Oncofusion

start / graph / gene-mapre1

Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q90-pan-fusion-core3

MAPRE1 / EB1 (Q15691) - a microtubule plus-end tracking protein that is BOTH a pan-MLL-fusion prey and a genuine KMT2A fusion partner in pro-B ALL

also called MAPRE1 · EB1 · End-binding protein 1 · APC-binding protein EB1 · Microtubule-associated protein RP/EB family member 1 · MARE1_HUMAN · Q15691

EB1 rides on the growing tips of microtubules, the cell's internal scaffolding rods, and helps steer them. Two separate things are true about it here: it turned up stuck to every MLL fusion protein in a fishing experiment, which may be an accident of abundance - and the EB1 gene is genuinely broken and joined to the KMT2A gene in at least one patient with pro-B acute lymphoblastic leukaemia, which is not an accident at all.

The same thing, for a scientist

MAPRE1/EB1 (Q15691, 268 aa) is the founding member of the EB family of microtubule plus-end tracking proteins. UniProt records only cytoplasmic and cytoskeletal compartments for it, on seven separate experimental citations, with no nuclear annotation of any kind (fetched live 2026-09-21). It co-purified with all seven MLL fusions in Skucha 2018 (MLL-AF4 p = 0.0273, 3|3, negative control 0|0, rank 26 of 42), and MAPRE2 and MAPRE3 are absent from the 960-protein network, so there is no EB module. Read as an interactor, that is a weak row on a protein with no reason to be in a nuclear lysate. **But MAPRE1 is also, independently, a KMT2A fusion partner in the canonical leukaemogenic orientation.** In an adult pro-B ALL patient, MLL exon 6 is fused in-frame to EB1 exon 5; both reciprocal transcripts were verified, and immunofluorescence showed the MLL-EB1 fusion protein localises to nuclei. The same group later showed that the EB1 coiled-coil four-helix bundle is required for MLL/EB1 to immortalise mouse bone marrow, that MLL/EB1 has low leukaemogenic ability relative to MLL/AF10, and that Ets1 is the selectively upregulated effector. So EB1 belongs to the dimerisation class of cytoplasmic MLL partners alongside GAS7, the septins and GPHN - and this graph, which already holds `fusion-kmt2a-gas7`, `fusion-kmt2a-gphn` and four septin fusions, holds nothing for EB1.

Go deeper
The Skucha row, stated in full

7 of 7 fusions. MLL-AF1p 0.000166 (12|6), MLL-AF4 0.0273 (3|3), MLL-AF9 0.00271 (10|9), MLL-CBP 0.00167 (5|8), MLL-EEN 0.000822 (15|16), MLL-ENL 0.000131 (14|18), MLL-GAS7 0.0088 (11|7); negative control 0|0 1. Rank 26 of 42 by MLL-AF4 p. The MLL-AF4 spectral total of 6 is the lowest in this tranche and rank 7 of seven baits, against 32 under MLL-ENL.

MLL-EB1 is a real fusion, in the right orientation and the right lineage

The MLL-EB1 fusion is not the VIM::KMT2A shape. MLL exon 6 is fused in frame to EB1 exon 5 - KMT2A is the 5' partner, the N-terminal AT-hooks, CxxC and menin-binding motifs are retained, and EB1 supplies the C-terminus. That is the canonical leukaemogenic architecture of every fusion this graph is built around. The patient had pro-B acute lymphoblastic leukaemia, which is the lineage of the index disease. Both MLL-EB1 and the reciprocal EB1-MLL transcripts were verified, the genomic break junctions were amplified and sequenced, and immunofluorescence localised the MLL-EB1 fusion protein to nuclei 2.

Fourteen years later the same group put it in mice: the EB1 coiled-coil four-helix bundle is required for MLL/EB1 to immortalise mouse bone marrow cells, which produced myeloid rather than lymphoid lines; MLL/EB1 has lower leukaemogenic ability than MLL/AF10, growing more slowly with increased apoptosis and inducing acute monocytic leukaemia with incomplete penetrance; and Ets1 is the selectively upregulated gene whose knockdown reduces engraftment and prolongs survival 3. That places EB1 squarely in the dimerisation class of cytoplasmic MLL partners.

