Rv2091c Still unknown · low auto-curated

H37Rv Rv2091c · MTBC0 mtbc0_002225 · 244 aa · 2377182–2377916 (-) · RefSeq NP_216607.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationDUF4333 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF4333. Function unknown.

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

Curated reference (UniProt)

UniProt P9WLJ5 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2091c

UniProt still lists this protein as Uncharacterized protein Rv2091c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4333)
Orthologous group2BYFJ
Gene Ontology (14) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0016020, GO:0016021, GO:0030312, GO:0031224, GO:0031226, GO:0044425, GO:0044459 +2 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)

pN/pS 0.417 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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
DUF4333PF14230.12 8.8e-25154–236 Domain of unknown function (DUF4333)

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

Closest characterised functional partner: Rv2520c (membrane protein), high confidence from genomic context alone (score 757 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1109c hyp hypothetical protein 781 781 ctx cooccurence:771
Rv3212 hyp hypothetical protein 767 767 ctx cooccurence:766
Rv3311 hyp hypothetical protein 759 759 ctx cooccurence:758
Rv2700 cei hyp hypothetical protein 758 758 ctx cooccurence:758
Rv2520c membrane protein 756 757 ctx cooccurence:756
Rv0556 transmembrane protein 755 755 ctx cooccurence:754
Rv0996 transmembrane protein 753 753 ctx cooccurence:752
Rv0863 hyp hypothetical protein 750 751 ctx cooccurence:748
Rv2446c integral membrane protein 750 751 ctx cooccurence:750
Rv0481c hyp hypothetical protein 750 750 ctx cooccurence:750
Rv1209 hyp hypothetical protein 757 748 ctx cooccurence:745
Rv1222 rseA anti-sigma E factor RseA 744 745 ctx cooccurence:741
Rv3415c hyp hypothetical protein 741 741 ctx cooccurence:741
Rv0475 hbhA heparin binding hemagglutinin HbhA 741 741 ctx cooccurence:738
Rv2138 lppL lipoprotein LppL 739 739 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

  • Legacy H37Rv annotation: membrane protein
  • MTBC0 PGAP product: DUF4333 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF4333 PF14230.12 (E=9e-25)
  • (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_216607.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4333 (PF14230.12)
  • 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 2BYFJ
  • Curated reference: UniProt P9WLJ5 (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 — 115 functional partner(s); context anchor Rv2520c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002225|Rv2091c|
MSGPQGSDPRQPWQPPGQGADHSSDPTVAAGYPWQQQPTQEATWQAPAYTPQYQQPADPAYPQQYPQPTPGYAQPEQFGAQPTQLGVPGQYGQYQQPGQYGQPGQYGQPGQYAPPGQYPGQYGPYGQSGQGSKRSVAVIGGVIAVMAVLFIGAVLILGFWAPGFFVTTKLDVIKAQAGVQQVLTDETTGYGAKNVKDVKCNNGSDPTVKKGATFECTVSIDGTSKRVTVTFQDNKGTYEVGRPQ