Rv2876 Resolved · medium auto-curated

H37Rv Rv2876 · MTBC0 - · 104 aa · 3187663–3187977 (+) · RefSeq NP_217392.1

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 P9WL39 SwissProt · reviewed · Predicted
UniProt nameUncharacterized protein Rv2876

UniProt still lists this protein as Uncharacterized protein Rv2876; 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 (DUF2631)
Orthologous group2CAUA

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 0.515 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
DUF2631PF10939.14 7.1e-3018–85 Protein of unknown function (DUF2631)

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

Closest characterised functional partner: lpqE (lipoprotein LpqE), high confidence from genomic context alone (score 955 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2200c ctaC cytochrome C oxidase subunit II 999 999 experimental:999
Rv3043c ctaD cytochrome C oxidase cytochrome 1 999 999 experimental:999
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 999 999 experimental:999
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 999 999 experimental:999
Rv2199c ctaF cytochrome c oxidase polypeptide 4 999 999 experimental:999
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 999 999 experimental:999
Rv2193 ctaE cytochrome C oxidase subunit III 999 999 experimental:999
Rv0432 sodC superoxide dismutase 997 998 experimental:997
Rv0863 hyp hypothetical protein 991 991 experimental:987
Rv3584 lpqE lipoprotein LpqE 954 955 ctx cooccurence:541 experimental:902
Rv1125 hyp hypothetical protein 770 770 ctx cooccurence:770
Rv3035 hyp hypothetical protein 759 759 ctx cooccurence:757
Rv0383c ttfA hyp hypothetical protein 759 759 ctx cooccurence:759
Rv1836c hyp hypothetical protein 743 743 ctx cooccurence:742
Rv1274 lprB lipoprotein LprB 739 740 ctx cooccurence:738

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): DUF2631 PF10939.14 (E=7e-30)
  • (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_217392.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2631 (PF10939.14)
  • 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 2CAUA
  • Curated reference: UniProt P9WL39 (SwissProt, reviewed; Predicted)
  • 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 — 101 functional partner(s); context anchor lpqE
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2876|
MFGQWEFDVSPTGGIAVASTEVEHFAGSQHEVDTAEVPSAAWGWSRIDHRTWHIVGLCIFGFLLAMLRGNHVGHVEDWFLITFAAVVLFVLARDLWGRRRGWIR