ndh Resolved · high auto-curated

H37Rv Rv1854c · MTBC0 mtbc0_001967 · 463 aa · 2119689–2121080 (-) · RefSeq NP_216370.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NADH dehydrogenase
MTBC0 PGAP re-annotationNAD(P)/FAD-dependent oxidoreductase
Revised (this work)NAD(P)/FAD-dependent oxidoreductase. Pfam: Pyr_redox_2 (PF07992.21), 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 P95160 SwissProt · reviewed · Evidence at protein level
UniProt nameType II NADH:quinone oxidoreductase Ndh
EC (curated) EC 1.6.5.9
Curated functionAlternative, nonproton pumping NADH:quinone oxidoreductase that delivers electrons to the respiratory chain by oxidation of NADH and reduction of quinones. Ndh is probably the main NADH dehydrogenase of M.tuberculosis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namendh
eggNOG descriptionNADH dehydrogenase
Orthologous groupCOG1252
EC number EC 1.6.99.3
KEGG orthology K03885
KEGG pathways map00190

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 0.49 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 7 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 5.5e-5216–339 Pyridine nucleotide-disulphide oxidoreductase
Pyr_redoxPF00070.34 2.6e-06174–257 Pyridine nucleotide-disulphide oxidoreductase

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

Closest characterised functional partner: Rv1855c (oxidoreductase), medium confidence from genomic context alone (score 597 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1855c oxidoreductase 596 597 ctx neighborhood:584
Rv1856c oxidoreductase 490 490 ctx neighborhood:482
Rv3628 ppa inorganic pyrophosphatase 494 469 coexpression:407
Rv0489 gpm1 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase 459 460 experimental:454
Rv3156 nuoL NADH-quinone oxidoreductase subunit L 507 427 coexpression:412
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 482 422 coexpression:415
Rv3339c icd1 isocitrate dehydrogenase 449 415 coexpression:413
Rv1240 mdh malate dehydrogenase 459 404
Rv2195 qcrA ubiquinol-cytochrome C reductase rieske iron-sulfur subunit 714 321 textmining:597
Rv1622c cydB cytochrome D ubiquinol oxidase subunit II CydB 485 275
Rv1623c cydA cytochrome D ubiquinol oxidase subunit I CydA 505 266
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 759 248 textmining:693
Rv2785c rpsO 30S ribosomal protein S15 452 228
Rv0247c succinate dehydrogenase iron-sulfur subunit 414 177
Rv2890c rpsB 30S ribosomal protein S2 405 162

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: NADH dehydrogenase
  • MTBC0 PGAP product: NAD(P)/FAD-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=6e-52), Pyr_redox PF00070.34 (E=3e-06)
  • (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_216370.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), 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 COG1252
  • Curated reference: UniProt P95160 (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 — 50 functional partner(s); context anchor Rv1855c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001967|Rv1854c|ndh
MSPQQEPTAQPPRRHRVVIIGSGFGGLNAAKKLKRADVDIKLIARTTHHLFQPLLYQVATGIISEGEIAPPTRVVLRKQRNVQVLLGNVTHIDLAGQCVVSELLGHTYQTPYDSLIVAAGAGQSYFGNDHFAEFAPGMKSIDDALELRGRILSAFEQAERSSDPERRAKLLTFTVVGAGPTGVEMAGQIAELAEHTLKGAFRHIDSTKARVILLDAAPAVLPPMGAKLGQRAAARLQKLGVEIQLGAMVTDVDRNGITVKDSDGTVRRIESACKVWSAGVSASRLGRDLAEQSRVELDRAGRVQVLPDLSIPGYPNVFVVGDMAAVEGVPGVAQGAIQGAKYVASTIKAELAGANPAEREPFQYFDKGSMATVSRFSAVAKIGPVEFSGFIAWLIWLVLHLAYLIGFKTKITTLLSWTVTFLSTRRGQLTITDQQAFARTRLEQLAELAAEAQGSAASAKVAS