nuoM Family assigned · medium auto-curated

H37Rv Rv3157 · MTBC0 mtbc0_003355 · 553 aa · 3546834–3548495 (+) · RefSeq NP_217673.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)NADH-quinone oxidoreductase subunit M
MTBC0 PGAP re-annotationNADH-quinone oxidoreductase subunit M
Revised (this work)NADH-quinone oxidoreductase subunit M. Pfam: Proton_antipo_M (PF00361.26).

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

Curated reference (UniProt)

UniProt P9WIW5 SwissProt · reviewed · Evidence at protein level
UniProt nameNADH-quinone oxidoreductase subunit M
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 (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namenuoM
eggNOG descriptionoxidoreductase, chain M
Orthologous groupCOG1008
EC number EC 1.6.5.3
KEGG orthology K00342
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 0.324 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 9 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
Proton_antipo_MPF00361.26 2.1e-64160–459 NADH:quinone oxidoreductase/Mrp antiporter, TM

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

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3146 nuoB NADH-quinone oxidoreductase subunit B 999 1000 ctx neighborhood:760 cooccurence:744 coexpression:941 experimental:928 database:871
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 999 1000 ctx neighborhood:874 cooccurence:686 coexpression:974 experimental:928 database:871 textmining:436
Rv3149 nuoE NADH-quinone oxidoreductase subunit E 999 1000 ctx neighborhood:760 coexpression:952 experimental:928 database:818 textmining:658
Rv3152 nuoH NADH-quinone oxidoreductase subunit H 999 1000 ctx neighborhood:874 cooccurence:773 coexpression:974 experimental:928 database:803 textmining:853
Rv3154 nuoJ NADH-quinone oxidoreductase subunit J 999 1000 ctx neighborhood:874 cooccurence:720 coexpression:976 experimental:922 textmining:687
Rv3151 nuoG NADH-quinone oxidoreductase subunit G 999 1000 ctx neighborhood:760 coexpression:970 experimental:928 database:800 textmining:450
Rv3147 nuoC NADH-quinone oxidoreductase subunit C 999 1000 ctx neighborhood:760 cooccurence:753 coexpression:864 experimental:928 database:731
Rv3158 nuoN NADH-quinone oxidoreductase subunit N 999 1000 ctx neighborhood:882 coexpression:976 experimental:997 database:844 textmining:611
Rv3155 nuoK NADH-quinone oxidoreductase subunit K 999 1000 ctx neighborhood:874 cooccurence:766 coexpression:898 experimental:922 textmining:622
Rv3150 nuoF NADH-quinone oxidoreductase subunit F 999 1000 ctx neighborhood:760 coexpression:949 experimental:928 database:800 textmining:474
Rv3148 nuoD NADH-quinone oxidoreductase subunit D 999 1000 ctx neighborhood:760 cooccurence:760 coexpression:882 experimental:928 database:731 textmining:686
Rv3145 nuoA NADH-quinone oxidoreductase subunit A 999 1000 ctx neighborhood:758 cooccurence:772 coexpression:878 experimental:928 database:803 textmining:685
Rv3156 nuoL NADH-quinone oxidoreductase subunit L 999 1000 ctx neighborhood:882 coexpression:976 experimental:997 textmining:663
Rv2196 qcrB ubiquinol-cytochrome C reductase cytochrome subunit B 988 984 coexpression:840 experimental:902
Rv0310c hyp hypothetical protein 979 979 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 M
  • MTBC0 PGAP product: NADH-quinone oxidoreductase subunit M
  • Pfam (hmmscan --cut_ga): Proton_antipo_M PF00361.26 (E=2e-64)
  • (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_217673.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Proton_antipo_M (PF00361.26)
  • 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 COG1008
  • Curated reference: UniProt P9WIW5 (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 — 111 functional partner(s); context anchor nuoB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003355|Rv3157|nuoM
MNNVPWLSVLWLVPLAGAVLIILLPPGRRRLAKWAGMVVSVLTLAVSIVVAAEFKPSAEPYQFVEKHSWIPAFGAGYTLGVDGIAVVLVLLTTVLIPLLLVAGWNDATDADDLSPASGRYPQRPAPPRLRSSGGERTRGVHAYVALTLAIESMVLMSVIALDVLLFYVFFEAMLIPMYFLIGGFGQGAGRSRAAVKFLLYNLFGGLIMLAAVIGLYVVTAQYDSGTFDFREIVAGVAAGRYGADPAVFKALFLGFMFAFAIKAPLWPFHRWLPDAAVESTPATAVLMMAVMDKVGTFGMLRYCLQLFPDPSTYFRPLIVTLAIIGVIYGAIVAIGQTDMMRLIAYTSISHFGFIIAGIFVMTTQGQSGSTLYMLNHGLSTAAVFLIAGFLIARRGSRSIADYGGVQKVAPILAGTFMVSAMATVSLPGLAPFISEFLVLLGTFSRYWLAAAFGVTALVLSAVYMLWLYQRVMTGPVAEGNERIGDLVGREMIVVAPLIALLLVLGVYPKPVLDIINPAVENTMTTIGQHDPAPSVAHPVPAVGASRTAEGPHP