Rv0095c Still unknown · low auto-curated

H37Rv Rv0095c · MTBC0 - · 136 aa · 104805–105215 (-) · RefSeq NP_214609.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown.

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 Q10891 SwissProt · reviewed · Uncertain
UniProt namePutative uncharacterized protein Rv0095c

UniProt still lists this protein as Putative uncharacterized protein Rv0095c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category V Defense mechanisms
eggNOG descriptionDomain of unknown function (DUF222)
Orthologous groupCOG1403

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 1.016 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 12 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
DUF222PF02720.23 1.8e-1076–135 Domain of unknown function (DUF222)

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

Closest characterised functional partner: PPE1 (PPE family protein PPE1), medium confidence from genomic context alone (score 561 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0096 PPE1 PPE family protein PPE1 657 561 ctx neighborhood:557
Rv0098 fcoT fatty acyl CoA thioesterase FcoT 541 527 ctx neighborhood:522
Rv0097 oxidoreductase 526 526 ctx neighborhood:521
Rv0101 nrp peptide synthetase Nrp 610 525 ctx neighborhood:521
Rv0100 hyp hypothetical protein 563 525 ctx neighborhood:521
Rv0099 fadD10 fatty-acid--CoA ligase FadD10 525 524 ctx neighborhood:521
Rv0094c hyp hypothetical protein 500 501 ctx neighborhood:485
Rv0093c membrane protein 413 413 ctx neighborhood:409
Rv2100 hyp hypothetical protein 644 89 textmining:626
Rv0064 transmembrane protein 539 84 textmining:518
Rv0515 hyp hypothetical protein 518 56 textmining:511
Rv0336 hyp hypothetical protein 655 55 textmining:650
Rv2517c hyp hypothetical protein 544 51 textmining:540
Rv1395 HTH-type transcriptional regulator 522 51 textmining:517
Rv1944c hyp hypothetical protein 656 50 textmining:653

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): hypothetical protein
  • Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=2e-10)
  • (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_214609.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
  • 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 COG1403
  • Curated reference: UniProt Q10891 (SwissProt, reviewed; Uncertain)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Model confidence: ESMFold per-residue pLDDT (mean 67.2, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 18 functional partner(s); context anchor PPE1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0095c|
MRYLPVSTRRIWVNPLCHFSFTVISGALFVSARRYDSNMLANSREELVEVFDALDADLDRLDEVSFEVLSTPERLRSLERLECLARRLPAAQHTLINQLDTQASEEELGGTLCCALANRLRITKPEAGRRSAEAKP