Oncofusion

start / graph / ptm-kmt2a-k1235-acetylation

Mechanismmoderate confidence 3 of 5: One strong study, or several smaller consistent ones.q165-the-retained-acetylation-site

KMT2A K1235 acetylation - inside the SIRT1-interaction region, retained, and the one member of the Choudhary quartet the source paper named and then never assayed

A third chemical-tag spot on MLL1 that sits inside the same stretch the clock enzymes grab hold of. The paper that studied the other two named this one in the same sentence and then never touched it again.

The same thing, for a scientist

Acetyl-K1235 of human KMT2A (Q03164). One of the four sites from the 2009 Choudhary acetylome; PMID 25751424 places it, with K1130 and K1133, inside the MLL1 region that interacts with CLOCK and SIRT1 (mapped to aa 650-1327) - and then performs no experiment on it. It carries no site-specific antibody, no mutant and no measurement. It is curated in UniProt as N6-acetyllysine, is re-observed in PRIDE PXD009839, sits in exon 7 (aa 1212-1338), and is RETAINED with a 103-residue margin to the exon 7/8 boundary - the tightest margin of the four.

Go deeper
The tightest margin of the four, and why that matters
siteexonresidues to the exon 7/8 boundary (1338)residues to the earliest UniProt-annotated breakpoint (1334)
K6363702698
K11305208204
K11335205201
K1235710399

K1235 is the one where retention could plausibly have failed, and it does not: even the earliest annotated KMT2A translocation breakpoint in UniProt's feature table, 1334..1335 for KMT2A-ZFYVE19, leaves 99 residues of margin 2. It is retained in every known KMT2A fusion.

It is also the only one of the four in exon 7, the last exon before the breakpoint cluster opens. Exon 7 is the exon that is intact in essentially every fusion transcript and truncated in none.

What is not known

Everything. There is no antibody, no mutant, no functional assay and no enzyme assignment for K1235 in any organism. Its entire evidence base is: two MS observations (Choudhary 2009 via the source paper's sentence, and PXD009839), plus UniProt curation derived from those. It is named in a high-profile paper and has never been studied, which is a different state from a site nobody has heard of, and arguably a more actionable one - an existing sentence in a Nature Structural & Molecular Biology paper is a citable justification for looking.

Facts and figures
uniprotQ03164
position1235
residueK
modificationacetylation
sequence context 1223 1247SEKKDSKESSVVKNVVDSSQKPTPS
fusion statusRETAINED
distance to exon78 boundary residues103
distance to earliest annotated breakpoint residues99
exon7
within sirt1 interaction regiontrue
uniprot curatedtrue
writerunknown
eraserunknown - never tested, though it lies inside the SIRT1-contact region
shown for fusionNO - nobody has looked in any fusion
sirt1 interaction region AA
[
  650,
  1327
]
pride deposits
[
  "PXD009839"
]
measurements
[
  {
    "quantity": "distance to the earliest UniProt-annotated KMT2A translocation breakpoint",
    "subject": "Q03164 K1235 to breakpoint 1334",
    "value": 99,
    "units": "residues",
    "n": 1,
    "universe": "the 7 SITE breakpoint annotations in the Q03164 feature table",
    "null": null,
    "note": "the tightest margin of the four Choudhary sites, and still comfortably retained"
  }
]
How this could bite us back
  • This site has a high-profile citation and no data. That combination is how an unstudied residue acquires the appearance of established biology - it will be cited as 'a known MLL1 acetylation site' by anyone who reads the sentence and not the figures.
Still open
  1. Is K1235 a SIRT1 substrate? It sits inside the mapped SIRT1-contact region and was never tested, while K1130/K1133 outside-of-nothing were. The paper's own logic predicts yes and the experiment was not done.
  2. Is K1235 acetylation the reason the source paper's pan-acetyl signal survives a K1130/3R double mutant? Fig 3e shows the site-specific antibody lost, but pan-acetyl signal would not be, and K1235 is the obvious remaining N-terminal candidate.
Every source behind this entry (3)
  1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    K1235 is one of four lysines reported acetylated in human MLL1, and PMID 25751424 places it inside the MLL1 region interacting with CLOCK and SIRT1 while performing no experiment on it.

    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 2015
    PMID 25751424DOI
    What this evidence cannot show

    The site's only appearances in the paper are the sentence listing the four Choudhary sites and the sentence placing three of them in the CLOCK/SIRT1 region. Its inclusion in the site-specific antibody is explicitly excluded - the antigen peptide APPIK(ac)PIK(ac)PVTR covers 1126-1137 only.

    Evidence that argues against this (1)
    • The paper names K1235 and then does nothing with it, so its inclusion in the 'CLOCK/SIRT1 region' rests entirely on a positional argument about a truncation-construct boundary. A construct boundary at 650-1327 is where the cloning primers were, not where the contact surface ends, so both the inclusion of K1235 and the exclusion of K636 could be wrong in either direction.
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    Position 1235 of Q03164 is a lysine, is curated by UniProt as N6-acetyllysine, and the earliest translocation breakpoint UniProt annotates on KMT2A is 1334..1335, leaving K1235 with 99 residues of margin.

    What this evidence cannot show

    Residue identity verified against the live UniProt Q03164 FASTA (3,969 aa) on 2026-09-24. Canonical isoform only. UniProt's SITE breakpoint annotations are a curated selection of published fusions, not a census of clinical breakpoints; a rarer 5' breakpoint could in principle fall earlier.

    Evidence that argues against this (1)
    • UniProt curates K1235 as N6-acetyllysine on the strength of the same large-scale MS evidence that feeds the PRIDE layer, so the UniProt annotation and the PXD009839 call are NOT independent confirmations of each other - they are one observation reported twice.
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

    Acetylation at Q03164 K1235 is reported in PRIDE PXD009839.

    EBI Proteins API - proteomics-ptm, Q03164 (KMT2A) - K1235 acetylation · EMBL-EBI Proteins API / PRIDE-reprocessed MS evidence 2026
    What this evidence cannot show

    One deposit, a human cytomegalovirus acetylome in fibroblasts. Same single-deposit weakness as K1130.

    Evidence that argues against this (1)
    • PXD009839 is an HCMV infection time-course. Acetylation changes are the explicit subject of that study, so a site detected there may be infection-induced rather than constitutive, and nothing establishes that K1235 is acetylated in an uninfected cell.
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