coWts (Capsaspora owczarzaki Warts/LATS ortholog) - curation notes

Automated deep research was unavailable (no deep-research provider key in this
environment). These notes are built manually from the cached full-text papers in
publications/ and from database lookups (UniProt, NCBI, InterPro, PANTHER, QuickGO)
made on 2026-10-01. No -deep-research-*.md file exists for this gene.

Identity

• UniProt A0A0D2VGR4 (TrEMBL, unreviewed), 1205 aa; UniProt ORF name CAOG_000619;
  EMBL KJE89067.1; RefSeq XP_004365490.1.
• Phillips & Pan 2024 name the targeted gene "coWts" with locus CAOG_00619
  PMID:38517944.
• Mapping check (NCBI efetch, 2026-10-01): RefSeq XP_004365490.1 has
  /locus_tag="CAOG_00619" and /product="serine/threonine protein kinase lats";
  the EMBL protein KJE89067.1 has /locus_tag="CAOG_000619" and
  /product="AGC/NDR/LATS protein kinase". UniProt A0A0D2VGR4 cross-references both,
  so CAOG_00619 (old 5-digit tag) = CAOG_000619 (new tag) = A0A0D2VGR4.

Domain architecture (UniProt / InterPro)

• Long N-terminal region (~1-640) that is largely disordered/low complexity.
• CDD cd21774 "Mob-binding domain found in the large tumor suppressor (LATS)
  subfamily" at 646-706 (InterPro API) - the MOB-binding (NTR) region typical of
  NDR/LATS kinases.
• Protein kinase domain 711-1045 (PROSITE PS50011) with ATP-binding Lys 740 and
  catalytic proton acceptor Asp 834 (PROSITE rules); AGC-kinase C-terminal domain
  1046-1119; predicted hydrophobic-motif phosphothreonine at 1108.
• UniProt CAUTION: "Lacks conserved residue(s) required for the propagation of
  feature annotation" (PRU00618, AGC C-terminal rule) - this is about feature
  propagation, not loss of the catalytic residues, which are annotated as present.
• FunFam 3.30.200.20:FF:000391 "Large tumor suppressor kinase 1".
• Overall architecture (C-terminal kinase preceded by MOB-binding region) matches
  Warts/LATS, not the Rho-effector kinases (ROCK/MRCK/citron have N-terminal kinase
  domains followed by coiled-coil, CRIB/PH/CNH regions).

PANTHER placement - a Track C observation

• PANTHER/TreeGrafter places A0A0D2VGR4 in PTHR22988:SF71 "CITRON RHO-INTERACTING
  KINASE", family PTHR22988 "MYOTONIC DYSTROPHY S/T KINASE-RELATED" (InterPro
  IPR050839 "Rho-associated Serine/Threonine Kinase"), E=9.6e-122 over 693-1110.
• The human members of PTHR22988 in the PANTHER 19 tree (treeinfo API, human filter)
  are MRCK alpha/beta/gamma, ROCK1/2 and CIT - Rho effector kinases. Human LATS1
  (O95835) and LATS2 (Q9NRM7) are instead in PTHR24356 (SF138 and SF149).
• Drosophila Warts (Q9VA38) is also classified into PTHR22988 (SF76) by current
  InterPro/UniProt - so the Warts/LATS clade is split across the two PANTHER families.
• GOA's PAINT IBAs for LATS1/LATS2/wts come from PTN002390470 (hippo signaling,
  G1/S transition, etc.), a LATS node. coWts did not receive any of those; instead its
  TreeGrafter node is PTN001122925, which (QuickGO with/from search, 2012
  annotations) propagates protein serine/threonine kinase activity, cytoplasm,
  cytoskeleton and actomyosin structure organization to many fungal and other
  non-model proteins, with no model-organism (human, fly, mouse, yeasts) members.
  The actomyosin/cytoskeleton terms are characteristic of the ROCK/MRCK/citron
  family, so on coWts they are a product of the family-boundary placement rather than
  of anything known about Warts/LATS.

Experimental findings (Phillips & Pan 2024, eLife)

• Knockout: both alleles had the kinase domain replaced by selectable markers
  PMID:38517944.
• coYki localization: WT mScarlet-coYki is mostly cytoplasmic; coWts-/- cells show
  nuclear >= cytoplasmic signal
  PMID:38517944.
  coWts-/- has a stronger effect than coHpo-/-
  PMID:38517944.
  Authors' conclusion: PMID:38517944
• Not measured: coWts kinase activity, coYki phosphorylation (no phospho-specific
  blots or Phos-tag), direct coWts-coYki interaction, coHpo -> coWts phosphorylation,
  or coWts subcellular localization. Mechanism is inferred from the 4SA mutant: coYki
  with the four predicted Wts/LATS sites mutated is nuclear
  PMID:35659869.
• Proliferation: not increased; slower in shaking culture
  PMID:38517944.
• Cell shape: subpopulation of elongated, contractile cells, rescued by coWts transgene
  PMID:38517944.
• Actomyosin analysis (Lifeact F-actin fibre, blebbistatin, LatB) was done in the
  coHpo mutant and WT, not in coWts
  PMID:38517944.
  Myosin's role remains unclear
  PMID:38517944.
• Aggregates: coWts-/- aggregates are less circular, more densely packed, and coWts-/-
  cells have shorter filopodia within aggregates
  PMID:38517944
  PMID:38517944.
• Phenotypes are phenocopied by hyperactive coYki 4SA and require coYki's TEAD-binding
  residue, i.e. they run through coYki transcription
  PMID:38517944
  PMID:38517944.
  Epistasis could not be tested
  PMID:38517944.
• RNA-seq: 609 genes differentially expressed in coWts-/-; shared set with coHpo/coYki
  PMID:38517944.

Earlier work

• Sebé-Pedrós et al. 2012 tested Capsaspora Yki, Sd and Hpo in Drosophila; coWts was
  aligned but not functionally tested (no "Co-Wts" experiment in the full text)
  PMID:22832104.
  Co-Hpo phosphorylated Drosophila Wts in S2R+ cells, i.e. Co-Hpo can act on a Wts
  substrate, but this used Dm-Wts.
• Review (Phillips 2024 TIBS) summarises the coWts knockout
  PMID:38729842.

Annotation judgements (summary)

• Kinase MF terms: accept on domain grounds (intact Lys/Asp), activity not measured.
• GO:1900181 negative regulation of protein localization to nucleus: accept the IEA;
  the knockout gives IMP-grade support (coYki is the protein whose nuclear
  localization increases). A separate NEW IMP row was tried but the validator rejects
  NEW for a term already in GOA, so the evidence is recorded in the IEA row's review.
• GO:0035329 hippo signaling: NEW IMP. Warts is a core kinase of the cascade (it does
  a step of the pathway rather than being regulated by it); comparator: Drosophila wts
  and human LATS1/2 carry it (IDA/IGI/IBA). Readout (coYki cytoplasmic retention) was
  shown genetically; phosphorylation steps were not.
• Cytoskeleton / actomyosin structure organization / cytoskeleton organization: these
  are not supported for coWts itself; phenotypes run through coYki-dependent
  transcription, and the source node is a ROCK/citron-family PANTHER placement.
• No NEW term for cell shape, aggregate cell density, or proliferation: these are
  downstream, transcription-mediated effects (participation test fails), and no GO term
  exists for "cell packing density within aggregates".