Rv0567 Resolved · high auto-curated

H37Rv Rv0567 · MTBC0 mtbc0_000597 · 339 aa · 661872–662891 (+) · RefSeq NP_215081.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methyltransferase/methylase
MTBC0 PGAP re-annotationmethyltransferase
Revised (this work)Methyltransferase. Pfam: Dimerisation (PF08100.19), Methyltransf_2 (PF00891.25), Methyltransf_23 (PF13489.13), MTS (PF05175.21), Methyltransf_12 (PF08242.19), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19).

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

Curated reference (UniProt)

UniProt O53764 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable methyltransferase/methylase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionDimerisation domain
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 1.474 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 8 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.39% of strains (565) · 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
DimerisationPF08100.19 1.7e-0814–88 O-methyltransferase dimerisation domain
Methyltransf_2PF00891.25 2.0e-40111–321 O-methyltransferase domain
Methyltransf_23PF13489.13 1.2e-06157–321 Methyltransferase domain
MTSPF05175.21 1.1e-06161–275 Methyltransferase small domain
Methyltransf_12PF08242.19 1.1e-07177–271 Methyltransferase domain
Methyltransf_25PF13649.13 4.2e-07177–270 Methyltransferase domain
Methyltransf_11PF08241.19 6.9e-06177–274 Methyltransferase domain

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

Closest characterised functional partner: cyp135B1 (cytochrome P450 Cyp135B1), medium confidence from genomic context alone (score 604 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0568 cyp135B1 cytochrome P450 Cyp135B1 604 604 ctx neighborhood:513
Rv0566c hyp hypothetical protein 429 429 ctx neighborhood:423
Rv0569 hyp hypothetical protein 415 415
Rv1310 atpD ATP synthase subunit beta 590 157 textmining:534
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 679 71 textmining:670
Rv3375 amiD amidase 864 47 textmining:864
Rv1911c lppC lipoprotein LppC 870 46 textmining:870
Rv1038c esxJ ESAT-6 like protein EsxJ 653 45 textmining:652
Rv2809 hyp hypothetical protein 870 44 textmining:870

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/methylase
  • MTBC0 PGAP product: methyltransferase
  • Pfam (hmmscan --cut_ga): Dimerisation PF08100.19 (E=2e-08), Methyltransf_2 PF00891.25 (E=2e-40), Methyltransf_23 PF13489.13 (E=1e-06), MTS PF05175.21 (E=1e-06), Methyltransf_12 PF08242.19 (E=1e-07), Methyltransf_25 PF13649.13 (E=4e-07), Methyltransf_11 PF08241.19 (E=7e-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_215081.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Dimerisation (PF08100.19), Methyltransf_2 (PF00891.25), Methyltransf_23 (PF13489.13), MTS (PF05175.21), Methyltransf_12 (PF08242.19), Methyltransf_25 (PF13649.13), Methyltransf_11 (PF08241.19)
  • 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 O53764 (TrEMBL, unreviewed; 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 — 9 functional partner(s); context anchor cyp135B1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000597|Rv0567|
MELSPDRIMAIGGGYGPSKVLLTAVGLGLFTELGDEAMTAEAIADRLGLLKRPAIDFLDALVSLDLLARDGDGPGSHYRNTPETAHFLDEARPTYAGGLLKIWNERNYRFWADLTEALKTGKAQSEVKQTGRPFFEALYADPRRLEAFMAAMDAASRRNIELLAKRFPFERYRRLCDVGCADGLLSRIVAAAHPHLQCVSFDLPAVTEIARRKLTAEGLGERVQACAGDFLADPLPAADVITMGQILHDWNLDRKQQLVAKAYEALSKEGAFIVIETLIDDARRENTTGLMMSLNMLIEFGDAFDYSAADFRGWCGEAGFRSFEVIPLAGGSSAAVAYK