Protein record

NSD2

Histone-lysine N-methyltransferase NSD2

O96028 at UniProt

Homo sapiens1365 amino acidsannotation supported

2annotated cores in NSD2

19PDB entries with observed PWWP1 coordinates

7model records for PWWP1

26frozen v1.2 assay / association records for PWWP1

Canonical sequence · Source-mapped regions

Protein domain architecture

1365 residues

PWWP annotation cores, other annotated regions, and deposited construct mappings share the canonical amino acid axis. The original Atlas PWWP intervals retain their source definitions.

PWWP annotation coreOther source annotationPredicted candidate, when present

7 additional source-supported regions · coordinates and evidence

UniProt feature coordinates accepted after exact canonical sequence identity check against the frozen Atlas. Source annotations can be inferred by sequence or curated from experiments; evidence codes remain attached. Other domain types link to their UniProt source because the Atlas records PWWP domains.

Source feature	Type	Amino acids	Evidence
PHD-type 1	Zinc finger	667–713	ECO:0000255 PROSITE-ProRule: PRU00146
PHD-type 2	Zinc finger	714–770	ECO:0000255 PROSITE-ProRule: PRU00146
PHD-type 3	Zinc finger	831–875	ECO:0000255 PROSITE-ProRule: PRU00146
AWS	Domain	1011–1061	ECO:0000255 PROSITE-ProRule: PRU00562
SET	Domain	1063–1180	ECO:0000255 PROSITE-ProRule: PRU00190
Post-SET	Domain	1187–1203	ECO:0000255 PROSITE-ProRule: PRU00155
PHD-type 4; atypical	Zinc finger	1239–1286	ECO:0000255 PROSITE-ProRule: PRU00146

Deposited construct mapping

4 selected examples

Colored segments map deposited polymer sequences to this canonical protein; dark segments have observed coordinates. Unmapped tags and engineered residues are not assigned canonical positions. These are not certified whole-fold boundaries.

9FOCchain A208–368

Mapping and construct evidence

Deposited polymer length: 176 residues. Mapped sequence identity: 100.0%. sequence differences or tags detected; biological versus engineered origin requires review.

PWWP1: 65 / 65 annotation-core Cα residues observed.

Frozen SIFTS aligned regions with construct-to-UniProt sequence comparison. Bars are mapped canonical segments; tags, insertions, and unmapped termini are not assigned canonical positions. PDB source.

Unmapped construct positions: 1–4, 166–176.

5VC8chain B211–350

Mapping and construct evidence

Deposited polymer length: 141 residues. Mapped sequence identity: 100.0%. sequence differences or tags detected; biological versus engineered origin requires review.

PWWP1: 65 / 65 annotation-core Cα residues observed.

Unmapped construct positions: 1–1.

9Y60chain A202–368

Mapping and construct evidence

Deposited polymer length: 174 residues. Mapped sequence identity: 99.4%. sequence differences or tags detected; biological versus engineered origin requires review.

PWWP1: 65 / 65 annotation-core Cα residues observed.

Source-recorded sequence differences:

[
  {
    "construct": "A",
    "entity_position": 161,
    "reference": "K",
    "uniprot_position": 361
  }
]

Unmapped construct positions: 1–1, 169–174.

29HGchain B1–1365

Mapping and construct evidence

Deposited polymer length: 1365 residues. Mapped sequence identity: 100.0%. no sequence difference detected by mapping; not proof of wild type.

PWWP1: 65 / 65 annotation-core Cα residues observed.

One mapped example per native domain, preferring frozen experimental representatives; up to four distinct mapped intervals.

Validated isoform differences · 12 PWWP correspondence records

Only source-validated PWWP core correspondences from the frozen v1.2 isoform audit; other-domain architectures are not projected onto isoforms. Coordinates in the isoform column refer to the individual isoform sequence; deleted cores remain absent.

