MYH9 (non-muscle myosin IIA) — the best-validated menin partner nobody in this field talks about, and the only one that maps to menin's N-terminus
also called MYH9 · NMHC II-A · non-muscle myosin heavy chain IIA · myosin-9 · P35579
Menin was found stuck to the motor protein that pinches a dividing cell in two, and the two were seen together in the pinch itself. Four different experiments in one paper agree, which is more than most menin partners have. It has been almost entirely ignored since, and it raises a question nobody asks: does a menin inhibitor do anything to cell division that has nothing to do with genes being switched on or off?
The same thing, for a scientist
MYH9 (UniProt P35579, 1960 aa, primary gene name read back) encodes non-muscle myosin heavy chain IIA. **PMID 14508515** (Obungu, Lee Burns, Agarwal, Chandrasekharapa, Adelstein, Marx; Oncogene 2003) isolated NMHC II-A from HeLa extracts by tandem affinity purification and mass spectrometry with menin as bait, and then confirmed it **four ways**: GST pull-down, co-immunoprecipitation, actin selection of myosin, and indirect immunofluorescence showing menin colocalising with this myosin isoform **in the cleavage furrow of dividing cells** [E1]. It also mapped regions: **the amino-terminal region of menin** and **the head domain of NMHC II-A** [E1]. By the standards of the menin interactome that is unusually thorough — more methods than FANCD2, more than any NF-kB subunit, and with a mapped region on both sides. **Three things make it worth an entry beyond bookkeeping.** First, the **menin region is the N-terminus**, distinct from the regions mapped for FANCD2 (214-390) and RelA (300-381), so menin's partners are not all competing for one surface. Second, **the phenotype is cytokinesis, not transcription** — a class of menin function this graph does not otherwise carry, and one that no menin-inhibitor study measures. Third, **it is a HeLa result**, which is the single most common caveat in menin biology and is stated here rather than glossed. **Counted absence:** MYH9 and non-muscle myosin IIA against KMT2A, MLL or menin returns 1 record and title-checking removes it [E2].
Four methods, one paper, twenty-three years of silence
| method | what it shows |
|---|---|
| tandem affinity purification + MS from HeLa extracts | NMHC II-A recovered with menin as bait |
| GST pull-down | direct association with recombinant protein |
| co-immunoprecipitation | association in cell lysate |
| actin selection of myosin | menin travels with the myosin in an actin-based selection, i.e. with functional myosin |
| indirect immunofluorescence | menin colocalises with NMHC II-A in the cleavage furrow |
The combination is what makes it strong: an AP-MS hit confirmed by a binary in vitro assay, a cellular association assay, a functional selection and a localisation. Very few entries in menin's IntAct record have more than one method.
And then nothing. A title/abstract query across MYH9 and its common spellings against KMT2A, MLL or menin returns a single record, a germline-predisposition study in high-hyperdiploid ALL that has nothing to do with menin 2. This is not a neglected result because it was weak; it is neglected because the field moved to chromatin in 2004 and did not come back.
The question this raises for menin inhibitors, which nobody has asked
If menin is at the cleavage furrow with non-muscle myosin IIA, menin has a job in cytokinesis. Two things follow that are checkable and unchecked.
1. Does a menin inhibitor perturb cytokinesis? No menin-inhibitor study measures cell division morphology, binucleation, or cytokinetic failure. Antiproliferative assays record fewer cells; they do not distinguish a differentiation block being released from a division failing. Since the clinical compounds occupy the MBM pocket and the MYH9 contact maps to the N-terminus, the honest prior is that a pocket inhibitor would not disturb it — which is itself worth saying, because it means this partner is one of the few that a menin inhibitor probably leaves alone.
2. Does it matter for the fusion? Probably not directly. The fusion protein retains menin-binding motifs at KMT2A's extreme N-terminus and recruits menin; whether the menin so recruited is also bound to myosin is unknown and, on a cleavage-furrow localisation, unlikely to be the same pool.
