MTBC Gene Atlas

Rv3263 Resolved · high auto-curated

H37Rv Rv3263 · MTBC0 mtbc0_003471 · 553 aa · 3665320–3666981 (+) · RefSeq NP_217780.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DNA methylase
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: N6_Mtase (PF02384.23), Eco57I (PF07669.18), M_Eco57I_C (PF22837.2).

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

Curated reference (UniProt)

UniProt P96868 TrEMBL · unreviewed · Inferred from homology
UniProt namesite-specific DNA-methyltransferase
EC (curated) EC 2.1.1.72

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionDNA methylase
Orthologous groupCOG0827

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 0.688 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.23% of strains (338) · 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
N6_MtasePF02384.23 1.8e-0431–188 N-6 DNA Methylase
Eco57IPF07669.18 1.6e-10100–216 Eco57I restriction-modification methylase
M_Eco57I_CPF22837.2 1.5e-90269–521 Type II methyltransferase M.Eco57I, C-terminal domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0339c iniR transcriptional regulator 889 889 coexpression:859
Rv1359 transcriptional regulator 876 877 coexpression:860
Rv1267c embR transcriptional regulator EmbR 875 876 coexpression:850
Rv3840 transcriptional regulator 865 860 coexpression:860
Rv3736 AraC/XylS family transcriptional regulator 860 860 coexpression:860
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 860 860 coexpression:860
Rv3183 higA3 transcriptional regulator 859 859 coexpression:859
Rv1151c cobB NAD-dependent protein deacylase 857 857 coexpression:857
Rv0212c nadR transcriptional regulator NadR 852 852 coexpression:852
Rv3124 moaR1 transcriptional regulator MoaR 849 850 coexpression:805
Rv1675c cmr HTH-type transcriptional regulator Cmr 848 848 coexpression:848
Rv3167c TetR family transcriptional regulator 848 848 coexpression:848
Rv1725c hyp hypothetical protein 848 848 coexpression:848
Rv1931c transcriptional regulator 845 845 coexpression:845
Rv0117 oxyS oxidative stress response regulatory protein OxyS 843 844 coexpression:820

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: DNA methylase
  • MTBC0 PGAP product: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): N6_Mtase PF02384.23 (E=2e-04), Eco57I PF07669.18 (E=2e-10), M_Eco57I_C PF22837.2 (E=2e-90)
  • (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_217780.1)
  • Domains: Pfam-A via hmmscan --cut_ga — N6_Mtase (PF02384.23), Eco57I (PF07669.18), M_Eco57I_C (PF22837.2)
  • 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 COG0827
  • Curated reference: UniProt P96868 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 106 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003471|Rv3263|
MQPSHPTRPGAVIRYVGSSLDTCPMTTFAGKTAASADKVRGGYYTPPAVARFLAHWVHQAGPKILEPSCGDGRILRELSAITDHAHGVELVAREAKKSRDFASVDTENLFTWLHKTQLGSWDGVAGNPPYIRFGNWASEQRDPALELMRRVGLRPTKLTNAWVPFVVASTTLARDGGRVGLVVPAELLQVTYAAQLREFLLSRYREITLVTFERLVFDGILQEVVLFCGVVGPGPAHIRTVRLGDANDLNALGDKDFTNESAPALLHEKEKWTKYFLDPAQIRLLRGLKQSATMIRLGELADVDVGIVTGRNSFFTFTDAKAQALGLRAHCVPLVSRSAQLSGLIYDEDCRACDVAGNHRTWLLDAADYPTDPALVAHITAGEAAGVHLGYKCSIRKPWWSTPSLWMPDLFMLRQIHFAPRLTVNAAAATSTDTVHRVRLDPNVDPATLAAVFHNSATFAFAEIMGRSYGGGILELEPREAEQLPMPPPAYGSAELAQDVDLLLKANEIDKALDVVDRHVLIDGLGLSPRLVAGCRAAWLTLRDRRTKRGSRR