tbx5a (Q9IAK8) notes

Setup and provenance

• Gene fetched earlier with just fetch-gene on Q9IAK8 (Swiss-Prot). That accession holds all 91 GOA rows.
  The genes were not re-fetched.
• Deep research failed. Edison returned 402 Payment Required and the OpenAI key is invalid. It was not
  retried. There is no -deep-research-*.md file. The literature research below was done by hand from the
  cached publications and from Europe PMC searches ("tbx5b AND zebrafish", "tbx5a AND tbx5b",
  "tbx5 AND teleost AND duplicat*").
• Extra PMIDs fetched for the pair: 34756968, 30532148, 33482174, 29382818, 27503876, 39079985 (and
  25623069, which turned out to be about mouse isoforms and was not used).

Identity

• T-box transcription factor TBX5-A, 492 aa. T-box DNA-binding domain at residues 62-237 (UniProt). Synonyms:
  heartstrings (hst), tbx5, tbx5.1. ZFIN ZDB-GENE-991124-7.
• Teleost-genome-duplication (TGD) paralog of tbx5b. The two proteins share 49.2% identity over the full
  length (compare_pair.py) and 83% within the T-box
  PMID:39079985.

Alleles (important for interpreting phenotypes)

• hst (heartstrings): ENU nonsense allele, premature termination codon (PTC).
  PMID:12223419
  The transcript is lost after 32 hpf, as expected from nonsense-mediated decay
  PMID:27503876.
  Pi-Roig et al. argue it is hypomorphic for laterality
  PMID:24759614
• oug (oudegracht, hu6499): truncated inside the T-box.
  PMID:34372968
  Jogging is normal in this allele:
  PMID:34372968
• tpl58 gene trap: truncates the protein after 50 aa. The authors raise allele-dependent compensation:
  PMID:29933372
• CRISPR F0 knockouts: PMID:33416493
• No RNA-less (promoter-deletion) allele has been reported.

Function

• Pectoral fin initiation (copy-specific).
  PMID:12223419
  PMID:12066188
  PMID:12810598
  Fin-field migration:
  PMID:34756968
• Heart.
  PMID:12223419
  AV canal: PMID:34372968
  tbx2b: PMID:19895804
  Proepicardium: PMID:20413782
  Regeneration: PMID:29933372
• Regulators. Pdlim7 sequesters Tbx5 on actin
  PMID:19895804.
  Kctd10 represses it PMID:24430697.
• Molecular function. EMSA on the tbx2b enhancer
  PMID:18347092.
  The extracted text does not state the species of the Tbx5 construct used.
• Retina (shared with tbx5b, morpholino-only).
  PMID:24759614
• Not required for the swim bladder.
  PMID:30352852

Annotation decisions (summary)

• ACCEPT: MF (T-box DNA binding and transcription factor activity), nucleus, heart development, heart
  looping, heart morphogenesis, chamber morphogenesis, proepicardium, pectoral fin development and fin bud
  (limb bud) formation, the regulation-of-transcription terms, and NOT swim bladder development.
• UNDECIDED:
• heart jogging (IMP/IGI). Morpholino-only, and contradicted by the hst and oug mutants, which jog
  normally. The cause (off-target effect or compensation) is unresolved.
• GO:0061629 IPI with Kctd10. Kctd10 is not a DNA-binding TF, so the term probably belongs on kctd10.
  Only the abstract is cached.
• MODIFY: GO:0006351 DNA-templated transcription changed to GO:0006357.
• REMOVE: protein binding (uninformative).
• MARK_AS_OVER_ANNOTATED: cardiac left ventricle formation (IBA; teleosts have a single ventricle; given a
  propagation_review), epithelium development (ARBA), protein-containing complex.
• KEEP_AS_NON_CORE: cytoplasm and actin cytoskeleton (Pdlim7 sequestration), AV valve formation and AV
  junction remodeling, optic nerve and retina (double morphants), cardiac muscle cell differentiation (cBAF),
  pericardium morphogenesis, cardiac muscle tissue regeneration, cell fate specification, pattern specification.
• No NEW terms. The fin-initiation and heart terms already present are enough.