Rv0688 Resolved · high auto-curated

H37Rv Rv0688 · MTBC0 mtbc0_000727 · 406 aa · 792026–793246 (+) · RefSeq NP_215202.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ferredoxin reductase
MTBC0 PGAP re-annotationFAD/NAD(P)-binding oxidoreductase
Revised (this work)FAD/NAD(P)-binding oxidoreductase. Pfam: Pyr_redox_2 (PF07992.21), Pyr_redox (PF00070.34), Reductase_C (PF14759.13).

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

Curated reference (UniProt)

UniProt P95034 TrEMBL · unreviewed · Evidence at protein level
UniProt nameFerredoxin reductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPyridine nucleotide-disulphide oxidoreductase
Orthologous groupCOG0446
EC number EC 1.18.1.3
KEGG orthology K00529
KEGG pathways map00071, map00360, map01120, map01220
KEGG modules M00545
Gene Ontology (124) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005634, GO:0005737, GO:0005739, GO:0005740, GO:0005743, GO:0005758, GO:0005829 +112 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 0.557 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 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 1.4e-6518–310 Pyridine nucleotide-disulphide oxidoreductase
Pyr_redoxPF00070.34 1.6e-18156–236 Pyridine nucleotide-disulphide oxidoreductase
Reductase_CPF14759.13 8.8e-12330–398 Reductase C-terminal

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

Closest characterised functional partner: Rv0687 (NAD-dependent oxidoreductase), high confidence from genomic context alone (score 878 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1869c reductase 913 914 database:900
Rv0687 NAD-dependent oxidoreductase 882 878 ctx neighborhood:867
Rv0253 nirD nitrite reductase small subunit NirD 830 820 coexpression:498 experimental:434
Rv3250c rubB rubredoxin RubB 746 731 coexpression:408 experimental:549
Rv3251c rubA rubredoxin RubA 746 730 coexpression:407 experimental:549
Rv2633c hyp hypothetical protein 730 714 coexpression:500 experimental:434
Rv3818 hyp hypothetical protein 730 714 coexpression:500 experimental:434
Rv3859c gltB glutamate synthase large subunit 709 590 ctx neighborhood:532
Rv1161 narG nitrate reductase subunit alpha 516 486 coexpression:471
Rv1736c narX nitrate reductase-like protein NarX 516 486 coexpression:471
Rv0686 membrane protein 482 482 ctx neighborhood:474
Rv1777 cyp144 cytochrome P450 Cyp144 495 463
Rv1256c cyp130 cytochrome P450 Cyp130 493 461
Rv3518c cyp142 cytochrome P450 monooxygenase Cyp142 488 446
Rv0511 hemD uroporphyrin-III C-methyltransferase 589 445

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: ferredoxin reductase
  • MTBC0 PGAP product: FAD/NAD(P)-binding oxidoreductase
  • Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=1e-65), Pyr_redox PF00070.34 (E=2e-18), Reductase_C PF14759.13 (E=9e-12)
  • (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_215202.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), Pyr_redox (PF00070.34), Reductase_C (PF14759.13)
  • 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 COG0446
  • Curated reference: UniProt P95034 (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 — 35 functional partner(s); context anchor Rv0687
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000727|Rv0688|
MNAHVTSREGVNEFDDGIVIVGGGLAAARTAEQLRRAGYSGRLTIVSDEVHLPYDRPPLSKEVLRSEVDDVALKPREFYDEKDIALRLGSAAVSLDTGEQTVTLADGTVLGYDELVIATGLVPRRIPSLPDLDGIRVLRSFDESMALRKHASAARHAVVVGAGFIGCEVAASLRGLGVDVVLVEPQPAPLASVLGEQIGQLVTRLHRDEGVDVRTGVTVAEVRGKGHVDAVVLTDGTELPADLVVVGIGSTPATEWLEGSGVEVDNGVICDKAGRTSAPNVWALGDVASWRDPMGHQARVEHWSNVADQARVVVPAMLGTDVPTGVVVPYFWSDQYDVKIQCLGEPHATDVVHLVEDDGRKFLAYYERDGVLVGVVGGGMAGKVMKVRGKIAAGAPIAEVLDQTQA