GLUD1 is a hexameric mitochondrial matrix dehydrogenase recovered on 11 spectra with non-zero control signal from a nuclear pulldown — and this corpus has already declined one KMT2A partner whose sole source was a cryo-EM structure of GLUD1 — declined
also called MLL-AF4-GLUD1 · KMT2A-GLUD1 · GDH1 · Glutamate dehydrogenase 1, mitochondrial
GLUD1 is a very abundant enzyme that lives inside mitochondria and works as a six-part barrel. It turns up in a pulldown done on cell nuclei, alongside fifteen other mitochondrial enzymes, and it also appeared in the negative control. This graph has already met GLUD1 once before as a passenger in somebody else's experiment.
The same thing, for a scientist
**Verdict: DECLINED on compartment.** GLUD1 (P00367, 558 aa, GDH1) is annotated *"Mitochondrion"* ECO:0000269|PubMed:19448744 with a minor ER pool from the same citation and **no nuclear annotation** [E1]. Its MLL-AF4 evidence is p = 0.0399, spectral counts 5|6 = 11, **neg_ctrl 0|1**, rank 88 of 291, one bait only [E2]. It is one of the sixteen mitochondrial proteins in a specific tail that is 14.5% mitochondrial against the shared core's 2.4% (Fisher p = 0.042) [E3]. Two features make GLUD1 a textbook AP-MS passenger rather than a borderline case: it is among the most abundant proteins in the mitochondrial matrix, and it assembles as a **homohexamer**, so a single contaminating particle contributes six copies' worth of peptides. **This corpus has already encountered exactly that behaviour**: `interface-kmt2a-klhl22-declined-a-cryoem-paper-about-glutamate-dehydrogenase` declined a KMT2A row whose only source was a HEK293F over-expression made to solve a CUL3–KLHL22–GDH1 cryo-EM structure [E4].
Why GLUD1 specifically
Three properties compound:
- Abundance. GLUD1 is one of the highest-copy proteins in the mitochondrial matrix. Detectability in any preparation that carries mitochondria is close to guaranteed, and this beat's own denominator control showed that control-column detectability in this dataset is a function of abundance rather than of stickiness.
- Hexameric assembly. GDH1 functions as a homohexamer. One contaminating complex delivers six subunits, so spectral counts overstate the number of contaminating particles by that factor. Eleven spectra is consistent with a very small number of carried-over complexes.
- Non-zero control. GLUD1's neg_ctrl is 0|1. It is the second of the six candidates with any control signal at all (LEF1 being the other). One count is weak, but its direction is unambiguous.
Against all that: GLUD1 is one of the few metabolic enzymes with a genuinely interesting non-canonical literature, and glutamine/glutamate metabolism is an active question in leukaemia. GLUD1[tiab] AND leukemia[tiab] returns 2 records 5 — not zero, and a beat wanting to pursue glutamate metabolism in KMT2A-rearranged disease has somewhere to start. That pursuit should not start here. This row is evidence about a nuclear preparation, not about a contact.
The corpus has met GLUD1 before, and the shape was the same
interface-kmt2a-klhl22-declined-a-cryoem-paper-about-glutamate-dehydrogenase records that IntAct's single KMT2A–KLHL22 record comes from PMID 37788672, a cryo-EM structure of CUL3–KLHL22 bound to the GDH1 hexamer, and that KMT2A is a HEK293F over-expression passenger there, not the paper's subject 4. So this graph now holds two independent instances in which GLUD1 sits beside KMT2A in a mass-spectrometry or structural dataset, in two different systems, by two different routes, neither of which is about either protein. Two independent appearances of an abundant protein in two unrelated pulldowns is what an abundant protein does; it is not corroboration, and reading it as such would be the error this entry exists to prevent.
