trxB2 Resolved · high auto-curated

H37Rv Rv3913 · MTBC0 mtbc0_004147 · 335 aa · 4425979–4426986 (+) · RefSeq NP_218430.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)thioredoxin reductase
MTBC0 PGAP re-annotationthioredoxin-disulfide reductase
Revised (this work)Thioredoxin-disulfide reductase. Pfam: Pyr_redox_2 (PF07992.21), FAD_binding_2 (PF00890.31), Pyr_redox_3 (PF13738.13), Pyr_redox (PF00070.34).

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

Curated reference (UniProt)

UniProt P9WHH1 SwissProt · reviewed · Evidence at protein level
UniProt nameThioredoxin reductase
EC (curated) EC 1.8.1.9
Curated functionEssential thiol-reducing enzyme that protects the cell from thiol-specific oxidizing stress. Plays a minor role in defense against oxidative and nitrosative stress. Is essential to establish and maintain infection in mice.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred nametrxB
eggNOG descriptionBelongs to the class-II pyridine nucleotide-disulfide oxidoreductase family
Orthologous groupCOG0492
EC number EC 1.8.1.9
KEGG orthology K00384, K03671
KEGG pathways map00450, map04621, map05418
Gene Ontology (57) GO:0000166, GO:0001666, GO:0003674, GO:0003824, GO:0004791, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006950 +45 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 0.295 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 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
Pyr_redox_2PF07992.21 1.2e-4916–304 Pyridine nucleotide-disulphide oxidoreductase
FAD_binding_2PF00890.31 8.9e-0516–51 FAD binding domain
Pyr_redox_3PF13738.13 1.8e-1891–287 Pyridine nucleotide-disulphide oxidoreductase
Pyr_redoxPF00070.34 3.1e-18158–230 Pyridine nucleotide-disulphide oxidoreductase

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

Closest characterised functional partner: trxC (thioredoxin TrxC), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3914 trxC thioredoxin TrxC 999 998 ctx neighborhood:882 fusion:890 experimental:770 textmining:951
Rv1471 trxB1 thioredoxin 998 983 experimental:770 database:900 textmining:886
Rv1464 csd cysteine desulfurase 923 920 database:900
Rv2428 ahpC alkyl hydroperoxide reductase subunit AhpC 955 896 coexpression:437 experimental:808 textmining:588
Rv1324 thioredoxin 911 795 experimental:770 textmining:589
Rv1470 trxA thioredoxin TrxA 942 793 experimental:770 textmining:736
Rv3912 rsmA anti-sigma-M factor RsmA 776 777 ctx neighborhood:776
Rv3910 murJ peptidoglycan biosynthesis protein 717 657 ctx neighborhood:653
Rv3915 cwlM peptidoglycan hydrolase 708 653 ctx neighborhood:632
Rv3911 sigM ECF RNA polymerase sigma factor SigM 722 612 ctx neighborhood:603
Rv3908 mutT4 mutator protein MutT 625 607 ctx neighborhood:549
Rv3909 hyp hypothetical protein 549 549 ctx neighborhood:549
Rv1937 oxygenase 714 529 experimental:456 textmining:420
Rv2874 dipZ integral membrane C-type cytochrome biogenesis protein DipZ 661 529 experimental:440
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 570 509

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: thioredoxin reductase
  • MTBC0 PGAP product: thioredoxin-disulfide reductase
  • Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=1e-49), FAD_binding_2 PF00890.31 (E=9e-05), Pyr_redox_3 PF13738.13 (E=2e-18), Pyr_redox PF00070.34 (E=3e-18)
  • (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_218430.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), FAD_binding_2 (PF00890.31), Pyr_redox_3 (PF13738.13), Pyr_redox (PF00070.34)
  • 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 COG0492
  • Curated reference: UniProt P9WHH1 (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 — 116 functional partner(s); context anchor trxC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004147|Rv3913|trxB2
MTAPPVHDRAHHPVRDVIVIGSGPAGYTAALYAARAQLAPLVFEGTSFGGALMTTTDVENYPGFRNGITGPELMDEMREQALRFGADLRMEDVESVSLHGPLKSVVTADGQTHRARAVILAMGAAARYLQVPGEQELLGRGVSSCATCDGFFFRDQDIAVIGGGDSAMEEATFLTRFARSVTLVHRRDEFRASKIMLDRARNNDKIRFLTNHTVVAVDGDTTVTGLRVRDTNTGAETTLPVTGVFVAIGHEPRSGLVREAIDVDPDGYVLVQGRTTSTSLPGVFAAGDLVDRTYRQAVTAAGSGCAAAIDAERWLAEHAATGEADSTDALIGAQR