MTUS2 (TIP150) - a microtubule plus-end tracking protein with 153 partners in the one yeast screen that reported it binding AFF4
also called MTUS2 · TIP150 · CAZIP · KIAA0774 · Microtubule-associated tumor suppressor candidate 2 · Cardiac zipper protein · Q5JR59
MTUS2 rides along the growing ends of microtubules in the cytoplasm. It was listed as a partner of the nuclear protein AFF4 on the strength of one yeast screen, in which it also bound 152 other proteins.
The same thing, for a scientist
MTUS2 (UniProt **Q5JR59, 1,369 aa**, alternative names *cardiac zipper protein* and *tracking protein of 150 kDa*) binds microtubules and, with MAPRE1/EB1, may target the depolymerase KIF2C to microtubule plus ends [E3]. It reaches this graph only through the 2026-09-21 interactome recount, which named it among the seventeen unwritten bait-supported partners on the strength of **three IntAct rows that are three assay annotations of one yeast two-hybrid screen** [E1]. The entry is `speculative`, and the deciding number is that **MTUS2 has 153 distinct partners within that same screen while AFF4 has 5** [E2]. UniProt places MTUS2 in the **cytoplasm and cytoskeleton (ECO:0000269)** with no nuclear annotation; AFF4 is nuclear and chromatin-associated [E3]. `(MTUS2[tiab] OR TIP150[tiab]) AND (MLL[tiab] OR KMT2A[tiab])` returns **0**, and the single leukaemia record is a tick-borne encephalitis virus transcriptomics paper [E4]. **No biology is proposed. This is a recorded rejection with its evidence attached, written so that the name in the gap list resolves to a reason rather than to silence.**
This is a prediction, not a measurement. No one has seen this protein in this shape. The colours say how much the software trusts itself, and that is worth reading before anything else — the orange stretches are places the model is effectively saying this part has no fixed shape.
I have never read one of these pictures before
A protein is one long chain of amino acids that folds up. The ribbon traces that chain from one end to the other; it is not a wire, it is a simplification of where the backbone runs. Drag to rotate, scroll to zoom.
Domains are the stretches of chain that do a particular job, and they are what the coloured blocks above the picture mark out. Click one and the view flies to it. In this project the important question about any domain is usually whether the fusion still has it — the labels say lost where it does not.
Anything in yellow sticks is a bound small molecule, which is usually the drug.
Everything the evidence is, and the one thing worth noticing
AFF4 as DB-fusion bait, MTUS2 as AD-fusion prey, in yeast: pooled primary screen, array retest, pairwise validation. Three MITAB rows, one publication, MI-score 0.56. Not recovered in the successor screen. No mammalian cell, no endogenous protein, no region, affinity or structure. The bait is wild-type AFF4, not AFF1 and not a fusion.
The one thing worth noticing is the name. MTUS2 carries Microtubule-associated tumor suppressor candidate 2 as its recommended name, which is a hypothesis embedded in a symbol. A reader scanning a partner list sees "tumour suppressor candidate" beside "AFF4" and has been handed a story that no experiment supports. The gene's paralogue MTUS1 is the one with the tumour-suppressor literature; MTUS2's designation is by family membership.
That is the same failure mode as brief rule 69's BICRA, whose protein name advertises the wrong partner, and rule 65's HDAC9 protein name containing "HD7". A protein name is a curator's summary, not a finding, and it is doing real work here because "tumour suppressor" is exactly the phrase that would promote this row into a hypothesis.
