oprA Resolved · high auto-curated
H37Rv Rv0516c · MTBC0 mtbc0_000544 ·
158 aa · 611516–611992 (-) ·
RefSeq NP_215030.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | anti-anti-sigma factor |
|---|---|
| MTBC0 PGAP re-annotation | osmosensory protein OprA |
| Revised (this work) | Osmosensory protein OprA. Pfam: STAS (PF01740.27), STAS_2 (PF13466.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O33361
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Osmosensory protein A |
| Curated function | Part of a signaling pathway that enables adaptation to osmotic stress through cell wall remodeling and virulence factor production. Unphosphorylated OprA forms a complex with the anti-anti-sigma-factor paralog Rv2638 that dissociates on OprA phosphorylation by PknD. Phosphorylation of OprA may stimulate the release of SigF from an inhibitory complex and enable the transcription of osmotically regulated genes, such as oprA and the ESX-1-associated virulence factor espA. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | Belongs to the anti-sigma-factor antagonist family |
| Orthologous group | COG1366 |
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 | 0.665 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 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 |
|---|---|---|---|---|
STAS | PF01740.27 | 5.3e-17 | 31–135 | STAS domain |
STAS_2 | PF13466.13 | 8.5e-09 | 38–112 | Mlab, STAS domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0517 (acyltransferase), medium confidence from genomic context alone (score 526 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1364c |
sigma factor regulatory protein | 992 | 991 | coexpression:928 experimental:859 |
Rv3287c rsbW |
anti-sigma factor RsbW | 844 | 728 | coexpression:506 experimental:454 textmining:452 |
Rv0263c hyp |
hypothetical protein | 716 | 716 | coexpression:716 |
Rv0264c hyp |
hypothetical protein | 716 | 716 | coexpression:716 |
Rv1354c hyp |
hypothetical protein | 709 | 690 | coexpression:647 |
Rv1173 fbiC |
FO synthase | 658 | 658 | coexpression:647 |
Rv0655 mkl |
ABC transporter ATP-binding protein | 644 | 645 | experimental:629 |
Rv3286c sigF |
RNA polymerase sigma factor SigF | 891 | 592 | textmining:745 |
Rv0517 |
acyltransferase | 526 | 526 ctx | neighborhood:494 |
Rv1876 bfrA |
bacterioferritin BfrA | 501 | 470 | coexpression:470 |
Rv1234 |
transmembrane protein | 476 | 456 | coexpression:456 |
Rv0167 yrbE1A |
membrane protein | 431 | 431 | experimental:408 |
Rv0168 yrbE1B |
membrane protein | 434 | 429 | experimental:408 |
Rv3500c yrbE4B |
integral membrane protein | 431 | 426 | experimental:408 |
Rv3501c yrbE4A |
integral membrane protein | 425 | 426 | experimental:408 |
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: anti-anti-sigma factor
- MTBC0 PGAP product: osmosensory protein OprA
- Pfam (hmmscan --cut_ga): STAS PF01740.27 (E=5e-17), STAS_2 PF13466.13 (E=9e-09)
- (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_215030.1)
- Domains: Pfam-A via hmmscan --cut_ga — STAS (PF01740.27), STAS_2 (PF13466.13)
- 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
COG1366 - Curated reference: UniProt O33361 (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 —
32 functional partner(s); context anchor
Rv0517 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000544|Rv0516c|oprA MTTTIPTSKSACSVTTRPGNAAVDYGGAQIRAYLHHLATVVTIRGEIDAANVEQISEHVRRFSLGTNPMVLDLSELSHFSGAGISLLCILDEDCRAAGVQWALVASPAVVEQLGGRCDQGEHESMFPMARSVHKALHDLADAIDRRRQLVLPLISRSA