Rv2952 Resolved · high auto-curated

H37Rv Rv2952 · MTBC0 mtbc0_003134 · 270 aa · 3325616–3326428 (+) · RefSeq NP_217468.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phthiotriol/phenolphthiotriol dimycocerosates methyltransferase
MTBC0 PGAP re-annotationphthiotriol/phenolphthiotriol dimycocerosates methyltransferase
Revised (this work)Phthiotriol/phenolphthiotriol dimycocerosates methyltransferase. Pfam: Methyltransf_23 (PF13489.13), 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 P9WIN3 SwissProt · reviewed · Evidence at protein level
UniProt namePhthiotriol/phenolphthiotriol dimycocerosates methyltransferase
EC (curated) EC 2.1.1.-
Curated functionCatalyzes the methylation of the lipid moiety of the intermediate compounds phthiotriol and glycosylated phenolphthiotriol dimycoserosates to form phthiocerol dimycocerosates (DIM A) and glycosylated phenolphthiocerol dimycocerosates (PGL).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionCatalyzes the methylation of the lipid moiety of the intermediate compounds phthiotriol and glycosylated phenolphthiotriol dimycoserosates to form phthiocerol dimycocerosates (DIM A) and glycosylated phenolphthiocerol dimycocerosates (PGL)
Orthologous groupCOG0500
Gene Ontology (25) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0008152, GO:0008168, GO:0008171, GO:0009273, GO:0009987, GO:0016020 +13 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 1.132 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 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_23PF13489.13 2.8e-0771–183 Methyltransferase domain
Ubie_methyltranPF01209.25 1.5e-0977–178 ubiE/COQ5 methyltransferase family
Methyltransf_31PF13847.13 8.9e-1681–184 Methyltransferase domain
Methyltransf_25PF13649.13 1.8e-2084–176 Methyltransferase domain
Methyltransf_11PF08241.19 8.3e-2485–178 Methyltransferase domain
Methyltransf_12PF08242.19 2.9e-1385–178 Methyltransferase domain

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

Closest characterised functional partner: Rv2953 (trans-acting enoyl reductase), high confidence from genomic context alone (score 923 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2953 trans-acting enoyl reductase 945 923 ctx neighborhood:724 coexpression:733
Rv2951c phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase 881 799 ctx neighborhood:597 database:500 textmining:435
Rv0329c hyp hypothetical protein 553 553 ctx cooccurence:553
Rv1405c methyltransferase 530 530 ctx cooccurence:530
Rv2067c hyp hypothetical protein 453 450
Rv1621c cydD cytochrome biosyntheisis ABC transporter ATP-binding protein/permease CydD 569 319
Rv1844c gnd1 6-phosphogluconate dehydrogenase 529 73 textmining:513
Rv3119 moaE1 molybdopterin synthase catalytic subunit 1 443 57 textmining:434
Rv3221c TB7.3 acetyl-CoA carboxylase biotin carboxyl carrier protein subunit 549 44 textmining:548
Rv3324c moaC3 cyclic pyranopterin monophosphate synthase accessory protein 436 41 textmining:436
Rv0968 hyp hypothetical protein 433 41 textmining:433

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: phthiotriol/phenolphthiotriol dimycocerosates methyltransferase
  • MTBC0 PGAP product: phthiotriol/phenolphthiotriol dimycocerosates methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_23 PF13489.13 (E=3e-07), Ubie_methyltran PF01209.25 (E=1e-09), Methyltransf_31 PF13847.13 (E=9e-16), Methyltransf_25 PF13649.13 (E=2e-20), Methyltransf_11 PF08241.19 (E=8e-24), Methyltransf_12 PF08242.19 (E=3e-13)
  • (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_217468.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_23 (PF13489.13), 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 P9WIN3 (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 — 11 functional partner(s); context anchor Rv2953
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003134|Rv2952|
MAFSRTHSLLARAGSTSTYKRVWRYWYPLMTRGLGNDEIVFINWAYEEDPPMDLPLEASDEPNRAHINLYHRTATQVDLGGKQVLEVSCGHGGGASYLTRTLHPASYTGLDLNQAGIKLCKKRHRLPGLDFVRGDAENLPFDDESFDVVLNVEASHCYPHFRRFLAEVVRVLRPGGYFPYADLRPNNEIAAWEADLAATPLRQLSQRQINAEVLRGIGNNSQKSRDLVDRHLPAFLRFAGREFIGVQGTQLSRYLEGGELSYRMYCFTKD