Homo sapiens · seed O00255 · 610 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026
Open in CODSWALLOP UniProt O00255 RCSB by accession PDBe-KB AlphaFold DB InterPro RCSB 7UJ4 PDBe
CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.
Every figure here is counted over the whole family rather than quoted from one entry.
7UJ4, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.
How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.
23 distinct constructs across 70 entries. 69 polymer entities differ from the UniProt canonical sequence in some way, 3 carry a recognised expression tag and 0 carry a fusion partner.
"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.
| Entities | Length | Best (Å) | Best entry | What was made |
|---|---|---|---|---|
| 19 | 489 | 1.27 | 4GQ4 | residues 1-593; 3 internal deletions; T541A |
| 9 | 550 | 2.10 | 6WNH | 1 internal deletion; M1S |
| 6 | 489 | 1.24 | 6O5I | residues 1-593; 3 internal deletions |
| 4 | 488 | 1.50 | 9WN9 | residues 2-583; 1 internal deletion; A5T |
| 4 | 488 | 1.80 | 9WKV | residues 2-583; 1 internal deletion; A5T, M322I |
| 3 | 480 | 1.45 | 4OG4 | residues 1-593; 4 internal deletions |
| 3 | 494 | 1.98 | 7O9Z | residues 1-584; 3 internal deletions; T541A |
| 3 | 507 | 1.85 | 9C93 | His6; TEV site; residues 1-583; 1 internal deletion; M1S, A5T |
| 2 | 489 | 1.31 | 9C4Y | residues 1-593; 3 internal deletions; T344M, T541A |
| 2 | 489 | 1.40 | 9C4W | residues 1-593; 3 internal deletions; G326R, T541A |
| 2 | 489 | 1.40 | 9C4Z | residues 1-593; 3 internal deletions; G326D, T541A |
| 2 | 489 | 1.46 | 9C4T | residues 1-593; 3 internal deletions; M322I, T541A |
| 1 | 472 | 1.95 | 3RE2 | residues 1-486; 1 internal deletion |
| 1 | 488 | 1.96 | 7UJ4 | residues 1-582; 1 internal deletion; A5T |
| 1 | 489 | 1.30 | 8VA5 | residues 1-593; 3 internal deletions; T344M |
| 1 | 489 | 1.85 | 8E90 | residues 1-583; 1 internal deletion; A5T, M322I |
| 1 | 490 | 1.90 | 6PKC | residues 1-583; 1 internal deletion; M1S, A5T |
| 1 | 505 | 2.10 | 7OA9 | residues 1-584; 2 internal deletions; T541A |
| 1 | 509 | 2.44 | 6BXH | residues 1-593; 2 internal deletions; T541A |
| 1 | 526 | 3.10 | 6S2K | residues 1-584; 1 internal deletion; T541A |
| 1 | 539 | 2.95 | 9Z4X | 2 internal deletions; M1S |
| 1 | 550 | 2.60 | 8IG0 | 1 internal deletion |
| 1 | 611 | 3.20 | 8GPN | matches the canonical sequence |
Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".
| Oligomeric state | Chains | Entries | Share |
|---|---|---|---|
| monomeric | 1 | 56 | 80.0% |
| dimeric | 2 | 11 | 15.7% |
| trimeric | 3 | 1 | 1.4% |
| tetrameric | 4 | 1 | 1.4% |
| undecameric | 11 | 1 | 1.4% |
45 entries have the depositor's assembly corroborated by PISA, 25 carry the depositor's word alone and 0 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 2 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 3U84, 3U85.
7PR4 entries
K5O4 entries
PG04 entries
TBF3 entries
9N63 entries
OQ42 entries
2IZ2 entries
CHD1 entries
GGB1 entries
0BR1 entries
GLV1 entries
0RO1 entries
| Component | Class | Name | Entries | Best (Å) |
|---|---|---|---|---|
| SO4 | ion | Sulfate Ion | 38 | 1.24 |
| DMS | cryoprotectant | Dimethyl Sulfoxide | 28 | 1.24 |
| PG4 | cryoprotectant | Tetraethylene Glycol | 27 | 1.24 |
| EDO | cryoprotectant | 1,2-Ethanediol | 26 | 1.30 |
| PEG | cryoprotectant | Di(Hydroxyethyl)ether | 20 | 1.30 |
| MG | ion | Magnesium Ion | 9 | 1.50 |
| GOL | cryoprotectant | Glycerol | 6 | 1.50 |
| EPE | buffer | 4-(2-Hydroxyethyl)-1-Piperazine Ethanesulfonic Acid | 5 | 1.27 |
| 1PE | cryoprotectant | Pentaethylene Glycol | 5 | 1.46 |
| PGE | cryoprotectant | Triethylene Glycol | 5 | 1.45 |
| 7PR | ligand | Praseodymium Triacetate | 4 | 2.10 |
| K5O | ligand | Ziftomenib | 4 | 1.30 |
| PG0 | ligand | 2-(2-Methoxyethoxy)ethanol | 4 | 1.46 |
| UNX | ion | Unknown Atom Or Ion | 3 | 1.27 |
| TBF | ligand | Tert-Butyl Formate | 3 | 1.45 |
| 7IX | buffer | (1r,2s,4r)-4-[[4-(5,6-Dimethoxypyridazin-3-Yl)phenyl]methylamino | 3 | 1.63 |
| 9N6 | ligand | N-Ethyl-5-Fluoro-2-{[5-(2-{(3r)-6-[(2-Methoxyethyl)(Methyl)amino | 3 | 1.80 |
| NA | ion | Sodium Ion | 3 | 1.63 |
| OQ4 | ligand | 2-({4-[7-({(1r,4r)-4-[(Ethanesulfonyl)amino]cyclohexyl}methyl)-2 | 2 | 1.85 |
| MES | buffer | 2-(N-Morpholino)-Ethanesulfonic Acid | 2 | 1.80 |
Parsed from the free text 69 depositors typed into
_exptl_crystal_grow.pdbx_details, out of 69
entries that recorded anything at all.
