OGT - the O-GlcNAc transferase, a Polycomb-complexome bait that pulls down KMT2A, and already the metabolic dial on DOT1L in this graph
also called O-GlcNAc transferase · OGT1 · O-GLCNAC · HRNT1 · UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit
OGT is the single enzyme that decorates thousands of nuclear proteins with a sugar tag, and when a 2016 study purified the human Polycomb machinery using OGT as one of its handles, KMT2A came out attached to it. This graph already records OGT keeping DOT1L alive through the same sugar tag, so OGT touches this cancer's machinery from two directions - but the KMT2A pull-down itself is one experiment in a kidney cell line that nobody has repeated.
The same thing, for a scientist
OGT (HGNC:8127, ENSG00000147162, UniProt O15294, 1,046 aa, Xq13.1) is the sole human O-linked N-acetylglucosamine transferase. It enters this project's core-complex interactome on exactly one curated row: IntAct IM-21659 from Hauri et al. 2016, tandem affinity purification, association, MI-score 0.35, **OGT bait / KMT2A prey**, host HEK293 [E1][E2]. The source paper is an AP-MS map of the human Polycomb complexome whose abstract names OGT1 as a component of two human PR-DUB deubiquitination complexes [E1] - so OGT's anchored role in that paper is PR-DUB, and the KMT2A row is a co-purifying prey in the same network, spoke-expanded, with no orthogonal validation reported for the pair. **It is not a demonstrated KMT2A-OGT contact and this entry does not present it as one.** What lifts OGT above a one-row prey is an independent, mechanistic OGT dependency this graph already holds: O-GlcNAcylation of DOT1L S1511 blocks the UBE3C ligase and sets DOT1L abundance from hexosamine flux, and OGT or HBP inhibition sensitises MLL-fusion cells to a DOT1L inhibitor [E3]. OGT is also a listed NSL-complex subunit here [E4].
What the interaction record actually is
One IntAct row, IM-21659, deposited 2013-10-28, last updated 2026-01-11. Detection MI:0676 tandem affinity purification; interaction type MI:0914 association; expansion MI:1060 spoke; experimental roles MI:0496 bait (OGT) / MI:0498 prey (KMT2A); host organism taxid:9606(Homo sapiens HEK293 embryonic kidney cell); curator annotation figure legend: Figure 1 and supplementary table 2 2.
Three consequences, all of which belong with any use of this row. (i) Method: AP-MS, not a binary assay - no two-hybrid, no reconstitution, no co-IP of the endogenous pair is reported for OGT-KMT2A. (ii) Cell type: HEK293 embryonic kidney. Not haematopoietic, not leukaemic, not KMT2A-rearranged. (iii) Direction: OGT was the handle. KMT2A came out of an OGT purification, which is the informative direction for asking whether OGT's complexes contain KMT2A and the uninformative direction for asking what KMT2A's complex contains.
Why OGT earns an entry anyway: the epigenetic role is not the AP-MS row
OGT has three separate footprints on the biology this project studies, and the interaction row is the weakest of them.
PR-DUB. Hauri et al. state that the two human PR-DUB deubiquitination complexes they resolve contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors, and that human PR-DUB and PRC1 bind distinct target-gene sets 1. PR-DUB removes H2AK119ub - the mark this project measured across cycles 104-105. An OGT sitting inside the eraser of that mark is a node on an axis the graph is actively working, whether or not it ever touches KMT2A.
DOT1L abundance. mechanism-dot1l-oglcnacylation-stability records that DOT1L is O-GlcNAcylated at the conserved S1511, that the modification impairs UBE3C-mediated degradation, and that inhibiting HBP or OGT increases sensitivity to a DOT1L inhibitor 3. That is a real, orthogonally supported OGT dependency in MLL-fusion leukaemia and it is a far stronger reason to care about OGT here than the interaction row is.
NSL. protein-nsl-complex lists OGT among the NSL subunits 4.
Localization and subnuclear address
UniProt O15294 carries ECO:0000269 experimental subcellular-location calls for nucleus, cytoplasm, mitochondrion and membrane, reflecting the ncOGT / mOGT / sOGT isoforms 5. There is no subnuclear assignment in the record - no speckle, no nucleolus, no lamina - so this entry makes none. Per rule 91 the uncoded comments were read alongside the coded ones; the isoform-scoped statements are the substantive ones here, because the mitochondrial isoform is a different protein pool from the nuclear one and an AP-MS row cannot say which pool produced it.
