KMT2A K1133 acetylation - the better-evidenced half of the pair, and the one that appears in the CBP/p300 acetylome itself
The second of two neighbouring spots on MLL1 that carry the same daily chemical tag. This one turns up in an experiment designed specifically to find what the enzymes CBP and p300 tag, which is the best clue yet about what puts the tag on.
The same thing, for a scientist
Acetyl-K1133 of human KMT2A (Q03164), three residues C-terminal to K1130 in the same tryptic peptide APPIK(1130)PIK(1133)PVTR. Same provenance and regulation as K1130, but better supported in deposited MS: PXD005252 (the Weinert CBP/p300 acetylome) and PXD009839. Its presence in a CBP/p300-focused deposit is the only site-resolved evidence that CBP or p300 is the writer, because the source paper's writer experiment used a pan-acetyl antibody it describes as C-terminally biased.
Why K1133 is the stronger of the pair
| K1130 | K1133 | |
|---|---|---|
| PRIDE deposits | 1 (PXD009839) | 2 (PXD005252, PXD009839) |
| in a CBP/p300-focused deposit | no | yes |
| also ubiquitinated | yes (PXD006201) | no |
| distance to CXXC | 17 aa | 14 aa |
They lie in the same tryptic peptide, so one MS identification could in principle localise to either. That they are reported separately with different deposit sets is weak evidence they are genuinely distinct sites - and it is also exactly what a localisation failure looks like. The endpoint serves no localisation probability for acetylation, so this cannot be resolved from the data available here 2.
The writer question, and the one lookup that would close it
PXD005252 is Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300 acetylome (Weinert et al., Cell 2018, DOI 10.1016/j.cell.2018.04.033), built around CBP/p300-specific catalytic inhibitors, a bromodomain inhibitor and gene knockout.
Acetyl-K1133 being in that deposit means the peptide was detected in that experiment. It does NOT mean the site was CBP/p300-dependent - the deposit contains the whole measured acetylome, not only the regulated subset. Reading that paper's quantitative supplementary tables for Q03164 K1133 under A-485 would assign a writer to this residue. It has not been done, and it is one lookup 2.
| uniprot | Q03164 |
|---|---|
| position | 1133 |
| residue | K |
| modification | acetylation |
| writer | CBP/p300 candidate - detected in PXD005252; dependence NOT established |
| eraser | SIRT1 |
| fusion status | RETAINED |
| distance to cxxc residues | 14 |
| distance to breakpoint cluster residues | 205 |
| exon | 5 |
| within sirt1 interaction region | true |
| tryptic peptide | APPIKPIKPVTR |
| peptide distinguishes fusion from wildtype | false |
| shown for fusion | NO - nobody has looked in any fusion |
pride deposits
[ "PXD005252", "PXD009839" ]
measurements
[
{
"quantity": "PRIDE deposits reporting this site",
"subject": "Q03164 K1133 acetylation",
"value": 2,
"units": "deposits",
"n": 21,
"universe": "21 acetylation site-calls on Q03164 in the EBI reprocessed-PRIDE set",
"null": null,
"note": "twice the deposit support of K1130; one of the two is the CBP/p300 acetylome"
},
{
"quantity": "distance from acetylation site to CXXC N-terminus",
"subject": "Q03164 K1133 to CXXC start 1147",
"value": 14,
"units": "residues",
"n": 1,
"universe": "UniProt Q03164 feature coordinates",
"null": null,
"note": "closer to the CXXC than K1130 is"
}
]- If CBP/p300 is confirmed as the writer, the pharmacology points at CBP/p300 inhibitors - A-485, CCS1477/inobrodib - which are already in leukaemia trials for entirely different reasons. A positive result here would be immediately over-read as a rationale for a drug class whose leukaemia activity is driven by MYC and the androgen receptor, not by KMT2A acetylation.
- Both CBP/p300 inhibition and SIRT1 modulation are global interventions on the acetylome. Neither has any prospect of being selective for one lysine on one protein, so a mechanism established here does not translate into a tractable intervention without an entirely new modality.
- Is K1133 acetylation lost when CBP/p300 catalysis is inhibited? PXD005252's own quantitative data would answer this and assign a writer to the residue. It is one supplementary-table lookup and it is the cheapest unanswered mechanistic question in this beat.
- Can K1130 and K1133 be distinguished by mass spectrometry at all, given they share a tryptic peptide? A targeted PRM assay with synthetic mono-acetylated standards would settle whether this graph should hold two entries or one.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
KMT2A is acetylated at K1133 (human numbering), erased by SIRT1, circadian and NAD+-responsive, and a K1133R substitution abolishes recognition by the site-specific antibody.
NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1 · Aguilar-Arnal L, Katada S, Orozco-Solis R, Sassone-Corsi P · Nature Structural & Molecular Biology 22(4):312-8 2015What this evidence cannot show
Site-level evidence is a custom antibody plus K->R validation on a fragment (Fig 3e). No catalytic assay carries a site mutant. No haematopoietic system was used.
Evidence that argues against this (1)
- The antibody logic does not establish what it is usually read as establishing. The antigen was the DOUBLY acetylated peptide APPIK(ac)PIK(ac)PVTR, so loss of signal against a single K1133R substitution shows that K1133 is required for the EPITOPE - which it would be whether or not K1133 itself carries an acetyl group in cells, since the substitution also changes the side chain the antibody contacts. A mono-acetyl-specific reagent, or targeted MS, would be needed to separate those. Pointedly, UniProt does not curate K1133 as N6-acetyllysine while it does curate K636, K1130 and K1235.
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Acetylation at Q03164 K1133 is reported in PRIDE PXD005252 - a deposit built around CBP/p300 catalytic inhibition - and in PXD009839.
EBI Proteins API - proteomics-ptm, Q03164 (KMT2A) - K1133 acetylation · EMBL-EBI Proteins API / PRIDE-reprocessed MS evidence 2026What this evidence cannot show
Detection in a CBP/p300-focused deposit is not a demonstration of CBP/p300 dependence; the deposit contains the whole acetylome it measured. The Weinert supplementary tables were NOT read. K1130 and K1133 lie in one tryptic peptide, so localisation within that peptide is an MS inference and no localisation probability is served for acetylation by this endpoint.
Evidence that argues against this (1)
- If the two are in fact one poorly localised modification, this graph should treat them as a single site - and the source paper's antibody, raised against a DOUBLY acetylated peptide, could not distinguish them either.
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Position 1133 of UniProt Q03164 is a lysine.
UniProtKB Q03164 (KMT2A_HUMAN) canonical sequence · UniProt 2026What this evidence cannot show
Residue identity verified against the live UniProt Q03164 FASTA (3,969 aa) on 2026-09-24, not taken from a paper's text. Canonical isoform only.
Evidence that argues against this (1)
- True but not the load-bearing question. K1130 and K1133 lie in one tryptic peptide, so every MS call here is a within-peptide localisation inference, and this endpoint serves no localisation probability for acetylation. That the position is a lysine does not distinguish it from the lysine three residues away.
- part of →KMT2A / MLL1 — the gene that breaks
Q03164 K1133, exon 5, retained in every classical KMT2A fusion
SIRT1 deacetylates K1133; catalytically dead SIRT1(H363Y) does not
same tryptic peptide APPIKPIKPVTR; the source antibody was raised against the doubly acetylated form
one of 71 retained MS-evidenced sites
the human numbering this entry uses