Rv3038c Family assigned · medium auto-curated

H37Rv Rv3038c · MTBC0 mtbc0_003230 · 327 aa · 3419735–3420718 (-) · RefSeq NP_217554.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationmethyltransferase domain-containing protein
Revised (this work)Methyltransferase domain-containing protein. Pfam: Ubie_methyltran (PF01209.25), Methyltransf_31 (PF13847.13), Methyltransf_23 (PF13489.13), Methyltransf_11 (PF08241.19), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19).

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

Curated reference (UniProt)

UniProt I6YAZ1 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 Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionMethyltransferase
Orthologous groupCOG0500

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 0.113 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 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
Ubie_methyltranPF01209.25 9.8e-1274–178 ubiE/COQ5 methyltransferase family
Methyltransf_31PF13847.13 6.1e-1880–180 Methyltransferase domain
Methyltransf_23PF13489.13 5.8e-1180–181 Methyltransferase domain
Methyltransf_11PF08241.19 1.6e-2382–179 Methyltransferase domain
Methyltransf_25PF13649.13 2.2e-2082–175 Methyltransferase domain
Methyltransf_12PF08242.19 3.0e-1482–177 Methyltransferase domain

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

Closest characterised functional partner: echA17 (enoyl-CoA hydratase EchA17), high confidence from genomic context alone (score 880 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3039c echA17 enoyl-CoA hydratase EchA17 879 880 ctx neighborhood:879
Rv3041c ABC transporter ATP-binding protein 879 880 ctx neighborhood:879
Rv3042c serB2 phosphoserine phosphatase SerB 879 879 ctx neighborhood:861
Rv3040c hyp hypothetical protein 878 879 ctx neighborhood:879
Rv3034c acetyltransferase 799 799 ctx cooccurence:764
Rv2186c hyp hypothetical protein 771 771 ctx cooccurence:771
Rv3030 S-adenosylmethionine-dependent methyltransferase 744 742 ctx cooccurence:706
Rv3043c ctaD cytochrome C oxidase cytochrome 1 732 722 ctx neighborhood:720
Rv3036c TB22.2 hyp hypothetical protein 702 703 ctx neighborhood:698
Rv3031 1,4-alpha-glucan-branching protein 688 688 ctx cooccurence:676
Rv2418c octT hyp hypothetical protein 673 673 ctx cooccurence:672
Rv3032 glycogen synthase 649 649 ctx cooccurence:646
Rv2695 hyp hypothetical protein 559 560 ctx cooccurence:558
Rv1632c hyp hypothetical protein 552 552 ctx cooccurence:549
Rv3037c S-adenosylmethionine-dependent methyltransferase 646 504 ctx neighborhood:493

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: methyltransferase domain-containing protein
  • Pfam (hmmscan --cut_ga): Ubie_methyltran PF01209.25 (E=1e-11), Methyltransf_31 PF13847.13 (E=6e-18), Methyltransf_23 PF13489.13 (E=6e-11), Methyltransf_11 PF08241.19 (E=2e-23), Methyltransf_25 PF13649.13 (E=2e-20), Methyltransf_12 PF08242.19 (E=3e-14)
  • (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_217554.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Ubie_methyltran (PF01209.25), Methyltransf_31 (PF13847.13), Methyltransf_23 (PF13489.13), Methyltransf_11 (PF08241.19), Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19)
  • 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 I6YAZ1 (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 — 20 functional partner(s); context anchor echA17
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003230|Rv3038c|
MTRSSNIPADATPNPHATAEQVAAARHDSKLAQVLYHDWEAENYDEKWSISYDQRCVDYARGRFDAIVPDEVIAQLPYDRALELGCGTGFFLLNLIQAGVARRGSVTDLSPGMVKVATRNGQALGLDIDGRVADAEGIPYDDDAFDLVVGHAVLHHIPDVELSLREVVRVLKPGGRFVFAGEPTTVGDGYARTLSTLTWRVVTNATKLPGLRGWRRPQGELDESSRAAALEALVDLHTFTPQDLQRIAHNAGAVEVQTATEEFTAAMLGWPLRTFECTVPPGRLGWGWARFAFTSWKTLGWVDANVWRHVVPKGWFYNVMITGVKPS