Rv0726c Resolved · high auto-curated

H37Rv Rv0726c · MTBC0 mtbc0_000768 · 367 aa · 822730–823833 (-) · RefSeq NP_215240.1

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 P9WFI7 SwissProt · reviewed · Evidence at protein level
UniProt namePutative S-adenosyl-L-methionine-dependent methyltransferase Rv0726c
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 Rv0726c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
eggNOG descriptionExhibits S-adenosyl-L-methionine-dependent methyltransferase activity
Orthologous groupCOG3315

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 0.427 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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
LCMPF04072.21 2.6e-7224–209 Leucine carboxyl methyltransferase

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

Closest characterised functional partner: serA2 (D-3-phosphoglycerate dehydrogenase SerA), medium confidence from genomic context alone (score 481 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0725c hyp hypothetical protein 650 649 ctx neighborhood:587
Rv0728c serA2 D-3-phosphoglycerate dehydrogenase SerA 481 481 ctx neighborhood:478
Rv0727c fucA L-fuculose phosphate aldolase FucA 481 481 ctx neighborhood:478
Rv2794c pptT 4'-phosphopantetheinyl transferase 449 449 ctx cooccurence:447
Rv3862c whiB6 transcriptional regulator WhiB6 444 50 textmining:439
Rv2752c rnj ribonuclease J 808 47 textmining:807
Rv0565c monooxygenase 803 44 textmining:803
Rv3261 fbiA 2-phospho-L-lactate transferase 550 44 textmining:549
Rv1014c pth peptidyl-tRNA hydrolase 402 42 textmining:402
Rv0402c mmpL1 transmembrane transport protein MmpL1 803 41 textmining:803
Rv3260c whiB2 transcriptional regulator WhiB2 655 41 textmining:655

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=3e-72)
  • (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_215240.1)
  • 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 P9WFI7 (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 — 11 functional partner(s); context anchor serA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000768|Rv0726c|
MTYTGSIRCEGDTWDLASSVGATATMVAAARAMATRAANPLINDQFAEPLVRAVGVDVLTRLASGELTASDIDDPERPNASMVRMAEHHAVRTKFFDEFFMDATRAGIRQVVILASGLDSRAYRLAWPAQTVVYEIDQPQVMEFKTRTLAELGATPTADRRVVTADLRADWPTALGAAGFDPTQPTAWSAEGLLRYLPPEAQDRLLDNVTALSVPDSRFATESIRNFKPHHEERMRERMTILANRWRAYGFDLDMNELVYFGDRNEPASYLSDNGWLLTEIKSQDLLTANGFQPFEDEEVPLPDFFYVSARLQRKHRQYPAHRKPAPSWRHTACPVNELSKSAAYTMTRSDAHQASTTAPPPPGLTG