The two facts are separate, and one of them is a hypothesis

A recurrent genomic partnership is not a protein interaction. The wild-type EB1 protein co-purifying with seven MLL fusions and the EB1 gene recombining with KMT2A in one patient are different claims about different molecules, and this entry does not let the second rescue the first.

What the coincidence does license is a hypothesis, stated as one. EB1 homodimerises through the same C-terminal coiled-coil that MLL/EB1 uses to oligomerise, so if any KMT2A::EB1 protein were present it would be expected to pull wild-type EB1 - but none of Skucha's seven baits is EB1, so that cannot explain this row. A second and more testable idea concerns the BAITS rather than the prey: three of the seven are cytoplasmic partners and MLL-GAS7 in particular is an F-BAR actin-binding protein, so the bait panel is not localisation-neutral, and a cytoskeletal prey recovered across it may be reporting bait chemistry rather than KMT2A biology. Neither idea is tested here.

No EB module, and a graph gap

Checked against the full 960-row table on 2026-09-21: MAPRE2 and MAPRE3 are absent from the network at any n, as are APC, CLIP1 and every other +TIP. MAPRE1 is alone. Separately: there is no fusion-kmt2a-mapre1 node in this graph's 1,924 - a companion entry is written in this tranche - and no EB1 or MAPRE1 mention anywhere in the corpus before this beat.

Verdict

As an interactor: probably contamination. Weak p, lowest spectral depth in the tranche, no nuclear annotation on seven experimental citations, no family module, and the clean negative control is the base rate for this set. As a KMT2A fusion partner: real, published, functionally validated in mouse, and previously invisible to this graph. The entry earns its place on the second fact.

