ZC3H18 (Q86VM9) - the CBC-to-exosome bridge in the pan-MLL-fusion core, and the ONLY member of this tranche whose own complex came with it

SYSTEM: the AP-MS host is JURKAT, a human T-ALL line, while KMT2A::AFF1 disease is B-lineage infant leukaemia; a partner requiring a B-cell or infant proteome cannot appear here and a T-lineage partner can appear spuriously. The bait is a Strep-HA-tagged, SINGLE-COPY, doxycycline-induced transgene at an FRT/Flp cassette, not the endogenous fusion. Prey came from bulk nuclear lysate (buffer C420, 420 mM NaCl) after a single STREP-Tactin step, so co-purification is NOT evidence of a direct contact. INCLUSION RULE: the paper kept the top 300 interactions per bait by combined p-value rather than applying a p threshold (Methods, verbatim: "All the identified bait-prey pairs were ranked by the combined p-value. The 300 most significant interactions per bait were retained."). Measured by this beat from the cached MOESM4 xlsx on 2026-09-21: 545 of the 2,049 per-bait p-values in the table (26.6%) exceed 0.05; within the MLL-AF4 column alone it is 186 of 291 (63.9%), and that column's maximum p is 0.175. MEASURED BY THIS BEAT, 2026-09-21, from the cached MOESM4 xlsx: across all 42 pan-fusion proteins the MLL-AF4 column carries the LOWEST total spectral counts of the seven baits for 34 of 42, and is sixth or seventh for 40 of 42. That is a bait-level property (transgene expression, purification depth or the DDX5/DDX17 GLM normalisation), not a statement about any one prey, so a low MLL-AF4 count must not be read as a weaker association than the same protein's count under another bait. For ZC3H18 the MLL-AF4 total (9 spectra over two replicates) is rank 7 of the seven baits, against a maximum of 54 under another bait. All seven per-bait values, p (replicate spectral counts): MLL-AF1p 0.0090 (7|4); MLL-AF4 0.0319 (5|4); MLL-AF9 0.0001 (18|18); MLL-CBP 0.0057 (4|20); MLL-EEN 0.0041 (14|13); MLL-ENL 0.0000 (27|27); MLL-GAS7 0.0000 (27|21). SPECIFIC TO THIS PROTEIN: four baits at or below 1e-4 with 40-plus total spectra, so the pan-fusion pattern is strong; the MLL-AF4 column is the second-shallowest gap in this tranche (9 spectra against 54). AND THE CONTROL THAT IS MISSING FROM THE PAPER MATTERS MOST HERE: the purifications are not reported to have been RNase-treated, so an RNA-bridged association cannot be distinguished from a protein-protein one for any RNA-binding prey, and ZC3H18 binds the cap-binding complex on every capped RNA. SELECTIVITY: the paper's named non-selectivity controls are RFC1, SF3A3 and CCT3 - knockdown inhibited MLL-wild-type K562 and HL-60 as much as MOLM-13 - against MEN1 as the selective positive. Only 40 of the 128 ('the 40 candidate genes with the highest confidence') entered that MLL-r versus MLL-wild-type re-screen, and the paper does not list which 40. This protein is not named among the controls, but that is NOT evidence of selectivity: it is equally consistent with the protein never having reached the second screen. Recorded as unknown, and this entry must not be read as nominating a target. Values re-read from the cached xlsx on 2026-09-21 and cross-checked against analyses/skucha-mll-fusion-interactome/results.json, whose two controls (128 proteins shared by >=5 baits and 42 by all seven, both matching the paper; MEN1 present with all seven) both PASS on today's re-run.

• IntAct has never curated this dataset, so no independent curator has re-examined these calls and no interactome-coverage metric built on IntAct can see them; the raw spectra at ProteomeXchange PXD009338 have not been reanalysed here. The authors themselves removed seven proteins from the shared set by hand as 'either frequently observed contaminants or ... not detected in human hematopoietic cell lines', which concedes that the rank cutoff lets contaminants through - and ACTB survived that filter, sitting in the pan-fusion 42 with a NON-ZERO negative control (3|3). Ten of the 42 carry a non-zero negative control: PSIP1 0|5, MCM2 0|2, ACTB 3|3, CSNK2A1 2|0, RUNX1 0|2, SF3A3 0|3, TCEB3 0|1, CHD4 2|2, SMARCC1 1|0, ZNF512 0|2 - counted by this beat from the xlsx neg_ctrl column, 2026-09-21. ProteomeXchange/PRIDE 2018
• The paper states that 'more than one third of proteins in the network of conserved MLL-fusion protein interaction partners were identified as essential in recent genome-wide screens'. Abundance and essentiality both raise the odds of recovery in an AP-MS experiment, so membership in the conserved core is partly a statement about how much of a protein is present in a nucleus, not only about what it binds. Skucha A et al. 2018

Human cells, 2013, Nature Structural & Molecular Biology; affinity purification, RNA immunoprecipitation and combinatorial depletion. Not haematopoietic, not a fusion system. Read from the abstract. Cited for the architecture - which is what makes the co-recovery of ZC3H18, RBM7, ZCCHC8 and ARS2 in the same network a module rather than a coincidence.

• MTREX/MTR4, the helicase at the centre of NEXT and the exosome's essential cofactor, is ABSENT from the Skucha 960-protein network at any n (this beat, from the xlsx, 2026-09-21). A NEXT complex without its helicase is not a functional NEXT complex, so the module is partial in the same way the CPSF row is partial. Skucha A et al. 2018

Human cells, 2018, Cell Reports; interaction proteomics, domain mutagenesis and genome-wide transcription analysis. Not haematopoietic, not a fusion system. Read from the abstract. The histone association is the load-bearing detail for this entry and it is an abstract-level statement about a modified region, not a mapped interface; no structure or stoichiometry was checked.

• An association with core histones is exactly what would make ZC3H18 a high-prior prey in ANY chromatin-protein purification, so the same result that makes this row mechanistically plausible also supplies the strongest alternative explanation for it. Skucha A et al. 2018