NSD1 (nuclear receptor-binding SET domain protein 1) domain architecture
also called NSD1 · nuclear receptor-binding SET domain protein 1
NSD1 is the 3' partner of NUP98::NSD1. 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 NSD1 (UniProt Q96L73, 2696 aa). An H3K36 methyltransferase. The catalytic AWS-SET-postSET cassette spans 1890-2082, preceded by four PHD fingers and two PWWP domains. Created so the 3D fusion viewer can resolve fusion-nup98-nsd1, 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-nup98-nsd1: no protein entry for NSD1. 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 |
|---|---|---|---|
| PWWP 1 | 323-388 | Domain | firm |
| PWWP 2 | 1756-1818 | Domain | firm |
| AWS | 1890-1940 | Domain | firm |
| SET | 1942-2059 | Domain | firm |
| Post-SET | 2066-2082 | Domain | firm |
| PHD-type 1 | 1543-1589 | Zinc finger | firm |
| PHD-type 2 | 1590-1646 | Zinc finger | firm |
| PHD-type 3 | 1707-1751 | Zinc finger | firm |
| PHD-type 4; atypical | 2118-2165 | Zinc finger | firm |
| Inhibits enzyme activity in the absence of bound histone | 2060-2066 | Region | soft |
4 PDB entries reference this protein.
| uniprot | Q96L73 |
|---|---|
| gene symbol | NSD1 |
| length AA | 2696 |
| protein name | Histone-lysine N-methyltransferase, H3 lysine-36 specific |
| alphafold ID | AF-Q96L73-F1 |
| n PDB total | 4 |
| uniprot verified | true |
| accession resolution | exact gene-name search, reviewed human only, gene symbol confirmed in the response |
| created for | fusion-nup98-nsd1 |
domains — the numbers behind the chart
[
{
"name": "PWWP 1",
"start": 323,
"end": 388,
"feature_type": "Domain",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "PWWP 2",
"start": 1756,
"end": 1818,
"feature_type": "Domain",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "AWS",
"start": 1890,
"end": 1940,
"feature_type": "Domain",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "SET",
"start": 1942,
"end": 2059,
"feature_type": "Domain",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "Post-SET",
"start": 2066,
"end": 2082,
"feature_type": "Domain",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "PHD-type 1",
"start": 1543,
"end": 1589,
"feature_type": "Zinc finger",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "PHD-type 2",
"start": 1590,
"end": 1646,
"feature_type": "Zinc finger",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "PHD-type 3",
"start": 1707,
"end": 1751,
"feature_type": "Zinc finger",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "PHD-type 4; atypical",
"start": 2118,
"end": 2165,
"feature_type": "Zinc finger",
"note": "UniProt folded-domain call.",
"boundary_precision": "firm"
},
{
"name": "Inhibits enzyme activity in the absence of bound histone",
"start": 2060,
"end": 2066,
"feature_type": "Region",
"note": "UniProt functional region, not a fold boundary. Soft edges; render as low confidence.",
"boundary_precision": "soft"
}
]PDB IDS
[ "3OOI", "6KQP", "6KQQ", "8C5L" ]
- Nothing here licenses targeting any part of NSD1. 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-nup98-nsd1 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 NSD1 (Histone-lysine N-methyltransferase, H3 lysine-36 specific) is 2696 residues (UniProt Q96L73) with the domain and region boundaries tabulated in this entry, and is referenced by 4 PDB entries.
UniProtKB Q96L73 (NSD1_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
Category error in the second half (Huang 2020, PMID 32868895): NSD1's SET domain is an autoinhibited CATALYTIC site needing covalent chemistry (BT5) to open a channel-like pocket, not a partner interface; and no KDM5A PHD-directed equivalent exists.
- part of →NUP98::NSD1, t(5;11)(q35;p15.5)
reference domain coordinates for the NSD1 side of this fusion
both are chromatin-modifying enzymes fused to the same 5' partner, NUP98, and both retain a reader module; a controlled comparison of what NUP98 contributes versus what the enzyme does