Rv3131 Resolved · medium auto-curated

H37Rv Rv3131 · MTBC0 mtbc0_003328 · 332 aa · 3517916–3518914 (+) · RefSeq NP_217647.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NAD(P)H nitroreductase
MTBC0 PGAP re-annotationNAD(P)H nitroreductase
Revised (this work)NAD(P)H nitroreductase.

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

Curated reference (UniProt)

UniProt P9WIZ7 SwissProt · reviewed · Evidence at protein level
UniProt namePutative NAD(P)H nitroreductase Rv3131
Curated functionStimulates pro-inflammatory cytokine expression via TLR2 signaling pathway. Activation of TLR2 results in the phosphorylation and activation of NF-kappa-B. Also induces TLR2 expression. May influence the innate immune responses to facilitate the survival of M.tuberculosis in the granulomatous microenvironment.

UniProt still lists this protein as Putative NAD(P)H nitroreductase Rv3131; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionnitroreductase
Orthologous groupCOG0778
Gene Ontology (13) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044424, GO:0044444, GO:0044464 +1 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 0.238 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: tgs1 (diacyglycerol O-acyltransferase), high confidence from genomic context alone (score 949 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3130c tgs1 diacyglycerol O-acyltransferase 980 949 ctx neighborhood:506 coexpression:863 textmining:626
Rv1738 hyp hypothetical protein 937 915 ctx cooccurence:419 coexpression:860
Rv3127 hyp hypothetical protein 912 893 coexpression:860
Rv3134c universal stress protein 946 892 coexpression:827 textmining:529
Rv1996 universal stress protein 918 890 coexpression:860
Rv2032 acg NAD(P)H nitroreductase 908 890 coexpression:852
Rv2031c hspX alpha-crystallin 918 864 coexpression:860 textmining:429
Rv0079 hyp hypothetical protein 908 860 coexpression:860
Rv2030c hyp hypothetical protein 919 841 coexpression:801 textmining:514
Rv2007c fdxA ferredoxin 937 836 coexpression:833 textmining:632
Rv1733c transmembrane protein 898 828 coexpression:806 textmining:433
Rv2626c hrp1 hypoxic response protein 893 818 coexpression:817 textmining:439
Rv0080 hyp hypothetical protein 916 811 coexpression:807 textmining:579
Rv2623 TB31.7 universal stress protein 891 810 coexpression:761 textmining:455
Rv2627c hyp hypothetical protein 808 808 coexpression:807

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: NAD(P)H nitroreductase
  • MTBC0 PGAP product: NAD(P)H nitroreductase
  • (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_217647.3)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0778
  • Curated reference: UniProt P9WIZ7 (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 — 56 functional partner(s); context anchor tgs1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003328|Rv3131|
MNTHFPDAETVRTVLTLAVRAPSIHNTQPWRWRVCPTSLELFSRPDMQLRSTDPDGRELILSCGVALHHCVVALASLGWQAKVNRFPDPKDRCHLATIGVQPLVPDQADVALAAAIPRRRTDRRAYSCWPVPGGDIALMAARAARGGVMLRQVSALDRMKAIVAQAVLDHVTDEEYLRELTIWSGRYGSVAGVPARNEPPSDPSAPIPGRLFAGPGLSQPSDVLPADDGAAILALGTETDDRLARLRAGEAASIVLLTATAMGLACCPITEPLEIAKTRDAVRAEVFGAGGYPQMLLRVGWAPINADPLPPTPRRELSQVVEWPEELLRQRC