UBAP2L (Q14157) - a BMI1-interacting protein essential for haematopoietic stem cell activity, in the pan-MLL-fusion core, and a stress-granule nucleator recovered from NUCLEAR lysate

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 UBAP2L the MLL-AF4 total (8 spectra over two replicates) is rank 7 of the seven baits, against a maximum of 47 under another bait. All seven per-bait values, p (replicate spectral counts): MLL-AF1p 0.0027 (5|4); MLL-AF4 0.0225 (6|2); MLL-AF9 0.0016 (9|10); MLL-CBP 0.0054 (5|4); MLL-EEN 0.0292 (4|8); MLL-ENL 0.0000 (21|26); MLL-GAS7 0.0001 (24|17). SPECIFIC TO THIS PROTEIN: the 6|2 MLL-AF4 replicate split is the most uneven in this tranche, and the headline cellular function of UBAP2L is CYTOPLASMIC (stress granules) while this is a nuclear-lysate purification - so a fractionation-carry-over reading is available. Against that: UniProt records nuclear and chromosome localisation for UBAP2L with experimental evidence codes, and the stress-granule partners in the network are shallow (G3BP1 and CAPRIN1 at 3 of 7, G3BP2 and UBAP2 absent), so a granule did not come along as a unit. 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

2014, Blood; mouse and human normal haematopoiesis with complex purification, expression profiling and knockdown, 15 authors. NORMAL haematopoiesis, not leukaemia, and no MLL fusion anywhere in the study. BMI1 itself is NOT in the Skucha 960-protein network at any n, so the interactome does not corroborate a BMI1 axis at the fusion. Read from the abstract. Cited for two things: UBAP2L has a documented, non-redundant requirement in the cell compartment this disease arises from, and it connects to a Polycomb thread this graph already carries.

• A requirement in long-term repopulating HSCs is an essential-function warning, not a therapeutic opening - the same shape as the paper's own non-selective controls RFC1, SF3A3 and CCT3. And because BMI1 is absent from the interactome, the BMI1 connection is an inference across two unrelated experiments rather than an observation in one. Skucha A et al. 2018

2020, Cell Death and Differentiation; cultured cells with overexpression, domain deletion and methyltransferase manipulation. Overexpression nucleating a condensate is weak evidence about endogenous behaviour, and this project's standing condensate rule applies in full: a punctate appearance is compatible with binding to spatially clustered sites, and neither 1,6-hexanediol nor classical FRAP distinguishes phase separation from that. Not haematopoietic, not a fusion system. CYTOPLASMIC biology, cited in an entry about a nuclear purification specifically so that the mismatch is on the record. Read from the abstract.

• The same paper reports that a UBAP2L domain deletion drives UBAP2L into the NUCLEUS, which means the nuclear pool of this protein is regulated and can be substantial - so a nuclear recovery is not automatically a fractionation artefact, and the cytoplasmic-contaminant reading is weaker than the protein's reputation suggests. Bordeleau ME et al. 2014