Rv0560c Resolved · high auto-curated

H37Rv Rv0560c · MTBC0 - · 241 aa · 650779–651504 (-) · RefSeq NP_215074.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)benzoquinone methyltransferase
MTBC0 PGAP re-annotation
Revised (this work)Benzoquinone methyltransferase. Pfam: TPMT (PF05724.18), MTS (PF05175.21), Methyltransf_23 (PF13489.13), PrmA (PF06325.20), Ubie_methyltran (PF01209.25), Methyltransf_25 (PF13649.13), Methyltransf_31 (PF13847.13), 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.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WKL5 SwissProt · reviewed · Evidence at protein level
UniProt name2-heptyl-1-hydroxyquinolin-4(1H)-one methyltransferase
EC (curated) EC 2.1.1.374
Curated functionInvolved in cellular response to chemical stress and may contribute to resistance toward antimicrobial natural compounds as well as drugs (Probable). Catalyzes the methylation and detoxification of the P.aeruginosa toxin 2-heptyl-1-hydroxy-4(1H)-quinolinone (HQNO) to 2-heptyl-1-methoxy-4(1H)-quinolinone (HMOQ). Can also methylate 3-bromo-2-heptyl-1-hydroxy-4(1H)-quinolinone, and shows much lower activity with 1-hydroxyquinolin-4(1H)-one, quercetin, 4-hydroxyquinolin-2(1H)-one (DHQ) and 4-hydroxyisoquinolin-1(2H)-one. In addition, N-methylates and abolishes the mycobactericidal activity of 3-me.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionThiopurine S-methyltransferase (TPMT)
Orthologous groupCOG0500
Gene Ontology (63) GO:0001101, GO:0001666, GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006873, GO:0006875, GO:0006879 +51 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)

pN/pS 0.258 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (186) · 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
TPMTPF05724.18 1.6e-1248–200 Thiopurine S-methyltransferase (TPMT)
MTSPF05175.21 3.1e-0861–157 Methyltransferase small domain
Methyltransf_23PF13489.13 9.4e-1163–171 Methyltransferase domain
PrmAPF06325.20 2.9e-0563–133 Ribosomal protein L11 methyltransferase (PrmA)
Ubie_methyltranPF01209.25 2.8e-0564–174 ubiE/COQ5 methyltransferase family
Methyltransf_25PF13649.13 4.1e-1966–160 Methyltransferase domain
Methyltransf_31PF13847.13 8.9e-1966–169 Methyltransferase domain
Methyltransf_11PF08241.19 1.0e-1467–164 Methyltransferase domain
Methyltransf_12PF08242.19 4.9e-1267–161 Methyltransferase domain

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

Closest characterised functional partner: menJ (oxidoreductase), high confidence from genomic context alone (score 745 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3160c TetR family transcriptional regulator 759 759 coexpression:731
Rv0561c menJ oxidoreductase 901 745 ctx neighborhood:707 textmining:630
Rv0559c hyp hypothetical protein 951 668 ctx neighborhood:668 textmining:860
Rv0562 grcC1 polyprenyl-diphosphate synthase GrcC 556 540 ctx neighborhood:529
Rv0290 eccD3 ESX-3 secretion system protein EccD 524 524 ctx cooccurence:522
Rv0676c mmpL5 transmembrane transport protein MmpL5 512 347
Rv0652 rplL 50S ribosomal protein L7/L12 407 155
Rv3692 moxR2 methanol dehydrogenase transcriptional regulator MoxR 461 93 textmining:431
Rv1938 ephB epoxide hydrolase EphB 403 89
Rv3164c moxR3 methanol dehydrogenase transcriptional regulator MoxR 672 82 textmining:658
Rv2887 HTH-type transcriptional regulator 874 72 textmining:870
Rv3215 entC isochorismate synthase 551 71 textmining:537
Rv0534c menA 1,4-dihydroxy-2-naphthoate octaprenyltransferase 465 61 textmining:454
Rv0880 HTH-type transcriptional regulator 520 59 textmining:512
Rv3648c cspA cold shock protein A 530 58 textmining:522

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): benzoquinone methyltransferase
  • Pfam (hmmscan --cut_ga): TPMT PF05724.18 (E=2e-12), MTS PF05175.21 (E=3e-08), Methyltransf_23 PF13489.13 (E=9e-11), PrmA PF06325.20 (E=3e-05), Ubie_methyltran PF01209.25 (E=3e-05), Methyltransf_25 PF13649.13 (E=4e-19), Methyltransf_31 PF13847.13 (E=9e-19), Methyltransf_11 PF08241.19 (E=1e-14), Methyltransf_12 PF08242.19 (E=5e-12)
  • (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_215074.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TPMT (PF05724.18), MTS (PF05175.21), Methyltransf_23 (PF13489.13), PrmA (PF06325.20), Ubie_methyltran (PF01209.25), Methyltransf_25 (PF13649.13), Methyltransf_31 (PF13847.13), 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 P9WKL5 (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 menJ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0560c|
MSTVLTYIRAVDIYEHMTESLDLEFESAYRGESVAFGEGVRPPWSIGEPQPELAALIVQGKFRGDVLDVGCGEAAISLALAERGHTTVGLDLSPAAVELARHEAAKRGLANASFEVADASSFTGYDGRFDTIVDSTLFHSMPVESREGYLQSIVRAAAPGASYFVLVFDRAAIPEGPINAVTEDELRAAVSKYWIIDEIKPARLYARFPAGFAGMPALLDIREEPNGLQSIGGWLLSAHLG