Rv1403c Resolved · high auto-curated

H37Rv Rv1403c · MTBC0 mtbc0_001504 · 274 aa · 1588942–1589766 (-) · RefSeq NP_215919.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methyltransferase
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: Ubie_methyltran (PF01209.25), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19), Methyltransf_12 (PF08242.19).

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

Curated reference (UniProt)

UniProt P9WLY9 SwissProt · reviewed · Inferred from homology
UniProt nameUncharacterized protein Rv1403c

UniProt still lists this protein as Uncharacterized protein Rv1403c; 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 descriptionMethyltransferase
Orthologous groupCOG0500

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 2.355 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 7 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.89% of strains (1291) · 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
Ubie_methyltranPF01209.25 4.4e-1144–151 ubiE/COQ5 methyltransferase family
Methyltransf_31PF13847.13 1.3e-0949–148 Methyltransferase domain
Methyltransf_25PF13649.13 1.3e-1853–145 Methyltransferase domain
Methyltransf_11PF08241.19 5.9e-1854–147 Methyltransferase domain
Methyltransf_12PF08242.19 1.7e-0754–147 Methyltransferase domain

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

Closest characterised functional partner: Rv1404 (transcriptional regulator), medium confidence from genomic context alone (score 580 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1405c methyltransferase 741 736 coexpression:729
Rv0575c oxidoreductase 726 716 coexpression:716
Rv1404 transcriptional regulator 900 580 ctx neighborhood:574 textmining:773
Rv0759c hyp hypothetical protein 785 168 textmining:753
Rv1407 fmu 16S rRNA m5C967 methyltransferase 886 163 textmining:870
Rv1726 oxidoreductase 816 98 textmining:805
Rv0195 two component transcriptional regulator 469 95 textmining:438
Rv0059 darT hyp hypothetical protein 568 65 textmining:558
Rv3772 hisC2 histidinol-phosphate aminotransferase 812 61 textmining:808
Rv0194 multidrug ABC transporter ATPase/permease 461 59 textmining:451
Rv0193c hyp hypothetical protein 871 55 textmining:870
Rv1435c hyp hypothetical protein 815 47 textmining:815
Rv1185c fadD21 fatty-acid--CoA ligase FadD21 435 47 textmining:432
Rv0917 betP glycine betaine transport integral membrane protein BetP 809 46 textmining:809
Rv1731 gabD2 succinate-semialdehyde dehydrogenase 634 46 textmining:632

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: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): Ubie_methyltran PF01209.25 (E=4e-11), Methyltransf_31 PF13847.13 (E=1e-09), Methyltransf_25 PF13649.13 (E=1e-18), Methyltransf_11 PF08241.19 (E=6e-18), Methyltransf_12 PF08242.19 (E=2e-07)
  • (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_215919.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ubie_methyltran (PF01209.25), Methyltransf_31 (PF13847.13), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19), Methyltransf_12 (PF08242.19)
  • 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 COG0500
  • Curated reference: UniProt P9WLY9 (SwissProt, reviewed; Inferred from homology)
  • 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 — 20 functional partner(s); context anchor Rv1404
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001504|Rv1403c|
MTVYTPTSERQAPATTHRQMWALGDYAAIAEELLAPLGPILVSTSGIRRGDRVLDVAAGSGNVSIPAAMAGAHVTASDLTPELLRRAQARAAAAGLELGWREANAEALPFSAGEFDAVLSTIGVMFAPRHQRTADELARVCRRGGKISTLNWTPEGFYGKLLSTIRPYRPTLPAGAPHEVWWGSEDYVSGLFRDHVSDIRTRRGSLTVDRFGCPDECRDYFKNFYGPAINAYRSIADSPECVATLDAEITELCREYLCDGVMQWEYLIFTARKC