Other fusion families
Not looked for, and not claimed. The DOT1L O-GlcNAc mechanism is reported for MLL-fusion leukaemia as a class rather than for a named index fusion 3. This entry asserts nothing about OGT in NUP98, CBFA2T3::GLIS2, RUNX1::RUNX1T1 or any other family. That is a genuine gap and it is listed as an open question rather than filled by inference.
| hgnc ID | HGNC:8127 |
|---|---|
| symbol | OGT |
| ensembl gene ID | ENSG00000147162 |
| uniprot | O15294 |
| length AA | 1046 |
| chromosomal location | Xq13.1 |
| identifier provenance | HGNC REST fetch/symbol/OGT and UniProtKB O15294 both retrieved live 2026-09-23. Neither was recalled. |
| subnuclear location | none assigned in UniProt; none asserted here |
| cell type of the observation | HEK293 embryonic kidney - not haematopoietic, not KMT2A-rearranged |
| epigenetic role | Sole human O-GlcNAc transferase. Component of two human PR-DUB complexes (the H2AK119ub eraser) per PMID 27705803; listed NSL-complex subunit here; sets DOT1L abundance via S1511 O-GlcNAc. |
| shown for fusion | NO - nobody has looked in any fusion. The interaction row is wild-type KMT2A in HEK293. The DOT1L O-GlcNAc mechanism is reported for MLL-fusion leukaemia as a class with no index fusion named. |
| evidence class | single publication, single method, spoke-expanded AP-MS, no orthogonal validation of the pair |
prev and alias symbols
[ "O-GLCNAC", "HRNT1", "MGC22921", "FLJ23071", "OGT1" ]
interaction with project baits
[
{
"bait": "KMT2A",
"bait_uniprot": "Q03164",
"partner_experimental_role": "bait",
"scaffold_experimental_role": "prey",
"method": "MI:0676 tandem affinity purification",
"interaction_type": "MI:0914 association",
"expansion": "MI:1060 spoke",
"mi_score": 0.35,
"imex": "IM-21659",
"pmid": "27705803",
"host_cell": "HEK293 embryonic kidney",
"n_rows": 1,
"n_publications": 1
}
]subcellular location uniprot
[ "Nucleus (ECO:0000269)", "Cytoplasm (ECO:0000269)", "Mitochondrion (ECO:0000269)", "Membrane (ECO:0000269)" ]
- OGT is the ONLY O-GlcNAc transferase in the human genome and its substrate set runs to thousands of nuclear and cytoplasmic proteins. An OGT inhibitor is an essential-function toxicity problem before it is an efficacy question, and combining one with a DOT1L inhibitor stacks two slow-acting epigenetic agents in an infant population.
- Because O-GlcNAc flux tracks nutrient availability, any OGT-directed effect is confounded by the metabolic state of the cell and of the patient; a synergy measured in high-glucose medium may not exist in marrow.
- If the DOT1L-stabilising route is the real dependency, resistance is cheap: a UBE3C loss-of-function, or any lesion raising DOT1L abundance post-translationally, restores the mark without needing OGT at all.
- The PR-DUB link cuts both ways. Inhibiting an H2AK119ub eraser raises a repressive mark genome-wide, and this graph has already found H2AK119ub unscoreable in the bulk, so the on-target pharmacodynamic readout for such an intervention does not currently exist.
- Does an OGT purification from a KMT2A-rearranged human leukaemia line (SEM or MV4-11) recover KMT2A or the fusion, or is the HEK293 row a kidney-cell artefact? One AP-MS experiment settles it.
- Is the OGT-KMT2A co-purification mediated by PR-DUB, given that PR-DUB is OGT's anchored complex in the source paper and PR-DUB erases the H2AK119ub this project has been measuring?
- Is KMT2A or KMT2A::AFF1 itself O-GlcNAcylated, and if so does it change menin binding, chromatin residence or turnover? No O-GlcNAc site on KMT2A was found by this beat.
- Is the OGT / DOT1L-inhibitor synergy retained in KMT2A::AFF1 B-lineage disease specifically, or is it an MLL-AF9 myeloid observation generalised?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Hauri et al. mapped the human Polycomb complexome by affinity purification mass spectrometry and identified two human PRC2 complexes and two PR-DUB deubiquitination complexes which contain the O-linked N-acetylglucosamine transferase OGT1 and several transcription factors; genome-wide profiling indicated that human PR-DUB and PRC1 bind distinct sets of target genes.
A High-Density Map for Navigating the Human Polycomb Complexome. · Hauri S, Comoglio F, Seimiya M, et al. · Cell Rep 2016What this evidence cannot show
ABSTRACT ONLY. The paper is not open access at Europe PMC (isOpenAccess=N, no PMCID served), so the full text, the bait list and the supplementary tables were not read. Every statement attributed to this citation is taken from the abstract. The abstract does NOT mention KMT2A, MLL or any fusion - the KMT2A-OGT pair is reachable only through the IntAct deposition [E2], which is why this entry keeps the two citations separate instead of merging them into one claim.
