Proteinstrongking

CBFA2T3 (ETO2 / MTG16) domain architecture

also called CBFA2T3 · ETO2 / MTG16

CBFA2T3 is the 5' partner of the CBFA2T3::GLIS2 fusion of infant acute megakaryoblastic leukemia. This entry lists where each of its functional parts sits along the protein, measured as residue numbers, so the fusion diagrams can draw which parts survive the break and which are thrown away.

The same thing, for a scientist

Reference domain architecture for CBFA2T3 (UniProt O75081, 653 aa). An ETO-family corepressor. Its NHR2 region is the oligomerisation element in this protein family, and its C-terminal MYND zinc finger is the corepressor-recruitment module. Created so the 3D fusion viewer can resolve fusion-cbfa2t3-glis2, which previously had no coordinates for this partner and silently dropped the lane. Domain fate in the fusion is asserted by the fusion entry, not here.

What it looks like

Transcriptional corepressor CBFA2T3653 aa

loading AF-O75081-F1…

AlphaFold AF-O75081-F1 ↗

colourshape

This is a prediction, not a measurement. No one has seen this protein in this shape. The colours say how much the software trusts itself, and that is worth reading before anything else — the orange stretches are places the model is effectively saying this part has no fixed shape.

very high (90+)confident (70–90)low (50–70)very low (<50)

I have never read one of these pictures before

A protein is one long chain of amino acids that folds up. The ribbon traces that chain from one end to the other; it is not a wire, it is a simplification of where the backbone runs. Drag to rotate, scroll to zoom.

Domains are the stretches of chain that do a particular job, and they are what the coloured blocks above the picture mark out. Click one and the view flies to it. In this project the important question about any domain is usually whether the fusion still has it — the labels say lost where it does not.

Anything in yellow sticks is a bound small molecule, which is usually the drug.

Go deeper

Why this entry exists

The join checker reported fusion-cbfa2t3-glis2: no protein entry for CBFA2T3. Without coordinates the comparative 3D viewer cannot draw the lane at all, and it was omitting it without warning rather than flagging it. This is a reference-coordinate entry: it asserts the architecture and nothing about the fusion.

Folded domains versus functional regions. UniProt mixes two very different annotation kinds. Domain, Zinc finger and DNA binding are fold calls with real boundaries. Region is a functional assertion that often spans disorder and can overlap other regions or run for hundreds of residues. Both are recorded with boundary_precision marking which is which, because drawing a soft functional region as a crisp box is exactly the kind of false precision this graph exists to avoid.

Architecture

Part	Residues	Kind	Precision
TAFH	171-266	Domain	firm
MYND-type	556-592	Zinc finger	firm
Mediates localization to the nucleus	1-435	Region	soft
Mediates interaction with PDE7A (in isoform 2)	1-430	Region	soft
Required for nucleolar targeting (in isoform 1)	1-127	Region	soft
Interaction with ZBTB33	145-242	Region	soft
Interaction with HIF1A	176-268	Region	soft
Nervy homology region 2 (NHR2); essential for down-regulation of PFKFB3, PFKFB4 and PDK1 expression	394-412	Region	soft
Nervy homology region 3 (NHR3); essential for down-regulation of PFKFB3, PFKFB4 and PDK1 expression	485-533	Region	soft
Mediates interaction with PRKAR2A	485-506	Region	soft
Coiled coil	488-543	Coiled coil	soft

1 PDB entries reference this protein.

Facts and figures

uniprot	O75081
gene symbol	CBFA2T3
length AA	653
protein name	Transcriptional corepressor CBFA2T3
alphafold ID	AF-O75081-F1
n PDB total	1
uniprot verified	true
accession resolution	exact gene-name search, reviewed human only, gene symbol confirmed in the response
created for	fusion-cbfa2t3-glis2

