narU Family assigned · medium auto-curated

H37Rv Rv0267 · MTBC0 mtbc0_000283 · 463 aa · 321713–323104 (+) · RefSeq NP_214781.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nitrite extrusion protein NarU
MTBC0 PGAP re-annotationNarK family nitrate/nitrite MFS transporter
Revised (this work)NarK family nitrate/nitrite MFS transporter. Pfam: MFS_1 (PF07690.22).

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

Curated reference (UniProt)

UniProt P95224 TrEMBL · unreviewed · Inferred from homology
UniProt nameNitrate/nitrite transporter

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred namenarU
eggNOG descriptionMajor Facilitator
Orthologous groupCOG2223
KEGG orthology K02575
KEGG pathways map00910
KEGG modules M00615

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) pseudogene candidate

pN/pS 0.197 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.88% of strains (2727) · clonal

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
MFS_1PF07690.22 1.2e-1757–384 Major Facilitator Superfamily

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

Closest characterised functional partner: narG (nitrate reductase subunit alpha), high confidence from genomic context alone (score 985 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1161 narG nitrate reductase subunit alpha 994 985 ctx cooccurence:719 coexpression:460 database:900 textmining:672
Rv1162 narH nitrate reductase subunit beta 991 985 ctx cooccurence:721 coexpression:469 database:900 textmining:450
Rv1736c narX nitrate reductase-like protein NarX 994 984 ctx cooccurence:721 coexpression:450 database:900 textmining:653
Rv1164 narI nitrate reductase subunit gamma 993 978 ctx cooccurence:613 coexpression:434 database:900 textmining:710
Rv0252 nirB nitrite reductase large subunit NirB 976 946 database:900 textmining:586
Rv0253 nirD nitrite reductase small subunit NirD 962 938 database:900 textmining:425
Rv1737c narK2 nitrate/nitrite transporter 948 924 ctx fusion:899
Rv2781c oxidoreductase 909 909 database:900
Rv0021c hyp hypothetical protein 908 908 database:900
Rv1163 narJ nitrate reductase subunit delta 944 795 ctx cooccurence:601 coexpression:466 textmining:738
Rv0260c transcriptional regulator 795 764 ctx cooccurence:574
Rv0266c oplA 5-oxoprolinase OplA 532 532 ctx neighborhood:531
Rv0265c iron ABC transporter substrate-binding lipoprotein 513 513 ctx neighborhood:506
Rv0259c hyp hypothetical protein 487 487
Rv0261c narK3 nitrate/nitrite transporter 541 483

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: nitrite extrusion protein NarU
  • MTBC0 PGAP product: NarK family nitrate/nitrite MFS transporter
  • Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=1e-17)
  • (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_214781.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22)
  • 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 COG2223
  • Curated reference: UniProt P95224 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 22 functional partner(s); context anchor narG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000283|Rv0267|narU
MALTTAPAIDYALPRQQDEGDHWIDDWRPEDPVFWETIGRPIARRNLIFSIFAEHVGFSVWMLWSIVVVQMTAAAPGHPAASGWALSASQALCLVAVPSGVGAFLRLPYTFAIPIFGGRNWTTVSAALLVIPCLLLAWAVSHPSLPFAVLVVIAATAGFGGGNFASSMANISFFYPEKDKGWALGLNAAGGNIGVAVVQKIIPPIVVAGSGVALSRAGLFFVPLAVAAAVCAFLFMNNLTEAKADVKPVWQSLRHADTWIMSLLYIGTFGSFIGYSAAFPTLLKTVFGRGDIALGWAFLGAGIGSLVRPLGGKLADRIGGARITAASFVMLAAGAAAALWSVQSVNLPVFFVSFMFLFVATGIGNGSSYRMISRIFQVKGEVAGGDPETMVNMRRQAAGALGIISSIGAFGGFVVPLAYAWSKVHFGNIEPALHFYVAFFLALLVVTWYCYLRRTTPMGQVGV