ogt Resolved · high auto-curated

H37Rv Rv1316c · MTBC0 mtbc0_001411 · 165 aa · 1486162–1486659 (-) · RefSeq NP_215832.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)methylated-DNA--protein-cysteine methyltransferase
MTBC0 PGAP re-annotationmethylated-DNA--protein-cysteine methyltransferase
Revised (this work)Methylated-DNA--protein-cysteine methyltransferase. Pfam: Methyltransf_1N (PF02870.22), DNA_binding_1 (PF01035.27).

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

Curated reference (UniProt)

UniProt P9WJW5 SwissProt · reviewed · Evidence at protein level
UniProt nameMethylated-DNA--protein-cysteine methyltransferase
EC (curated) EC 2.1.1.63
Curated functionInvolved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred nameogt
eggNOG descriptionInvolved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction the enzyme is irreversibly inactivated
Orthologous groupCOG0350
EC number EC 2.1.1.63
KEGG orthology K00567
Gene Ontology (41) GO:0003674, GO:0003824, GO:0003908, GO:0005575, GO:0005623, GO:0005886, GO:0006139, GO:0006259, GO:0006281, GO:0006304, GO:0006307, GO:0006725 +29 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 0.221 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 2 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_1NPF02870.22 2.8e-162–71 6-O-methylguanine DNA methyltransferase, ribonuclease-like domain
DNA_binding_1PF01035.27 8.5e-3875–154 6-O-methylguanine DNA methyltransferase, DNA binding domain

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

Closest characterised functional partner: alkA (bifunctional regulatory protein/DNA repair enzyme AlkA), high confidence from genomic context alone (score 954 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1317c alkA bifunctional regulatory protein/DNA repair enzyme AlkA 987 954 ctx neighborhood:881 coexpression:567 textmining:742
Rv1318c adenylate cyclase 785 786 ctx neighborhood:786
Rv1210 tagA DNA-3-methyladenine glycosylase I TagA 793 785 ctx fusion:667
Rv1321 nucS endonuclease NucS 724 637 ctx neighborhood:634
Rv1322 hyp hypothetical protein 492 491 ctx neighborhood:478
Rv1319c adenylate cyclase 466 466 ctx neighborhood:466
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 594 459 ctx neighborhood:459
Rv1320c adenylate cyclase 450 450 ctx neighborhood:450
Rv2703 sigA RNA polymerase sigma factor SigA 469 449 experimental:418
Rv2710 sigB RNA polymerase sigma factor SigB 480 446 experimental:418
Rv2623 TB31.7 universal stress protein 427 428 coexpression:419
Rv1636 TB15.3 iron-regulated universal stress protein 427 428 coexpression:419
Rv1996 universal stress protein 427 428 coexpression:419
Rv2624c universal stress protein 427 427 coexpression:418
Rv3134c universal stress protein 427 427 coexpression:418

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: methylated-DNA--protein-cysteine methyltransferase
  • MTBC0 PGAP product: methylated-DNA--protein-cysteine methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_1N PF02870.22 (E=3e-16), DNA_binding_1 PF01035.27 (E=9e-38)
  • (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_215832.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_1N (PF02870.22), DNA_binding_1 (PF01035.27)
  • 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 COG0350
  • Curated reference: UniProt P9WJW5 (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 — 32 functional partner(s); context anchor alkA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001411|Rv1316c|ogt
MIHYRTIDSPIGPLTLAGHGSVLTNLRMLEQTYEPSRTHWTPDPGAFSGAVDQLNAYFAGELTEFDVELDLRGTDFQQRVWKALLTIPYGETRSYGEIADQIGAPGAARAVGLANGHNPIAIIVPCHRVIGASGKLTGYGGGINRKRALLELEKSRAPADLTLFD