Rv3066 Family assigned · medium auto-curated

H37Rv Rv3066 · MTBC0 mtbc0_003258 · 202 aa · 3452071–3452679 (+) · RefSeq NP_217582.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)DeoR family transcriptional regulator
MTBC0 PGAP re-annotationTetR/AcrR family transcriptional regulator
Revised (this work)TetR/AcrR family transcriptional regulator. Pfam: TetR_N (PF00440.30), TetR_C_31 (PF17940.7).

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

Curated reference (UniProt)

UniProt I6X658 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionBacterial regulatory proteins, tetR family
Orthologous groupCOG3226

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 0.373 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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 5.0e-0719–64 Bacterial regulatory proteins, tetR family
TetR_C_31PF17940.7 1.5e-0987–183 Tetracyclin repressor-like, C-terminal domain

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

Closest characterised functional partner: mmr (multidrug resistance protein Mmr), high confidence from genomic context alone (score 885 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3065 mmr multidrug resistance protein Mmr 959 885 ctx neighborhood:881 textmining:660
Rv3183 higA3 transcriptional regulator 857 857 coexpression:833
Rv2788 sirR transcriptional repressor SirR 830 830 coexpression:830
Rv1725c hyp hypothetical protein 827 827 coexpression:804
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 822 823 coexpression:800
Rv1167c transcriptional regulator 804 805 coexpression:805
Rv1674c transcriptional regulator 801 801 coexpression:801
Rv1151c cobB NAD-dependent protein deacylase 800 800 coexpression:800
Rv3736 AraC/XylS family transcriptional regulator 799 800 coexpression:800
Rv0494 HTH-type transcriptional regulator 799 799 coexpression:799
Rv3167c TetR family transcriptional regulator 798 799 coexpression:799
Rv1267c embR transcriptional regulator EmbR 796 796 coexpression:796
Rv0212c nadR transcriptional regulator NadR 790 791 coexpression:746
Rv1395 HTH-type transcriptional regulator 815 789 coexpression:736
Rv0674 hyp hypothetical protein 788 788 coexpression:788

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: DeoR family transcriptional regulator
  • MTBC0 PGAP product: TetR/AcrR family transcriptional regulator
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=5e-07), TetR_C_31 PF17940.7 (E=1e-09)
  • (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_217582.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_31 (PF17940.7)
  • 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 COG3226
  • Curated reference: UniProt I6X658 (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 — 77 functional partner(s); context anchor mmr
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003258|Rv3066|
MTAGSDRRPRDPAGRRQAIVEAAERVIARQGLGGLSHRRVAAEANVPVGSTTYYFNDLDALREAALAHAANASADLLAQWRSDLDKDRDLAATLARLTTVYLADQDRYRTLNELYMAAAHRPELQRLARLWPDGLLALLEPRIGRRAANAVTVFFDGATLHALITGTPLSTDELTDAIARLVADGPEQREVGQSAHAGRTPD