NPM1 (nucleophosmin) domain architecture
also called NPM1 · nucleophosmin
NPM1 is the 5' partner of NPM1::ALK anaplastic large cell lymphoma. 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 NPM1 (UniProt P06748, 294 aa). A nucleolar chaperone. UniProt annotates no folded domain at all, only functional regions and two nuclear localisation signals; the 243-294 region required for nucleolar localisation is the part most often invoked in fusion biology. Created so the 3D fusion viewer can resolve fusion-npm1-alk, 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.
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.
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.
Why this entry exists
The join checker reported fusion-npm1-alk: no protein entry for NPM1. 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 |
|---|---|---|---|
| Required for interaction with SENP3 | 1-186 | Region | soft |
| Necessary for interaction with APEX1 | 1-117 | Region | soft |
| Interaction with NOP2 | 187-215 | Region | soft |
| Required for nucleolar localization | 243-294 | Region | soft |
| Nuclear localization signal | 152-157 | Motif | soft |
| Nuclear localization signal | 191-197 | Motif | soft |
8 PDB entries reference this protein.
| uniprot | P06748 |
|---|---|
| gene symbol | NPM1 |
| length AA | 294 |
| protein name | Nucleophosmin |
| alphafold ID | AF-P06748-F1 |
| n PDB total | 8 |
| uniprot verified | true |
| accession resolution | exact gene-name search, reviewed human only, gene symbol confirmed in the response |
| created for | fusion-npm1-alk |
domains — the numbers behind the chart
[
{
"name": "Required for interaction with SENP3",
"start": 1,
"end": 186,
"feature_type": "Region",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
"boundary_precision": "soft"
},
{
"name": "N-terminal core / oligomerisation domain (beta-barrel)",
"start": 1,
"end": 117,
"feature_type": "Region",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence. UniProt annotates this span as 'Necessary for interaction with APEX1'; structurally it is the pentameric core beta-barrel (PDB 2P1B, residues 9-122 observed).",
"boundary_precision": "soft",
"aliases": [
"N-terminal core domain",
"NPM1 oligomerisation domain",
"core beta-barrel",
"nucleophosmin-core",
"oligomerization domain"
],
"alias_basis": "UniProt labels 1-117 'Necessary for interaction with APEX1', which is a binding annotation rather than a structural name, and the fusion entries refer to the same span as the oligomerisation domain. They are the same region: PDB 2P1B, 'Crystal structure of human nucleophosmin-core', resolves UniProt residues 9-122 and its primary paper is titled for the PENTAMER-PENTAMER interface (PMID 17879352, fetched 2026-09-19). Renamed and aliased so fusion-npm1-alk's 3' lane resolves; the UniProt wording is preserved in the note."
},
{
"name": "Interaction with NOP2",
"start": 187,
"end": 215,
"feature_type": "Region",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
"boundary_precision": "soft"
},
{
"name": "Required for nucleolar localization",
"start": 243,
"end": 294,
"feature_type": "Region",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
"boundary_precision": "soft"
},
{
"name": "Nuclear localization signal",
"start": 152,
"end": 157,
"feature_type": "Motif",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
"boundary_precision": "soft"
},
{
"name": "Nuclear localization signal",
"start": 191,
"end": 197,
"feature_type": "Motif",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
"boundary_precision": "soft"
}
]PDB IDS
[ "2LLH", "2P1B", "2VXD", "5EHD", "7OBG", "7OBH", "8AH2", "8AS5" ]
- Nothing here licenses targeting any part of NPM1. 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.
- Where does the fusion-npm1-alk 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.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
Human NPM1 (Nucleophosmin) is 294 residues (UniProt P06748) with the domain and region boundaries tabulated in this entry, and is referenced by 8 PDB entries.
UniProtKB P06748 (NPM1_HUMAN): sequence length, domain, zinc-finger, DNA-binding, repeat, motif and region features, and PDB cross-references · UniProt Consortium · UniProtKB 2026What 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
- E_npm1_core_oligomerisationestablished confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
The NPM1 N-terminal region spanning UniProt residues ~1-117 is the oligomerisation core: PDB 2P1B resolves residues 9-122 as the nucleophosmin-core, and the structure paper is titled for the plasticity of its pentamer-pentamer interface. This is the region retained in NPM1 fusions and responsible for their forced oligomerisation.
Crystal structure of human nucleophosmin-core reveals plasticity of the pentamer-pentamer interface · Lee HH, Kim HS, Kang JY, Lee BI, et al. · Proteins 69(3):672-8 2007What this evidence cannot show
Read as title and structure metadata rather than full text. 2P1B is a 2.75 A crystal structure and resolves 9-122, so the '1-117' boundary is the UniProt region annotation, not a structurally observed limit - the first eight residues are not seen. Pentamer and decamer states are both reported for nucleophosmin and the relevant oligomeric state in a fusion context is not settled by this entry.
Evidence that argues against this (1)
- Naming this span 'the oligomerisation domain' is a simplification the structure itself warns against: the paper's finding is that the pentamer-pentamer interface is PLASTIC, so the region mediates a variable assembly rather than one fixed oligomer. Treating it as a rigid module is exactly the error this graph made with the PML coiled coil, where a clean boundary turned out to be 106 residues short. Lee HH et al. 2007
where the new NES sits in the protein
Domain architecture of the same protein, including the nucleolar localisation signal disrupted by NPM1c.
- co-occurs with →ALK (anaplastic lymphoma kinase) domain architecture
the two halves of NPM1::ALK; their architectures are only interpretable together
- part of →NPM1::ALK (NPM-ALK), t(2;5)(p23;q35)
reference domain coordinates for the NPM1 side of this fusion