The value of the entry is therefore mostly negative and mostly about hygiene: menin has at least one well-validated, mechanistically unrelated, non-transcriptional partner, which is a standing argument against treating menin as a single-function chromatin adaptor. That argument is exactly what the beat was dispatched to test, and MYH9 is the cleanest evidence for it — better evidence than FANCD2, and in a direction nobody had proposed.
| uniprot | P35579 |
|---|---|
| length AA | 1960 |
| uniprot resolution | gene_exact:MYH9 AND organism_id:9606 AND reviewed:true; exactly one reviewed record; primary gene name read back as MYH9; length 1960 aa checked against the entry on 2026-09-20 |
menin contact
{
"methods": [
"tandem affinity purification with mass spectrometry",
"GST pull-down",
"co-immunoprecipitation",
"actin selection of myosin",
"indirect immunofluorescence colocalisation"
],
"menin_region": "amino-terminal region (deletion mapping; no residue boundaries reported in the abstract)",
"partner_region": "head domain of NMHC II-A",
"system": "HeLa",
"localisation": "cleavage furrow of dividing cells",
"source_pmid": "14508515",
"n_source_publications_in_intact": 1
}menin surface comparison
{
"MYH9": "N-terminal region",
"FANCD2": "214-390 sufficient",
"RELA": "300-381 necessary",
"KMT2A_MBM1_and_JunD": "the central peptide-binding cavity, which is the clinical drug site",
"implication": "menin's partners do not all use one surface, so a pocket inhibitor cannot be assumed to displace them all"
}literature
{
"kmt2a_menin_records_raw": 1,
"kmt2a_menin_records_title_checked": 0,
"aliases_searched": [
"MYH9",
"nonmuscle myosin IIA",
"non-muscle myosin IIA"
],
"query": "(MYH9[tiab] OR \"nonmuscle myosin IIA\"[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR menin[tiab])"
}depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -0.9044,
"chronos_mean_other_leukaemia": -0.6396,
"difference": -0.2648,
"pan_essentiality_all_lines": -0.5525,
"selectivity_rank": 135,
"rank_denominator": 17728,
"provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
"how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}- If menin does contribute to cytokinesis, chronic menin inhibition in a growing child touches a process every dividing tissue needs - and nothing in the current safety monitoring would detect it.
- Conversely, the N-terminal mapping is the best available argument that a pocket inhibitor spares this function, and that argument would be much stronger with an actual experiment behind it.
- A well-validated non-transcriptional menin partner weakens the clean-probe assumption directly: menin is not only a chromatin adaptor, so 'the drug removed menin, therefore the chromatin axis did X' has an unmeasured alternative.
- Does a clinical menin inhibitor affect cytokinesis? No study measures binucleation or furrow morphology under any menin inhibitor, and the N-terminal mapping predicts it should not - which makes it a cheap negative control that would strengthen every other claim about the drug's specificity.
- Is the menin-MYH9 association present in haematopoietic cells, or is it a HeLa phenomenon?
- Does menin have a cytokinesis phenotype at all? A menin-null MEF line and a binucleation count would answer a twenty-three-year-old question in a week.
- Where exactly in menin's N-terminus? The published mapping is a fragment, and menin residues 1-40 are also where the graph's structural work on the MBM pocket begins.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
Tandem affinity purification and mass spectrometry from cultured HeLa cell extracts identified non-muscle myosin type II-A heavy chain as a menin-interacting protein; the interaction was confirmed by GST pull-down, by co-immunoprecipitation and by actin selection of myosin; the amino-terminal region of menin and the head domain of NMHC II-A were identified as the regions required; and menin colocalised with this myosin isoform in the cleavage furrow of dividing cells by indirect immunofluorescence.
Menin, a tumor suppressor, associates with nonmuscle myosin II-A heavy chain. · Obungu VH, Lee Burns A, Agarwal SK, Chandrasekharapa SC, Adelstein RS, Marx SJ · Oncogene 2003What this evidence cannot show
HeLa cells throughout, with tagged menin as the TAP bait. HeLa is the single most over-represented system in menin biology and a cervical carcinoma line has no lineage relationship to a blast. The region mapping is by deletion constructs, so 'amino-terminal region of menin' is a fragment boundary, not an interface. The functional conclusion in the paper is hedged: menin 'could participate in cell division'.
