Rv3405c Family assigned · medium auto-curated

H37Rv Rv3405c · MTBC0 mtbc0_003619 · 188 aa · 3850141–3850707 (-) · RefSeq NP_217922.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator
MTBC0 PGAP re-annotationhelix-turn-helix domain-containing protein
Revised (this work)Helix-turn-helix domain-containing protein. Pfam: TetR_N (PF00440.30).

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

Curated reference (UniProt)

UniProt P9WMC3 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional repressor Rv3405c
Curated functionNegatively regulates the expression of sulfate ester dioxygenase Rv3406 and its own expression. Binds specifically to the inverted repeat sequence of the intergenic region between Rv3405c and Rv3406.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptiontranscriptional
Orthologous groupCOG1309
KEGG orthology K22295
Gene Ontology (41) GO:0000976, GO:0001067, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737 +29 more

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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
TetR_NPF00440.30 1.9e-1623–69 Bacterial regulatory proteins, tetR family

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

Closest characterised functional partner: Rv3406 (dioxygenase), high confidence from genomic context alone (score 786 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1151c cobB NAD-dependent protein deacylase 806 799 coexpression:799
Rv3406 dioxygenase 971 786 ctx neighborhood:786 textmining:870
Rv3183 higA3 transcriptional regulator 767 767 coexpression:767
Rv2282c LysR family HTH-type transcriptional regulator 764 761 coexpression:731
Rv3066 DeoR family transcriptional regulator 740 740 coexpression:740
Rv3840 transcriptional regulator 738 738 coexpression:738
Rv3488 hyp hypothetical protein 738 734 coexpression:734
Rv1960c parD1 antitoxin ParD1 734 734 coexpression:734
Rv0494 HTH-type transcriptional regulator 740 733 coexpression:732
Rv0603 hyp hypothetical protein 733 733 coexpression:733
Rv3830c TetR family transcriptional regulator 730 730 coexpression:730
Rv3736 AraC/XylS family transcriptional regulator 733 729 coexpression:729
Rv1027c kdpE transcriptional regulator KdpE 716 716 coexpression:716
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 703 703 coexpression:703
Rv3291c lrpA transcriptional regulator LrpA 696 687 coexpression:687

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: HTH-type transcriptional regulator
  • MTBC0 PGAP product: helix-turn-helix domain-containing protein
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=2e-16)
  • (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_217922.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30)
  • 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 COG1309
  • Curated reference: UniProt P9WMC3 (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 — 41 functional partner(s); context anchor Rv3406
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003619|Rv3405c|
MTTRPATDRRKMPTGREEVAAAILQAATDLFAERGPAATSIRDIAARSKVNHGLVFRHFGTKDQLVGAVLDHLGTKLTRLLHSEAPADIIERALDRHGRVLARALLDGYPVGQLQQRFPNVAELLDAVRPRYDSDLGARLAVAHALALQFGWRLFAPMLRSATGIDELTGDELRLSVNDAVARILEPH