Rv0281 Resolved · high auto-curated

H37Rv Rv0281 · MTBC0 mtbc0_000300 · 302 aa · 344292–345200 (+) · RefSeq NP_214795.1

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 P9WFI9 SwissProt · reviewed · Evidence at protein level
UniProt namePutative S-adenosyl-L-methionine-dependent methyltransferase Rv0281
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 Rv0281; 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 (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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, 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 1.8e-6518–198 Leucine carboxyl methyltransferase

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

Closest characterised functional partner: eccC3 (ESX-3 secretion system protein EccC3), high confidence from genomic context alone (score 917 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0284 eccC3 ESX-3 secretion system protein EccC3 916 917 ctx neighborhood:498 coexpression:797
Rv0282 eccA3 ESX-3 secretion system protein EccA 916 907 ctx neighborhood:499 coexpression:798
Rv0283 eccB3 ESX-3 secretion system protein EccB3 901 902 ctx neighborhood:499 coexpression:733
Rv0280 PPE3 PPE family protein PPE3 826 773 ctx neighborhood:713
Rv2751 hyp hypothetical protein 764 764 ctx cooccurence:764
Rv0286 PPE4 PPE family protein PPE4 581 581 ctx neighborhood:451
Rv0290 eccD3 ESX-3 secretion system protein EccD 534 534
Rv0285 PE5 PE family protein PE5 490 490 ctx neighborhood:490
Rv0291 mycP3 membrane-anchored mycosin MycP 439 439
Rv0289 espG3 ESX-3 secretion-associated protein EspG3 426 426
Rv0287 esxG ESAT-6 like protein EsxG 704 421 textmining:510
Rv2794c pptT 4'-phosphopantetheinyl transferase 407 408 ctx cooccurence:404
Rv0288 esxH ESAT-6-like protein EsxH 587 372
Rv2059 hyp hypothetical protein 459 279
Rv0106 hyp hypothetical protein 405 237

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=2e-65)
  • (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_214795.1)
  • 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 P9WFI9 (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 eccC3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000300|Rv0281|
MRTEGDSWDITTSVGSTALFVATARALEAQKSDPLVVDPYAEAFCRAVGGSWADVLDGKLPDHKLKSTDFGEHFVNFQGARTKYFDEYFRRAAAAGARQVVILAAGLDSRAYRLPWPDGTTVFELDRPQVLDFKREVLASHGAQPRALRREIAVDLRDDWPQALRDSGFDAAAPSAWIAEGLLIYLPATAQERLFTGIDALAGRRSHVAVEDGAPMGPDEYAAKVEEERAAIAEGAEEHPFFQLVYNERCAPAAEWFGERGWTAVATLLNDYLEAVGRPVPGPESEAGPMFARNTLVSAARV