Rv1523 Resolved · high auto-curated

H37Rv Rv1523 · MTBC0 mtbc0_001630 · 347 aa · 1727462–1728505 (+) · RefSeq NP_216039.1

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: Methyltransf_23 (PF13489.13), Methyltransf_29 (PF03141.23), 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 Q50584 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable methyltransferase
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

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 1.531 · 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 0.16% of strains (228) · 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
Methyltransf_23PF13489.13 1.1e-12145–269 Methyltransferase domain
Methyltransf_29PF03141.23 1.8e-05155–263 Putative S-adenosyl-L-methionine-dependent methyltransferase
Ubie_methyltranPF01209.25 2.1e-10156–260 ubiE/COQ5 methyltransferase family
Methyltransf_31PF13847.13 1.6e-17161–271 Methyltransferase domain
Methyltransf_25PF13649.13 1.7e-22164–256 Methyltransferase domain
Methyltransf_11PF08241.19 2.7e-25165–259 Methyltransferase domain
Methyltransf_12PF08242.19 8.7e-14165–258 Methyltransferase domain

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

Closest characterised functional partner: Rv1524 (glycosyltransferase), high confidence from genomic context alone (score 898 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1524 glycosyltransferase 898 898 ctx neighborhood:721 coexpression:651
Rv1525 wbbL2 rhamnosyl transferase WbbL 666 666 ctx neighborhood:598
Rv1522c mmpL12 transmembrane transport protein MmpL12 833 575 ctx neighborhood:567 textmining:624
Rv0558 menH demethylmenaquinone methyltransferase 425 425 ctx cooccurence:425
Rv2067c hyp hypothetical protein 405 400
Rv3322c methyltransferase 887 166 textmining:871
Rv1758 cut1 cutinase 502 154 textmining:436
Rv0131c fadE1 acyl-CoA dehydrogenase FadE1 520 59 textmining:511
Rv3448 eccD4 ESX-4 secretion system protein EccD4 684 53 textmining:680
Rv3392c cmaA1 cyclopropane mycolic acid synthase CmaA 529 50 textmining:525
Rv1832 gcvB glycine dehydrogenase 467 49 textmining:463
Rv1895 zinc-binding alcohol dehydrogenase 871 46 textmining:871
Rv3514 PE_PGRS57 PE-PGRS family protein PE_PGRS57 652 41 textmining:652

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): Methyltransf_23 PF13489.13 (E=1e-12), Methyltransf_29 PF03141.23 (E=2e-05), Ubie_methyltran PF01209.25 (E=2e-10), Methyltransf_31 PF13847.13 (E=2e-17), Methyltransf_25 PF13649.13 (E=2e-22), Methyltransf_11 PF08241.19 (E=3e-25), Methyltransf_12 PF08242.19 (E=9e-14)
  • (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_216039.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_23 (PF13489.13), Methyltransf_29 (PF03141.23), 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 Q50584 (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 — 13 functional partner(s); context anchor Rv1524
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001630|Rv1523|
MTITALTVTLPLLWRRLTTAGVKYADQGHFVGSAGVPAADAGGRDAASEQIARWTQTCTVVLVCGHGPAKWAFRSWCTSRSCDTLPVALRYRLQSNPLVGKLTTKYFLPLGTRQVGDHVVFFNFGYEEDPPMALPLSESDEPNRYCIQLYHQTASQVDLTGKEVLEVSCGAGGGASYIARNLGPASYTGLDLNPASIDLCRAKHRLPGLQFVQGDAQNLPFPDESFDAVVNVEASHQYPDFRGFLAEVARVLRPGGHFLYTDSRRNPVVAEWEAALADAPLRTISQRDIGAQAKRGLDANTARSQEAIGRRAPVLLAGLTRCAVRVLDWDLRRGGGFSYRIYLFAKD