Rv3249c Family assigned · medium auto-curated
H37Rv Rv3249c · MTBC0 mtbc0_003457 ·
211 aa · 3651895–3652530 (-) ·
RefSeq NP_217766.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | TetR family transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | TetR family transcriptional regulator |
| Revised (this work) | TetR family transcriptional regulator. Pfam: TetR_N (PF00440.30), TetR_C_35 (PF18556.7). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05892
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional regulator AlkX |
| Curated function | Represses the expression of the alkB-rubAB operon, which encodes the alkane hydroxylase AlkB and the rubredoxins RubA and RubB. Acts by binding to the promoter region of the operon. In addition, EMSA analysis show that AlkX can bind to the promoter region of mmpS1 and mmpL3 and to the intragenic region of mmpL11, suggesting that it may participate in the regulatory network that controls the expression of MmpL lipid transporters. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Transcriptional regulator |
| Orthologous group | COG1309 |
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 | 0.278 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 2 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.66% of strains (955) · clonal |
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 | 5.2e-09 | 29–71 | Bacterial regulatory proteins, tetR family |
TetR_C_35 | PF18556.7 | 7.5e-34 | 98–200 | Bacterial Tetracyclin repressor, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: alkB (transmembrane alkane 1-monooxygenase AlkB), high confidence from genomic context alone (score 947 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3252c alkB |
transmembrane alkane 1-monooxygenase AlkB | 947 | 947 ctx | neighborhood:881 cooccurence:488 |
Rv3250c rubB |
rubredoxin RubB | 922 | 910 ctx | neighborhood:881 |
Rv3251c rubA |
rubredoxin RubA | 864 | 865 ctx | neighborhood:830 |
Rv3248c sahH |
adenosylhomocysteinase | 774 | 774 ctx | neighborhood:771 |
Rv0885 hyp |
hypothetical protein | 715 | 715 ctx | cooccurence:713 |
Rv3247c tmk |
thymidylate kinase | 703 | 703 ctx | neighborhood:703 |
Rv1065 hyp |
hypothetical protein | 685 | 686 ctx | cooccurence:683 |
Rv0464c hyp |
hypothetical protein | 660 | 661 ctx | cooccurence:653 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 606 | 606 ctx | cooccurence:604 |
Rv3346c |
transmembrane protein | 601 | 601 ctx | cooccurence:601 |
Rv1274 lprB |
lipoprotein LprB | 598 | 598 ctx | cooccurence:594 |
Rv3035 hyp |
hypothetical protein | 572 | 570 ctx | cooccurence:570 |
Rv3253c |
cationic amino acid transport integral membrane protein | 555 | 556 ctx | neighborhood:553 |
Rv1476 |
membrane protein | 549 | 549 ctx | cooccurence:547 |
Rv1318c |
adenylate cyclase | 545 | 546 ctx | cooccurence:545 |
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 family transcriptional regulator
- Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=5e-09), TetR_C_35 PF18556.7 (E=8e-34)
- (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_217766.1)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_35 (PF18556.7)
- 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 O05892 (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 —
40 functional partner(s); context anchor
alkB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003457|Rv3249c| MSTPSATVAPVKRIPYAEASRALLRDSVLDAMRDLLLTRDWSAITLSDVARAAGISRQTIYNEFGSRQGLAQGYALRLADRLVDNVHASLDANVGNFYEAFLQGFRSFFAESAADPLVISLLTGVAKPDLLQLITTDSAPIITRASARLAPAFTDTWVATTDNDANVLSRAIVRLCLSYVSMPPEADHDVAADLARLITPFAERHGVINVP