Facts and figures
uniprotQ15691
length AA268
accession resolutionResolved live 2026-09-21: `gene_exact:MAPRE1 AND organism_id:9606 AND reviewed:true` returns exactly ONE reviewed row; gene_primary MAPRE1, Q15691, entry name MARE1_HUMAN, 268 aa, protein name 'Microtubule-associated protein RP/EB family member 1 (APC-binding protein EB1) (End-binding protein 1) (EB1)', no gene synonyms. Matches the accession in Skucha's own table.
identifier hazardNOT IN data/symbol-collisions.json AS OF 2026-09-21 (registry read before searching, per rule 88), AND A ROW IS WARRANTED. The alias `EB1` is a bare two-character-plus-digit string used across biology: Epstein-Barr virus nuclear antigen abbreviations, EB1 as an Epstein-Barr cell line, and EBF1 is a different B-cell transcription factor one character away. Measured here: `EB1[tiab]` against the KMT2A clause returns 2 records and BOTH are on topic (the 2005 fusion report and the 2019 mouse model), so no damage was done - but that is luck given the string. Rule 65 readback SUCCEEDS here: the protein name contains both 'MAPRE1'-adjacent wording and the literal 'EB1'. Note also the retired-symbol lesson: the fusion literature publishes as MLL-EB1, never as KMT2A::MAPRE1, so a current-symbol search misses it - `MAPRE1[tiab]` against the KMT2A clause returns 2 and `EB1[tiab]` returns 2, overlapping in only one record.
localizationCYTOPLASM AND CYTOSKELETON ONLY. UniProt Q15691, fetched live 2026-09-21: 'Cytoplasm, cytoskeleton' ECO:0000269 on seven PMIDs (10188731, 12388762, 21646404, 23001180, 25225338, 28814570, 9724749); also centrosome, spindle, spindle pole, Golgi apparatus and cell membrane, all ECO:0000269. There is NO nuclear location comment, coded or uncoded. This is one of the best-annotated cytoplasmic records in the tranche and it contains no nucleus. NOTE the separate fact that the MLL-EB1 FUSION protein is nuclear by immunofluorescence (Fu 2005) - that is the fusion, which carries KMT2A's nuclear localisation determinants, not wild-type EB1.
subnuclear localizationNOT APPLICABLE for wild-type MAPRE1 - a protein with no nuclear annotation of any kind across seven experimental localisation citations. Recorded as not applicable rather than as an unmeasured absence, following the HLA-A / NRAS / B2M / PROM1 / CD33 / ELOVL1 precedent, so it does not enter the denominator of unmeasured subnuclear compartments. For the MLL-EB1 FUSION protein the subnuclear compartment IS an open and unmeasured question: Fu 2005 reports 'localized in the nuclei' with no subnuclear resolution.
localization shown for fusionPARTIAL, and the two halves must not be merged. Wild-type MAPRE1: NO - nobody has imaged or fractionated it in any cell expressing any KMT2A fusion. The MLL-EB1 fusion protein: YES at whole-nucleus resolution only - immunofluorescence in Fu 2005 places it in nuclei, with no subnuclear compartment and no comparison to wild-type KMT2A.
shown for fusionTwo separate things. (1) INTERACTION: co-purification with all seven MLL fusions including MLL-AF4 in Jurkat (p = 0.0273, the lowest spectral depth in this tranche); shRNA-screened in MLL-AF9 MOLM-13, score unpublished; no independent experiment ties wild-type EB1 protein to any KMT2A fusion. (2) FUSION PARTNER: MLL-EB1 in human adult pro-B ALL (MLL exon 6 :: EB1 exon 5, nuclear by IF), and MLL/EB1 immortalisation of mouse bone marrow requiring the EB1 coiled-coil, producing acute monocytic leukaemia with Ets1 as the critical effector.
selectivityUNKNOWN, and BARRED from any target list. Not named among the paper's controls and not known to be among the 40 re-screened. EB1 is required for mitotic spindle function in every dividing cell; there is no selective window, and this entry's own verdict on the interaction is that it is probably an artefact. The one place selectivity would be a real question is the MLL-EB1 fusion protein itself, and nobody has asked it - no menin-dependency, no DOT1L-dependency and no drug experiment exists on MLL/EB1.
absence classnever-measured
absence class noteFor the INTERACTION with wild-type EB1: never-measured outside the two screen hosts; the MOLM-13 shRNA score is measured-not-reported. For the MLL-EB1 FUSION: the mouse model exists, but no menin-dependency, DOT1L-dependency, occupancy or drug experiment has ever been run on it - never-measured. PRIDE checked: PXD009338 is the only relevant deposition.
graph contextMAPRE1 and EB1 appear in ZERO of this graph's 1,924 node files before this beat, and there was no `fusion-kmt2a-mapre1` node despite the graph holding fusion nodes for the analogous coiled-coil partners GAS7, GPHN and four septins. A companion fusion entry is written in this tranche.
