Rv2954c Resolved · high auto-curated

H37Rv Rv2954c · MTBC0 mtbc0_003136 · 241 aa · 3327841–3328566 (-) · RefSeq NP_217470.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation[2%2C4-di-O-methyl-alpha-L-fucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->3)-2-O-methyl-alpha-L-rhamnopyranosyl] dimycocerosyl phenol-phthiocerol 3'''-O-methyltransferase
Revised (this work)[2%2C4-di-O-methyl-alpha-L-fucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->3)-2-O-methyl-alpha-L-rhamnopyranosyl] dimycocerosyl phenol-phthiocerol 3'''-O-methyltransferase. Pfam: Methyltransf_23 (PF13489.13), Methyltransf_9 (PF08003.18), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), 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 I6X5U4 TrEMBL · unreviewed · Evidence at protein level
UniProt nameMethyltransferase type 12 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namersmJ
eggNOG descriptionmethyltransferase activity
Orthologous groupCOG0500
EC number EC 2.1.1.197, EC 2.1.1.242
KEGG orthology K02169, K15984
KEGG pathways map00780, map01100
KEGG modules M00572

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 1.009 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (165) · 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 4.1e-0834–131 Methyltransferase domain
Methyltransf_9PF08003.18 9.4e-0637–153 Protein of unknown function (DUF1698)
Methyltransf_25PF13649.13 5.6e-1143–125 Methyltransferase domain
Methyltransf_12PF08242.19 1.9e-1144–125 Methyltransferase domain
Methyltransf_11PF08241.19 1.0e-0944–125 Methyltransferase domain

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

Closest characterised functional partner: iniB (isoniazid inducible protein IniB), high confidence from genomic context alone (score 784 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0341 iniB isoniazid inducible protein IniB 784 784 ctx cooccurence:770
Rv2955c hyp hypothetical protein 968 780 ctx neighborhood:460 database:500 textmining:864
Rv1004c membrane protein 778 779 ctx cooccurence:771
Rv3347c PPE55 PPE family protein PPE55 774 774 ctx cooccurence:772
Rv2209 integral membrane protein 774 774 ctx cooccurence:773
Rv0355c PPE8 PPE family protein PPE8 774 774 ctx cooccurence:773
Rv1917c PPE34 PPE family protein PPE34 773 774 ctx cooccurence:771
Rv0304c PPE5 PPE family protein PPE5 773 773 ctx cooccurence:771
Rv3343c PPE54 PPE family protein PPE54 773 773 ctx cooccurence:770
Rv3350c PPE56 PPE family protein PPE56 773 773 ctx cooccurence:772
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 772 772 ctx cooccurence:772
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 771 771 ctx cooccurence:771
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 770 770 ctx cooccurence:770
Rv2082 hyp hypothetical protein 768 768 ctx cooccurence:761
Rv0305c PPE6 PPE family protein PPE6 767 768 ctx cooccurence:765

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: hypothetical protein
  • MTBC0 PGAP product: [2%2C4-di-O-methyl-alpha-L-fucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->3)-2-O-methyl-alpha-L-rhamnopyranosyl] dimycocerosyl phenol-phthiocerol 3'''-O-methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_23 PF13489.13 (E=4e-08), Methyltransf_9 PF08003.18 (E=9e-06), Methyltransf_25 PF13649.13 (E=6e-11), Methyltransf_12 PF08242.19 (E=2e-11), Methyltransf_11 PF08241.19 (E=1e-09)
  • (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_217470.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_23 (PF13489.13), Methyltransf_9 (PF08003.18), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), 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 I6X5U4 (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 — 138 functional partner(s); context anchor iniB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003136|Rv2954c|
MRLPGMLRPTAERHFHSIFYLRHNARRQEHLATLGLDLGNKSVLEVGAGIGDHTQFFLDRGCKVLCTEPRGENLDVIRQRFGSNPNVTVDHLDLDGDLPAEAHQYDVVYCYGVLYHLSRPAEALAWMCDRAVDLLLLETCVSYSGEDEPFLVSERASSPSQAITGTGCRPSRVWVMNRLREKMPHVYVTATQPRHRQFPLDWRANGPIASTGLARAVFVASRAPLNLPTLVEELPMVQRRC