| partner a | gene-kmt2a |
|---|---|
| partner a uniprot | Q03164 |
| partner a length AA | 3969 |
| partner b | GLUD1 |
| partner b uniprot | P00367 |
| partner b length AA | 558 |
| verdict | DECLINED |
| verdict scope | Declined on compartment, abundance and oligomeric state. Not a claim that glutamate or glutamine metabolism is irrelevant to KMT2A-rearranged leukaemia; that question needs a drug-name and pathway-phrase literature search this entry did not run. |
| adjudicated by | Q180-the-af4-specific-interactors, cycle 159, 2026-09-24 |
| source publication pmid | 29777171 |
| source dataset | PXD009338, Skucha 2018 seven-bait MLL-fusion AP-MS |
| detection method | single-step StrepTactin affinity purification from Jurkat nuclear extract, LC-MS/MS spectral counting with a GLM background model |
| experimental role partner | prey |
| experimental role kmt2a | bait (as the MLL-AF4 fusion) |
| bait exists in dataset | true |
| n publications | 1 |
| n methods | 1 |
| orthogonal method exists | false |
| intact curated | false |
| af4 p | 0.0399 |
| af4 spectral | 5|6 |
| af4 spectral total | 11 |
| neg ctrl | 0|1 |
| neg ctrl total | 1 |
| rank in af4 by p | 88 |
| n fusions | 1 |
| oligomeric state | homohexamer - one contaminating particle contributes six subunits' worth of peptides |
| same length paralogue | GLUD2 (P49448), 558 aa, not resolved by this dataset and absent from Supplementary Table 5 |
| druggability | Not assessable from this row. GDH1 is itself a druggable enzyme with tool inhibitors, which makes it more important, not less, to keep this row out of any target rationale. |
| absence class | measured-not-searched |
| absence class note | The peptide evidence for these eleven spectra is in PXD009338 and unread. So is whether any of them distinguish GLUD1 from GLUD2. |
| shown for fusion | MLL-AF4 only, as one prey row in one AP-MS experiment in a Jurkat T-ALL host with a tagged transgene. |
| epigenetic readout | none - no histone mark, occupancy or chromatin measurement exists for GLUD1 in any KMT2A context. |
host cell lines
[ "Jurkat (human T-ALL)" ]
compartment mismatch
{
"partner_compartments": [
"Mitochondrion [ECO:0000269|PubMed:19448744]",
"Endoplasmic reticulum (minor) [ECO:0000269|PubMed:19448744]"
],
"partner_nuclear_annotation": "none at any evidence level",
"sample_compartment": "nuclear extract",
"class_rate": "16 of 110 MLL-AF4-only preys are mitochondrial against 1 of 42 pan-fusion; Fisher two-sided p 0.0417"
}measurements
[
{
"quantity": "spectral_counts",
"subject": "GLUD1|MLL-AF4",
"value": 11,
"units": "spectra (5|6 over two replicates)",
"n": 2,
"universe": "Skucha 2018 Suppl Table 5, MLL-AF4 column",
"null": 1,
"note": "null column is the neg_ctrl total (0|1); p = 0.0399, rank 88 of 291. As a homohexamer, 11 spectra corresponds to few contaminating particles."
}
]interface residues a
[]
structures
[]
ligands
[]
- GDH1 has tool inhibitors, so this is a row that could plausibly be turned into a drug proposal. It should not be. A metabolic intervention justified by a contaminated nuclear pulldown would put an infant on a pathway inhibitor for a contact that was never measured.
- Glutamate dehydrogenase is essential to normal hepatic and neuronal nitrogen handling; GLUD1 gain-of-function causes hyperinsulinism-hyperammonaemia, so the therapeutic window for inhibiting it is a real question and not a formality.
- Do any of the eleven GLUD1 spectra distinguish GLUD1 from its 558-aa paralogue GLUD2? Answerable from PXD009338.
- Is there a glutaminolysis or glutamate-dehydrogenase dependency in KMT2A-rearranged leukaemia? A real question, unanswered here, and one that needs drug-name and pathway-phrase queries (EGCG, R162, purpurin, 'glutaminolysis') rather than the GLUD1 symbol - rule 71.
