narX Family assigned · medium auto-curated

H37Rv Rv1736c · MTBC0 mtbc0_001849 · 652 aa · 1974300–1976258 (-) · RefSeq NP_216252.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nitrate reductase-like protein NarX
MTBC0 PGAP re-annotationrespiratory nitrate reductase subunit gamma
Revised (this work)Respiratory nitrate reductase subunit gamma. Pfam: Molybdopterin (PF00384.28), Nitrate_red_del (PF02613.21), Nitrate_red_gam (PF02665.20).

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

Curated reference (UniProt)

UniProt P9WJQ1 SwissProt · reviewed · Evidence at protein level
UniProt nameNitrate reductase-like protein NarX
Curated functionDoes not seem to have nitrate reductase activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namenarI
eggNOG descriptionnitrate reductase, gamma subunit
Orthologous groupCOG2180
EC number EC 1.7.5.1
KEGG orthology K00370, K00374
KEGG pathways map00910, map01120, map02020
KEGG modules M00529, M00530, M00804
Gene Ontology (7) GO:0001666, GO:0006950, GO:0008150, GO:0009628, GO:0036293, GO:0050896, GO:0070482

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 0.404 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 7 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 0.87% of strains (1270) · convergent

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 7.7e-15118–245 Molybdopterin oxidoreductase
Nitrate_red_delPF02613.21 3.5e-11291–407 Nitrate reductase delta subunit
Nitrate_red_gamPF02665.20 5.9e-88419–639 Nitrate reductase gamma subunit

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

Closest characterised functional partner: narK2 (nitrate/nitrite transporter), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1737c narK2 nitrate/nitrite transporter 999 1000 ctx neighborhood:882 cooccurence:762 coexpression:903 database:900 textmining:910
Rv1162 narH nitrate reductase subunit beta 999 999 ctx cooccurence:774 coexpression:730 experimental:829 database:900 textmining:653
Rv1164 narI nitrate reductase subunit gamma 996 994 coexpression:728 experimental:773 database:900 textmining:424
Rv0267 narU nitrite extrusion protein NarU 994 984 ctx cooccurence:721 coexpression:450 database:900 textmining:653
Rv2329c narK1 nitrate/nitrite transporter 991 984 ctx cooccurence:723 coexpression:445 database:900 textmining:473
Rv0261c narK3 nitrate/nitrite transporter 987 983 ctx cooccurence:706 coexpression:448 database:900
Rv0252 nirB nitrite reductase large subunit NirB 973 947 coexpression:473 database:900 textmining:519
Rv0253 nirD nitrite reductase small subunit NirD 953 941 coexpression:417 database:900
Rv1161 narG nitrate reductase subunit alpha 917 910 database:900
Rv2781c oxidoreductase 901 901 database:900
Rv0021c hyp hypothetical protein 900 901 database:900
Rv1163 narJ nitrate reductase subunit delta 931 883 coexpression:729 experimental:510 textmining:439
Rv1997 ctpF cation transporter ATPase F 892 862 coexpression:862
Rv2029c pfkB 6-phosphofructokinase PfkB 888 860 coexpression:860
Rv2028c universal stress protein 860 860 coexpression:860

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-like protein NarX
  • MTBC0 PGAP product: respiratory nitrate reductase subunit gamma
  • Pfam (hmmscan --cut_ga): Molybdopterin PF00384.28 (E=8e-15), Nitrate_red_del PF02613.21 (E=4e-11), Nitrate_red_gam PF02665.20 (E=6e-88)
  • (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_216252.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Molybdopterin (PF00384.28), Nitrate_red_del (PF02613.21), Nitrate_red_gam (PF02665.20)
  • 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 COG2180
  • Curated reference: UniProt P9WJQ1 (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 — 57 functional partner(s); context anchor narK2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001849|Rv1736c|narX
MTVTPRTGSRIEELLARSGRFFIPGEISADLRTVTRRGGRDGDVFYRDRWSHDKVVRSTHGVNCTGSCSWKIYVKDGIITWETQETDYPSVGPDRPEYEPRGCPRGAAFSWYTYSPTRVRHPYARGVLVEMYREAKARLGDPVAAWADIQADPRRRRRYQRARGKGGLVRVSWAEATEMIAAAHVHTISTYGPDRVAGFSPIPAMSMVSHAAGSRFVELIGGVMTSFYDWYADLPVASPQVFGDQTDVPESGDWWDVVWQCASVLLTYPNSRQLGTAEELLAHIDGPAADLLGRTVSELRRADPLTAATRYVDTFDLRGRATLYLTYWTAGDTRNRGREMLAFAQTYRSTDVAPPRGETPDFLPVVLEFAATVDPEAGRRLLSGYRVPIAALCNALTEAALPYAHTVAAVCRTGDMMGELFWTVVPYVTMTIVAVGSWWRYRYDKFGWTTRSSQLYESRLLRIASPMFHFGILVVIVGHGIGLVIPQSWTQAAGLSEGAYHVQAVVLGSIAGITTLAGVTLLIYRRRTRGPVFMATTVNDKVMYLVLVAAIVAGLGATALGSGVVGEAYNYRETVSVWFRSVWVLQPRGDLMAEAPLYYQIHVLIGLALFALWPFTRLVHAFSAPIGYLFRPYIIYRSREELVLTRPRRRGW