Rv0094c Still unknown · low auto-curated

H37Rv Rv0094c · MTBC0 - · 317 aa · 103710–104663 (-) · RefSeq NP_214608.1

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 Q50655 TrEMBL · unreviewed · Predicted
UniProt nameHNH nuclease domain-containing protein

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 2.349 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 7 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 1.3e-712–223 Domain of unknown function (DUF222)

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

Closest characterised functional partner: Rv0093c (membrane protein), medium confidence from genomic context alone (score 677 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3467 hyp hypothetical protein 831 832 coexpression:831
Rv1702c hyp hypothetical protein 802 803 coexpression:797
Rv3776 hyp hypothetical protein 760 761 ctx cooccurence:688
Rv0515 hyp hypothetical protein 744 745 ctx cooccurence:730
Rv0336 hyp hypothetical protein 742 742 ctx cooccurence:730
Rv0393 hyp hypothetical protein 734 734 ctx cooccurence:726
Rv2100 hyp hypothetical protein 732 733 ctx cooccurence:677
Rv0093c membrane protein 677 677 ctx neighborhood:630
Rv1765c hyp hypothetical protein 667 668 ctx cooccurence:657
Rv2015c hyp hypothetical protein 630 630 ctx cooccurence:626
Rv1587c hyp hypothetical protein 587 587 coexpression:580
Rv1378c hyp hypothetical protein 548 549 ctx cooccurence:542
Rv3074 hyp hypothetical protein 546 546 ctx cooccurence:532
Rv0095c hyp hypothetical protein 500 501 ctx neighborhood:485
Rv1303 hyp hypothetical protein 456 457 ctx cooccurence:455

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=1e-71)
  • (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_214608.1)
  • 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 Q50655 (TrEMBL, unreviewed; 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 — 25 functional partner(s); context anchor Rv0093c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0094c|
MSTRQAAEADLAGKAAQYRPDELARYAQRVMDWLHPDGDLTDTERARKRGITLSNQQYDGMSRLSGYLTPQARATFEAVLAKLAAPGATNPDDHTPVIDTTPDAAAIDRDTRSQAQRNHDGLLAGLRALIASGKLGQHNGLPVSIVVTTTLTDLQTGAGKGFTGGGTLLPMADVIRMTSHAHHYSPASGRYPQAIFDHGTPLALYHTKRLASPAQRIMLFANDRGCTKPGCDAPAYHSQAHHVTAWTSTGRTDITELTLACGPDNRLAEKGWTTHNNTHGHTEWLPPPHLDHGQPRTNTFHHPERFLHNQDDDDKPD