PAFAH1B1 (LIS1) review notes

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

Sources: UniProt P43034, cached GOA-cited publications, plus newly cached PMID:20403325 and PMID:22956769 (both verified via PubMed esummary). No Falcon deep-research file was present at review time.

Two separable roles:

  1. Dynein-1 regulator (core). LIS1 binds the dynein motor domain in the pre-powerstroke state and induces a persistent-force state PMID:20403325. Human cryo-EM defines the LIS1-dynein interface PMID:36692009. LIS1 also contacts dynactin p150 during complex assembly PMID:38547289. In migrating neurons it couples the nucleus to the centrosome PMID:15173193, and knockdown in rat progenitors abolishes interkinetic nuclear oscillations PMID:16144905.
  2. MF chosen: GO:0140659 cytoskeletal motor regulator activity (added as NEW; matches the nucleokinesis module). GO:0140660 activator was not used because LIS1 both promotes assembly and restrains motility depending on context.
  3. PAF-AH (I) beta subunit (non-catalytic). UniProt: "The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity". Crystal structure PMID:15572112. Captured with complex GO:0008247 (ACCEPT) and NEW GO:0030234 enzyme regulator activity; PAF metabolic/catabolic process kept as non-core (LIS1 does not catalyse).

Decisions of note:
- 21 protein-binding rows: 2 MODIFY (DYNC1H1 structural papers -> dynein heavy chain binding; + dynactin binding for PMID:38547289); rest REMOVE as uninformative.
- Behavioural/synaptic IMP/ISS rows from patient-mutation and Lis1+/- mouse papers marked over-annotated (indirect consequences of migration defects).
- Heparin binding (ISS from bovine IDA, PMID:8028668): UNDECIDED; abstract silent, likely purification behaviour.
- nuclear migration IEA: MODIFY to nuclear migration along microtubule + interkinetic nuclear migration.

Deep research (Falcon) incorporated

PAFAH1B1-deep-research-falcon.md arrived after the first pass. It agrees with the review: [file:human/PAFAH1B1/PAFAH1B1-deep-research-falcon.md "LIS1 acts upstream and during this assembly process rather than functioning as a permanent cargo adaptor."] and [ "LIS1 regulates or scaffolds the complex but is unnecessary for the chemical hydrolysis step"]. It also reports (via reviews, not verified here) that disrupting both PAF-AH catalytic subunits does not reproduce the LIS1 brain phenotype, consistent with treating the PAF-AH role as non-core for neuronal migration. It leans toward "activation factor"; retained the regulator parent (GO:0140659) and raised activator (GO:0140660) as a suggested question.