narK3 Resolved · high auto-curated

H37Rv Rv0261c · MTBC0 mtbc0_000277 · 469 aa · 313141–314550 (-) · RefSeq NP_214775.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nitrate/nitrite transporter
MTBC0 PGAP re-annotationnitrate/nitrite transporter
Revised (this work)Nitrate/nitrite 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 P95218 TrEMBL · unreviewed · Inferred from homology
UniProt nameProbable integral membrane nitrite extrusion protein NarK3

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred namenarK
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)

pN/pS 0.301 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (377) · 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 6.0e-1540–406 Major Facilitator Superfamily

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

Closest characterised functional partner: narH (nitrate reductase subunit beta), high confidence from genomic context alone (score 984 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1162 narH nitrate reductase subunit beta 991 984 ctx cooccurence:708 coexpression:461 database:900 textmining:482
Rv1161 narG nitrate reductase subunit alpha 990 984 ctx cooccurence:702 coexpression:449 database:900 textmining:464
Rv1736c narX nitrate reductase-like protein NarX 987 983 ctx cooccurence:706 coexpression:448 database:900
Rv1164 narI nitrate reductase subunit gamma 983 977 ctx cooccurence:588 coexpression:433 database:900
Rv0252 nirB nitrite reductase large subunit NirB 971 946 database:900 textmining:496
Rv1737c narK2 nitrate/nitrite transporter 940 940 ctx fusion:855 cooccurence:575
Rv0253 nirD nitrite reductase small subunit NirD 952 936 database:900
Rv2781c oxidoreductase 909 908 database:900
Rv0021c hyp hypothetical protein 908 908 database:900
Rv0260c transcriptional regulator 913 894 ctx neighborhood:585 cooccurence:631
Rv1372 pks18 alpha-pyrone synthesis polyketide synthase-like protein 810 810 coexpression:810
Rv0259c hyp hypothetical protein 775 775 ctx neighborhood:567
Rv1163 narJ nitrate reductase subunit delta 824 752 ctx cooccurence:520 coexpression:462
Rv1371 membrane protein 753 730 coexpression:730
Rv0262c aac aminoglycoside 2'-N-acetyltransferase 593 594 ctx neighborhood:513

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/nitrite transporter
  • MTBC0 PGAP product: nitrate/nitrite transporter
  • Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=6e-15)
  • (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_214775.1)
  • 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 P95218 (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 — 30 functional partner(s); context anchor narH
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000277|Rv0261c|narK3
MGRSHQISDWDPEDSVAWEAGNKFIARRNLIWSVAAEHVGFSVWSLWSVMVLFMPTSVYGFSAGDKFLLGATATLVGACLRFPYTFATAKFGGRNWTIFSALVLLIPTVGSILLLANPGLPLWPYLVCGALAGLGGGNFAASMTNINAFFPQRLKGAALALNAGGGNLGVPMVQLVGLLVIATAGDREPYWVCAIYLVLLAVAGLGAALYMDNLTEYRIELNTMRAVVSEPHTWVISLLYIGTFGSFIGFSFAFGQVLQINFIASGQSTAQASLHAAQIAFLGPLLGSLSRIYGGKLADRIGGGRVTLAAFCAMLLATGILISASTFGDHLAGPMPTATMVGYVIGFTALFILSGIGNGSVYKMIPSIFEARSHSLQISEAERRQWSRSMSGALIGLAGAVGALGGVGVNLALRESYLTSGTATSAFWAFGVFYLVASVLTWAIYVRRGLKSAGELVPATTAPAGLAYV