verdictAS AN INTERACTOR: probably contamination - weakest spectral depth in the tranche, no nuclear annotation on seven experimental citations, no family module, and a clean control that is the base rate. AS A KMT2A FUSION PARTNER: real, published twice, functionally validated in mouse, and previously absent from this graph.
skucha 2018
{
  "bait": "MLL-AF4 (= KMT2A::AFF1)",
  "p_value": 0.0273,
  "spectral_counts": "3|3",
  "n_fusions_of_seven": 7,
  "negative_control_counts": "0|0",
  "per_bait": {
    "MLL-AF1p": "0.000166 (12|6)",
    "MLL-AF4": "0.0273 (3|3)",
    "MLL-AF9": "0.00271 (10|9)",
    "MLL-CBP": "0.00167 (5|8)",
    "MLL-EEN": "0.000822 (15|16)",
    "MLL-ENL": "0.000131 (14|18)",
    "MLL-GAS7": "0.0088 (11|7)"
  },
  "af4_spectral_rank_of_seven": 7,
  "af4_p_rank_within_the_42_pan_fusion": 26,
  "af4_spectral_total": "6 - the lowest index-fusion depth of the nine proteins in this tranche",
  "source": "analyses/skucha-mll-fusion-interactome/results.json, re-derived from the cached MOESM4 xlsx 2026-09-21; run.py re-run, both controls PASS"
}
is itself a kmt2a fusion partner
{
  "answer": "YES, and in the canonical leukaemogenic orientation",
  "fusion": "MLL-EB1 (KMT2A::MAPRE1)",
  "breakpoint": "MLL exon 6 fused in frame to EB1 exon 5; reciprocal EB1-MLL also verified",
  "locus": "MAPRE1 at 20q11.2 - the first chromosome 20 gene found fused to MLL",
  "disease": "adult pro-B acute lymphoblastic leukaemia, n = 1 patient",
  "fusion_protein_localisation": "nuclei, by immunofluorescence (Fu 2005)",
  "functional_validation": "MLL/EB1 immortalises mouse bone marrow and induces acute monocytic leukaemia with incomplete penetrance; requires the EB1 coiled-coil four-helix bundle; low leukaemogenic ability versus MLL/AF10; Ets1 is the critical upregulated effector (Fu 2019)",
  "partner_class": "dimerisation / oligomerisation via a coiled-coil, the same class as GAS7, the septins and GPHN - all of which this graph already holds as fusion nodes",
  "graph_gap_closed_in_this_tranche": "fusion-kmt2a-mapre1"
}
complex membership
{
  "complex": "EB family of microtubule plus-end tracking proteins (+TIPs)",
  "partners_in_the_960": {},
  "absent_from_the_960": [
    "MAPRE2",
    "MAPRE3",
    "APC",
    "CLIP1",
    "MAP7",
    "MAP7D2",
    "MAP7D3",
    "ACTL6A"
  ],
  "reading": "ISOLATED. No EB paralogue and no other +TIP is in the network at any n. MAPRE1 is not a member of any of the twelve complexes tested in analyses/mll-fusion-interactome-complexes/; no cytoskeletal module was tested there, which is a gap in that analysis and is recorded in this beat's memo."
}
cell types and states
[
  "Jurkat (human T-ALL) - the AP-MS host, nuclear lysate, tagged single-copy transgene",
  "MOLM-13 (human MLL-AF9 AML) - shRNA screen host, six shRNAs, per-gene score unpublished",
  "human adult pro-B ALL blasts - the MLL-EB1 index patient",
  "mouse bone marrow, retroviral transduction/transplantation - MLL/EB1 immortalisation, producing MYELOID lines and acute monocytic leukaemia",
  "no infant cell and no KMT2A::AFF1 cell of any kind"
]
functionally screened in the source paper
{
  "screened": true,
  "shrnas_for_this_gene": 6,
  "design": "Supplementary Table 6 / MOESM5 is the shRNA library for the negative-selection screen: 768 data rows, 128 unique gene symbols, EXACTLY 6 shRNAs each - counted with openpyxl by this beat on 2026-09-21. Host is MLL-AF9-expressing MOLM-13, a human myeloid line.",
  "set_identity_measured_by_this_beat": "The 128 symbols in the shRNA library are the SAME SET as the 128 rows of MOESM4 with n_fusions >= 5, checked by set difference on 2026-09-21: the only four mismatches are alias spellings (JADE2/PHF15, JADE3/PHF16, KMT2A/MLL, NIFK/MKI67IP). This matters for the contamination question. The paper says 'Seven proteins were manually removed as these were either frequently observed contaminants or were not detected in human hematopoietic cell lines. The final set was comprised of 128 proteins.' Because the table's >=5 set is already exactly 128, those seven are NOT recoverable from Supplementary Table 5 - and every protein in this tranche is in the post-removal 128 and was carried into the functional screen.",
  "what_this_does_NOT_establish": "A per-gene result. Scores are presented only as heatmaps (Fig. 2c/2d); no per-gene depletion value is tabulated anywhere in the paper or its supplementary files, so for any individual gene the outcome is measured-not-reported. It is also MLL-AF9 MOLM-13, a myeloid line, not the index fusion and not B-lineage.",
