Rv2959c Resolved · high auto-curated

H37Rv Rv2959c · MTBC0 mtbc0_003142 · 245 aa · 3333276–3334013 (-) · RefSeq NP_217475.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)rhamnosyl O-methyltransferase
MTBC0 PGAP re-annotationrhamnosyl O-methyltransferase
Revised (this work)Rhamnosyl O-methyltransferase. Pfam: RMNT_CmcI (PF04989.19), Methyltransf_24 (PF13578.13).

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

Curated reference (UniProt)

UniProt P9WIM5 SwissProt · reviewed · Evidence at protein level
UniProt nameRhamnosyl O-methyltransferase
EC (curated) EC 2.1.1.-
Curated functionCatalyzes the O-methylation of the hydroxyl group located on C-2 of the first rhamnosyl residue linked to the phenolic group of glycosylated phenolphthiocerol dimycocerosates (PGL) and p-hydroxybenzoic acid derivatives (p-HBAD).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category V Defense mechanisms
eggNOG descriptionCatalyzes the O-methylation of the hydroxyl group located on C-2 of the first rhamnosyl residue linked to the phenolic group of glycosylated phenolphthiocerol dimycocerosates (PGL) and p-hydroxybenzoic acid derivatives (p-HBAD)
Orthologous groupCOG3510
Gene Ontology (52) GO:0005575, GO:0005623, GO:0005886, GO:0006022, GO:0006023, GO:0006024, GO:0006029, GO:0006082, GO:0006790, GO:0006807, GO:0008150, GO:0008152 +40 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 0.862 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 3.32% of strains (4817) · 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
RMNT_CmcIPF04989.19 1.8e-7850–244 Rhamnosyl O-methyltransferase/CmcI
Methyltransf_24PF13578.13 1.0e-0684–191 Methyltransferase domain

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

Closest characterised functional partner: Rv2958c (PGL/p-HBAD biosynthesis glycosyltransferase), high confidence from genomic context alone (score 814 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2958c PGL/p-HBAD biosynthesis glycosyltransferase 979 814 ctx neighborhood:529 database:500 textmining:891
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 633 633 ctx cooccurence:633
Rv2075c hyp hypothetical protein 626 626 ctx cooccurence:626
Rv2231A vapC16 ribonuclease VapC16 602 602 ctx cooccurence:602
Rv0355c PPE8 PPE family protein PPE8 600 600 ctx cooccurence:598
Rv3350c PPE56 PPE family protein PPE56 592 592 ctx cooccurence:590
Rv2082 hyp hypothetical protein 586 586 ctx cooccurence:584
Rv0104 hyp hypothetical protein 586 586 ctx cooccurence:586
Rv3347c PPE55 PPE family protein PPE55 580 580 ctx cooccurence:578
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 571 571 ctx cooccurence:571
Rv3343c PPE54 PPE family protein PPE54 565 566 ctx cooccurence:560
Rv0304c PPE5 PPE family protein PPE5 564 565 ctx cooccurence:562
Rv2949c chorismate pyruvate-lyase 905 545 ctx cooccurence:517 textmining:800
Rv2209 integral membrane protein 543 543 ctx cooccurence:543
Rv1004c membrane protein 543 543 ctx cooccurence:543

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: rhamnosyl O-methyltransferase
  • MTBC0 PGAP product: rhamnosyl O-methyltransferase
  • Pfam (hmmscan --cut_ga): RMNT_CmcI PF04989.19 (E=2e-78), Methyltransf_24 PF13578.13 (E=1e-06)
  • (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_217475.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RMNT_CmcI (PF04989.19), Methyltransf_24 (PF13578.13)
  • 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 COG3510
  • Curated reference: UniProt P9WIM5 (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 — 47 functional partner(s); context anchor Rv2958c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003142|Rv2959c|
MGLVWRSRTSLVGQLIGLVRLVASFAAQLFYRPSDAVAEEYHKWYYGNLVWTKTTYMGINCWKSVSDMWNYQEILSELQPSLVIEFGTRYGGSAVYFANIMRQIGQPFKVLTVDNSHKALDPRARREPDVLFVESSSTDPAIAEQIQRLKNEYPGKIFAILDSDHSMNHVLAEMKLLRPLLSAGDYLVVEDSNINGHPVLPGFGPGPYEAIEAYEDEFPNDYKHDAERENKFGWTSAPNGFLIRN