Isoform	Length	PWWP core	Source-mapped positions	Retention / source edits
O96028-2	713	PWWP1	None	absent Official deletion removes entire annotated core; incidental alignment matches cannot restore deleted residues. Official sequence edits VSP_021414 · canonical 1–652 · deletion VSP_021423 · canonical 653–712 · equal length replacement
O96028-2	713	PWWP2	228–290 63 / 63 mapped residues; span may contain gaps	complete
O96028-3	647	PWWP1	222–286 65 / 65 mapped residues; span may contain gaps	complete
O96028-3	647	PWWP2	None	absent Official deletion removes entire annotated core; incidental alignment matches cannot restore deleted residues. Official sequence edits VSP_021419 · canonical 628–647 · equal length replacement VSP_021422 · canonical 648–1365 · deletion
O96028-4	584	PWWP1	None	absent
O96028-4	584	PWWP2	99–161 63 / 63 mapped residues; span may contain gaps	complete
O96028-5	629	PWWP1	222–286 65 / 65 mapped residues; span may contain gaps	complete
O96028-5	629	PWWP2	None	absent
O96028-6	484	PWWP1	222–286 65 / 65 mapped residues; span may contain gaps	complete
O96028-6	484	PWWP2	None	absent
O96028-7	273	PWWP1	222–273 52 / 65 mapped residues; span may contain gaps	partial Use source-defined positions for equal-length replacement; replacement is not unchanged sequence. Official sequence edits VSP_021415 · canonical 255–273 · equal length replacement VSP_021416 · canonical 274–1365 · deletion
O96028-7	273	PWWP2	None	absent

Viewing NSD2 PWWP1

Canonical annotation interval 222–286 · UniProtKB reviewed feature. annotation core; not a certified complete folded domain or pocket.

Alternative PWWP annotations and interval provenance

[
  {
    "end": 285,
    "identifier": "SM00293",
    "integrated_identifier": "IPR000313",
    "model": "SM00293",
    "name": "domain with conserved PWWP motif",
    "representative": false,
    "score": 1.4e-14,
    "source": "smart",
    "source_url": "https://www.ebi.ac.uk/interpro/api/entry/all/protein/uniprot/O96028/?page_size=200",
    "start": 220
  },
  {
    "end": 303,
    "identifier": "IPR000313",
    "integrated_identifier": null,
    "model": null,
    "name": "PWWP domain",
    "representative": false,
    "score": null,
    "source": "interpro",
    "source_url": "https://www.ebi.ac.uk/interpro/api/entry/all/protein/uniprot/O96028/?page_size=200",
    "start": 220
  },
  {
    "end": 347,
    "identifier": "IPR047434",
    "integrated_identifier": null,
    "model": null,
    "name": "Nuclear SET domain-containing protein 2, first PWWP domain",
    "representative": false,
    "score": null,
    "source": "interpro",
    "source_url": "https://www.ebi.ac.uk/interpro/api/entry/all/protein/uniprot/O96028/?page_size=200",
    "start": 220
  },
  {
    "end": 347,
    "identifier": "cd20162",
    "integrated_identifier": "IPR047434",
    "model": "cd20162",
    "name": "first PWWP domain found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins",
    "representative": false,
    "score": 2.23547e-88,
    "source": "cdd",
    "source_url": "https://www.ebi.ac.uk/interpro/api/entry/all/protein/uniprot/O96028/?page_size=200",
    "start": 220
  },
  {
    "end": 286,
    "identifier": "PS50812",
    "integrated_identifier": "IPR000313",
    "model": "PS50812",
    "name": "PWWP domain profile",
    "representative": false,
    "score": null,
    "source": "profile",
    "source_url": "https://www.ebi.ac.uk/interpro/api/entry/all/protein/uniprot/O96028/?page_size=200",
    "start": 222
  },
  {
    "end": 303,
    "identifier": "PF00855",
    "integrated_identifier": "IPR000313",
    "model": "PF00855",
    "name": "PWWP domain",
    "representative": false,
    "score": 1.3e-14,
    "source": "pfam",
    "source_url": "https://www.ebi.ac.uk/interpro/api/entry/all/protein/uniprot/O96028/?page_size=200",
    "start": 223
  }
]

PWWP1 · source-classified Phase 6A evidence

Ligands & Bioactivity

Explore all domain compounds →

31 chemical or preparation profiles · 34 domain-attributed assay / association observations. Counts refer to the curated snapshot.

