yhcC (P0ADW6) notes

Deep research was unavailable for this gene (no deep-research provider run; RADICAL_SAM
project Phase 2). Built from cached primary literature (including a 2026 preprint found by
PubMed search), UniProt and a local motif check.

Identity

• 309 aa radical SAM protein, Elp3/MiaB/NifB-like clan (Pfam PF04055 + PF16199
  Radical_SAM_C; InterPro IPR005911 YhcC-like; NCBIfam TIGR01212). PANTHER
  PTHR11135:SF1 "PROTEIN YHCC".
• The cluster-binding motif is not a clean CxxxCxxC: UniProt places the [4Fe-4S]
  ligands at C33, C45 and C48 (ECO:0000250 from Q9X0Z6), and a regex scan of the sequence
  finds no CxxxCxxC; the spacing is C33-x11-C45-x2-C48. Checked locally on the UniProt
  sequence.
• UniProt FUNCTION: [file:ECOLI/yhcC/yhcC-uniprot.txt "In vitro, can cleave
  S-adenosyl-L-methionine into methionine"] and COFACTOR "Binds 1 [4Fe-4S] cluster",
  both ECO:0000269|PubMed:25117543.

Function: YhcC is the anaerobic MnmL of E. coli

Boswinkle et al. 2026 (bioRxiv preprint, full text cached) assign the function
PMID:42239373:

• In vivo: "we find YhcC is necessary for cmnm5s2U demodification in vivo under anaerobic
  growth"; ΔyhcC grown anoxically accumulates cmnm5s2U and makes no mnm5s2U even though
  mnmC is present ["Additionally, cmnm5s2U accumulated in tRNAs extracted from the ΔyhcC
  mutant grown under anoxic conditions despite the presence of mnmC."]; complementation
  restores mnm5s2U, and a C33A cluster-ligand variant does not ["showing that the
  conversion of cmnn5s2U to nm5s2U relies on YhcC catalysis"]. Under aerobic growth ΔyhcC
  has no phenotype, because MnmC1 needs O2.
• In vitro: purified, [4Fe-4S]-reconstituted YhcC binds tRNA ["found that YhcC binds tRNA
  with a KD of approximately 5 μM"] and converts cmnm5s2U to nm5s2U ["providing direct in
  vitro evidence that YhcC catalyzes the cmnm5s2U to nm5s2U reaction on tRNA"], SAM
  dependently.
• Earlier: PMID:25117543 validated YhcC as a genuine iron-sulfur protein; the preprint
  restates it ["YhcC has also been confirmed to bind a [4Fe-4S] cluster and is capable of
  cleaving SAM to methionine and 5'-deoxyadenosine in the presence of a chemical
  reductant"].
• Regulation: FNR-activated anaerobically; gene neighbour arcB.
• The authors propose renaming the gene ["yhcC should be renamed to mnmL in E. coli and in
  related facultative anaerobes"]. Review keeps the symbol yhcC (current UniProt/GOA
  nomenclature).
• Family context: MnmL was identified in B. subtilis and S. mutans as the YtqA-subgroup
  rSAM enzyme needed for mnm5s2U PMID:38551342.
• Independently cited in a 2026 review [PMID:42517620: "under anaerobiosis, this reaction
  is catalyzed by YhcC, a radical SAM-dependent enzyme that is orthologous to MnmL"].

Caveat: the primary source is a preprint. Evidence is genetic plus in vitro with purified
protein, and it is corroborated by the peer-reviewed B. subtilis MnmL work and by the
review above, so the assignment is treated as established here.

Ontology gap

No GO MF term exists for the cmnm5s2U -> nm5s2U demodification. Checked QuickGO and OLS
(2026-10-19) for "carboxymethylaminomethyl", "5-aminomethyl-2-thiouridine", "cmnm5",
"methylaminomethyl": the only MF hits are GO:0004808 (the MnmC2 methyltransferase step) and
GO:0141102 (an unrelated 2'-O-ribose methyltransferase). E. coli MnmC (P77182), which
performs the same demodification aerobically, carries only GO:0016645 oxidoreductase
activity, acting on the CH-NH group of donors for its MnmC1 domain. Rhea has the oxidative
version of the reaction (RHEA:72279, with a generic acceptor A) but not a SAM-dependent
one. Proposed a new MF term; BP is covered by GO:0002098 tRNA wobble uridine modification.

Curation decisions

• GO:0003824 MODIFY to the proposed new term (reaction now known).
• GO:0051536 MODIFY to GO:0051539; GO:0051539 (IDA) ACCEPT and core: catalysis is
  established, so the cluster is the catalytic cofactor.
• NEW: GO:0000049 tRNA binding (IDA, EMSA), GO:1904047 SAM binding (IC, per the project
  convention for members with established catalysis), GO:0002098 tRNA wobble uridine
  modification (IMP; YhcC catalyses a step itself, so participation is satisfied).
• No cytoplasm row added: localization was not determined, only inferred.