Rv0146 Resolved · high auto-curated

H37Rv Rv0146 · MTBC0 mtbc0_000157 · 310 aa · 172557–173489 (+) · RefSeq NP_214660.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)S-adenosylmethionine-dependent methyltransferase
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: LCM (PF04072.21).

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

Curated reference (UniProt)

UniProt P9WFJ3 SwissProt · reviewed · Evidence at protein level
UniProt namePutative S-adenosyl-L-methionine-dependent methyltransferase Rv0146
EC (curated) EC 2.1.1.-
Curated functionExhibits S-adenosyl-L-methionine-dependent methyltransferase activity.

UniProt still lists this protein as Putative S-adenosyl-L-methionine-dependent methyltransferase Rv0146; 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 descriptionExhibits S-adenosyl-L-methionine-dependent methyltransferase activity
Orthologous groupCOG3315
Gene Ontology (44) GO:0002682, GO:0002684, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0009605, GO:0009607, GO:0016020 +32 more

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) pseudogene candidate

pN/pS 0.519 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 4 missense, 2 nonsense, 0 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 6.00% of strains (8716) · 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)

PfamAccessioni-EvalueResiduesDescription
LCMPF04072.21 4.9e-6718–204 Leucine carboxyl methyltransferase

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

Closest characterised functional partner: Rv0145 (S-adenosylmethionine-dependent methyltransferase), high confidence from genomic context alone (score 837 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0145 S-adenosylmethionine-dependent methyltransferase 836 837 ctx neighborhood:816
Rv0147 aldehyde dehydrogenase 785 785 ctx neighborhood:775
Rv0144 transcriptional regulator 743 743 ctx neighborhood:739
Rv0148 short-chain type dehydrogenase/reductase 708 708 ctx neighborhood:699
Rv0149 quinone oxidoreductase 509 508 ctx neighborhood:503
Rv0143c transmembrane protein 415 415 ctx neighborhood:413

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: S-adenosylmethionine-dependent methyltransferase
  • MTBC0 PGAP product: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): LCM PF04072.21 (E=5e-67)
  • (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_214660.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LCM (PF04072.21)
  • 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 COG3315
  • Curated reference: UniProt P9WFJ3 (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 — 6 functional partner(s); context anchor Rv0145
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000157|Rv0146|
MRTHDDTWDIKTSVGATAVMVAAARAVETDRPDPLIRDPYARLLVTNAGAGAIWEAMLDPTLVAKAAAIDAETAAIVAYLRSYQAVRTNFFDTYFASAVAAGIRQVVILASGLDSRAYRLDWPAGTIVYEIDQPKVLSYKSTTLAENGVTPSAGRREVPADLRQDWPAALRDAGFDPTARTAWLAEGLLMYLPAEAQDRLFTQVGAVSVAGSRIAAETAPVHGEERRAEMRARFKKVADVLGIEQTIDVQELVYHDQDRASVADWLTDHGWRARSQRAPDEMRRVGRWVEGVPMADDPTAFAEFVTAERL