Rv1703c Resolved · high auto-curated

H37Rv Rv1703c · MTBC0 mtbc0_001812 · 249 aa · 1941146–1941895 (-) · RefSeq NP_216219.4

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methyltransferase
MTBC0 PGAP re-annotationO-methyltransferase
Revised (this work)O-methyltransferase. Pfam: Methyltransf_3 (PF01596.24), 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 L0TAD5 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable O-methyltransferase Rv1703c
EC (curated) EC 2.1.1.-
Curated functionSpecifically methylates an O atom of its substrate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionO-Methyltransferase
Orthologous groupCOG4122
EC number EC 2.1.1.6
KEGG orthology K00545
KEGG pathways map00140, map00350, map00965, map01100, map04728

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 2.012 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 6 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_3PF01596.24 6.8e-1555–204 O-methyltransferase
Methyltransf_24PF13578.13 1.5e-1192–203 Methyltransferase domain

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

Closest characterised functional partner: scpB (segregation and condensation protein ScpB), high confidence from genomic context alone (score 709 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3170 aofH flavin-containing monoamine oxidase 939 936 database:900
Rv0761c adhB alcohol dehydrogenase B 905 905 database:900
Rv1530 adh alcohol dehydrogenase 904 905 database:900
Rv1862 adhA alcohol dehydrogenase A 907 904 database:900
Rv0162c adhE1 zinc-type alcohol dehydrogenase subunit E 900 901 database:900
Rv1710 scpB segregation and condensation protein ScpB 709 709 ctx neighborhood:544
Rv2126c PE_PGRS37 PE-PGRS family protein PE_PGRS37 696 696 ctx cooccurence:696
Rv1220c methyltransferase 691 691 ctx cooccurence:691
Rv1709 scpA segregation and condensation protein ScpA 679 680 ctx neighborhood:544
Rv1704c cycA D-serine/alanine/glycine transporter protein CycA 673 673 ctx neighborhood:664
Rv1713 engA GTPase Der 620 621 ctx neighborhood:544
Rv3176c mesT epoxide hydrolase MesT 570 571 ctx cooccurence:563
Rv1712 cmk cytidylate kinase 565 566 ctx neighborhood:544
Rv1711 RNA pseudouridine synthase 562 563 ctx neighborhood:544
Rv1708 initiation inhibitor protein 557 558 ctx neighborhood:544

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: O-methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_3 PF01596.24 (E=7e-15), Methyltransf_24 PF13578.13 (E=1e-11)
  • (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_216219.4)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_3 (PF01596.24), 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 COG4122
  • Curated reference: UniProt L0TAD5 (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 — 28 functional partner(s); context anchor scpB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001812|Rv1703c|
MIRKARIAPLRWSVWRMAAGIRNITTTGQIGDGREAAAVDYVLAHAGAGNIDDVLATIDKFAYEKSMLINVGDEKGTLLDAAVRRADPALALELGTYLGYGALRIARAAPEARVYSVELAEANASNARRIWAHAGVDDRVVCVVGTIGDGGRTLDALTEHGFATGTLDFVFLDHDKKAYLPDLQSILDRGWLHPGSIVVADNVRVPGAPKYRAYMRRQQGMSWNTIEHKTHLEYQTLVPDLVLESEYLG