| uniprot | Q5JR59 |
|---|---|
| gene symbol | MTUS2 |
| length AA | 1369 |
| alphafold ID | AF-Q5JR59-F1 |
| protein class | microtubule plus-end tracking protein; largely coiled-coil |
| uniprot resolution | gene_exact:MTUS2 AND organism_id:9606 AND reviewed:true returned ONE reviewed row on 2026-09-21; primary gene name read back as MTUS2; entry MTUS2_HUMAN; 1,369 aa; synonyms CAZIP, KIAA0774, TIP150. |
| localization | Cytoplasm, cytoskeleton (UniProt Q5JR59, ECO:0000269, retrieved 2026-09-21). No nuclear annotation. |
| localization evidence code | ECO:0000269 |
| domains note | No domain boundaries asserted; the coiled-coil and MAPRE1-binding segment ranges were not read back from UniProt with residue numbers this cycle. |
| name is a hypothesis not a finding | The recommended name is 'Microtubule-associated tumor suppressor candidate 2'. UniProt's own function comment says only that MTUS2 binds microtubules and may target KIF2C to plus ends - no tumour-suppressor function is asserted. The tumour-suppressor literature belongs to the paralogue MTUS1. Same family as brief rules 65 and 69, where a protein name misleads a reader who checks it. |
| shown for fusion | Nobody has looked in any fusion. The assay is wild-type AFF4 against MTUS2 in yeast; there is no MTUS2 experiment in AFF1, in any KMT2A fusion, or in any human cell. |
| verdict | Written as a recorded rejection rather than as a partner. Prey degree 153 in the one screen that reported it, cytoplasmic, no literature. |
domains
[]
interaction with the core complex
{
"partner": "AFF4",
"partner_accession": "Q9UHB7",
"our_protein_role": "prey (AD fusion) in two rows; neutral component in the validation row",
"methods": [
"psi-mi:\"MI:1112\"(two hybrid prey pooling approach)",
"psi-mi:\"MI:0397\"(two hybrid array)",
"psi-mi:\"MI:1356\"(validated two hybrid)"
],
"host_system": "Saccharomyces cerevisiae (taxid:4932)",
"source_publications": [
"25416956"
],
"distinct_experiments": 1,
"intact_acs": [
"intact:EBI-10627130",
"intact:EBI-10321239",
"intact:EBI-10473975"
],
"intact_miscore": 0.56,
"replicated_in_huri_luck_2020": false,
"region_mapped": false,
"affinity_measured": false,
"structures": [],
"compartment_mismatch": "MTUS2 cytoplasmic/cytoskeletal, AFF4 nuclear and chromatin-associated"
}promiscuity controls 2026 09 21 — the numbers behind the chart
{
"distinct_partners_in_rolland_2014": 153,
"distinct_partners_in_bioplex_3_0": 22,
"distinct_partners_all_of_intact": 189,
"distinct_publications_all_of_intact": 11,
"comparator_aff4_in_rolland_2014": 5
}counted absences
{
"kmt2a": {
"query": "(MTUS2[tiab] OR TIP150[tiab]) AND (MLL[tiab] OR KMT2A[tiab])",
"records": 0
},
"leukaemia": {
"query": "(MTUS2[tiab] OR TIP150[tiab]) AND (leukemia[tiab] OR leukaemia[tiab])",
"records_raw": 1,
"records_on_topic": 0,
"pmid": "35685361"
},
"aliases_searched": [
"MTUS2",
"TIP150"
],
"aliases_not_searched": [
"CAZIP",
"KIAA0774",
"cardiac zipper protein"
],
"date": "2026-09-21",
"bound": "zero in titles and abstracts over two of five aliases; the retired KIAA clone identifier was not tried; supporting figures not searched"
}- Nothing here touches an intervention. The hazard is that 'Microtubule-associated tumor suppressor candidate 2' appearing beside AFF4 in a partner table would generate a plausible-sounding tumour-suppressor story with no experiment behind it, which is the specific mistake this entry exists to prevent.
- Does searching the retired identifier KIAA0774 surface any functional literature for MTUS2? This project has measured a tenfold undercount from omitting retired symbols, and two of MTUS2's five aliases went unsearched here.
- Is MTUS2 expressed at all in lymphoid cells? A protein that is absent from the lineage cannot be a partner in it, and a single expression lookup would make this rejection considerably stronger than a degree argument.
- E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
IntAct records AFF4 and MTUS2 as interacting in three rows, all from PMID 25416956 / IMEx IM-23318, in host Saccharomyces cerevisiae, annotated two hybrid prey pooling approach, two hybrid array and validated two hybrid, MI-score 0.56, with no other source publication.
IntAct molecular interaction database, PSICQUIC MITAB 2.7, query id:Q5JR59 AND id:Q9UHB7, 3 rows retrieved 2026-09-21 · IntAct (EMBL-EBI) 2026What this evidence cannot show
Three rows, one publication, one screen, one assay class. Not recovered in HuRI (Luck 2020), although IntAct cannot distinguish 'tested and failed' from 'not in the search space'. No region, affinity, structure or mammalian-cell evidence, and the bait is wild-type AFF4.
