MTBC Gene Atlas

Rv2956 Resolved · high auto-curated

H37Rv Rv2956 · MTBC0 mtbc0_003138 · 243 aa · 3329843–3330574 (+) · RefSeq NP_217472.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation[alpha-L-fucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->3)-2-O-methyl-alpha-L-rhamnopyranosyl] dimycocerosyl phenol-phthiocerol 2'''-O-methyltransferase
Revised (this work)[alpha-L-fucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->3)-2-O-methyl-alpha-L-rhamnopyranosyl] dimycocerosyl phenol-phthiocerol 2'''-O-methyltransferase. Pfam: Methyltransf_21 (PF05050.20).

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

Curated reference (UniProt)

UniProt I6Y242 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
eggNOG descriptionMethyltransferase FkbM domain
Orthologous groupCOG2242

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 0.418 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.27% of strains (399) · 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_21PF05050.20 1.8e-2345–215 Methyltransferase FkbM domain

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

Closest characterised functional partner: Rv2957 (PGL/p-HBAD biosynthesis glycosyltransferase), high confidence from genomic context alone (score 961 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2957 PGL/p-HBAD biosynthesis glycosyltransferase 987 961 ctx neighborhood:601 coexpression:820 database:500 textmining:688
Rv2955c hyp hypothetical protein 952 867 ctx neighborhood:544 cooccurence:462 database:500 textmining:658
Rv2954c hyp hypothetical protein 857 595 ctx cooccurence:400 textmining:662
Rv2959c rhamnosyl O-methyltransferase 444 326
Rv1512 epiA nucleotide-sugar epimerase EpiA 903 287 textmining:870
Rv2958c PGL/p-HBAD biosynthesis glycosyltransferase 703 176 textmining:655
Rv2886c resolvase 601 156 textmining:547
Rv1511 gmdA GDP-D-mannose dehydratase GmdA 695 114 textmining:670
Rv2960c hyp hypothetical protein 871 54 textmining:870
Rv0605 IS1536 family serine type transposase 549 47 textmining:547
Rv2792c resolvase 549 47 textmining:547
Rv3828c resolvase 514 47 textmining:511
Rv2953 trans-acting enoyl reductase 513 46 textmining:511
Rv2979c resolvase 548 45 textmining:547
Rv0921 resolvase 548 44 textmining:547

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: [alpha-L-fucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->3)-2-O-methyl-alpha-L-rhamnopyranosyl] dimycocerosyl phenol-phthiocerol 2'''-O-methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_21 PF05050.20 (E=2e-23)
  • (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_217472.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_21 (PF05050.20)
  • 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 COG2242
  • Curated reference: UniProt I6Y242 (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 — 16 functional partner(s); context anchor Rv2957
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003138|Rv2956|
MKSLKLARFIARSAAFEVSRRYSERDLKHQFVKQLKSRRVDVVFDVGANSGQYAAGLRRAAYKGRIVSFEPLSGPFTILESKASTDPLWDCRQHALGDSDGTVTINIAGNAGQSSSVLPMLKSHQNAFPPANYVGTQEASIHRLDSVAPEFLGMNGVAFLKVDVQGFEKQVLAGGKSTIDDHCVGMQLELSFLPLYEGGMLIPEALDLVYSLGFTLTGLLPCFIDANNGRMLQADGIFFREDD