Evidence that argues against this (1)
- An AP-MS network reports co-purification, not contact. This design cannot distinguish an OGT-KMT2A contact from both proteins being present in one purification through a third subunit, and no binary or reconstitution assay for this pair was found by this beat. source 2026
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
IntAct serves exactly one curated human OGT-KMT2A row: PSI-MI MI:0676 tandem affinity purification, MI:0914 association, MI:1060 spoke expansion, OGT experimental role MI:0496 bait and KMT2A MI:0498 prey, MI-score 0.35, host organism taxid:9606 Homo sapiens HEK293 embryonic kidney cell, IMEx IM-21659, source publication PMID 27705803.
IntAct molecular interaction database (EMBL-EBI), PSICQUIC tab27 record for id:O15294 AND id:Q03164 2026What this evidence cannot show
Retrieved live 2026-09-23 through the PSICQUIC tab27 endpoint. Rule 93 applies: PSICQUIC under-reports relative to the IntAct REST endpoint and cannot reach processed-chain identifiers, so one row is a FLOOR on this pair and not a census. The count was not cross-checked against REST for this specific pair.
Evidence that argues against this (1)
- A single spoke-expanded AP-MS row with no second publication and no second method is the weakest class of interaction evidence this graph recognises; this project's own instrument flags the pair single_method_single_paper. source 2026
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
DOT1L is O-GlcNAcylated at the conserved residue S1511; the modification impairs the interaction with the E3 ligase UBE3C and so stabilises DOT1L, hexosamine biosynthetic pathway flux therefore raises H3K79 methylation and HOXA9/MEIS1 expression in MLL-fusion leukaemia, and inhibiting HBP or OGT increases cellular sensitivity to a DOT1L inhibitor.
mechanism-dot1l-oglcnacylation-stability (this graph) - see that entry for the primary citation 2026What this evidence cannot show
GRAPH-INTERNAL POINTER, NOT AN INDEPENDENT VERIFICATION. This item cites this graph's existing mechanism entry rather than re-deriving the primary paper, because that entry already carries the primary citation and this beat did not re-read it. Flagged explicitly so nobody counts it as a second source.
Evidence that argues against this (1)
- An OGT dependency mediated through DOT1L is a reason to care about OGT in this disease but is NOT evidence for an OGT-KMT2A contact. Conflating the two would be exactly the inflation this entry is written to avoid. source 2026
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
OGT is a listed subunit of the NSL complex in this graph's protein-nsl-complex entry, which is reached from KANSL1.
What this evidence cannot show
Graph-internal. Not independently re-verified against a primary NSL composition paper by this beat.
Evidence that argues against this (1)
- This is a graph-internal assertion that was not re-verified against a primary NSL composition paper by this beat. Complex rosters in this corpus are explicitly NOT counted as entries for their subunits by the project's own instrument, and a subunit list is exactly the kind of field that goes stale when a complex's composition is revised. source 2026
- E5established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProt O15294 is 1,046 aa and carries ECO:0000269 experimental subcellular-location calls for nucleus, cytoplasm, mitochondrion and membrane, with no subnuclear compartment assigned.
What this evidence cannot show
Fetched live 2026-09-23. Rule 91: an ECO:0000269 code means a curator read an experiment in the cited paper, not that the paper is the founding or the best observation for that location; the cited papers were not opened.
Evidence that argues against this (1)
- Rule 91, applied to the case that motivated it: KMT2A's own UniProt record carries three location comments of which the two fragment-scoped ones are UNCODED, so filtering on ECO:0000269 keeps the least useful line. The same filter was applied here, so OGT's isoform- and condition-scoped location statements may have been discarded, and the four coded locations listed are a partial picture of where this protein is. source 2026
- co-occurs with →KMT2A / MLL1 — the gene that breaks
OGT bait / KMT2A prey in one spoke-expanded TAP-MS row, IntAct IM-21659, HEK293 - co-purification, not a demonstrated contact
O-GlcNAcylates DOT1L S1511, blocking UBE3C-mediated degradation and setting DOT1L abundance from hexosamine flux
OGT is the enzyme in this mechanism
listed NSL-complex subunit
- related to →Plain-English: chromatin and epigenetics — the sticky notes on the DNA, and which ones matter here
O-GlcNAc as a chromatin-directed modification; OGT sits in the human PR-DUB complexes that erase H2AK119ub