Tmlh notes
- 2026-10-09: Initial review. Tmlh (CG4335, Q9VDM7) is the fly ortholog of human TMLHE,
mitochondrial trimethyllysine dioxygenase (EC 1.14.11.8, RHEA:14181 in UniProt, ARBA-derived).
- Only fly paper: Okada et al. 2023 EMBO J PMID:37140455. Tumour-derived NetrinB suppresses
fat-body Tmlh: "Ras‐induced dysplastic tissues secrete NetB, which humorally inhibits TMLHE
expression in the fat body, leading to reduction of carnitine biosynthesis (Fig 5M)."
Also "TMLHE knockdown in the fat body aggravates organismal survival over the oncogenic stress."
and "TMLHE plays an important role in carnitine biosynthesis and hence acetyl‐CoA production from
fatty acids (Fig 4A)." PMID:37140455
- Enzymatic activity of the fly protein has not been assayed; MF accepted by orthology (ISS from
human Q9NVH6 and IEA from Rhea/EC).
- Decisions: mitochondrion IBA MODIFY -> mitochondrial matrix (already ISS); iron ion binding
MODIFY -> ferrous iron binding; generic oxidoreductase/2OG dioxygenase MODIFY -> GO:0050353.
- Carillo et al. 2020 review PMID:33371457: "Blast analysis indicates that in Drosophila,
Dmel/CG4335 is the putative orthologous gene, which is an uncharacterized gene harbored on the
right arm of chromosome 3."
- Falcon deep research (Tmlh-deep-research-falcon.md) concurs: identity as TMLHE ortholog, mitochondrial
targeting sequence, activity inferred by orthology only; also notes CG4335 transcript changes in
Lipin nuclear-mutant RNA-seq (fat body). Did not find the Okada 2023 paper.