  "the_filter_is_leaky_and_here_is_the_proof": "'Survived the authors' manual contaminant removal' is weaker than it sounds. CCT3 is also in the 128 and was also screened, and the CCT/TRiC chaperonin is the canonical AP-MS contaminant - the companion analysis analyses/mll-fusion-interactome-complexes/ uses it as its NEGATIVE control and it is still significant against a nuclear background (q = 2.7e-05, 8 of 9 subunits in the MLL-AF4 column). The authors' own named essentiality controls were RFC1, SF3A3 and CCT3. So the manual removal did not remove a canonical contaminant complex, and membership in the 128 is not the authors certifying a protein as a real partner.",
  "absence_class_for_the_per_gene_score": "measured-not-reported",
  "library_symbol": "MAPRE1"
}
bounded literature
{
  "query": "MAPRE1[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab] OR \"t(4;11)\"[tiab])",
  "querytranslation": "\"MAPRE1\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract])",
  "count": 2,
  "second_query": "EB1[tiab] AND the identical KMT2A clause",
  "second_querytranslation": "\"EB1\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract] OR \"t 4 11\"[Title/Abstract])",
  "second_count": 2,
  "union": 3,
  "what_they_are": "Title-checked 2026-09-21. 15751040 (MLL fused to EB1 in pro-B ALL) - on topic, the fusion. 30974389 (Ets1 in MLL/EB1 mouse BMT) - on topic, the fusion. 38175436 (two cases of mycosis fungoides with large cell transformation and KMT2A rearrangements) - off topic for MAPRE1. ZERO records report an interaction between wild-type EB1 protein and an MLL fusion. The retired/alias lesson applies: the fusion literature writes MLL-EB1 and never KMT2A::MAPRE1, so the two symbol queries return overlapping-but-different sets and neither alone is sufficient.",
  "date": "2026-09-21",
  "tool": "NCBI esearch db=pubmed",
  "names_tried": [
    "MAPRE1",
    "EB1"
  ],
  "positive_control": "MEN1[tiab] AND the identical five-term KMT2A clause returns 85.",
  "bound": "Titles and abstracts only; supporting figures not searched (rule 80). Cytogenetic term quoted, querytranslation read back with no injected [UID] term (rule 95). One tag per term (rule 94)."
}
what would settle it
[
  "Reanalyse PXD009338 for MAPRE2, MAPRE3, APC and CLIP1 peptides below the rank cutoff. Family-wide sub-threshold presence would make this +TIP carryover.",
  "For the fusion, not the interaction: is MLL/EB1 menin-dependent? Nobody has run a menin inhibitor against it, and a coiled-coil-class fusion with low leukaemogenic potential is exactly the comparator the menin-interface hypothesis needs.",
  "Nuclear/cytoplasmic fractionation blot of wild-type EB1 in any KMT2A-rearranged line. One gel."
]
How this could bite us back
  • MAPRE1 must not reach a target list. EB1 is required for spindle function in every dividing cell, and the interaction this entry is nominally about is probably not real.
  • The bite-back that matters is on the fusion, not the protein: MLL/EB1 immortalised mouse marrow into a MYELOID disease although the index patient had pro-B ALL. Any claim built on this model has to carry that lineage switch in the claim, not the caveat.
  • A coiled-coil partner supplying only oligomerisation means the partner's own biology may be irrelevant to the disease. That is reassuring for drugging KMT2A and discouraging for anyone hoping EB1's microtubule function is a handle.
Still open
  1. Is MLL/EB1 menin-dependent? It is a coiled-coil dimerisation fusion with unusually low leukaemogenic potential, which makes it an informative comparator for the menin-interface hypothesis, and no menin inhibitor has ever been put near it.
  2. Ets1 is the MLL/EB1 effector and is not a canonical MLL-fusion target. Is Ets1 induced by KMT2A::AFF1? The mouse transcriptome comparison was against MLL/AF10 only.
  3. Two of the nine deferred pan-fusion preys - MAPRE1 and VIM - are recurrent KMT2A rearrangement partners and none of the other 33 pan-fusion proteins is. The null was NOT computed by this beat, so this is an observation and explicitly not an enrichment claim. What fraction of any comparable protein set are recurrent fusion partners?
  4. The bait panel is not localisation-neutral: MLL-GAS7's partner is an F-BAR actin-binding protein and two more baits are endocytic. Does the cytoskeletal prey signal in this table track bait identity? Per-bait spectral counts for ACTB, VIM, MAPRE1, MAP7D1 and LUZP1 are all in the table and nobody has looked.
Every source behind this entry (3)
  1. E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper

    MAPRE1/EB1 co-purified with all seven Strep-HA-tagged MLL fusions from nuclear lysates of isogenic human Jurkat T-ALL cells; for MLL-AF4 (= KMT2A::AFF1) the combined p-value is 0.0273 with spectral counts 3|3 and a negative control of 0|0, and it is in the paper's final post-filter set of 128 that entered the MOLM-13 shRNA screen.

    MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. · Skucha A, Ebner J, Schmoellerl J, Roth M, Eder T, Cesar-Razquin A, Stukalov A, Vittori S, Muhar M, Lu B, Aichinger M, Jude J, Mueller AC, Gyorffy B, Vakoc CR, Valent P, Bennett KL, Zuber J, Superti-Furga G, Grebien F · Nature Communications 2018
    PMID 29777171DOI
    What this evidence cannot show

    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 after a single STREP-Tactin step, so co-purification is NOT evidence of a direct contact and is not evidence that the two proteins are ever in the same complex. INCLUSION RULE: the paper kept a fixed number of top-ranked interactions per bait rather than applying a p threshold. Methods, read verbatim from the PMC full text by this beat on 2026-09-21: "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: within the MLL-AF4 column 186 of 291 listed p-values (63.9%) exceed 0.05, and that column's maximum p is 0.175. BAIT DEPTH: for all nine proteins in this tranche the MLL-AF4 spectral total is rank 7 of the seven baits - measured protein by protein - so a low MLL-AF4 count is a bait property (transgene expression, purification depth, or the GLM normalisation) and must not be read as a weaker association than the same protein's count under another bait. HOW TO READ THE NEGATIVE CONTROL, measured by this beat on 2026-09-21 over all 960 rows of MOESM4: the Spearman correlation between a protein's neg_ctrl spectral total and its maximum per-bait spectral total is +0.461, and the median maximum per-bait spectral count is 42 for the 145 proteins (15.1%) with a non-zero negative control against 8 for the 815 with 0|0. A dirty negative control in this table is therefore substantially a statement about protein ABUNDANCE, not about specificity, and a clean 0|0 is substantially a statement that two control replicates were not deep enough to see the protein at all. Two consequences. (1) PSIP1/LEDGF - the one pan-fusion partner with a solved co-crystal against the KMT2A N-terminus - carries 0|5, the second-dirtiest control of the 42, so a non-zero control cannot be used to call a protein a contaminant. (2) A 0|0 control is not purity; it is an unestimated baseline. The paper's GLM estimates each prey's baseline abundance A0,j from the control purifications, so a prey the controls never saw has its baseline set by a floor rather than by data, which is the direction that inflates apparent specificity. WHERE THIS ROW SITS AMONG THE 42, measured by this beat on 2026-09-21: ranked by MLL-AF4 p-value the pan-fusion set runs from MEN1 at 9.75e-16 to SMC3 at 0.174. The three WEAKEST MLL-AF4 calls in the whole pan-fusion set - SMC3 0.174, NOLC1 0.134, TRIM28 0.129 - all already have entries in this graph, and gene-nolc1 and gene-trim28 both carry confidence_overall 'weak' with those p-values recorded. So p > 0.05 in the index-fusion column is not a disqualifier in this corpus; it is a confidence tier that two existing entries already occupy. SPECIFIC TO THIS PROTEIN: MLL-AF4 p = 0.0273, rank 26 of 42, and a combined spectral total of 6 across two replicates - the LOWEST index-fusion depth of the nine proteins in this tranche. UniProt Q15691 records NO nuclear compartment on any of its seven experimental localisation citations. MAPRE2 and MAPRE3 are absent from the 960 at any n, so there is no EB module. A further confound specific to cytoskeletal preys in this table and not noted by the source paper: the bait panel is not localisation-neutral - MLL-AF1p (EPS15) and MLL-EEN (SH3GL1/endophilin) are endocytic partners and MLL-GAS7 is an F-BAR actin-binding protein, so 'recovered by all seven' does not mean 'recovered across a neutral set of baits'. SELECTIVITY: not named among the paper's controls (RFC1, SF3A3, CCT3 non-selective; MEN1 selective), not known to be among the unpublished 40 re-screened. Recorded as unknown. run.py re-run 2026-09-21, both controls PASS.