17 profiles

Deposited research ligands

11 profiles

Studied without research structure

2 profiles

Experiment-specific controls

UNC71451 observations · 0 research-ligand entries UNC88841 observations · 0 research-ligand entries

1 profiles

Ambiguous / indirect evidence

HS131 observations · 0 research-ligand entries

5 other deposited components in this domain (not pharmacological ligands)

Buffers, ions, cryoprotectants and solvents remain recorded as deposited chemical components.

4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID · Other PDB component · not a studied ligand ETHANOL · Other PDB component · not a studied ligand 1,2-ETHANEDIOL · Other PDB component · not a studied ligand GLYCEROL · Other PDB component · not a studied ligand SULFATE ION · Other PDB component · not a studied ligand

14 protein-level observations — no specific PWWP-domain attribution

These observations concern NSD2 in its reported experimental context. They are excluded from the selected domain's measurement counts.

UNC8153 · In-cell western degradation · = 0.35 ± 0.13 µM · PMID:36976643
UNC8153 · In-cell western degradation · = 79 ± 1 percent · PMID:36976643
UNC7753 · In-cell western degradation · = 1.2 ± 0.3 µM · PMID:36976643
UNC7753 · In-cell western degradation · = 81 percent · PMID:36976643
UNC8587 · Immunoblot cellular control · No change in H3K36me2 in the matched control condition. · PMID:36976643
UNC8269 · In-cell western degradation · = 59 ± 6 percent · PMID:38965384
UNC8269 · In-cell western degradation · = 1.01 ± 0.37 µM · PMID:38965384
UNC8325 · In-cell western degradation · = 71 ± 3 percent · PMID:38965384
UNC8325 · In-cell western degradation · = 0.71 ± 0.25 µM · PMID:38965384
UNC8732 · In-cell western degradation · = 97 ± 2 percent · PMID:38965384
UNC8732 · In-cell western degradation · = 0.06 ± 0.03 µM · PMID:38965384
LLC0424 · Immunoblot degradation · = 20 nM · PMID:38687638
LLC0424 · Immunoblot degradation · = 96 percent · PMID:38687638
BPP · Binding selectivity; assay method not verified in Figure S2 · Source reports non-detectable affinity in the tested selectivity comparison. · PMID:39031937

Open this domain in Structural & Binding Landscape →

Phase 6B · newly investigated source evidence

Additional experimental observations

Explore Phase 6B evidence

PWWP1 — exact-domain measurements

These measurements were recorded for the specifically assigned PWWP-domain construct, separately from whole-protein cellular responses.

UNC10088 · IC50 =248 ± 22 nM (TR-FRET competitive displacement of biotinylated UNC7096) · original figure. Without FBXO22 FIST domain
UNC10088 · IC50 =101 ± 8 nM (TR-FRET competitive displacement of biotinylated UNC7096) · original figure. With wild-type FBXO22 FIST domain; source-reported cooperative factor alpha = 3.3, not 248/101

2 new whole-protein cellular degradation results — NOT assigned to PWWP1

UNC10415667 · DC50 =460 nM · Cellular HiBiT protein-degradation dose response · publication figure
UNC12149 · DC50 =120 nM · Cellular HiBiT protein-degradation dose response · publication figure

No new unmodified parent binary PWWP-bound PDB structure is claimed for these entries. Original Phase 5/6A numbers remain unchanged.

PWWP1 · Deposited coordinates

Experimental coverage and AlphaFold correspondence

19 entry / domain records

One representative chain per PDB entry and native domain. RMSD uses fixed UniProt correspondence and all common Cα atoms; it is reported only for ≥40 atoms and ≥80% core coverage. A value is descriptive, not a prediction benchmark.

