Oncofusion

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Proteinestablished confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.Qn-nup98-family

TOP1 domain architecture (UniProt P11387)

also called TOP1 · DNA topoisomerase 1

TOP1 is the enzyme partner in the NUP98::TOP1 fusion. Its business end is a single large catalytic region in the back half of the protein, and the fusion keeps all of it, including the exact amino acid that cuts DNA.

The same thing, for a scientist

Reference domain architecture for TOP1 (UniProt P11387, 765 aa). The **Topo IB-type catalytic domain spans 432-765** and contains the **catalytic active site at Tyr723**, which forms the O-(3'-phospho-DNA)-tyrosine intermediate. The N-terminal 199 residues are annotated disordered. Several DNA-interaction sites are annotated as single residues (316, 364, 412, 443, 501, 532, 574, 632, 650) and as short regions (425-426, 488-493, 585-587); single residues are recorded in `data.sites` rather than as domains so that a one-residue lane is never drawn. Created so the 3D fusion viewer can resolve `fusion-nup98-top1`, whose lane previously had no coordinates for the 3' partner. The fusion's junction is NUP98 exon 13 to TOP1 exon 8 in all ten reported cases, which retains the catalytic domain intact.

What it looks like
DNA topoisomerase 1765 aa
Topo IB-type catalyticTopo IB-type catalytic · residues 432–765 · UniProt feature call, fetched this session.0200400600
loading AF-P11387-F1…
AlphaFold AF-P11387-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
How this accession was resolved

UniProt's gene_exact: search matches synonyms, so a search hit is not proof of identity. This entry was built by fetching https://rest.uniprot.org/uniprotkb/P11387.json directly and reading back the primary gene name from genes[0].geneName.value (TOP1) and the length from sequence.length (765 aa), then copying every feature boundary out of the same fetched record 1.

UniProt lists no gene-name synonyms for TOP1. The catalytic Tyr723 is recorded in data.active_site, not as a domain, because a single residue is not drawable as a lane.

Facts and figures
uniprotP11387
gene symbolTOP1
length AA765
protein nameDNA topoisomerase 1
alphafold IDAF-P11387-F1
resolution noteFetched from the UniProt REST API this session; primary gene name asserted from genes[0].geneName.value, not from a gene_exact search, which matches synonyms.
uniprot gene name synonyms
[]
domains
[
  {
    "name": "Topo IB-type catalytic",
    "start": 432,
    "end": 765,
    "feature_type": "Domain",
    "note": "UniProt feature call, fetched this session.",
    "boundary_precision": "firm"
  }
]
disordered regions
[
  {
    "start": 1,
    "end": 199
  }
]
active site
{
  "residue": 723,
  "description": "O-(3'-phospho-DNA)-tyrosine intermediate"
}
sites
{
  "dna_interaction_residues": [
    316,
    364,
    412,
    443,
    501,
    532,
    574,
    632,
    650
  ],
  "dna_interaction_regions": [
    [
      425,
      426
    ],
    [
      488,
      493
    ],
    [
      585,
      587
    ]
  ],
  "note": "Single residues are recorded here, not in domains[], so no one-residue lane is drawn."
}
How this could bite us back
  • Drawing a domain map implies the domains are what matter; in at least one NUP98 partner the annotated enzymatic domain was a passenger and a short unannotated interaction stretch did the work, so a tidy lane can mislead about mechanism.
Still open
  1. Which residue of TOP1 does the patient fusion breakpoint fall on? The founding reports describe the junction at exon or domain level, not residue level.
  2. Are any of these domains dispensable for transformation in the fusion context? No separation-of-function mutant of this partner has been reported within the fusion.
Every source behind this entry (1)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    TOP1 is UniProt P11387, 765 aa (DNA topoisomerase 1), with the domain boundaries listed in data.domains.

    UniProtKB entry P11387, DNA topoisomerase 1 (TOP1) · UniProt Consortium · UniProtKB 2026
    What this evidence cannot show

    Primary gene name and sequence length were read back from the fetched record rather than assumed from a search result. UniProt feature boundaries are curated from primary literature of varying age and are revised; they are reference coordinates for drawing, not experimental measurements of this fusion.

    Evidence that argues against this (2)
    • Retaining the catalytic domain does not establish that the catalytic activity is used by the fusion. No catalytically dead (Tyr723Phe) NUP98-TOP1 construct has been reported, and in the sister NUP98::DDX10 fusion the annotated enzymatic function turned out to be a passenger. Shima Y et al. 2025
    • The domain boundary 432-765 covers 44% of the protein and is a single UniProt call; finer structural work divides the topoisomerase I catalytic region into core and C-terminal subdomains, so a single lane understates the internal architecture. Ahuja HG et al. 1999
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