kstR Family assigned · medium auto-curated
H37Rv Rv3574 · MTBC0 mtbc0_003793 ·
199 aa · 4040161–4040760 (+) ·
RefSeq NP_218091.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | HTH-type transcriptional regulator KstR |
|---|---|
| MTBC0 PGAP re-annotation | cholesterol catabolism transcriptional regulator KstR |
| Revised (this work) | Cholesterol catabolism transcriptional regulator KstR. Pfam: TetR_N (PF00440.30), TetR_C_20 (PF17925.7). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96856
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional repressor KstR |
| Curated function | Controls the expression of genes used for utilizing diverse lipids as energy sources. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | kstR |
| eggNOG description | Transcriptional regulator |
| Orthologous group | COG1309 |
| KEGG orthology |
K22107
|
| Gene Ontology (45) |
GO:0000976, GO:0001067, GO:0003674, GO:0003676, GO:0003677, GO:0003690, GO:0003700, GO:0005488, GO:0005515, GO:0005575, GO:0005622, GO:0005623 +33 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 | 0.171 · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
TetR_N | PF00440.30 | 8.8e-16 | 21–65 | Bacterial regulatory proteins, tetR family |
TetR_C_20 | PF17925.7 | 2.5e-38 | 86–192 | Tetracyclin repressor-like, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE34 (acyl-CoA dehydrogenase FadE34), high confidence from genomic context alone (score 862 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3573c fadE34 |
acyl-CoA dehydrogenase FadE34 | 901 | 862 ctx | neighborhood:730 cooccurence:503 |
Rv3541c chsH1 hyp |
hypothetical protein | 819 | 790 ctx | cooccurence:760 |
Rv3542c chsH2 hyp |
hypothetical protein | 785 | 785 ctx | cooccurence:754 |
Rv3521 hyp |
hypothetical protein | 771 | 765 ctx | cooccurence:765 |
Rv3522 ltp4 |
lipid transfer protein | 800 | 717 ctx | cooccurence:712 |
Rv3552 |
CoA-transferase subunit beta | 716 | 716 ctx | cooccurence:715 |
Rv3551 |
CoA-transferase subunit alpha | 746 | 694 ctx | cooccurence:692 |
Rv3527 hyp |
hypothetical protein | 689 | 690 ctx | cooccurence:688 |
Rv3526 kshA |
3-ketosteroid-9-alpha-monooxygenase oxygenase subunit | 924 | 659 ctx | cooccurence:651 textmining:787 |
Rv3515c fadD19 |
acyl-CoA synthetase | 796 | 655 ctx | cooccurence:632 textmining:434 |
Rv3570c hsaA |
flavin-dependent monooxygenase oxygenase subunit HsaA | 827 | 637 ctx | cooccurence:634 textmining:544 |
Rv3531c hyp |
hypothetical protein | 654 | 632 ctx | cooccurence:628 |
Rv3568c hsaC |
extradiol dioxygenase | 847 | 606 ctx | cooccurence:605 textmining:629 |
Rv3529c hyp |
hypothetical protein | 592 | 584 ctx | cooccurence:568 |
Rv3550 echA20 |
enoyl-CoA hydratase EchA20 | 700 | 571 ctx | cooccurence:565 |
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 KstR
- MTBC0 PGAP product: cholesterol catabolism transcriptional regulator KstR
- Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=9e-16), TetR_C_20 PF17925.7 (E=3e-38)
- (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_218091.3)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_20 (PF17925.7)
- 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 P96856 (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 —
45 functional partner(s); context anchor
fadE34 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003793|Rv3574|kstR MAVLAESELGSEAQRERRKRILDATMAIASKGGYEAVQMRAVADRADVAVGTLYRYFPSKVHLLVSALGREFSRIDAKTDRSAVAGATPFQRLNFMVGKLNRAMQRNPLLTEAMTRAYVFADASAASEVDQVEKLIDSMFARAMANGEPTEDQYHIARVISDVWLSNLLAWLTRRASATDVSKRLDLAVRLLIGDQDSA