PDB	Chain	Observed core Cα	Class	Method / resolution	AF RMSD Å	Review
29HG	B	65 / 65	Complexes	ELECTRON MICROSCOPY 4.0 Å	1.59	No classification flag
29HH	B	65 / 65	Complexes	ELECTRON MICROSCOPY 4.2 Å	1.59	No classification flag
29HI	B	65 / 65	Complexes	ELECTRON MICROSCOPY 5.9 Å	1.58	No classification flag
5VC8	B	65 / 65	Complexes	X-RAY DIFFRACTION 1.8 Å	1.6	Required
6UE6	B	65 / 65	Co-Crystals	X-RAY DIFFRACTION 2.4 Å	1.19	Required
6XCG	A	65 / 65	Co-Crystals	X-RAY DIFFRACTION 1.64 Å	1.44	Required
9EXW	A	65 / 65	Co-Crystals	X-RAY DIFFRACTION 2.43 Å	1.48	No classification flag
9EXX	A	65 / 65	Co-Crystals	X-RAY DIFFRACTION 1.943 Å	1.5	No classification flag
9EXY	B	65 / 65	Co-Crystals	X-RAY DIFFRACTION 1.699 Å	1.51	No classification flag
9FOC	A	65 / 65	Co-Crystals	X-RAY DIFFRACTION 1.618 Å	1.39	No classification flag
9Y60	A	65 / 65	Co-Crystals	X-RAY DIFFRACTION 2.023 Å	1.46	No classification flag
9Y61	A	65 / 65	Complexes	ELECTRON MICROSCOPY 3.1 Å	1.45	No classification flag
7LMT	D	62 / 65	Co-Crystals	X-RAY DIFFRACTION 2.27 Å	0.948	Required
7MDN	D	62 / 65	Co-Crystals	X-RAY DIFFRACTION 2.42 Å	0.949	Required
7VLN	C	62 / 65	Co-Crystals	X-RAY DIFFRACTION 3.09 Å	1.01	No classification flag
9KN9	A	62 / 65	Co-Crystals	X-RAY DIFFRACTION 2.0 Å	0.869	No classification flag
9KNA	A	62 / 65	Co-Crystals	X-RAY DIFFRACTION 2.92 Å	0.742	No classification flag
9KNB	A	59 / 65	Co-Crystals	X-RAY DIFFRACTION 1.84 Å	0.49	No classification flag
9FOE	A	58 / 65	Co-Crystals	X-RAY DIFFRACTION 1.963 Å	0.451	No classification flag

PWWP1 · Measured preparations

Frozen v1.2 assay records

Explore evidence links

This retained table is the original source projection. The Phase 5 Ligands & Bioactivity section above includes added observations and reviewed target context. Values remain attached to their assay, construct and preparation. A crystal structure does not transfer affinity to another construct or stereoisomer. Assay pages preserve field-level source-verification states where reviewed; unreviewed null fields remain uncurated.

