TEAD1 (human, P28347) - curation notes

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environment). These notes were written manually from the cached publications in
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-deep-research-*.md file exists for this gene.

Identity and domains

• TEA domain DNA-binding transcription factor (TEF-1); four human paralogs TEAD1-4.
• Domain layout: PMID:20123905.
• Motif: UniProt FUNCTION: binds "SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates" transcription; also the M-CAT motif.
• Mouse mTEF-1 is the ubiquitous M-CAT (A element) binding factor of the beta-MHC promoter
  PMID:8396764 (abstract only).
• Disease: Sveinsson chorioretinal atrophy, TEAD1 Y406H, in the YAP-binding interface.

Core function: DNA-binding partner of YAP/TAZ

• PMID:18579750
• ChIP-on-chip: PMID:18579750.
• CTGF reporter: PMID:18579750.
• Paralog caveat: the knockdowns used one shRNA against three paralogs
  PMID:18579750.
  TEAD1 was not in the Gal4-TF screen library and was tested separately
  PMID:18579750.
  TEAD1-specific evidence is ChIP, reporter, dominant-negative TEAD1-deltaC and the TEAD1 fusion experiments.
• TAZ: all four TEADs co-purify with TAZ PMID:19324877;
  TEAD1 activated by TAZ separately; TEAD3/4 more potently than TEAD1/2. The CTGF-promoter dominant
  negative is TEAD1-deltaC PMID:19324877.
• Structure (YAP 50-171 with TEAD1 194-411, PDB 3KYS): PMID:20123905;
  Y406 is the key TEAD1 residue PMID:20123905.
• Cofactors: VGLL4 PMID:15140898;
  fly Vestigial PMID:9869635.
• miR-222 promoter in gastric cancer cells (TEAD1-specific siRNA + ChIP):
  PMID:26045994.
• PTM: AARS1 lactylates TEAD1 K108 PMID:38512451.

GO-CAM

gocams/index.tsv has TEAD1 in two human models: 6690711d00001771 (AARS1 mediates
lactylation of YAP1 and TEAD1, promoting activation of Hippo signaling) and
6690711d00001806 (SIRT1 delactylation). In both, TEAD1 is typed as GO:0003700
DNA-binding transcription factor activity, part of GO:0035329 hippo signaling, in
GO:0005634 nucleus. Consistent with the core functions chosen here.

Ancestral vs animal-specific

• Ancestral, pre-Holozoa: TEA-domain DNA-binding TF activity. TEAD family members exist in
  fungi PMID:38729842.
  The PAINT IBA node PTN000216669 includes yeast TEC1 (SGD:S000000287) among donors, consistent with this.
• Ancestral, Holozoa: docking of a Yorkie-type coactivator. Holozoan Sd/TEAD homologs keep the YAP-binding tyrosine
  PMID:22832104;
  Capsaspora Co-Sd and Co-Yki co-IP and co-activate a Hippo-responsive reporter in fly cells
  PMID:22832104;
  PMID:22832104.
  In Capsaspora itself, hyperactive coYki phenotypes need the TEAD-binding residue
  PMID:38517944
  (indirect: coSd was not perturbed). A VGLL4/Tgi ortholog is also in Capsaspora
  PMID:38729842.
  The review frames TEAD as predating Yorkie, with Yorkie joining the two modules
  PMID:38729842.
• Choanoflagellates: PMID:38729842 does not report TEAD experiments in choanoflagellates; it notes that
  their Yorkie TEAD-binding helices are poorly conserved and
  PMID:38729842.
• Animal-specific: growth/proliferation control and organ development. In Capsaspora,
  PMID:38729842,
  so the proliferation output of YAP/TAZ-TEAD is not evidently ancestral. Embryonic organ development
  (IBA on PTN000931329) and cardiac/muscle roles are animal recruitments.

Decisions summary

• ACCEPT: DNA-binding TF activity rows (IBA/ISA/IDA/IMP/IEA), cis-regulatory DNA binding, activator activity,
  hippo signaling (all 5 rows; GO convention places the TEAD effectors here), TEAD-YAP complex, nucleus/nucleoplasm/chromatin,
  transcription regulator complex, positive regulation of transcription.
• MODIFY: DNA binding (TAS) -> GO:0000978; positive regulation of cell growth -> GO:0008284 (assays measure cell number);
  protein binding with YAP1/WWTR1/Vg -> GO:0001223 transcription coactivator binding; with VGLL4 -> GO:0001221.
• REMOVE: protein binding with RAD51 (2 BioPlex rows) and PFKM-only row (uninformative).
• KEEP_AS_NON_CORE: embryonic organ development (IBA), positive regulation of miRNA transcription.
• MARK_AS_OVER_ANNOTATED: protein-containing complex assembly (IMP).
• PMID:28473536 (methyl-SELEX): cached text has no TEAD1 result; accepted, deferring to the curator.