nuoH Family assigned · medium auto-curated

H37Rv Rv3152 · MTBC0 mtbc0_003350 · 410 aa · 3541984–3543216 (+) · RefSeq NP_217668.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NADH-quinone oxidoreductase subunit H
MTBC0 PGAP re-annotationNADH-quinone oxidoreductase subunit NuoH
Revised (this work)NADH-quinone oxidoreductase subunit NuoH. Pfam: NADHdh (PF00146.27).

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

Curated reference (UniProt)

UniProt P9WIX1 SwissProt · reviewed · Evidence at protein level
UniProt nameNADH-quinone oxidoreductase subunit H
EC (curated) EC 7.1.1.-
Curated functionNDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be menaquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namenuoH
eggNOG descriptionNDH-1 shuttles electrons from NADH, via FMN and iron- sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be menaquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient
Orthologous groupCOG1005
EC number EC 1.6.5.3
KEGG orthology K00337
KEGG pathways map00190, map01100
KEGG modules M00144

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 1.743 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 5 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
NADHdhPF00146.27 2.9e-12215–334 NADH dehydrogenase

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

Closest characterised functional partner: nuoF (NADH-quinone oxidoreductase subunit F), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 999 1000 ctx neighborhood:725 coexpression:952 experimental:928 database:583 textmining:584
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 999 1000 ctx neighborhood:724 cooccurence:772 coexpression:983 experimental:997 database:731 textmining:599
Rv3145 nuoA NADH-quinone oxidoreductase subunit A 999 1000 ctx neighborhood:762 cooccurence:774 coexpression:973 experimental:997 database:803 textmining:689
Rv3156 nuoL NADH-quinone oxidoreductase subunit L 999 1000 ctx neighborhood:874 cooccurence:774 coexpression:976 experimental:922 textmining:810
Rv3157 nuoM NADH-quinone oxidoreductase subunit M 999 1000 ctx neighborhood:874 cooccurence:773 coexpression:974 experimental:928 database:803 textmining:853
Rv3149 nuoE NADH-quinone oxidoreductase subunit E 999 1000 ctx neighborhood:727 coexpression:963 experimental:928 database:620 textmining:590
Rv3146 nuoB NADH-quinone oxidoreductase subunit B 999 1000 ctx neighborhood:721 cooccurence:770 coexpression:980 experimental:997 database:731
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 999 1000 ctx neighborhood:881 fusion:633 cooccurence:758 coexpression:976 experimental:997 database:731 textmining:744
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 999 1000 ctx neighborhood:722 cooccurence:769 coexpression:955 experimental:997 database:731 textmining:686
Rv3158 nuoN NADH-quinone oxidoreductase subunit N 999 1000 ctx neighborhood:874 cooccurence:773 coexpression:970 experimental:928 database:747 textmining:735
Rv3154 nuoJ NADH-quinone oxidoreductase subunit J 999 1000 ctx neighborhood:881 cooccurence:751 coexpression:976 experimental:997 textmining:688
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 999 1000 ctx neighborhood:764 coexpression:965 experimental:928 database:583
Rv3155 nuoK NADH-quinone oxidoreductase subunit K 999 1000 ctx neighborhood:881 cooccurence:773 coexpression:957 experimental:924 textmining:625
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 987 984 coexpression:855 experimental:894
Rv2193 ctaE cytochrome C oxidase subunit III 981 976 coexpression:859 experimental:794

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-quinone oxidoreductase subunit H
  • MTBC0 PGAP product: NADH-quinone oxidoreductase subunit NuoH
  • Pfam (hmmscan --cut_ga): NADHdh PF00146.27 (E=3e-122)
  • (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_217668.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NADHdh (PF00146.27)
  • 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 COG1005
  • Curated reference: UniProt P9WIX1 (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 — 140 functional partner(s); context anchor nuoF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003350|Rv3152|nuoH
MTTFGHDTWWLVAAKAIAVFVFLMLTVLVAILAERKLLGRMQLRPGPNRVGPKGALQSLADGIKLALKESITPGGIDRFVYFVAPIISVIPAFTAFAFIPFGPEVSVFGHRTPLQITDLPVAVLFILGLSAIGVYGIVLGGWASGSTYPLLGGVRSTAQVISYEVAMGLSFATVFLMAGTMSTSQIVAAQDGVWYAFLLLPSFVIYLISMVGETNRAPFDLPEAEGELVAGFHTEYSSLKFAMFMLAEYVNMTTVSALAATLFFGGWHAPWPLNMWASANTGWWPLIWFTAKVWGFLFIYFWLRATLPRLRYDQFMALGWKLLIPVSLVWVMVAAIIRSLRNQGYQYWTPTLVFSSIVVAAAMVLLLRKPLSAPGARASARQRGDEGTSPEPAFPTPPLLAGATKENAGG