskeletal motor regulator activity row.
• Searched for newer PAC1/Lis1 literature and cached the final peer-reviewed version of the
  2025 Geohring et al. preprint as PMID:41571912. The 2026 Nature Chemical Biology paper
  directly refines Pac1 mechanism by showing that nucleotide states in AAA1, AAA3 and AAA4
  tune Pac1 binding stoichiometry and that the 1 dynein:1 Pac1-dimer state opens/stabilizes
  uninhibited dynein through Pac1-linker contacts required for in-cell spindle movement.