Rv0770 Resolved · high auto-curated

H37Rv Rv0770 · MTBC0 mtbc0_000819 · 295 aa · 867680–868567 (+) · RefSeq NP_215284.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationNAD(P)-dependent oxidoreductase
Revised (this work)NAD(P)-dependent oxidoreductase. Pfam: NAD_binding_2 (PF03446.22), NAD_binding_11 (PF14833.12).

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

Curated reference (UniProt)

UniProt P9WNY3 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized oxidoreductase Rv0770
EC (curated) EC 1.1.-.-

UniProt still lists this protein as Uncharacterized oxidoreductase Rv0770; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
eggNOG descriptionDehydrogenase
Orthologous groupCOG2084
EC number EC 1.1.1.31, EC 1.1.1.60
KEGG orthology K00020, K00042
KEGG pathways map00280, map00630, map01100

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 1.417 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 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
NAD_binding_2PF03446.22 2.6e-3810–165 NAD binding domain of 6-phosphogluconate dehydrogenase
NAD_binding_11PF14833.12 1.2e-08170–280 NAD-binding of NADP-dependent 3-hydroxyisobutyrate dehydrogenase

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

Closest characterised functional partner: Rv0771 (4-carboxymuconolactone decarboxylase), high confidence from genomic context alone (score 991 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0771 4-carboxymuconolactone decarboxylase 990 991 ctx neighborhood:882 coexpression:901
Rv0768 aldA aldehyde dehydrogenase AldA 957 956 ctx neighborhood:746 coexpression:832
Rv0762c hyp hypothetical protein 955 956 ctx neighborhood:677 cooccurence:531 coexpression:730
Rv0764c cyp51 lanosterol 14-alpha demethylase 950 950 ctx neighborhood:677 coexpression:801
Rv0765c oxidoreductase 951 949 ctx neighborhood:677 coexpression:802
Rv0766c cyp123 cytochrome P450 Cyp123 895 895 ctx neighborhood:677 coexpression:687
Rv0763c ferredoxin 849 850 ctx neighborhood:677 coexpression:449
Rv0772 purD phosphoribosylamine--glycine ligase 848 848 ctx neighborhood:847
Rv0769 oxidoreductase 783 775 ctx neighborhood:773
Rv0767c HTH-type transcriptional regulator 715 715 ctx neighborhood:505 cooccurence:440
Rv0761c adhB alcohol dehydrogenase B 709 709 ctx neighborhood:643
Rv0311 hyp hypothetical protein 615 616 ctx cooccurence:479
Rv3359 oxidoreductase 491 492
Rv1071c echA9 enoyl-CoA hydratase EchA9 496 477
Rv0760c hyp hypothetical protein 495 477

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: oxidoreductase
  • MTBC0 PGAP product: NAD(P)-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): NAD_binding_2 PF03446.22 (E=3e-38), NAD_binding_11 PF14833.12 (E=1e-08)
  • (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_215284.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NAD_binding_2 (PF03446.22), NAD_binding_11 (PF14833.12)
  • 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 COG2084
  • Curated reference: UniProt P9WNY3 (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 — 24 functional partner(s); context anchor Rv0771
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000819|Rv0770|
MTAHPETPRLGYIGLGNQGAPMAKRLLDWPGGLTVFDVRVEAMAPFVEGGATAAASVSDVAEADIISITVFDDAQVSSVITADNGLATHAKPGTIVAIHSTIADTTAVDLAEKLKPQGIHIVDAPVSGGAAAAAKGELAVMVGADDEAFQRIKEPFSRWASLLIHAGEPGAGTRMKLARNMLTFVSYAAAAEAQRLAEACGLDLVALGKVVRHSDSFTGGAGAIMFRNTTAPMEPADPLRPLLEHTRGLGEKDLSLALALGEVVSVDLPLAQLALQRLAAGLGVPHPDTEPAKET