Rv1978 Resolved · high auto-curated

H37Rv Rv1978 · MTBC0 mtbc0_002100 · 282 aa · 2244521–2245369 (+) · RefSeq NP_216494.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationclass I SAM-dependent methyltransferase
Revised (this work)Class I SAM-dependent methyltransferase. Pfam: Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), Methyltransf_11 (PF08241.19).

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

Curated reference (UniProt)

UniProt O53979 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) pseudogene candidate

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 5.77% of strains (8380) · 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_25PF13649.13 1.2e-1182–174 Methyltransferase domain
Methyltransf_12PF08242.19 9.3e-1083–161 Methyltransferase domain
Methyltransf_11PF08241.19 3.4e-0783–175 Methyltransferase domain

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

Closest characterised functional partner: Rv2687c (antibiotic ABC transporter permease), high confidence from genomic context alone (score 773 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2687c antibiotic ABC transporter permease 773 773 ctx cooccurence:772
Rv2686c antibiotic ABC transporter permease 772 772 ctx cooccurence:771
Rv3912 rsmA anti-sigma-M factor RsmA 760 761 ctx cooccurence:759
Rv0210 hyp hypothetical protein 732 733 ctx cooccurence:732
Rv1181 pks4 polyketide beta-ketoacyl synthase 743 730 ctx cooccurence:726
Rv3604c transmembrane protein 725 725 ctx cooccurence:725
Rv2633c hyp hypothetical protein 723 724 ctx cooccurence:722
Rv0955 integral membrane protein 718 718 ctx cooccurence:718
Rv3896c hyp hypothetical protein 698 699 ctx cooccurence:698
Rv0804 hyp hypothetical protein 697 697 ctx cooccurence:688
Rv3786c hyp hypothetical protein 677 677 ctx cooccurence:655
Rv1733c transmembrane protein 666 666 ctx cooccurence:665
Rv0204c transmembrane protein 643 643 ctx cooccurence:631
Rv2378c mbtG L-lysine N6-monooxygenase 649 636 ctx cooccurence:635
Rv2812 transposase 630 630 ctx cooccurence:630

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: class I SAM-dependent methyltransferase
  • Pfam (hmmscan --cut_ga): Methyltransf_25 PF13649.13 (E=1e-11), Methyltransf_12 PF08242.19 (E=9e-10), Methyltransf_11 PF08241.19 (E=3e-07)
  • (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_216494.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_25 (PF13649.13), Methyltransf_12 (PF08242.19), Methyltransf_11 (PF08241.19)
  • 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 O53979 (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 — 58 functional partner(s); context anchor Rv2687c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002100|Rv1978|
MGEANIREQAIATMPRGGPDASWLDRRFQTDALEYLDRDDVPDEVKQKIIGVLDRVGTLTNLHEKYARIALKLVSDIPNPRILELGAGHGKLSAKILELHPTATVTISDLDPTSVANIAAGELGTHPRARTQVIDATAIDGHDHSYDLAVFALAFHHLPPTVACKAIAEATRVGKRFLIIDLKRQKPLSFTLSSVLLLPLHLLLLPWSSMRSSMHDGFISALRAYSPSALQTLARAADPGMQVEILPAPTRLFPPSLAVVFSRSSSAPTESSECSADRQPGE