YAP1 (human, P46937) - curation notes

Automated deep research was unavailable (no deep-research provider keys in this
environment). These notes were written by hand from the cached publications in
publications/ (several are abstract-only; see full_text_available:) and from the
sister reviews of Capsaspora coYki (genes/CAPO3/coYki/) and S. rosetta yorkie
(genes/SALRS/yorkie/). No -deep-research-*.md file exists for this gene.

Core molecular function

• YAP1 has no DNA-binding domain. It is a coactivator that pairs with TEADs
  PMID:20368466.
• TEADs are required for YAP-dependent transcription and growth
  PMID:18579750;
  PMID:18579750.
• Structure of YAP(50-171) bound to TEAD1
  PMID:20123905.
• WW domain-PPxY interactions: p73 PMID:11278685;
  PTPN14 PMID:22525271;
  angiomotins PMID:21187284.
• p73 coactivation after DNA damage
  PMID:18280240.

Regulation (Hippo pathway)

• LATS phosphorylation leads to cytoplasmic retention
  PMID:17974916;
  PMID:18158288.
• S127 phosphorylation leads to 14-3-3 binding, and a phosphodegron leads to degradation
  PMID:20048001.
• Junction and polarity sequestration: PMID:21145499;
  PMID:31835537.

Animal tissue-level roles (downstream, animal-specific)

• Epidermal stem cell proliferation via TEAD
  PMID:21376238.
• gp130/IL-6 family to Src/Yes to YAP in intestinal regeneration
  PMID:25731159.
• Organ size PMID:21808241.
• MSC fate (YAP1/TAZ together) PMID:29496737.
• Ciliogenesis (YAP/TAZ together) PMID:25849865.

Paralog caution: many studies (PMID:25849865, PMID:29496737, PMID:25796446,
PMID:21145499, PMID:35429439) manipulate YAP and TAZ (WWTR1) together. I accepted
those rows as YAP1 annotations in deference to the curators, but flagged the issue as
a suggested question.

Premetazoan evidence: what is ancestral vs animal-specific

• Ancestral (present in Capsaspora): TEAD binding and TEAD-dependent coactivation
  PMID:22832104;
  tandem WW domains and HXRXXS LATS sites PMID:38729842;
  regulation by cytoplasmic sequestration via the Hippo kinase cascade, and transcriptional
  output that depends on the TEAD interface PMID:38517944.
• Not ancestral, i.e. an animal recruitment: control of proliferation and organ size.
  PMID:35659869;
  PMID:38729842.
• Choanoflagellate caveat: srYki (S. rosetta) TBD is degenerate
  PMID:38729842.
  The repo's motif scan (genes/SALRS/yorkie/yorkie-bioinformatics/RESULTS.md) found no
  LxxLF or PxSFF TEAD-binding motif in F2UDK1. So YAP-TEAD coupling may have diverged or been
  lost in that lineage. This is inconclusive.

Interpretation for the GO annotations: GO:0003713, GO:0140297, GO:0140552, GO:0070064 and
GO:0035329 describe ancestral activities. The proliferation, organ-growth, regeneration
and differentiation process rows are animal-specific outputs. I kept them as non-core,
except for the IBA-supported positive regulation of epithelial cell proliferation, which I accepted.

GO-CAM

gocams/index.tsv lists YAP1 (P46937 / P46937-2) in 12 models. In most of them
(Hippo signaling core components; WWC2/WWC3 variants; MAP4K4; STRIPAK; contact
inhibition; AARS1/SIRT1 lactylation; GPR87) YAP1 is a transcription coregulator activity
node part_of hippo signaling in the nucleus. In the KRT14/KRT15 models (69c59f8a...) it is
transcription coactivator activity in positive regulation of keratinocyte proliferation.
In the ZDHHC7-SCRIB model (62900b6400001749) it is transcription coactivator activity in
polarized epithelial cell differentiation. That model is the source of the IC row for
GO:0030859, which I kept as non-core rather than removing.

Decision summary

• 164 protein binding IPI rows. Rows whose partners are DNA-binding TFs (TEADs, p73/p63,
  RUNX1, SMAD1, NFE2) are MODIFY to GO:0140297. Rows whose partners are 14-3-3 are MODIFY to
  GO:0071889. All others (mixed or regulatory partners, high-throughput screens) are REMOVE as
  uninformative; the interactions themselves are not disputed.
• REMOVE GO:0000976 and GO:0000978 (sequence-specific DNA binding): YAP1 lacks a DBD.
• MARK_AS_OVER_ANNOTATED: chromatin binding (indirect), heart process, protein-containing
  complex assembly (x2), negative regulation of gene expression.
• UNDECIDED (abstract only): GO:0000122 (PMID:25849865) and GO:0035331 (PMID:35429439).
• No NEW annotations proposed.