MTBC Gene Atlas

Rv0526 Resolved · high auto-curated

H37Rv Rv0526 · MTBC0 - · 216 aa · 616846–617496 (+) · RefSeq NP_215040.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)thioredoxin
MTBC0 PGAP re-annotation—
Revised (this work)Thioredoxin. Pfam: Redoxin (PF08534.17), AhpC-TSA (PF00578.28), Thioredoxin (PF00085.27).

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 O06392 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible thioredoxin protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
O Post-translational modification, protein turnover, chaperones
Preferred nameccsX
eggNOG descriptionAlkyl hydroperoxide reductase
Orthologous groupCOG0526

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 0.356 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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
RedoxinPF08534.17 1.3e-1672–188 Redoxin
AhpC-TSAPF00578.28 1.5e-1678–184 AhpC/TSA family
ThioredoxinPF00085.27 3.9e-0588–136 Thioredoxin

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

Closest characterised functional partner: ccdA (cytochrome C-type biogenesis protein CcdA), high confidence from genomic context alone (score 991 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0525 hyp hypothetical protein 992 993 ctx neighborhood:865 coexpression:943
Rv0527 ccdA cytochrome C-type biogenesis protein CcdA 996 991 ctx neighborhood:882 cooccurence:464 coexpression:863 textmining:657
Rv0529 ccsA cytochrome C-type biogenesis protein CcsA 995 990 ctx neighborhood:833 coexpression:937 textmining:584
Rv0528 transmembrane protein 983 977 ctx neighborhood:833 coexpression:844
Rv0524 hemL glutamate-1-semialdehyde 2,1-aminomutase 991 974 ctx neighborhood:865 coexpression:816 textmining:675
Rv2428 ahpC alkyl hydroperoxide reductase subunit AhpC 840 830 experimental:468 database:611
Rv0137c msrA peptide methionine sulfoxide reductase MsrA 832 821 experimental:562 database:596
Rv3303c lpdA NAD(P)H quinone reductase LpdA 809 801 experimental:410 database:550
Rv2855 mtr mycothione reductase 758 748 experimental:410 database:550
Rv0794c oxidoreductase 758 747 experimental:410 database:550
Rv0462 lpdC dihydrolipoamide dehydrogenase 756 745 experimental:410 database:550
Rv2713 sthA pyridine nucleotide transhydrogenase 757 741 experimental:410 database:550
Rv0530 hyp hypothetical protein 710 710 ctx neighborhood:667
Rv0570 nrdZ vitamin B12-dependent ribonucleoside-diphosphate reductase 712 697 database:578
Rv3051c nrdE ribonucleoside-diphosphate reductase subunit alpha 710 696 database:578

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): thioredoxin
  • Pfam (hmmscan --cut_ga): Redoxin PF08534.17 (E=1e-16), AhpC-TSA PF00578.28 (E=1e-16), Thioredoxin PF00085.27 (E=4e-05)
  • (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_215040.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Redoxin (PF08534.17), AhpC-TSA (PF00578.28), Thioredoxin (PF00085.27)
  • 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 COG0526
  • Curated reference: UniProt O06392 (TrEMBL, unreviewed; 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 — 113 functional partner(s); context anchor ccdA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0526|
MQSRATRRSGALTMRRLVIAAAVSALLLTGCSGRDAVAQGGTFEFVSPGGKTDIFYDPPASRGRPGPLSGPELADPARSVSLDDFPGQVVVVNVWGQWCGPCRAEVSQLQRVYDATRGAGVSFLGIDVRDNNRQAPQDFINDRHVTYPSIYDPAMRTLIAFGGKYPTSVIPSTLVLDRQHRVAAVFLRELLAADLQPVVERVAEEEPSGRAPVGAQ