Median pH 7.9
(range 6.0 to 8.0).
70 entries carry a wwPDB validation report: 35 clean, 30 worth a check and 5 with something to explain. Median clashscore 3.74, median RSRZ outliers 4.26%, median R-free minus R-work 0.035. 70 have released structure factors.
| Organism | Entries | Best (Å) | Ligand-bound | Seed covered |
|---|---|---|---|---|
| Homo sapiens | 69 | 1.24 | 52 | 100% |
| Nematostella vectensis | 1 | 1.95 | 0 | 73% |
610 residues, numbered every ten. Every identity figure in this document is measured against this sequence.
active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions
Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.
One record per paper, not per entry.
| Year | Citation |
|---|---|
| 2025 | Design of Potent Menin-KMT2A Interaction Inhibitors with Improved In Vitro ADME Properties and Reduced hERG Affinity. Acs Med.Chem.Lett. doi:10.1021/acsmedchemlett.4c00311 |
| 2024 | Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. Lancet Oncol doi:10.1016/S1470-2045(24)00386-3 |
| 2024 | Drug-resistant menin variants retain high binding affinity and interactions with MLL1. J.Biol.Chem. doi:10.1016/j.jbc.2024.107777 |
| 2024 | Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in KMT2A- and NPM1-altered leukemias. Blood doi:10.1182/blood.2023022480 |
| 2023 | MEN1 mutations mediate clinical resistance to menin inhibition. Nature doi:10.1038/s41586-023-05755-9 |
| 2023 | A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1. Cancer Cell Int doi:10.1186/s12935-023-02877-y |
| 2023 | Menin "reads" H3K79me2 mark in a nucleosomal context. Science doi:10.1126/science.adc9318 |
| 2021 | Discovery of M-1121 as an Orally Active Covalent Inhibitor of Menin-MLL Interaction Capable of Achieving Complete and Long-Lasting Tumor Regression. J.Med.Chem. doi:10.1021/acs.jmedchem.1c00789 |
| 2020 | Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia. J.Clin.Invest. doi:10.1172/JCI129126 |
| 2020 | Covalent and noncovalent constraints yield a figure eight-like conformation of a peptide inhibiting the menin-MLL interaction. Eur.J.Med.Chem. doi:10.1016/j.ejmech.2020.112748 |
| 2020 | Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin-MLL Interaction with StrongIn VivoAntitumor Activity. J.Med.Chem. doi:10.1021/acs.jmedchem.0c00547 |
| 2019 | A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell doi:10.1016/j.ccell.2019.11.001 |
| 2019 | Structure-Based Discovery of M-89 as a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein-Protein Interaction. J.Med.Chem. doi:10.1021/acs.jmedchem.9b00021 |
| 2018 | Complexity of Blocking Bivalent Protein-Protein Interactions: Development of a Highly Potent Inhibitor of the Menin-Mixed-Lineage Leukemia Interaction. J.Med.Chem. doi:10.1021/acs.jmedchem.8b00071 |
| 2018 | Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein-Protein Interaction. Angew. Chem. Int. Ed. Engl. doi:10.1002/anie.201711828 |
| 2016 | Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL). J.Med.Chem. doi:10.1021/acs.jmedchem.5b01305 |
| 2015 | Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein-Ligand Complexes. J.Med.Chem. doi:10.1021/acs.jmedchem.5b00975 |
| 2015 | Pharmacologic Inhibition of the Menin-MLL Interaction Blocks Progression of MLL Leukemia In Vivo. Cancer Cell doi:10.1016/j.ccell.2015.02.016 |
| 2014 | High-Affinity Small-Molecule Inhibitors of the Menin-Mixed Lineage Leukemia (MLL) Interaction Closely Mimic a Natural Protein-Protein Interaction. J.Med.Chem. doi:10.1021/jm401868d |
| 2013 | Structure-Based Design of High-Affinity Macrocyclic Peptidomimetics to Block the Menin-Mixed Lineage Leukemia 1 (MLL1) Protein-Protein Interaction. J.Med.Chem. doi:10.1021/jm3015298 |
| 2012 | Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia. Blood doi:10.1182/blood-2012-05-429274 |
| 2012 | The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature doi:10.1038/nature10806 |
| 2011 | Crystal Structure of Menin Reveals Binding Site for Mixed Lineage Leukemia (MLL) Protein. J.Biol.Chem. doi:10.1074/jbc.M111.258186 |
| Wild-type Menin complexed with DSP-5336 To Be Published | |
| Wild-type Menin complexed with DS-1594 To Be Published | |
| [M322I] Menin complexed with JNJ-75276617 To Be Published | |
| Wild-type Menin complexed with JNJ-75276617 To Be Published | |
| Crystal structure of Human Menin in complex with BD-08 To Be Published | |
| [M322I] Menin complexed with DSP-5336 To Be Published | |
| [M322I] Menin complexed with KO-539 To Be Published | |
| Crystal structure of Human Menin in complex with Fragment 21 To Be Published | |
| Crystal structure of Human Menin in apo form To Be Published | |
| Crystal structure of Human Menin with fragment 16 To Be Published | |
| Wild-type Menin complexed with KO-539 To Be Published | |
| Menin in complex with MI-853 To Be Published | |
| Human Menin in complex with AJ21 To Be Published |