LATS1 (human, O95835) review notes

Automated deep research was unavailable: no provider keys. These notes were compiled
by hand from the UniProt record, the cached publications in publications/, the
GO-CAM index and the PANTHER PAINT file. No *-deep-research-*.md file was created.

Core biology

• Hippo pathway effector kinase. LATS1 binds and phosphorylates YAP and keeps it in the cytoplasm
  PMID:18158288;
  the S127 site creates a 14-3-3 binding site
  PMID:22863277.
• Activation: WWC proteins bring LATS1/2 together with SAV1, which recruits MST1/2
  PMID:35429439.
  MOB1A and MOB1B are the LATS-binding coactivators
  PMID:19739119.
• Nuclear pool. CRL4-DCAF1 ubiquitylates and inhibits nuclear Lats1/2
  PMID:25026211.

Mitosis and cytokinesis (LATS1-specific literature)

• Localization: centrosome in interphase, then spindle poles, spindle and midbody in mitosis
  PMID:10518011.
• CDK1 regulation
  PMID:9988268.
• Ploidy and the tetraploidy checkpoint
  PMID:15122335.
• Cytokinesis via LIMK1
  PMID:15220930.

Other functions

• ERalpha degradation in breast epithelium, independent of kinase activity
  [PMID:28068668 "In the presence of LATS, ERα was targeted for ubiquitination and Ddb1-cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation.";
  PMID:28068668 "suggesting that the kinase activity of LATS1 is dispensable for ERα regulation"].
• NLRP3 inflammasome
  PMID:39173637.
• Wnt crosstalk via TAZ-DVL
  PMID:20412773.

GO-CAM

gocams/index.tsv lists LATS1 in 7 human models. In six Hippo models (core components; the
WWC2 and WWC3 variants; MAP4K4; STRIPAK/STRN4; TAZ cytoplasmic retention) it is
protein serine/threonine kinase activity, part of hippo signaling, in the cytoplasm. In
model 66e382fb00002738 (ZDHHC1-NLRP3) it is the kinase acting on NLRP3, part of
positive regulation of NLRP3 inflammasome complex assembly. This matches core function 1.

PAINT / IBA

PTHR24356 node PTN002390470 carries four IBDs that reach human LATS1:
- hippo signaling: seeds fly wts, mouse Lats1/2, human LATS1/2. ACCEPT; LATS1 is itself a
seed, which is expected and not circular.
- regulation of organ growth: seed mouse Lats2. KEEP_AS_NON_CORE for human.
- positive regulation of apoptotic process: seed fly wts only. KEEP_AS_NON_CORE, indirect.
- G1/S transition: seeds LATS2 only. MARK_AS_OVER_ANNOTATED for LATS1, a LATS2-specific
claim. Human LATS1 data concern the tetraploidy checkpoint.
The propagation audit (projects/ORIGINS_OF_MULTICELLULARITY/propagation-audit.md) found
these organ-growth, apoptosis and G1/S IBDs over-reach into choanoflagellate Warts. That is a
node-placement issue and does not decide the human rows.

Ancestral versus animal-specific

• Ancestral (premetazoan): Warts-dependent cytoplasmic retention of Yorkie. In Capsaspora,
  PMID:38517944.
  The kinase biochemistry is also conserved: a Fonticula Warts can replace LATS1/2 in mammalian cells
  PMID:38729842.
• Ancestral output looks cytoskeletal rather than proliferative
  [PMID:38517944 "Loss of coHpo or coWts does not increase cell proliferation, consistent with our previous conclusion that the Hippo pathway does not significantly affect proliferation in Capsaspora.";
  PMID:38729842 "these results suggest that the ancestral function of the Hippo pathway in unicellular organisms may have involved regulation of the cytoskeleton and not cell proliferation."].
  The human LATS1-LIMK1 cytokinesis axis is a cytoskeletal function, but no paper shows it
  directly descends from the premetazoan role. That remains a question.
• In S. rosetta, warts knockout enlarges rosettes but slows proliferation
  [DOI:10.1101/2024.07.13.603360 "warts pac1 cells grew into giant rosettes containing about twice as many cells as wild-type ones";
  DOI:10.1101/2024.07.13.603360 "On the other hand, hippopac1 and warts pac1 KO clones proliferated markedly slower"].
  This is a preprint.
• Animal-specific: proliferation and organ-size control
  PMID:38729842.
  The ERalpha, mammary-differentiation and NLRP3-inflammasome roles also involve
  vertebrate-specific partners. Their age has not been tested.

Decisions worth flagging

• 35 protein binding rows. 26 were REMOVEd as uninformative. 9 were MODIFYed: kinase partners
  (CDK1, CDK2, LIMK1, STK11, STK3, NUAK1) to protein kinase binding, SIAH2 to ubiquitin protein
  ligase binding, and ESR1 to nuclear receptor binding.
• GO:0030331 obsolete nuclear estrogen receptor binding: MODIFY to GO:0016922.
• The ISS nucleus row cites YAP1 (P46937) as WITH/FROM, which is an odd source. Kept as
  non-core because of the separate CRL4-DCAF1 nuclear-pool evidence.
• UNDECIDED: TGF-beta regulation (mouse ISS/IEA), and the synaptic terms from rat via Ensembl.
  The source papers are not cached.
• MARK_AS_OVER_ANNOTATED: hormone-mediated signaling, which comes from systemic phenotypes of
  Lats1 knockout mice.