Evidence that argues against this (1)
- Rolland et al. present their map as deliberately unbiased and of at least literature-curated quality, so the assay class is not itself grounds for dismissal. The discount applied here is prey degree and compartment, both properties of this pair. Rolland T et al. 2014
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysis
MTUS2 has 153 distinct partners within PMID 25416956 and 22 within BioPlex 3.0, against AFF4's 5 in the 2014 screen.
The four AFF4 two-hybrid partners are three rows of one screen, not three experiments · Oncofusion knowledge graph, ana-the-aff4-two-hybrid-quartet-is-one-screen-and-three-of-the-four-preys-are-hubs 2026What this evidence cannot show
Degrees computed from IntAct's import of each publication on 2026-09-21, deduplicated to distinct accessions. No base rate for the screen's degree distribution was computed, so the load-bearing comparison is 153 against AFF4's own 5 in the same assay. The drop to 22 in BioPlex 3.0 shows the degree is assay-specific and is consistent with a two-hybrid-specific stickiness, but 22 is not itself low.
Evidence that argues against this (1)
- A 153-fold-elevated two-hybrid degree in one screen and a modest AP-MS degree in another is also what a genuinely multivalent scaffold looks like. Degree flags the pair as uninformative about AFF4; it does not establish that MTUS2 binds nothing specifically. Huttlin EL et al. 2021
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProt annotates MTUS2 in cytoplasm and cytoskeleton (ECO:0000269) with no nuclear annotation, and describes it as binding microtubules and, together with MAPRE1, possibly targeting the depolymerase KIF2C to microtubule plus ends; it is UniProt Q5JR59, 1,369 aa, primary gene name MTUS2, synonyms CAZIP, KIAA0774 and TIP150.
UniProtKB entry Q5JR59 (MTUS2_HUMAN, Microtubule-associated tumor suppressor candidate 2), subcellular location and function comments with evidence codes · UniProtKB/Swiss-Prot 2026What this evidence cannot show
Retrieved 2026-09-21 with evidence codes read, per brief rule 91. The whole function comment is hedged in the source ('may target', 'may regulate'). Absence of a nuclear annotation is not a measured absence of nuclear MTUS2, and yeast two-hybrid forces both constructs into the yeast nucleus by design, so the assay cannot see a compartment mismatch. The recommended name asserts a tumour-suppressor candidacy that the function comment does not support.
Evidence that argues against this (1)
- Microtubule plus-end tracking proteins are cytoplasmic in interphase but are exposed to chromatin during mitosis when the nuclear envelope breaks down, so a compartment argument based on interphase annotation is not airtight for this protein class. Rolland T et al. 2014
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
No literature connects MTUS2 to KMT2A, MLL or leukaemia: (MTUS2[tiab] OR TIP150[tiab]) AND (MLL[tiab] OR KMT2A[tiab]) returns 0 records, and the single leukaemia record is PMID 35685361, an RNA profiling study of tick-borne encephalitis virus-infected neurons and astrocytes.
PubMed counted-absence search for MTUS2/TIP150 against MLL, KMT2A and leukaemia, run 2026-09-21 · PubMed (NCBI) 2026What this evidence cannot show
Operand control: the same alias pair against leukemia/leukaemia returns 1, so the query shape is capable of returning non-zero. Aliases searched: MTUS2, TIP150. Not searched: CAZIP, KIAA0774, 'cardiac zipper protein'. KIAA0774 in particular is the kind of retired clone identifier that brief's retired-symbol rule says carries older functional literature, and it was not tried. Zero in titles and abstracts; supporting figures not searched.
Evidence that argues against this (1)
- The retired KIAA clone identifier was not searched, and this project has measured a tenfold undercount from exactly that omission in the septin family. The absence is bounded by a two-alias list and should be read that way. Huttlin EL et al. 2017
yeast two-hybrid hit in Rolland 2014; prey degree 153 in the same screen, cytoskeletal protein, not usable
second-highest-degree prey of the four