Rv2732c Family assigned · medium

H37Rv Rv2732c · MTBC0 mtbc0_002906 · 204 aa · 3066790–3067404 (-) · RefSeq NP_217248.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Radical-SAM tRNA-modifying enzyme of the MiaB family (tRNA-2-methylthio-N6-dimethylallyladenosine synthase-like). RefSeq leaves it 'hypothetical protein'.

Curated reference (UniProt)

UniProt O33237 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2F4G5

Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 0.715 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.16% of strains (239) · clonal

pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.

Domains (Pfam, hmmscan --cut_ga)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: miaB ((dimethylallyl)adenosine tRNA methylthiotransferase), high confidence from genomic context alone (score 882 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2733c miaB (dimethylallyl)adenosine tRNA methylthiotransferase 882 882 ctx neighborhood:882
Rv3205c hyp hypothetical protein 780 781 ctx cooccurence:774
Rv2446c integral membrane protein 777 777 ctx cooccurence:772
Rv3850 hyp hypothetical protein 775 775 ctx cooccurence:772
Rv3212 hyp hypothetical protein 774 775 ctx cooccurence:772
Rv1109c hyp hypothetical protein 774 774 ctx cooccurence:773
Rv0556 transmembrane protein 774 774 ctx cooccurence:773
Rv0358 hyp hypothetical protein 774 774 ctx cooccurence:773
Rv3438 hyp hypothetical protein 773 773 ctx cooccurence:772
Rv1632c hyp hypothetical protein 772 773 ctx cooccurence:772
Rv3217c integral membrane protein 771 771 ctx cooccurence:765
Rv1166 lpqW monoacyl phosphatidylinositol tetramannoside-binding protein LpqW 767 767 ctx cooccurence:765
Rv0383c ttfA hyp hypothetical protein 766 766 ctx cooccurence:766
Rv0475 hbhA heparin binding hemagglutinin HbhA 764 764 ctx cooccurence:762
Rv2171 lppM lipoprotein LppM 763 763 ctx cooccurence:762

STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.

Evidence

  • Foldseek vs AFDB-SwissProt: MiaB tRNA methylthiotransferase, TM 0.72, E 5e-19
  • Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.

Sources

  • Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
  • Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217248.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
  • Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021, doi:10.1093/molbev/msab293), eggNOG 5.0 DB (Huerta-Cepas et al. 2019) — OG 2F4G5
  • Curated reference: UniProt O33237 (TrEMBL, unreviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 129 functional partner(s); context anchor miaB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002906|Rv2732c|
MMSHEHDAGDLDALRAEIEAAERRVAREIEPGARALVVAILVFVLLGSFILPHTGSVRGWDVLFSSHGAGRAAVALPSRVFAWLALVFGVGFSMLALLTRRWALAWVALAGSAMASGTGLLAVWSRQTVAAGHPGPGIGLIVAWITAIVLTFHWAQVVWSRTIVQLAAEERRRRVVAQQQCKTLLDHVQTDSEAGTTPDRGTDR