kstR2 Family assigned · medium auto-curated

H37Rv Rv3557c · MTBC0 mtbc0_003774 · 200 aa · 4020706–4021308 (-) · RefSeq NP_218074.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)HTH-type transcriptional regulator KstR2
MTBC0 PGAP re-annotationTetR family transcriptional regulator KstR2
Revised (this work)TetR family transcriptional regulator KstR2. 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 P9WMB9 SwissProt · reviewed · Evidence at protein level
UniProt nameHTH-type transcriptional repressor KstR2
Curated functionControls the expression of a small regulon that may play a role in the utilization of cholesterol.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namekstR2
eggNOG descriptiontranscriptional
Orthologous groupCOG1309
KEGG orthology K22108
Gene Ontology (35) GO:0003674, GO:0003676, GO:0003677, GO:0003700, GO:0005488, GO:0005515, GO:0006355, GO:0008150, GO:0009889, GO:0010468, GO:0010556, GO:0010565 +23 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 3.5e-1715–61 Bacterial regulatory proteins, tetR family
TetR_C_24PF17932.7 1.7e-1981–195 Tetracyclin repressor-like, C-terminal domain

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

Closest characterised functional partner: fadA6 (acetyl-CoA acetyltransferase FadA), high confidence from genomic context alone (score 810 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3556c fadA6 acetyl-CoA acetyltransferase FadA 930 810 ctx neighborhood:799 textmining:648
Rv0158 transcriptional regulator 794 795 coexpression:731
Rv3855 ethR HTH-type transcriptional repressor EthR 791 778 coexpression:748
Rv3060c GntR family transcriptional regulator 743 736 coexpression:735
Rv3555c hyp hypothetical protein 485 485 ctx neighborhood:480
Rv3574 kstR HTH-type transcriptional regulator KstR 961 460 ctx cooccurence:453 textmining:931
Rv3521 hyp hypothetical protein 459 459 ctx cooccurence:456
Rv3552 CoA-transferase subunit beta 511 454 ctx cooccurence:436
Rv3542c chsH2 hyp hypothetical protein 451 451 ctx cooccurence:448
Rv3541c chsH1 hyp hypothetical protein 468 448 ctx cooccurence:445
Rv3558 PPE64 PPE family protein PPE64 436 436 ctx neighborhood:434
Rv3560c fadE30 acyl-CoA dehydrogenase FadE30 866 427 textmining:777
Rv1176c hyp hypothetical protein 419 408
Rv1014c pth peptidyl-tRNA hydrolase 400 401
Rv3551 CoA-transferase subunit alpha 612 400

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 KstR2
  • MTBC0 PGAP product: TetR family transcriptional regulator KstR2
  • Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=4e-17), TetR_C_24 PF17932.7 (E=2e-19)
  • (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_218074.1)
  • 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 P9WMB9 (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 — 42 functional partner(s); context anchor fadA6
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003774|Rv3557c|kstR2
MDRVAGQVNSRRGELLELAAAMFAERGLRATTVRDIADGAGILSGSLYHHFASKEEMVDELLRGFLDWLFARYRDIVDSTANPLERLQGLFMASFEAIEHHHAQVVIYQDEAQRLASQPRFSYIEDRNKQQRKMWVDVLNQGIEEGYFRPDLDVDLVYRFIRDTTWVSVRWYRPGGPLTAQQVGQQYLAIVLGGITKEGV