- GLS (glutaminase) is also in the AF4-specific tail, at p = 0.106, and has 5 corpus mentions and a decision entry from the Q109 serine panel. Do GLS and GLUD1 appearing together in the same tail mean anything, or is it two abundant mitochondrial enzymes in the same contaminated preparation? The second reading is the default and nothing here displaces it.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
GLUD1 is UniProt P00367 (DHE3_HUMAN), primary gene symbol GLUD1, 558 aa, 'Glutamate dehydrogenase 1, mitochondrial (GDH 1) (EC 1.4.1.3)', annotated to Mitochondrion with ECO:0000269|PubMed:19448744 plus a minor endoplasmic-reticulum pool from the same citation, and no nuclear annotation at any evidence level.
UniProtKB P00367 (DHE3_HUMAN), Glutamate dehydrogenase 1, mitochondrial — accession, primary gene name, length and subcellular-location comment retrieved 2026-09-24 · UniProt Consortium, EMBL-EBI/SIB/PIR 2026What this evidence cannot show
Resolved by accession with the primary gene name read back (rules 62, 65); the only listed synonym is GLUD, and there is no row in data/symbol-collisions.json. Note the paralogue GLUD2 (P49448, X-linked, 558 aa) shares the same length and high sequence identity with GLUD1, so the length check gives no protection between them - the sheet's accession is P00367 and that is what is asserted here. The expected_absent_terms entry records the absence of a nuclear comment as part of the claim.
Evidence that argues against this (1)
- GLUD1 and GLUD2 are both 558 aa and highly similar, so the same shared-peptide problem raised for RGPD8 applies here in a milder form, and it cuts in an unexpected direction: if some of the eleven spectra are GLUD2, the identification is even less specific than stated. Neither this entry nor the source study resolves the pair, and GLUD2 does not appear anywhere in Supplementary Table 5. UniProt Consortium 2026
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
GLUD1's entire evidence as an MLL-AF4 partner is one prey row in Skucha 2018 Supplementary Table 5: p = 0.0399, spectral counts 5|6 (11 summed), neg_ctrl 0|1, rank 88 of 291, recovered under MLL-AF4 and none of the other six baits.
MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. · Skucha A, Ebner J, Schmöllerl J, Roth M, et al. (20 authors; Grebien F senior author) · Nature Communications 2018What this evidence cannot show
Read from the cached Supplementary Table 5 workbook with the column map asserted against the sheet's header row. GLUD1 is not discussed anywhere in the paper. At rank 88 of 291 it sits below the point where the MLL-AF4 list is majority non-significant, and its p of 0.0399 is a rank-selected call in a list that runs to p = 0.175.
Evidence that argues against this (1)
- Eleven spectra balanced across replicates (5 and 6) is the most reproducible detection of the six candidates after LEF1, and a control of 0|1 is one count, not a meaningful baseline. On the raw numbers GLUD1 looks better than RGPD8, RPA2 or CEP112, and this entry declines it on compartment and abundance rather than on the counts - which is a judgement about priors, not a reading of the data. Nature Communications 2018
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
GLUD1 is one of sixteen mitochondrial proteins among the 110 MLL-AF4-only preys (14.5%), against one of 42 (2.4%) among the pan-fusion preys of the same bait, Fisher exact two-sided p = 0.0417, in a purification performed on nuclear extract.
Compartment audit of the Skucha 2018 MLL-AF4 prey classes against live UniProt, run 2026-09-24 by Q180. Script analyses/q180-is-af4-specificity-a-depth-artefact/compartment_of_the_tail.py, output compartment_of_the_tail.json; 152 of 152 accessions resolved. · This repository (script and JSON committed) plus UniProtKB REST 2026What this evidence cannot show
The pan-fusion comparison arm is selected for abundant nuclear proteins by construction, so part of the contrast is definitional. At n = 42 the Fisher p is fragile. Annotations were counted at any ECO level (rule 91), and 58 of the 110 singletons fall in neither compartment and are not interpreted.