Preparation / identity	Assay and result	Construct	Evidence and source
HS13 paper label exact identity unresolved	Quantitative assay verification pending No verified numeric value abstract reported covalent association	Uncurated	PMID:42442058 PubMed_primary_article_abstract_only Primary abstract reports Kd 8.33 µM and C294 covalency; full assay method, construct, uncertainty and exact chemical identity not verified. Main value remains null. Assay conditions and interpretation {} Abstract describes C294 covalency and an affinity value; full assay details were inaccessible, so numerical pharmacology is intentionally uncurated.
MR837 (3f) exact single CCD identity	SPR Kd = 7.0 µM ± 3.0 direct binding affinity	Uncurated	PMID:33522809 primary_article_selected_indexed_full_text_passages; original figures and supplement not independently opened Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent. Assay conditions and interpretation {} Distinct condition from the lower-DMSO SPR measurement; do not average.
MR837 (3f) exact single CCD identity	SPR Kd = 3.4 µM ± 0.4 direct binding affinity	Uncurated	PMID:33522809 primary_article_selected_indexed_full_text_passages; original figures and supplement not independently opened Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent. Assay conditions and interpretation {"DMSO_percent": 0.5} Lower-DMSO measurement; preserve assay conditions.
MRT866 exact single CCD identity	SPR Kd = 349.0 nM ± 19.0 direct binding affinity	Uncurated	PMID:34782742 Phase 3 primary full-text Methods, Results and figure legends through official NCBI BioC; actual publisher supplement; assay-specific scope retained 349 ± 19 nM verified in Results; MRT866-specific SPR construct/protocol, replicate definition and uncertainty statistic remain unresolved. Crystallography 211–350 is not assigned as the binding-assay construct. Assay conditions and interpretation {} Interpretation not recorded in this snapshot.
UNC6934 exact single CCD identity	SPR Kd = 91.0 nM ± 8.0 direct binding affinity	208–368	PMID:34782742 Phase 3 primary full-text Methods, Results and figure legends through official NCBI BioC; actual publisher supplement; assay-specific scope retained SPR temperature and exact uncertainty definition are not specified in the inspected assay-specific source. Triplicate experiments reported. Preparation/assay construct differs from crystallization 211–350. Assay conditions and interpretation {"phase3_verification": "SV02A", "protein_construct": "NSD2 208–368", "purified_tags": "AviTag/NSD2(208–368)/polyhistidine; biotinylated", "source_protocol_highest_concentration_uM": 2} Interpretation not recorded in this snapshot.
UNC6934 exact single CCD identity	AlphaScreen IC50 = 104.0 nM ± 13.0 biochemical interaction inhibition	208–368	PMID:34782742 Phase 3 primary full-text Methods, Results and figure legends through official NCBI BioC; actual publisher supplement; assay-specific scope retained 23°C is the antagonist preincubation temperature, not a verified readout temperature. Final DMSO fraction and SD-versus-SEM definition for ±13 nM are not explicit in the inspected assay-specific text. Assay conditions and interpretation {"phase3_verification": "SV02A", "protein_construct": "NSD2 208–368", "readout": "His-NSD2-PWWP1 binding to H3K36me2 designer nucleosome", "tag": "6His", "temperature_scope": "23°C compound/protein and nucleosome preincubation; bead incubation room temperature"} Binding-interaction assay, not a direct catalytic SET-domain inhibition measurement.
UNC6934 exact single CCD identity	NanoBRET PPI half-response = 1.23 µM ± 0.25 cellular interaction response	Uncurated	PMID:34782742 Phase 3 primary full-text Methods, Results and figure legends through official NCBI BioC; actual publisher supplement; assay-specific scope retained NanoLuc construct boundaries, readout temperature and SD-versus-SEM are not explicit in the inspected source. Results say EC50 while Discussion says IC50; neutral half-response label retained. Assay conditions and interpretation {"cell_line": "U2OS", "readout": "NSD2 PWWP1–histone H3.3 interaction"} Main Results calls this EC50; Discussion calls it IC50. Original value retained without conflating it with Kd.
UNC6934 exact single CCD identity	SPR Kd = 0.24 µM ± 0.03 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
UNC6934 exact single CCD identity	SPR Kd = 1.33 µM ± 0.19 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
UNC7145 paper label exact identity unresolved	SPR no appreciable binding No verified numeric value negative binding test	208–368	PMID:34782742 Phase 3 primary full-text Methods, Results and figure legends through official NCBI BioC; actual publisher supplement; assay-specific scope retained Primary-source concentration discrepancy: Results report no appreciable binding up to 20 uM, but SPR Methods state 2 uM as highest concentration. Neither is converted into a Kd bound; human source review required. Assay conditions and interpretation {"highest_tested_concentration_uM": 20, "phase3_verification": "SV02A", "purified_tags": "AviTag/NSD2(208–368)/polyhistidine; biotinylated", "source_protocol_highest_concentration_uM": 2} No appreciable binding up to 20 µM; this is not a measured infinite Kd.
compound 11 (Collie 2025) assayed stereoisomeric mixture not single chemical identity	SPR Kd = 1.02 µM ± 0.19 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded. Compound 11 is the assayed preparation; 9FOC models two stereoisomer CCDs. Do not assign the aggregate affinity separately to each pure stereoisomer.
compound 11 (Collie 2025) assayed stereoisomeric mixture not single chemical identity	SPR Kd = 2.3 µM ± 0.31 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded. Compound 11 is the assayed preparation; 9FOC models two stereoisomer CCDs. Do not assign the aggregate affinity separately to each pure stereoisomer.
