narL Resolved · high auto-curated

H37Rv Rv0844c · MTBC0 mtbc0_000899 · 216 aa · 943607–944257 (-) · RefSeq NP_215359.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)nitrate/nitrite response transcriptional regulator NarL
MTBC0 PGAP re-annotationtwo-component system response regulator NarL
Revised (this work)Two-component system response regulator NarL. Pfam: Response_reg (PF00072.31), GerE (PF00196.26).

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

Curated reference (UniProt)

UniProt P9WGM5 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein NarL
Curated functionMember of the two-component regulatory system NarS/NarL that regulates genes involved in aerobic nitrate metabolism. Upon phosphorylation by NarS, functions as a transcription regulator by direct binding to promoter regions of target genes together with DevR to regulate their expression during aerobic nitrate metabolism.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namenarL
eggNOG descriptionresponse regulator
Orthologous groupCOG2197
KEGG orthology K07684
KEGG pathways map02020
KEGG modules M00471

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 2.441 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 7 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
Response_regPF00072.31 4.1e-2511–122 Response regulator receiver domain
GerEPF00196.26 3.0e-15154–207 Bacterial regulatory proteins, luxR family

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

Closest characterised functional partner: narS (sensor histidine kinase NarS), high confidence from genomic context alone (score 970 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0845 narS sensor histidine kinase NarS 987 970 ctx neighborhood:783 cooccurence:767 textmining:596
Rv3132c devS two component sensor histidine kinase DevS 877 792 ctx cooccurence:612 textmining:437
Rv2788 sirR transcriptional repressor SirR 851 790 coexpression:731
Rv2027c dosT two component sensor histidine kinase DosT 912 770 ctx cooccurence:573 textmining:635
Rv3208 TetR family transcriptional regulator 751 751 coexpression:751
Rv3328c sigJ ECF RNA polymerase sigma factor SigJ 743 734 coexpression:734
Rv0377 HTH-type transcriptional regulator 734 723 coexpression:687
Rv0195 two component transcriptional regulator 712 713 ctx cooccurence:708
Rv0273c transcriptional regulator 615 615 coexpression:615
Rv1033c trcR two component transcriptional regulator TrcR 698 541
Rv0624 vapC30 ribonuclease VapC30 474 474 coexpression:474
Rv0600c two component sensor kinase HK1 563 444
Rv0902c prrB two component sensor histidine kinase PrrB 653 406 textmining:441
Rv1027c kdpE transcriptional regulator KdpE 706 388 textmining:540
Rv2359 zur zinc uptake regulation protein 430 369

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 response transcriptional regulator NarL
  • MTBC0 PGAP product: two-component system response regulator NarL
  • Pfam (hmmscan --cut_ga): Response_reg PF00072.31 (E=4e-25), GerE PF00196.26 (E=3e-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_215359.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Response_reg (PF00072.31), GerE (PF00196.26)
  • 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 COG2197
  • Curated reference: UniProt P9WGM5 (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 — 35 functional partner(s); context anchor narS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000899|Rv0844c|narL
MSNPQPEKVRVVVGDDHPLFREGVVRALSLSGSVNVVGEADDGAAALELIKAHLPDVALLDYRMPGMDGAQVAAAVRSYELPTRVLLISAHDEPAIVYQALQQGAAGFLLKDSTRTEIVKAVLDCAKGRDVVAPSLVGGLAGEIRQRAAPVAPVLSAREREVLNRIACGQSIPAIAAELYVAPSTVKTHVQRLYEKLGVSDRAAAVAEAMRQRLLD