Rv0493c Family assigned · medium auto-curated

H37Rv Rv0493c · MTBC0 - · 329 aa · 583701–584690 (-) · RefSeq NP_215007.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Tocopherol_cycl (PF14249.13) domain(s); putative function inferred from the domain architecture.

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 P9WKU7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0493c

UniProt still lists this protein as Uncharacterized protein Rv0493c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2CDI5

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 0.971 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 7 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.38% of strains (555) · clonal

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
Tocopherol_cyclPF14249.13 3.6e-2933–302 Tocopherol cyclase

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

Closest characterised functional partner: Rv0492c (GMC-type oxidoreductase), high confidence from genomic context alone (score 976 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0492c GMC-type oxidoreductase 976 976 ctx neighborhood:881 cooccurence:770
Rv0492A hyp hypothetical protein 957 957 ctx neighborhood:882 coexpression:651
Rv0494 HTH-type transcriptional regulator 823 823 ctx neighborhood:622 cooccurence:549
Rv1648 transmembrane protein 716 716 ctx cooccurence:716
Rv1775 hyp hypothetical protein 700 700 ctx cooccurence:699
Rv1270c lprA lipoprotein LprA 680 681 ctx cooccurence:676
Rv3413c rsdA anti-sigma-D factor RsdA 648 648 ctx cooccurence:648
Rv0538 membrane protein 636 636 ctx cooccurence:634
Rv3788 hyp hypothetical protein 634 634 ctx cooccurence:629
Rv2113 integral membrane protein 609 609 ctx cooccurence:607
Rv1966 mce3A Mce family protein Mce3A 605 606 ctx cooccurence:602
Rv3903c cpnT hyp hypothetical protein 595 595 ctx cooccurence:595
Rv3071 hyp hypothetical protein 586 587 ctx cooccurence:583
Rv1024 membrane protein 582 583 ctx cooccurence:580
Rv2761c hsdS type I restriction/modification system specificity determinant HsdS 522 522 ctx cooccurence:522

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): Tocopherol_cycl PF14249.13 (E=4e-29)
  • (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_215007.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Tocopherol_cycl (PF14249.13)
  • 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 2CDI5
  • Curated reference: UniProt P9WKU7 (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 — 29 functional partner(s); context anchor Rv0492c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0493c|
MGESTTQPAGGAAVDDETRSAALPRWRGAAGRLEVWYATLSDPLTRTGLWVHCETVAPTTGGPYAHGWVTWFPPDAPPGTERFGPQPAQPAAGPAWFDIAGVRMAPAELTGRTRSLAWELSWKDTAAPLWTFPRVAWERELLPGAQVVIAPTAVFAGSLAVGETTHRVDSWRGSVAHIYGHGNAKRWGWIHADLGDGDVLEVVTAVSHKPGLRRLAPLAFVRFRIDGKDWPASPLPSLRMRTTLGVRHWQLEGRIGGREALIRVDQPPERCVSLGYTDPDGAKAVCTNTEQADIHIELGGRHWSVLGTGHAEVGLRGTAAPAIKEGTPA