narG Family assigned · medium auto-curated

H37Rv Rv1161 · MTBC0 mtbc0_001250 · 1232 aa · 1295769–1299467 (+) · RefSeq NP_215677.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nitrate reductase subunit alpha
MTBC0 PGAP re-annotationnitrate reductase subunit alpha
Revised (this work)Nitrate reductase subunit alpha. Pfam: Molybdopterin (PF00384.28), NarG_dom_V (PF28599.1), Molydop_binding (PF01568.28).

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

Curated reference (UniProt)

UniProt P9WJQ3 SwissProt · reviewed · Evidence at protein level
UniProt nameNitrate reductase alpha subunit
EC (curated) EC 1.7.5.1
Curated functionThe alpha chain is the actual site of nitrate reduction (Probable). Supports anaerobic growth of E.coli on glycerol in an E.coli mutant lacking endogenous nitrate reductase.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namenarG
eggNOG descriptionBelongs to the prokaryotic molybdopterin-containing oxidoreductase family
Orthologous groupCOG5013
EC number EC 1.7.5.1
KEGG orthology K00370
KEGG pathways map00910, map01120, map02020
KEGG modules M00529, M00530, M00804
Gene Ontology (64) GO:0000302, GO:0001101, GO:0003674, GO:0003824, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006807, GO:0006950 +52 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 0.301 · purifying
Polymorphic sites (≥ 0.1% of strains) 14 synonymous, 13 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
MolybdopterinPF00384.28 2.8e-60118–828 Molybdopterin oxidoreductase
NarG_dom_VPF28599.1 5.6e-48908–1028 Nitrate reductase alpha chain, domain V
Molydop_bindingPF01568.28 4.0e-201086–1195 Molydopterin dinucleotide binding domain

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

Closest characterised functional partner: narH (nitrate reductase subunit beta), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1162 narH nitrate reductase subunit beta 999 1000 ctx neighborhood:825 cooccurence:774 coexpression:961 experimental:829 database:900 textmining:921
Rv1164 narI nitrate reductase subunit gamma 999 1000 ctx neighborhood:763 cooccurence:774 coexpression:797 experimental:773 database:900 textmining:939
Rv1163 narJ nitrate reductase subunit delta 999 998 ctx neighborhood:763 cooccurence:774 coexpression:932 experimental:510 textmining:937
Rv1737c narK2 nitrate/nitrite transporter 998 988 ctx cooccurence:759 coexpression:449 database:900 textmining:853
Rv0267 narU nitrite extrusion protein NarU 994 985 ctx cooccurence:719 coexpression:460 database:900 textmining:672
Rv2329c narK1 nitrate/nitrite transporter 993 984 ctx cooccurence:717 coexpression:446 database:900 textmining:627
Rv0261c narK3 nitrate/nitrite transporter 990 984 ctx cooccurence:702 coexpression:449 database:900 textmining:464
Rv0252 nirB nitrite reductase large subunit NirB 970 948 coexpression:484 database:900 textmining:465
Rv0253 nirD nitrite reductase small subunit NirD 964 942 coexpression:430 database:900 textmining:410
Rv1736c narX nitrate reductase-like protein NarX 917 910 database:900
Rv2781c oxidoreductase 901 902 database:900
Rv0021c hyp hypothetical protein 900 901 database:900
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 854 801 experimental:788
Rv1165 typA GTP-binding translation elongation factor 786 761 ctx neighborhood:746
Rv1166 lpqW monoacyl phosphatidylinositol tetramannoside-binding protein LpqW 693 694 ctx neighborhood:686

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: nitrate reductase subunit alpha
  • MTBC0 PGAP product: nitrate reductase subunit alpha
  • Pfam (hmmscan --cut_ga): Molybdopterin PF00384.28 (E=3e-60), NarG_dom_V PF28599.1 (E=6e-48), Molydop_binding PF01568.28 (E=4e-20)
  • (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_215677.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Molybdopterin (PF00384.28), NarG_dom_V (PF28599.1), Molydop_binding (PF01568.28)
  • 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 COG5013
  • Curated reference: UniProt P9WJQ3 (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 — 48 functional partner(s); context anchor narH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001250|Rv1161|narG
MTVTPHVGGPLEELLERSGRFFTPGEFSADLRTVTRRGGREGDVFYRDRWSHDKVVRSTHGVNCTGSCSWKIYVKDGIITWETQQTDYPSVGPDRPEYEPRGCPRGASFSWYSYSPTRVRYPYARGVLVEMYREAKTRLGDPVLAWADIQADPERRRRYQQARGKGGLVRVSWAEASEMVAAAHVHTIKTYGPDRVAGFSPIPAMSMVSHAAGSRFVELIGGVMTSFYDWYADLPVASPQVFGDQTDVPESGDWWDASYLVMWGSNVPITRTPDAHWMAEARYRGAKVVVVSPDYADNTKFADEWVRCAAGTDTALAMAMGHVILSECYVRNQVPFFVDYVRRYTDLPFLIKLEKRGDLLVPGKFLTAADIGEESENAAFKPALLDELTNTVVVPQGSLGFRFGEDGVGKWNLDLGSVVPALSVEMDKAVNGDRSAELVTLPSFDTIDGHGETVSRGVPVRRAGKHLVCTVFDLMLAHYGVARAGLPGEWPTGYHDRTQQNTPAWQESITGVPAAQAIRFAKEFARNATESGGRSMIIMGGGICHWFHSDVMYRSVLALLMLTGSMGRNGGGWAHYVGQEKVRPLTGWQTMAMATDWSRPPRQVPGASYWYAHTDQWRYDGYGADKLASPVGRGRFAGKHTMDLLTSATAMGWSPFYPQFDRSSLDVADEARAAGRDVGDYVAEQLAQHKLKLSITDPDNPVNWPRVLTVWRANLIGSSGKGGEYFLRHLLGTDSNVQSDPPTDGVHPRDVVWDSDIPEGKLDLIMSIDFRMTSTTLVSDVVLPAATWYEKSDLSSTDMHPYVHSFSPAIDPPWETRSDFDAFAAIARAFSALAKRHLGTRTDVVLTALQHDTPDEMAYPDGTERDWLATGEVPVPGRTMSKLTVVERDYTAIYDKWLTLGPLIDQFGMTTKGYTVHPFREVSELAANFGVMNSGVAVGRPAITTAKRMADVILALSGTCNGRLAVEGFLELEKRTGQRLAHLAEGSEERRITYADTQARPVPVITSPEWSGSESGGRRYAPFTINIEHLKPFHTLTGRMHFYLAHDWVEELGEQLPVYRPPLDMARLFNQPELGPTDDGLGLTVRYLTPHSKWSFHSTYQDNLYMLSLSRGGPTMWMSPGDAAKINVRDNDWVEAVNANGIYVCRAIVSHRMPEGVVFVYHVQERTVDTPRTETNGKRGGNHNALTRVRIKPSHLAGGYGQHAFAFNYLGPTGNQRDEVTVVRRRSQEVRY