iniR Family assigned · medium auto-curated

H37Rv Rv0339c · MTBC0 mtbc0_000359 · 832 aa · 409273–411771 (-) · RefSeq NP_214853.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transcriptional regulator
MTBC0 PGAP re-annotationisoniazid response ATPase/transcriptional regulator IniR
Revised (this work)Isoniazid response ATPase/transcriptional regulator IniR. Pfam: 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 O33269 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namegerE
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG2771

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 0.559 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 13 synonymous, 18 missense, 1 nonsense, 2 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 0.27% of strains (390) · 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
GerEPF00196.26 8.6e-14762–816 Bacterial regulatory proteins, luxR family

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

Closest characterised functional partner: embR (transcriptional regulator EmbR), high confidence from genomic context alone (score 897 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1267c embR transcriptional regulator EmbR 899 897 ctx cooccurence:506 coexpression:800
Rv1963c mce3R transcriptional repressor Mce3R 891 891 ctx cooccurence:608 coexpression:734
Rv3263 DNA methylase 889 889 coexpression:859
Rv1776c transcriptional regulator 867 868 ctx cooccurence:500 coexpression:746
Rv3124 moaR1 transcriptional regulator MoaR 860 856 coexpression:785
Rv3736 AraC/XylS family transcriptional regulator 859 854 coexpression:802
Rv1675c cmr HTH-type transcriptional regulator Cmr 847 842 coexpression:818
Rv0342 iniA isoniazid inductible protein IniA 837 837 ctx cooccurence:774
Rv3183 higA3 transcriptional regulator 840 835 coexpression:812
Rv0343 iniC iIsoniazid inductible protein IniC 852 834 ctx cooccurence:774
Rv1359 transcriptional regulator 834 834 coexpression:813
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 833 833 coexpression:833
Rv2488c LuxR family transcriptional regulator 835 828 coexpression:806
Rv3840 transcriptional regulator 824 822 coexpression:822
Rv1027c kdpE transcriptional regulator KdpE 823 817 coexpression:795

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: transcriptional regulator
  • MTBC0 PGAP product: isoniazid response ATPase/transcriptional regulator IniR
  • Pfam (hmmscan --cut_ga): GerE PF00196.26 (E=9e-14)
  • (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_214853.1)
  • Domains: Pfam-A via hmmscan --cut_ga — 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 COG2771
  • Curated reference: UniProt O33269 (TrEMBL, unreviewed; 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 — 116 functional partner(s); context anchor embR
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000359|Rv0339c|iniR
MQHRGCKNRGQAYDASVTDSLTEVPPAARRALLELANAPTVPVKVLITGGIGTGKTTVLAAARDTLRRSGLTVLACPPPDGEPPETALVIDDAQLLTDTELLRLTERVADSRLTVVAAAEAREHHRALRALTMALERDRPRISLGPLPVAEHLRDCTAGLPFLIHAVSARAQAPAQAAKVALIERLRRLDEPTLDTLLMMSLTHELGVSDVAAALGISVTDARGLVDRAHASGLIESSHTAAFLQSVHDAIAQIVGNAHHHEVETSLLRSQLDISPVSAELALRLAEHGLRDERLADILTRYAADTRDASVRCARLYRAAVHAGAKGLTVRLADALARTGDCTAAATLADDLLSSPDATERAAAVRVAASVAVHDGNTGHAAELFGWLGPHPDTMVSSAATIVFAANGDLATARATLRLKDAGPPTMAARCARNLAEGLLLTMDQPYPVAMAKLGQAIATEQSLSQVIPDSPAALVTLAAIHAGDPVRARSVIGRAVRAGADPLFQRRHLLLSGWIKMQEGQLPSASADVAAASAGTHLHRRDALWAAALQTAISRRTGDIGALQQHWYAAMEALAEYSLDLFALLPLGELWVAAARMRQVDQLQHTLDQALTLLDSLGNPALWSNSLHWAGVHAGILANSPESVAPHGQALGAMVAHSTLAQALSDAGRTWLRVLAENVDADEVTAAARSLSHVGLTSDATRLAGQAALQTSDARVSGAMLQLARDLKLGNDFGEPPSGAGDTEPASGTPPAPRQPPAGSPLSDREREVAELLLLGMPYRDIGARLFISAKTVEHHVARIRQRLGAGSRSEMLSMLRAMLAPESLTADERR