KMT2A K636 acetylation - the forgotten member of the Choudhary quartet, retained, and outside the SIRT1-interaction region
One of four chemical tag spots found on MLL1 in a 2009 survey. The famous follow-up paper mentioned it once and then ignored it, because it sits outside the stretch the paper was interested in.
The same thing, for a scientist
Acetyl-K636 of human KMT2A (Q03164), one of the four sites the 2009 Choudhary acetylome reported and the only one of the four the 2015 circadian paper explicitly set aside - it lies OUTSIDE the CLOCK/SIRT1-interacting region that the paper identified around K1130/K1133/K1235. It is nonetheless RETAINED (702 residues N-terminal to the breakpoint cluster) and is independently re-observed in two PRIDE deposits including the CBP/p300 acetylome. Nothing functional is known about it in any system.
Why the source paper dropped it
"Interestingly, K1130, K1133 and K1235 are located within the MLL1 region that interacts with CLOCK and SIRT1" 1
K636 is not. The paper's truncation mapping put the SIRT1 contact at aa 650-1327, and 636 falls 14 residues short of it. That is the entire reason K636 disappears from the paper after one sentence - it was excluded on a positional criterion, not on evidence that it is unmodified or unimportant.
For a leukaemia reader that criterion is irrelevant. The question here is retention, not circadian relevance, and K636 is retained with a much larger margin than K1130 (702 vs 208 residues). It sits between the AT-hooks and the CXXC, in exon 3.
| uniprot | Q03164 |
|---|---|
| position | 636 |
| residue | K |
| modification | acetylation |
| sequence context 624 648 | HSRSEPQYFSSAKYAKEGLIRKPIF |
| fusion status | RETAINED |
| distance to breakpoint cluster residues | 702 |
| exon | 3 |
| within sirt1 interaction region | false |
| eraser | unknown - never tested |
| shown for fusion | NO - nobody has looked in any fusion |
sirt1 interaction region AA
[ 650, 1327 ]
pride deposits
[ "PXD005252", "PXD041171" ]
measurements
[
{
"quantity": "distance from acetylation site to breakpoint cluster start",
"subject": "Q03164 K636 to exon 8 start 1338",
"value": 702,
"units": "residues",
"n": 1,
"universe": "Ensembl ENST00000534358 exon boundaries",
"null": null,
"note": "3.4x the margin of K1130; retained under any plausible breakpoint including rare 5' ones"
},
{
"quantity": "distance from K636 to the mapped SIRT1-interaction region",
"subject": "Q03164 K636 to region start 650",
"value": 14,
"units": "residues",
"n": 1,
"universe": "the M1-M6 truncation mapping in PMID 25751424",
"null": null,
"note": "outside, but only just - and the 650 boundary is a truncation-construct boundary, not a measured contact edge"
}
]- An entry for a site nobody has studied risks giving the site standing it has not earned. It is here because the enumeration should be complete and because its exclusion from the source paper had a weak reason, not because there is evidence it matters.
- Is K636 deacetylated by SIRT1 too? It was excluded from the source paper on the grounds that it sits 14 residues outside a truncation-construct boundary, which is not evidence about the enzyme. The paper's own site-specific antibody cannot answer it, but a pan-acetyl IP plus MS under EX527 could.
- Does K636 acetylation do anything? Nothing is known in any system. It is the only one of the four Choudhary sites with no functional literature at all, which makes it either uninteresting or unexamined and there is currently no way to tell which.
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper
K636 is one of four lysines reported acetylated in human MLL1 by the 2009 global acetylome, and PMID 25751424 explicitly places only K1130, K1133 and K1235 - not K636 - within the CLOCK/SIRT1-interacting region it mapped to aa 650-1327.
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
The paper performs no experiment on K636 at all - no antibody, no mutant, no measurement. Its only appearance is in the sentence listing the four Choudhary sites. Everything about its regulation is therefore unknown, including whether SIRT1 touches it.
Evidence that argues against this (1)
- The paper's exclusion of K636 is a positional argument against a truncation-construct boundary at aa 650. That boundary is where a cloning primer was placed, not a measured edge of the SIRT1 contact, so 'K636 is outside the SIRT1 region' is weaker than it sounds and could be an artefact of construct design.
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Acetylation at Q03164 K636 is reported in PRIDE PXD005252 (CBP/p300 acetylome) and PXD041171.
EBI Proteins API - proteomics-ptm, Q03164 (KMT2A) - K636 acetylation · EMBL-EBI Proteins API / PRIDE-reprocessed MS evidence 2026What this evidence cannot show
Two deposits, one of which (PXD041171) is an HCMV/SIRT2 study in fibroblasts. Detection, not dependence.
Evidence that argues against this (1)
- Both deposits reporting K636 also report K928, K1243 and K2958, so they are broad acetylome surveys rather than targeted evidence about this residue. Detection in a survey is not evidence of regulation.
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
Position 636 of Q03164 is a lysine; the local sequence is HSRSEPQYFSSAKYAKEGLIRKPIF (aa 624-648).
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. Canonical isoform only.
Evidence that argues against this (1)
- The sequence context around K636 (…SSAKYAKEGLIRK…) contains three lysines within eleven residues, so site localisation within the tryptic peptide is an inference and a neighbouring lysine could be the true acceptor.
- part of →KMT2A / MLL1 — the gene that breaks
Q03164 K636, exon 3, retained with a 702-residue margin
one of 10 retained acetylation sites