Evidence that argues against this (1)
- A class rate does not convict a member. Of the sixteen mitochondrial proteins in the tail, GLS and C1QBP both have reported non-canonical nuclear pools in the literature, so the class is not homogeneous and treating it as such would decline real biology along with the background. GLUD1 is declined because it is additionally abundant and hexameric, not merely because it is in the class. This repository 2026
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
This corpus has previously declined a different KMT2A partner, KLHL22, because its sole supporting record came from a HEK293F over-expression performed to obtain a cryo-EM structure of CUL3–KLHL22 bound to the GLUD1/GDH1 hexamer (PMID 37788672), with KMT2A a pulldown passenger — the second independent dataset in this graph in which GLUD1 and KMT2A co-occur without either being the subject.
KMT2A-KLHL22 - DECLINED. The single source is a cryo-EM structure of KLHL22-CUL3 bound to glutamate dehydrogenase, and KMT2A is a HEK293F pull-down passenger with no nuclear rationale · This repository, entry interface-kmt2a-klhl22-declined-a-cryoem-paper-about-glutamate-dehydrogenase 2026What this evidence cannot show
The adjudication is quoted from an existing entry in this corpus, but PMID 37788672 WAS independently fetched by this beat on 2026-09-24 and resolves to Teng F, Wang Y, Liu M, Tian S, Stjepanovic G, Su MY, 'Cryo-EM structure of the KLHL22 E3 ligase bound to an oligomeric metabolic enzyme', Structure 2023 Nov 2 - the title names the enzyme only as 'an oligomeric metabolic enzyme', so the identification of that enzyme as GDH1 comes from the earlier entry's reading of the paper body and not from the title. The full text was not read here. The two datasets are genuinely independent in system (HEK293F over-expression for cryo-EM versus Jurkat nuclear-extract AP-MS) and in route, which is what makes the co-occurrence worth recording.
Evidence that argues against this (1)
- The natural but wrong reading of this item is that two independent datasets placing GLUD1 near KMT2A CORROBORATE a contact. They do not: an abundant protein appears near everything, and the correct inference from two appearances of an abundant protein in two unrelated pulldowns is that the protein is abundant. If GLUD1 had appeared twice as a specific, low-abundance, high-scoring prey the reading would be different. This repository, entry interface-kmt2a-klhl22-declined-a-cryoem-paper-about-glutamate-dehydrogenase 2026
- E5moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
GLUD1 has a small but non-empty leukaemia literature independent of this row: GLUD1[tiab] AND leukemia[tiab] returns 2 records on 2026-09-24, and there is no record linking GLUD1 to KMT2A or to any MLL fusion.
PubMed esearch via scripts/pubmed_safe.py, run 2026-09-24 by Q180; one [tiab] tag per term (rule 94), querytranslation read back as "GLUD1"[Title/Abstract] AND "leukemia"[Title/Abstract], non-empty. · NCBI PubMed E-utilities 2026What this evidence cannot show
Bounded by titles and abstracts (rule 80). Name list tried: GLUD1 only. NOT tried: GDH1, GDH, 'glutamate dehydrogenase', 'glutaminolysis', the British spelling leukaemia, or the drug-name route rule 71 requires (EGCG, R162, purpurin and other GDH inhibitors) - and a pathway named by its drug is exactly the case rule 71 says a symbol search misses. The 2 is therefore a floor and a weak one; the two titles were not read.
Evidence that argues against this (1)
- Rule 71 applies squarely here and this evidence item fails it: glutaminolysis in leukaemia is a real literature that a GLUD1 symbol search cannot reach, because papers name the pathway or the inhibitor rather than the enzyme. A beat wanting to know whether glutamate dehydrogenase matters in KMT2A-rearranged disease must run the drug-name and pathway-phrase queries, and this count says nothing about that question. It bears only on whether GLUD1 has been linked to KMT2A specifically, and there the answer is no by any route tried. NCBI PubMed E-utilities 2026
same class-level compartment argument; GLUD1 adds abundance and hexameric assembly
the second independent dataset in this graph placing GLUD1 beside KMT2A without either being the subject; co-occurrence of an abundant protein, not corroboration
- related to →KMT2A / MLL1 — the gene that breaks
declined KMT2A::AFF1-GLUD1 pair: 11 spectra, a matrix hexamer, non-zero negative control
GLUD1 is the other mitochondrial enzyme the definition retains while excluding AFF1, AFF4 and ELL