    Evidence that argues against this (2)
    • The clean 0|0 negative control is the base rate, not a discriminator: 32 of the 42 pan-fusion proteins (76.2%) carry 0|0, counted by this beat on 2026-09-21, and over all 960 rows neg_ctrl total correlates with maximum per-bait spectral abundance at Spearman +0.461. MAPRE1's maximum per-bait total is 32, near the bottom of the range where two control replicates could see anything. Raw spectra at PXD009338 have not been reanalysed and IntAct has never curated this dataset. ProteomeXchange/PRIDE 2018
    • Microtubule-associated and cytoskeletal proteins are among the most frequently observed background proteins in affinity purification-mass spectrometry; the CRAPome authors state that a study's own limited negative controls do not capture a complete background set, which is the condition this row was scored under. No contaminant-repository frequency for Q15691 was retrieved by this beat and it is the cheapest available external check. Mellacheruvu D et al. 2013
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In an adult patient with pro-B acute lymphoblastic leukaemia, the EB1 (MAPRE1) gene at 20q11.2 is fused to MLL, with MLL exon 6 joined in frame to EB1 exon 5; both the MLL-EB1 and the reciprocal EB1-MLL transcripts were verified by RT-PCR, the genomic break junctions were amplified and sequenced, and immunofluorescence staining showed the MLL-EB1 fusion proteins localised in the nuclei.

    PMID 15751040DOI
    What this evidence cannot show

    n = 1 patient, an ADULT with pro-B ALL - the right lineage for this graph but not an infant. Southern blot, cDNA panhandle PCR, RT-PCR and long-distance PCR; the nuclear localisation is an immunofluorescence result on the fusion protein, with no stated construct details in the abstract and no fractionation. The break junctions show multiple breaks with duplicated, deleted and inverted fragments plus 2 bp non-template insertions, which the authors read as a DNA damage-repair origin - so this is a complex rearrangement, not a clean reciprocal translocation. Read from the abstract. This citation says nothing about whether wild-type EB1 protein binds an MLL fusion.

    Evidence that argues against this (1)
    • MLL/EB1 is a WEAK oncoprotein by the same group's own mouse work: lower leukaemogenic ability than MLL/AF10, slower growth with increased apoptosis, acute monocytic leukaemia with incomplete penetrance and longer survival, and it produced myeloid rather than lymphoid lines despite coming from a pro-B ALL patient. So the partner that the index patient's disease was lymphoid does not transfer to the model. Fu JF et al. 2019
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    The coiled-coil four-helix bundle structure of EB1 within MLL/EB1 is required to immortalise mouse bone marrow cells; MLL/EB1 has low leukaemogenic ability relative to MLL/AF10, inducing acute monocytic leukaemia with incomplete penetrance, and Ets1 is selectively upregulated by MLL/EB1 - shRNA knockdown of Ets1 reduced CD115 expression, apoptosis rate, competitive engraftment to marrow and spleen, and leukaemia incidence, and prolonged survival.

    PMID 30974389DOI
    What this evidence cannot show

    MOUSE retroviral transduction / bone marrow transplantation, and the disease produced is MYELOID (acute monocytic leukaemia) although the index patient was pro-B ALL - a lineage switch that must be stated in any claim built on this (rule 73). Transcriptome comparison is against MLL/AF10, not against the index fusion KMT2A::AFF1. Ets1 is one gene selected from 318 differentially induced by at least two-fold. Read from the abstract. This establishes that EB1 is a functional MLL fusion partner of the dimerisation class; it establishes nothing about wild-type EB1 as an interactor.

    Evidence that argues against this (1)
    • The mechanism identified - a coiled-coil four-helix bundle supplying oligomerisation - is the generic dimerisation mechanism shared by the septin, GPHN and GAS7 partners, so nothing about EB1's microtubule biology is required by the fusion. That cuts BOTH ways for this entry: it strengthens the fusion claim (the mechanism is understood) and weakens any attempt to use the fusion as evidence that KMT2A and EB1 belong in the same complex, since a dimerisation module can be supplied by any coiled-coil. Fu JF et al. 2005
Connected to