Rv2506 Family assigned · medium auto-curated

H37Rv Rv2506 · MTBC0 mtbc0_002668 · 215 aa · 2844602–2845249 (+) · RefSeq NP_217022.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)TetR 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_24 (PF17932.7).

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

Curated reference (UniProt)

UniProt O06169 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable transcriptional regulatory protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptionTranscriptional regulator
Orthologous groupCOG1309

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 0.189 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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 3.5e-1830–76 Bacterial regulatory proteins, tetR family
TetR_C_24PF17932.7 7.8e-08100–180 Tetracyclin repressor-like, C-terminal domain

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

Closest characterised functional partner: Rv2499c (oxidase regulatory-like protein), high confidence from genomic context alone (score 829 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2499c oxidase regulatory-like protein 870 829 ctx neighborhood:714 cooccurence:413
Rv0339c iniR transcriptional regulator 802 802 coexpression:802
Rv3055 TetR family transcriptional regulator 788 788 coexpression:788
Rv2501c accA1 acetyl/propionyl-CoA carboxylase subuit alpha 871 781 ctx neighborhood:714 textmining:436
Rv2498c citE citrate (pro-3S)-lyase subunit beta 918 776 ctx neighborhood:714 textmining:651
Rv2502c accD1 acetyl-/propionyl-CoA carboxylase subunit beta 884 761 ctx neighborhood:714 textmining:536
Rv0067c transcriptional regulator 761 761 coexpression:761
Rv2500c fadE19 acyl-CoA dehydrogenase FadE19 795 753 ctx neighborhood:714
Rv3060c GntR family transcriptional regulator 744 737 coexpression:736
Rv3840 transcriptional regulator 734 734 coexpression:734
Rv3855 ethR HTH-type transcriptional repressor EthR 801 732 coexpression:732
Rv0691c mftR mycofactocin biosynthesis transcriptional regulator MftR 739 732 coexpression:732
Rv0273c transcriptional regulator 730 730 coexpression:730
Rv1189 sigI ECF RNA polymerase sigma factor SigI 730 730 coexpression:730
Rv3183 higA3 transcriptional regulator 729 729 coexpression:729

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: TetR family transcriptional regulator
  • MTBC0 PGAP product: TetR/AcrR family transcriptional regulator
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=3e-18), TetR_C_24 PF17932.7 (E=8e-08)
  • (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_217022.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_24 (PF17932.7)
  • 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 COG1309
  • Curated reference: UniProt O06169 (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 — 47 functional partner(s); context anchor Rv2499c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002668|Rv2506|
MTASAPDGRPGQPEATNRRSQLKSDRRFQLLAAAERLFAERGFLAVRLEDIGAAAGVSGPAIYRHFPNKESLLVELLVGVSARLLAGARDVTTRSANLAAALDGLIEFHLDFALGEADLIRIQDRDLAHLPAVAERQVRKAQRQYVEVWVGVLRELNPGLAEADARLMAHAVFGLLNSTPHSMKAADSKPARTVRARAVLRAMTVAALSAADRCL