compound 12 (Collie 2025) paper label exact identity unresolved	SPR Kd = 1.47 µM ± 0.13 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 12 (Collie 2025) paper label exact identity unresolved	SPR Kd = 2.8 µM ± 0.31 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 12 (Collie 2025) paper label exact identity unresolved	HTRF displacement IC50 = 2.49 µM ± 0.06 biochemical interaction inhibition	208–368	PMID:40959233 Phase 3 primary Table 1 and actual Collie supporting PDF pages 7, 9 and 14; Carlino supporting PDF contents inspected, but the inherited main-article HTRF method remains not inspected after documented access attempts. HTRF full conditions are referenced to Carlino et al. 2024 DOI 10.1021/acs.jmedchem.4c00215. Its main protocol remains inaccessible after official repository checks. The actual supplement was inspected but contains no HTRF protocol. Table 1 reports SEM; independence level of HTRF replicates is not specified. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": 2, "uncertainty_type": "SEM"} Probe displacement from the H3K36me2 binding site; not catalytic SET-domain inhibition.
compound 13 (Collie 2025) paper label exact identity unresolved	SPR Kd = 0.75 µM ± 0.04 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 13 (Collie 2025) paper label exact identity unresolved	SPR Kd = 1.52 µM ± 0.05 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 13 (Collie 2025) paper label exact identity unresolved	HTRF displacement IC50 = 1.31 µM ± 0.06 biochemical interaction inhibition	208–368	PMID:40959233 Phase 3 primary Table 1 and actual Collie supporting PDF pages 7, 9 and 14; Carlino supporting PDF contents inspected, but the inherited main-article HTRF method remains not inspected after documented access attempts. HTRF full conditions are referenced to Carlino et al. 2024 DOI 10.1021/acs.jmedchem.4c00215. Its main protocol remains inaccessible after official repository checks. The actual supplement was inspected but contains no HTRF protocol. Table 1 reports SEM; independence level of HTRF replicates is not specified. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SEM"} Probe displacement from the H3K36me2 binding site; not catalytic SET-domain inhibition.
compound 5 (Collie 2025) assayed stereoisomeric mixture not single chemical identity	SPR Kd = 0.16 µM ± 0.03 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 5 (Collie 2025) assayed stereoisomeric mixture not single chemical identity	SPR Kd = 0.92 µM ± 0.03 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 6 (Collie 2025) paper label exact identity unresolved	SPR Kd = 0.71 µM ± 0.09 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 6 (Collie 2025) paper label exact identity unresolved	SPR Kd = 5.83 µM ± 0.64 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 6 (Collie 2025) paper label exact identity unresolved	HTRF displacement IC50 = 1.24 µM ± 0.08 biochemical interaction inhibition	208–368	PMID:40959233 Phase 3 primary Table 1 and actual Collie supporting PDF pages 7, 9 and 14; Carlino supporting PDF contents inspected, but the inherited main-article HTRF method remains not inspected after documented access attempts. HTRF full conditions are referenced to Carlino et al. 2024 DOI 10.1021/acs.jmedchem.4c00215. Its main protocol remains inaccessible after official repository checks. The actual supplement was inspected but contains no HTRF protocol. Table 1 reports SEM; independence level of HTRF replicates is not specified. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": 2, "uncertainty_type": "SEM"} Probe displacement from the H3K36me2 binding site; not catalytic SET-domain inhibition.
compound 7 (Collie 2025) exact single CCD identity	SPR Kd = 0.15 µM ± 0.02 direct binding affinity	208–368	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 7 (Collie 2025) exact single CCD identity	SPR Kd = 0.76 µM ± 0.01 direct binding affinity	211–350	PMID:40959233 Phase 3 primary Table 1 and actual supporting PDF pages 7, 9 and 14; the inherited HTRF method remains explicitly not inspected Assay-specific buffer and temperature verified from SI page 9; tag/construct from Table S2. Exact per-row kinetic-versus-steady-state fit choice and exact n beyond table footnote not specified. Chemical preparation identity remains as curated. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 211–350", "purified_tags": "N-terminal GS remnant; C-terminal Avi; biotinylated after GST/6His removal", "replicates": "at least 3", "uncertainty_type": "SD"} Affinity pertains to assay construct; crystal mutations and boundaries are separately recorded.
compound 7 (Collie 2025) exact single CCD identity	HTRF displacement IC50 = 0.21 µM ± 0.01 biochemical interaction inhibition	208–368	PMID:40959233 Phase 3 primary Table 1 and actual Collie supporting PDF pages 7, 9 and 14; Carlino supporting PDF contents inspected, but the inherited main-article HTRF method remains not inspected after documented access attempts. HTRF full conditions are referenced to Carlino et al. 2024 DOI 10.1021/acs.jmedchem.4c00215. Its main protocol remains inaccessible after official repository checks. The actual supplement was inspected but contains no HTRF protocol. Table 1 reports SEM; independence level of HTRF replicates is not specified. Assay conditions and interpretation {"assay_substitutions": "not listed for assay constructs; 9FOE crystallographic mutants kept separate", "phase3_verification": "SV05A/SV05B", "protein_construct": "NSD2 208–368", "purified_tags": "N-terminal Avi; C-terminal 6His; biotinylated", "replicates": "at least 3", "uncertainty_type": "SEM"} Probe displacement from the H3K36me2 binding site; not catalytic SET-domain inhibition.

