Rv2197c Resolved · medium auto-curated

H37Rv Rv2197c · MTBC0 - · 214 aa · 2461504–2462148 (-) · RefSeq NP_216713.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotation
Revised (this work)Transmembrane protein.

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 P9WLI9 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2197c

UniProt still lists this protein as Uncharacterized protein Rv2197c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2561)
Orthologous group2AGKA

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 0.924 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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
DUF2561PF10812.13 6.4e-1061–206 Protein of unknown function (DUF2561)

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

Closest characterised functional partner: mmpS3 (membrane protein MmpS3), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2198c mmpS3 membrane protein MmpS3 884 884 ctx neighborhood:881
Rv2199c ctaF cytochrome c oxidase polypeptide 4 754 754 ctx neighborhood:740
Rv2200c ctaC cytochrome C oxidase subunit II 604 604 ctx neighborhood:598
Rv2201 asnB asparagine synthetase 473 473 ctx neighborhood:470
Rv0175 Mce associated membrane protein 457 458 coexpression:458

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): transmembrane protein
  • Pfam (hmmscan --cut_ga): DUF2561 PF10812.13 (E=6e-106)
  • (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_216713.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2561 (PF10812.13)
  • 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 2AGKA
  • Curated reference: UniProt P9WLI9 (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 — 5 functional partner(s); context anchor mmpS3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2197c|
MVSRYSAYRRGPDVISPDVIDRILVGACAAVWLVFTGVSVAAAVALMDLGRGFHEMAGNPHTTWVLYAVIVVSALVIVGAIPVLLRARRMAEAEPATRPTGASVRGGRSIGSGHPAKRAVAESAPVQHADAFEVAAEWSSEAVDRIWLRGTVVLTSAIGIALIAVAAATYLMAVGHDGPSWISYGLAGVVTAGMPVIEWLYARQLRRVVAPQSS