mtr Resolved · high auto-curated

H37Rv Rv2855 · MTBC0 - · 459 aa · 3165205–3166584 (+) · RefSeq YP_177910.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)mycothione reductase
MTBC0 PGAP re-annotation
Revised (this work)Mycothione reductase. Pfam: Pyr_redox_2 (PF07992.21), Pyr_redox_3 (PF13738.13), Lys_Orn_oxgnase (PF13434.13), Pyr_redox (PF00070.34), Pyr_redox_dim (PF02852.29).

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 P9WHH3 SwissProt · reviewed · Evidence at protein level
UniProt nameMycothione reductase
EC (curated) EC 1.8.1.15
Curated functionCatalyzes the NAD(P)H-dependent reduction of mycothione (the oxidized disulfide form of mycothiol) to mycothiol.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namemtr
eggNOG descriptionBelongs to the class-I pyridine nucleotide-disulfide oxidoreductase family
Orthologous groupCOG1249
EC number EC 1.8.1.15
KEGG orthology K17883
Gene Ontology (41) GO:0000166, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006790, GO:0008150, GO:0008152 +29 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) pseudogene candidate

pN/pS 0.334 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 4 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 1.05% of strains (1528) · 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
Pyr_redox_2PF07992.21 2.6e-474–316 Pyridine nucleotide-disulphide oxidoreductase
Pyr_redox_3PF13738.13 2.2e-08119–304 Pyridine nucleotide-disulphide oxidoreductase
Lys_Orn_oxgnasePF13434.13 2.9e-05127–190 L-lysine 6-monooxygenase/L-ornithine 5-monooxygenase
Pyr_redoxPF00070.34 2.8e-15174–249 Pyridine nucleotide-disulphide oxidoreductase
Pyr_redox_dimPF02852.29 5.0e-29345–454 Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain

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

Closest characterised functional partner: bkdC (branched-chain keto acid dehydrogenase E2 component), high confidence from genomic context alone (score 918 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 999 999 coexpression:756 experimental:970 database:844
Rv2496c bkdB 3-methyl-2-oxobutanoate dehydrogenase subunit beta 950 946 coexpression:645 experimental:465 database:617
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 922 918 ctx cooccurence:442 coexpression:451 experimental:443 database:565
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 933 908 coexpression:454 experimental:443 database:565
Rv2854 hyp hypothetical protein 883 877 ctx neighborhood:869
Rv1734c hyp hypothetical protein 866 860 coexpression:451 experimental:443 database:565
Rv0843 dehydrogenase 864 852 coexpression:500 database:580
Rv2497c bkdA 3-methyl-2-oxobutanoate dehydrogenase subunit alpha 860 848 coexpression:497 database:580
Rv1017c prsA ribose-phosphate pyrophosphokinase 793 777 database:615
Rv2874 dipZ integral membrane C-type cytochrome biogenesis protein DipZ 765 753 experimental:410 database:550
Rv0526 thioredoxin 758 748 experimental:410 database:550
Rv1677 dsbF lipoprotein DsbF 754 743 experimental:410 database:550
Rv3673c membrane-anchored thioredoxin-like protein 753 743 experimental:410 database:550
Rv0816c thiX thioredoxin ThiX 752 741 experimental:410 database:550
Rv2878c mpt53 soluble secreted antigen Mpt53 752 741 experimental:410 database:550

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): mycothione reductase
  • Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=3e-47), Pyr_redox_3 PF13738.13 (E=2e-08), Lys_Orn_oxgnase PF13434.13 (E=3e-05), Pyr_redox PF00070.34 (E=3e-15), Pyr_redox_dim PF02852.29 (E=5e-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 YP_177910.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), Pyr_redox_3 (PF13738.13), Lys_Orn_oxgnase (PF13434.13), Pyr_redox (PF00070.34), Pyr_redox_dim (PF02852.29)
  • 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 COG1249
  • Curated reference: UniProt P9WHH3 (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 — 114 functional partner(s); context anchor bkdC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2855|mtr
METYDIAIIGTGSGNSILDERYASKRAAICEQGTFGGTCLNVGCIPTKMFVYAAEVAKTIRGASRYGIDAHIDRVRWDDVVSRVFGRIDPIALSGEDYRRCAPNIDVYRTHTRFGPVQADGRYLLRTDAGEEFTAEQVVIAAGSRPVIPPAILASGVDYHTSDTVMRIAELPEHIVIVGSGFIAAEFAHVFSALGVRVTLVIRGSCLLRHCDDTICERFTRIASTKWELRTHRNVVDGQQRGSGVALRLDDGCTINADLLLVATGRVSNADLLDAEQAGVDVEDGRVIVDEYQRTSARGVFALGDVSSPYLLKHVANHEARVVQHNLLCDWEDTQSMIVTDHRYVPAAVFTDPQIAAVGLTENQAVAKGLDISVKIQDYGDVAYGWAMEDTSGIVKLITERGSGRLLGAHIMGYQASSLIQPLIQAMSFGLTAAEMARGQYWIHPALPEVVENALLGLR