raaS Family assigned · medium auto-curated
H37Rv Rv1219c · MTBC0 mtbc0_001307 ·
212 aa · 1371165–1371803 (-) ·
RefSeq NP_215735.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | transcriptional regulator |
|---|---|
| MTBC0 PGAP re-annotation | transcriptional regulator RaaS |
| Revised (this work) | Transcriptional regulator RaaS. Pfam: TetR_N (PF00440.30), TetR_C_25 (PF17933.7). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O86312
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | HTH-type transcriptional regulatory protein RaaS |
| Curated function | Regulates the expression of the Rv1217c-Rv1218c multidrug efflux system and its own expression. Acts by binding to promoter regions of Rv1219c and upstream of the Rv1218c gene. Important for survival in prolonged stationary phase and during macrophage infection. May be used to eliminate non-growing mycobacteria. |
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 | 1.285 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 4 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 | 7.6e-14 | 12–57 | Bacterial regulatory proteins, tetR family |
TetR_C_25 | PF17933.7 | 3.0e-45 | 89–192 | Tetracyclin repressor-like, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1217c (tetronasin ABC transporter integral membrane protein), high confidence from genomic context alone (score 919 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1217c |
tetronasin ABC transporter integral membrane protein | 983 | 919 ctx | neighborhood:881 textmining:800 |
Rv1218c |
tetronasin ABC transporter ATP-binding protein | 981 | 908 ctx | neighborhood:882 textmining:803 |
Rv1216c |
integral membrane protein | 916 | 812 ctx | neighborhood:801 textmining:573 |
Rv0677c mmpS5 |
membrane protein MmpS5 | 810 | 731 | coexpression:731 |
Rv1215c hyp |
hypothetical protein | 943 | 726 ctx | neighborhood:725 textmining:803 |
Rv1220c |
methyltransferase | 912 | 576 ctx | neighborhood:574 textmining:803 |
Rv0523c hyp |
hypothetical protein | 455 | 455 ctx | cooccurence:452 |
Rv1214c PE14 |
PE family protein PE14 | 450 | 450 ctx | neighborhood:444 |
Rv1014c pth |
peptidyl-tRNA hydrolase | 400 | 401 | |
Rv3050c |
AsnC family transcriptional regulator | 663 | 335 | textmining:514 |
Rv0676c mmpL5 |
transmembrane transport protein MmpL5 | 469 | 284 | |
Rv2779c |
Lrp/AsnC family transcriptional regulator | 679 | 89 | textmining:663 |
Rv0452 |
transcriptional regulator | 530 | 64 | textmining:519 |
Rv0880 |
HTH-type transcriptional regulator | 556 | 54 | textmining:550 |
Rv3159c PPE53 |
PPE family protein PPE53 | 435 | 50 | textmining:430 |
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: transcriptional regulator
- MTBC0 PGAP product: transcriptional regulator RaaS
- Pfam (hmmscan --cut_ga): TetR_N PF00440.30 (E=8e-14), TetR_C_25 PF17933.7 (E=3e-45)
- (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_215735.1)
- Domains: Pfam-A via hmmscan --cut_ga — TetR_N (PF00440.30), TetR_C_25 (PF17933.7)
- 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 O86312 (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 —
21 functional partner(s); context anchor
Rv1217c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001307|Rv1219c|raaS MRSADLTAHARIREAAIEQFGRHGFGVGLRAIAEAAGVSAALVIHHFGSKEGLRKACDDFVAEEIRSSKAAALKSNDPTTWLAQMAEIESYAPLMAYLVRSMQSGGELAKMLWQKMIDNAEEYLDEGVRAGTVKPSRDPRARARFLAITGGGGFLLYLQMHENPTDLRAALRDYAHDMVLPSLEVYTEGLLADRAMYEAFLAEAQQGEAHVG