Evidence that argues against this (1)
- No subsequent study has tested a menin cytokinesis function, and no large-scale menin interactome has recovered MYH9. Non-muscle myosin IIA is abundant and is a recurrent background protein in affinity purification, which is the standard objection to an AP-MS-derived myosin hit - though it does not explain the cleavage-furrow colocalisation. Huttlin EL et al. 2021
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
There is no MYH9 literature in KMT2A-rearranged leukaemia or in menin biology beyond the founding 2003 paper. A title/abstract search over MYH9 and 'nonmuscle myosin IIA' against KMT2A, MLL or menin returns 1 record, a study of predisposing germline mutations in high-hyperdiploid childhood ALL, which is removed by title-checking. Checked count: 0.
PubMed counted-absence search for MYH9 against KMT2A/MLL/menin, run 2026-09-20, hit title-checked · PubMed (NCBI) 2026What this evidence cannot show
MYH9 is a well-known fusion partner in other cancers (MYH9::ALK, MYH9::USP6) and a well-known cause of MYH9-related platelet disorders, so the gene is not obscure; it is specifically unstudied in this intersection. The hyphenation variant 'non-muscle myosin IIA' was searched in a second pass and returned the same single record.
Evidence that argues against this (1)
- A title-checked search count is two judgements stacked: the query decides what is reachable, and the reader decides what is 'on-beat'. Both are recorded here, which is the right practice, but neither is a measurement. This project has since established that field-scoped queries can return zero regardless of the literature, and that a symbol-level count misses work indexed under the pathway or the complex rather than the gene - so a small count bounds what was found, not what exists. Shan X et al. 2017
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
IntAct curates the MEN1-MYH9 pair from PMID 14508515 with three distinct methods - anti-bait co-immunoprecipitation, cosedimentation, and fluorescence microscopy scored as colocalization - making it the menin partner with the most method diversity from a single publication in the MEN1 record.
IntAct molecular interaction database, PSICQUIC MITAB 2.7 query on interactor O00255 (MEN1), retrieved 2026-09-20 · IntAct (EMBL-EBI) 2026What this evidence cannot show
Method diversity within one paper is not independence: the same reagents, the same cells and the same laboratory produced all three, and colocalization is curated as an interaction method in IntAct while being, strictly, a spatial observation. Diversity of method is worth more than repetition of one method and worth less than replication by another group.
Evidence that argues against this (1)
- A curated interaction inherits every limitation of the single experiment behind it. Anti-bait co-immunoprecipitation and affinity-capture mass spectrometry cannot distinguish a direct contact from a shared-complex association, tagged-bait overexpression can create contacts that do not occur at endogenous stoichiometry, and a partner curated from one publication has by definition never been independently replicated. The enumeration is accurate about the database; the database is not a statement about the blast. Heppner C et al. 2001
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
MYH9 is UniProt P35579, 1960 aa, primary gene name read back as MYH9, recommended name Myosin-9.
UniProtKB entry P35579 (MYH9_HUMAN, Myosin-9) · UniProtKB/Swiss-Prot 2026What this evidence cannot show
A database record. Resolved with gene_exact, which matches synonyms; exactly one reviewed human record returned, and the primary gene name and length were read back off the entry rather than assumed.
Evidence that argues against this (1)
- A reviewed database record fixes the canonical sequence and primary symbol on the date it was read, and nothing more. It does not establish that the protein is expressed in KMT2A-rearranged blasts, which isoform is present, or that the subunit acts in this disease. Accession and length are asserted so that a swap fails verify-accessions.py - a defence this graph needs because IKK-family and NF-kB subunit names collide heavily in the older literature - not because the record carries biological weight. Xiu Y et al. 2018
TAP-MS, GST pull-down, co-IP, actin selection; menin N-terminus to NMHC II-A head domain
a well-validated non-transcriptional menin partner mapping to a different surface