Rv0224c Resolved · high auto-curated

H37Rv Rv0224c · MTBC0 mtbc0_000238 · 254 aa · 268244–269008 (-) · RefSeq NP_214738.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methyltransferase
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: Methyltransf_23 (PF13489.13), Methyltransf_11 (PF08241.19), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WJZ9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized methyltransferase Rv0224c
EC (curated) EC 2.1.1.-

UniProt still lists this protein as Uncharacterized methyltransferase Rv0224c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionMethyltransferase
Orthologous groupCOG0500
Gene Ontology (2) GO:0008150, GO:0040007

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 missense, 0 nonsense, 0 frameshift

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)

PfamAccessioni-EvalueResiduesDescription
Methyltransf_23PF13489.13 1.3e-0956–158 Methyltransferase domain
Methyltransf_11PF08241.19 1.2e-1763–155 Methyltransferase domain
Methyltransf_25PF13649.13 7.4e-1163–152 Methyltransferase domain
Methyltransf_12PF08242.19 4.0e-0763–153 Methyltransferase domain

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

Closest characterised functional partner: aftD (alpha-(1->3)-arabinofuranosyltransferase), high confidence from genomic context alone (score 800 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0225 hyp hypothetical protein 898 898 ctx neighborhood:615 cooccurence:745
Rv0236c aftD alpha-(1->3)-arabinofuranosyltransferase 807 800 ctx cooccurence:653
Rv0226c transmembrane protein 749 749 ctx cooccurence:743
Rv0227c membrane protein 736 736 ctx cooccurence:734
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 629 630 ctx cooccurence:628
Rv3802c membrane protein 614 614 ctx cooccurence:592
Rv3635 transmembrane protein 613 614 ctx cooccurence:607
Rv0228 acyltransferase 571 571 ctx cooccurence:567
Rv0223c aldehyde dehydrogenase 547 543 ctx neighborhood:543
Rv1489A hyp hypothetical protein 473 474 ctx cooccurence:472
Rv1684 hyp hypothetical protein 465 465
Rv1476 membrane protein 450 451 ctx cooccurence:448
Rv3794 embA arabinosyltransferase A 434 434 ctx cooccurence:429
Rv0885 hyp hypothetical protein 431 432 ctx cooccurence:430
Rv0555 menD bifunctional 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase/2-oxoglutarate decarboxylase 451 152

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

  • Legacy H37Rv annotation: methyltransferase
  • MTBC0 PGAP product: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_23 PF13489.13 (E=1e-09), Methyltransf_11 PF08241.19 (E=1e-17), Methyltransf_25 PF13649.13 (E=7e-11), Methyltransf_12 PF08242.19 (E=4e-07)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

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_214738.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_23 (PF13489.13), Methyltransf_11 (PF08241.19), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19)
  • 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 COG0500
  • Curated reference: UniProt P9WJZ9 (SwissProt, reviewed; 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 — 16 functional partner(s); context anchor aftD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000238|Rv0224c|
MAVTDVFARRATLRRSLRLLADFRYEQRDPARFYRTLAADTAAMIGDLWLATHSEPPVGRTLLDVGGGPGYFATAFSDAGVGYIGVEPDPDEMHAAGPAFTGRPGMFVRASGMALPFADDSVDICLSSNVAEHVPRPWQLGTEMLRVTKPGGLVVLSYTVWLGPFGGHEMGLSHYLGGARAAARYVRKHGHPAKNNYGSSLFAVSAAEGLRWAAGTGAALAVFPRYHPRWAWWLTSVPVLREFLVSNLVLVLTP