domains

domains — the numbers behind the chart

[
  {
    "name": "TAFH",
    "start": 171,
    "end": 266,
    "feature_type": "Domain",
    "note": "UniProt folded-domain call.",
    "boundary_precision": "firm",
    "aliases": [
      "NHR1",
      "TAFH/NHR1",
      "NHR1 (TAF110-like)",
      "Nervy homology region 1"
    ],
    "alias_basis": "InterPro IPR003894 is named \"TAFH/NHR1\", establishing that the ETO-family TAFH domain and NHR1 are the same domain under two naming conventions."
  },
  {
    "name": "MYND-type",
    "start": 556,
    "end": 592,
    "feature_type": "Zinc finger",
    "note": "UniProt folded-domain call.",
    "boundary_precision": "firm"
  },
  {
    "name": "Mediates localization to the nucleus",
    "start": 1,
    "end": 435,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Mediates interaction with PDE7A (in isoform 2)",
    "start": 1,
    "end": 430,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Required for nucleolar targeting (in isoform 1)",
    "start": 1,
    "end": 127,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Interaction with ZBTB33",
    "start": 145,
    "end": 242,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Interaction with HIF1A",
    "start": 176,
    "end": 268,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Nervy homology region 2 (NHR2); essential for down-regulation of PFKFB3, PFKFB4 and PDK1 expression",
    "start": 394,
    "end": 412,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Nervy homology region 3 (NHR3); essential for down-regulation of PFKFB3, PFKFB4 and PDK1 expression",
    "start": 485,
    "end": 533,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Mediates interaction with PRKAR2A",
    "start": 485,
    "end": 506,
    "feature_type": "Region",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  },
  {
    "name": "Coiled coil",
    "start": 488,
    "end": 543,
    "feature_type": "Coiled coil",
    "note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
    "boundary_precision": "soft"
  }
]

PDB IDS

[
  "9DE2"
]

How this could bite us back

Nothing here licenses targeting any part of CBFA2T3. These are coordinates, not a druggability claim; a domain with crisp boundaries is not thereby a ligandable pocket.
Drawing UniProt `Region` features as boxes in the viewer risks implying structural knowledge that does not exist. They are marked soft and should be rendered differently from fold calls.

Still open

Where does the fusion-cbfa2t3-glis2 breakpoint fall relative to these boundaries, and is the junction codon actually mapped or only inferred from cDNA?
Which of these parts are retained in the fusion, and is retention ever being confused with requirement for transformation?
Do InterPro and the deposited crystal constructs agree with these UniProt boundaries? Where they do not, the disagreement should be recorded rather than silently resolved in UniProt's favour.

Every source behind this entry (1)

E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
Human CBFA2T3 (Transcriptional corepressor CBFA2T3) is 653 residues (UniProt O75081) with the domain and region boundaries tabulated in this entry, and is referenced by 1 PDB entries.
UniProtKB O75081 (CBFA2T3_HUMAN): sequence length, domain, zinc-finger, DNA-binding, repeat, motif and region features, and PDB cross-references · UniProt Consortium · UniProtKB 2026
What this evidence cannot show
Accession resolved by exact gene-name search restricted to reviewed human entries and confirmed against the gene symbol returned, because a previous lookup in this project silently resolved to the wrong gene. Coordinates are for the canonical isoform only; several of these proteins have isoforms that shift numbering. UniProt `Region` features are curator functional calls, not folds.
Evidence that argues against this (1)
- Domain boundaries are not a settled fact and differ between sources. InterPro, Pfam, SMART and individual crystal-structure constructs routinely disagree with UniProt by tens of residues, and published figures often use construct boundaries rather than database ones. Any downstream claim that a breakpoint falls just inside or just outside a domain is therefore only as firm as the boundary definition it assumes, which for every `Region` feature here is soft. InterPro Consortium 2026

Connected to

part of →CBFA2T3::GLIS2, inv(16)(p13.3q24.3)
reference domain coordinates for the CBFA2T3 side of this fusion
analogous to →RUNX1T1 (ETO / MTG8) domain architecture
ETO-family paralogues with the same TAFH / NHR2 / NHR3 / MYND architecture; both contribute the identical corepressor module to a different leukemia fusion