nuoA Family assigned · medium auto-curated

H37Rv Rv3145 · MTBC0 mtbc0_003343 · 128 aa · 3534384–3534770 (+) · RefSeq NP_217661.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NADH-quinone oxidoreductase subunit A
MTBC0 PGAP re-annotationNADH-quinone oxidoreductase subunit A
Revised (this work)NADH-quinone oxidoreductase subunit A. Pfam: Oxidored_q4 (PF00507.25).

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

Curated reference (UniProt)

UniProt P9WIW7 SwissProt · reviewed · Evidence at protein level
UniProt nameNADH-quinone oxidoreductase subunit A
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 a 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 namenuoA
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 a 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 groupCOG0838
EC number EC 1.6.5.3
KEGG orthology K00330
KEGG pathways map00190, map01100
KEGG modules M00144
Gene Ontology (18) GO:0003674, GO:0003824, GO:0003954, GO:0005575, GO:0008137, GO:0008150, GO:0008152, GO:0016020, GO:0016491, GO:0016651, GO:0016655, GO:0030964 +6 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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 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)

PfamAccessioni-EvalueResiduesDescription
Oxidored_q4PF00507.25 1.8e-3119–127 NADH-ubiquinone/plastoquinone oxidoreductase, chain 3

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3155 nuoK NADH-quinone oxidoreductase subunit K 999 1000 ctx neighborhood:762 cooccurence:774 coexpression:979 experimental:997 textmining:625
Rv3152 nuoH NADH-quinone oxidoreductase subunit H 999 1000 ctx neighborhood:762 cooccurence:774 coexpression:973 experimental:997 database:803 textmining:689
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 999 1000 ctx neighborhood:762 cooccurence:754 coexpression:979 experimental:928 database:731
Rv3146 nuoB NADH-quinone oxidoreductase subunit B 999 1000 ctx neighborhood:879 cooccurence:762 coexpression:973 experimental:997 database:731 textmining:630
Rv3149 nuoE NADH-quinone oxidoreductase subunit E 999 1000 ctx neighborhood:879 coexpression:937 experimental:928 database:620 textmining:644
Rv3158 nuoN NADH-quinone oxidoreductase subunit N 999 1000 ctx neighborhood:758 cooccurence:773 coexpression:943 experimental:997 database:747 textmining:819
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 999 1000 ctx neighborhood:879 cooccurence:765 coexpression:968 experimental:928 database:731
Rv3154 nuoJ NADH-quinone oxidoreductase subunit J 999 1000 ctx neighborhood:762 cooccurence:766 coexpression:858 experimental:997 textmining:675
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 999 1000 ctx neighborhood:879 coexpression:884 experimental:928 database:583 textmining:662
Rv3157 nuoM NADH-quinone oxidoreductase subunit M 999 1000 ctx neighborhood:758 cooccurence:772 coexpression:878 experimental:928 database:803 textmining:685
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 999 1000 ctx neighborhood:879 coexpression:927 experimental:928 database:583 textmining:518
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 999 1000 ctx neighborhood:879 cooccurence:769 coexpression:967 experimental:997 database:731
Rv3156 nuoL NADH-quinone oxidoreductase subunit L 999 999 ctx neighborhood:758 cooccurence:773 coexpression:851 experimental:928 textmining:625
Rv3143 response regulator 998 998 ctx neighborhood:477 experimental:997
Rv0310c hyp hypothetical protein 979 978 experimental:928 database:667

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 A
  • MTBC0 PGAP product: NADH-quinone oxidoreductase subunit A
  • Pfam (hmmscan --cut_ga): Oxidored_q4 PF00507.25 (E=2e-31)
  • (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_217661.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Oxidored_q4 (PF00507.25)
  • 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 COG0838
  • Curated reference: UniProt P9WIW7 (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 — 172 functional partner(s); context anchor nuoK
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003343|Rv3145|nuoA
MNVYIPILVLAALAAAFAVVSVVIASLVGPSRFNRSKQAAYECGIEPASTGARTSIGPGAASGQRFPIKYYLTAMLFIVFDIEIVFLYPWAVSYDSLGTFALVEMAIFMLTVFVAYAYVWRRGGLTWD