Rv3037c Resolved · high auto-curated

H37Rv Rv3037c · MTBC0 - · 358 aa · 3397214–3398290 (-) · RefSeq NP_217553.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)S-adenosylmethionine-dependent methyltransferase
MTBC0 PGAP re-annotation
Revised (this work)S-adenosylmethionine-dependent methyltransferase. Pfam: Thump_like (PF18096.7).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WJZ3 SwissProt · reviewed · Inferred from homology
UniProt nameUncharacterized S-adenosylmethionine-dependent methyltransferase Rv3037c
EC (curated) EC 2.1.1.-

UniProt still lists this protein as Uncharacterized S-adenosylmethionine-dependent methyltransferase Rv3037c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category J Translation, ribosomal structure and biogenesis
eggNOG descriptionDNA repair
Orthologous groupCOG2263
Gene Ontology (33) GO:0001510, GO:0003674, GO:0003824, GO:0006139, GO:0006396, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0008168, GO:0008173, GO:0009451 +21 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) pseudogene candidate

pN/pS 0.679 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 6 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 3.03% of strains (4393) · 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
Thump_likePF18096.7 3.3e-18281–356 THUMP domain-like

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

Closest characterised functional partner: serB2 (phosphoserine phosphatase SerB), medium confidence from genomic context alone (score 539 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3036c TB22.2 hyp hypothetical protein 578 578 ctx neighborhood:578
Rv3042c serB2 phosphoserine phosphatase SerB 539 539 ctx neighborhood:472
Rv2848c cobB cobyrinic acid A,C-diamide synthase 514 514 coexpression:514
Rv3038c hyp hypothetical protein 646 504 ctx neighborhood:493
Rv3438 hyp hypothetical protein 494 494 ctx cooccurence:494
Rv3041c ABC transporter ATP-binding protein 492 493 ctx neighborhood:490
Rv3753c hyp hypothetical protein 492 493 ctx cooccurence:490
Rv3039c echA17 enoyl-CoA hydratase EchA17 491 492 ctx neighborhood:490
Rv3040c hyp hypothetical protein 491 492 ctx neighborhood:490
Rv2267c stf3 hyp hypothetical protein 466 466 ctx cooccurence:466
Rv3311 hyp hypothetical protein 421 421 ctx cooccurence:421
Rv2731 hyp hypothetical protein 420 421 ctx cooccurence:419
Rv3043c ctaD cytochrome C oxidase cytochrome 1 409 409 ctx neighborhood:409
Rv2446c integral membrane protein 408 409 ctx cooccurence:405
Rv2135c hyp hypothetical protein 521 191 textmining:433

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): S-adenosylmethionine-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): Thump_like PF18096.7 (E=3e-18)
  • (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_217553.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Thump_like (PF18096.7)
  • 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 COG2263
  • Curated reference: UniProt P9WJZ3 (SwissProt, reviewed; 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 — 21 functional partner(s); context anchor serB2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3037c|
MRARFGDRAPWLVETTLLRRRAAGKLGELCPNVGVSQWLFTDEALQQATAAPVARHRARRLAGRVVHDATCSIGTELAALRELAVRAVGSDIDPVRLAMARHNLAALGMEADLCRADVLHPVTRDAVVVIDPARRSNGRRRFHLADYQPGLGPLLDRYRGRDVVVKCAPGIDFEEVGRLGFEGEIEVISYRGGVREACLWSAGLAGSGIRRRASILDSGEQIGDDEPDDCGVRPAGKWIVDPDGAVVRAGLVRNYGARHGLWQLDPQIAYLSGDRLPPALRGFEVLEQLAFDERRLRQVLSALDCGAAEILVRGVAIDPDALRRRLRLRGSRPLAVVITRIGAGSLSHVTAYVCRPSR