TBXT (Brachyury, O15178) review notes

Automated deep research was unavailable for this review (no deep-research provider
keys); these notes are compiled manually from the UniProt record, the GOA file, and the
cached publications in publications/. Full-text availability is noted per paper.

Sources read

Molecular function

• UniProt (by similarity to mouse P20293): binds the palindromic T site
  5'-TTCACACCTAGGTGTGAA-3' and activates transcription from it; T-box DNA-binding
  domain residues 51-219.
• Human/mouse direct target: PMID:21632880 -> GO:0000978, GO:0000981, GO:0045944, chromatin.
• Activator: PMID:22164283 Supports GO:0001228 (activator) as a more precise
  MF than GO:0000981; proposed as NEW.
• Human disease variant in the T-box impairs DNA binding: PMID:24253444
• Partner-TF interaction (secondary): PMID:22164283; the repression of Mixl1 does not use T
  sites PMID:22164283. This is the basis of the
  mouse IDA/IPI annotations (BHF-UCL) that were transferred to human by ISS
  (GO:0003714, GO:0000122, GO:0061629, GO:0000978). Kept as non-core; the corepressor
  claim is from overexpression reporter assays.

Location

• Nucleus: PMID:22611028; also cytoplasmic staining in invading tumour cells.

Biological process

• Mesoderm formation and axial development PMID:8963900;
  PMID:8963900
• Notochord: human SAVA syndrome with persistent notochordal canal (PMID:24253444);
  mouse T carries GO:0030903 notochord development by IMP (MGI, PMID:15384171,
  PMID:8155581, PMID:8293872; checked in QuickGO 2026-10-01). Human lacks this term in
  GOA, so it is proposed as NEW (comparator check: the mouse ortholog carries it by
  IMP; this is a gap in transfer, not a convention against TFs carrying the term).
• Cardiac: Brachyury acts upstream of MesP1 in cardiovascular progenitor specification
  PMID:21632880. Heart morphogenesis and cardiac myoblast differentiation are therefore
  indirect, early-mesoderm consequences; kept as non-core.
• Primitive streak formation (NAS PMID:18593560): the cached Mesp1 abstract does not
  mention Brachyury. Brachyury is expressed in the streak PMID:22164283. Kept as non-core rather than
  removed (full text not available; plausible biology).
• Signal transduction (NAS PMID:8963900): nothing in the abstract supports it; TBXT is a
  nuclear TF, not a signal transducer. Removed.

GO-CAM

gocams/index.tsv has no rows for TBXT / O15178 (checked 2026-10-01).

Premetazoan evolution (PMID:24043797, full text)

• T-box genes are of opisthokont origin; Brachyury is the oldest class: PMID:24043797
• Present in filastereans (Capsaspora, Ministeria), ichthyosporeans and early-branching
  fungi; lost in Dikarya and choanoflagellates: PMID:24043797 So no choanoflagellate Brachyury is known; the
  absence is interpreted as secondary loss.
• CoBra partially rescues dominant-negative XBra: PMID:24043797 The authors caution that the XBra_En construct
  may hit other T-box genes, and the Tbx7-class CoTbx3 rescues equally well.
• CoBra lacks target specificity: it strongly activates all mesendodermal genes,
  including chordin, which metazoan Brachyury (sponge, cnidarian, frog) does not
  activate ("pan-Tbox" behaviour).
• DNA-binding motif conserved: PMID:24043797
• Specificity mapped to the N- and C-terminal regions outside the T-box (chimera
  CoBra-XBra-CoBra behaves like CoBra), and attributed to cofactor interactions (e.g.
  Smad1, absent from Capsaspora).

Ancestral vs animal-specific for human TBXT:
- Ancestral (pre-metazoan, at least Holozoa/opisthokont): sequence-specific binding of
the T-box motif and the capacity to activate transcription from it (GO:0000978,
GO:0000981/GO:0001228, nucleus/chromatin).
- Animal-specific: target-gene specificity (restricted, cofactor-dependent target
set), and all developmental process roles (mesoderm formation, notochord
development, somitogenesis, primitive streak, cardiac progenitor specification).
Notochord roles are chordate-specific. Capsaspora is unicellular, so these process
terms cannot apply to CoBra; its endogenous function is unknown.