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PWWP1 · Prediction evidence

Predicted models

7 model records

Domain retention uses independently reconstructed UniProt isoform edits. Local pLDDT is not experimental confirmation and does not establish interdomain orientation.

Model	Origin	Core retention	Core mean pLDDT	Full mean pLDDT	Cautions
AF-O96028-F1:v6 Canonical	GDM	complete	87.1	65.6
AF-O96028-2-F1:v6	GDM	absent	—	79.1	partial_or_absent_mapped_core
AF-O96028-3-F1:v6	GDM	complete	93.2	59.3
AF-O96028-4-F1:v6	GDM	absent	—	83.2	partial_or_absent_mapped_core
AF-O96028-5-F1:v6	GDM	complete	93.3	59.1
AF-O96028-6-F1:v6	GDM	complete	92.4	61.6
AF-O96028-7-F1:v6	GDM	partial	67.4	55.4	partial_or_absent_mapped_core; low_mean_core_confidence

PWWP1 · Structural correspondence

Human annotation-core comparisons

17 pairs

Structural alignment establishes a residue correspondence for these cropped cores. It does not establish equivalent ligand pockets, function or selectivity.

Domain pair	Aligned Cα	US-align RMSD Å	TM score A / B	View
ARID4A PWWP1 NSD2 PWWP1	55	2.16	0.493 / 0.664	Aligned core viewer
BRD1 PWWP1 NSD2 PWWP1	58	2.45	0.56 / 0.697	Aligned core viewer
BRPF1 PWWP1 NSD2 PWWP1	59	2.15	0.587 / 0.733	Aligned core viewer
BRPF3 PWWP1 NSD2 PWWP1	62	2.64	0.582 / 0.719	Aligned core viewer
DNMT3A PWWP1 NSD2 PWWP1	55	1.5	0.797 / 0.732	Aligned core viewer
DNMT3B PWWP1 NSD2 PWWP1	55	1.5	0.792 / 0.728	Aligned core viewer
HDGF PWWP1 NSD2 PWWP1	53	2.43	0.654 / 0.6	Aligned core viewer
HDGFL2 PWWP1 NSD2 PWWP1	55	1.79	0.795 / 0.72	Aligned core viewer
HDGFL3 PWWP1 NSD2 PWWP1	55	1.8	0.783 / 0.71	Aligned core viewer
MSH6 PWWP1 NSD2 PWWP1	62	1.42	0.838 / 0.816	Aligned core viewer
NSD2 PWWP1 NSD3 PWWP1	63	0.98	0.922 / 0.936	Aligned core viewer
NSD2 PWWP1 NSD3 PWWP2	54	2.28	0.654 / 0.671	Aligned core viewer
NSD2 PWWP1 PSIP1 PWWP1	54	2.23	0.646 / 0.654	Aligned core viewer
NSD2 PWWP1 PWWP2B PWWP1	55	1.4	0.751 / 0.795	Aligned core viewer
NSD2 PWWP1 PWWP3A PWWP1	52	2.08	0.638 / 0.663	Aligned core viewer
NSD2 PWWP1 ZMYND11 PWWP1	51	1.72	0.673 / 0.812	Aligned core viewer
NSD2 PWWP1 ZMYND8 PWWP1	50	1.31	0.674 / 0.825	Aligned core viewer