rshA Resolved · high auto-curated
H37Rv Rv3221A · MTBC0 - ·
101 aa · 3598051–3598356 (-) ·
RefSeq YP_177945.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | anti-sigma factor RshA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Anti-sigma factor RshA. Pfam: zf-HC2 (PF13490.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WJ69
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Anti-sigma factor RshA |
| Curated function | An redox-regulated anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigH. ECF sigma factors are held in an inactive form by a cognate anti-sigma factor. RshA and some peptides derived from it inhibit the sigma factor activity of SigH. Probably releases SigH during oxidative stress. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | rsrA |
| eggNOG description | anti-sigma factor |
| Orthologous group | COG5662 |
| Gene Ontology (40) |
GO:0000988, GO:0000989, GO:0003674, GO:0005488, GO:0006950, GO:0006979, GO:0008150, GO:0008270, GO:0009266, GO:0009408, GO:0009593, GO:0009628 +28 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) | 2 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
zf-HC2 | PF13490.12 | 2.8e-10 | 23–56 | Putative zinc-finger |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sigH (ECF RNA polymerase sigma factor SigH), high confidence from genomic context alone (score 983 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3223c sigH |
ECF RNA polymerase sigma factor SigH | 999 | 983 ctx | neighborhood:882 experimental:800 textmining:953 |
Rv3222c hyp |
hypothetical protein | 978 | 979 ctx | neighborhood:882 coexpression:826 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 728 | 728 ctx | neighborhood:720 |
Rv3224 |
iron-regulated short-chain dehydrogenase/reductase | 720 | 721 ctx | neighborhood:717 |
Rv3224B |
Rv3224B, len: 72 aa. Conserved hypothetical protein (possibly gene fragment), similar to C-terminal part of ML0799|AL583919_131 conserved hy | 719 | 720 ctx | neighborhood:717 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 704 | 705 | coexpression:703 |
Rv3681c whiB4 |
transcriptional regulator WhiB4 | 608 | 590 | |
Rv3414c sigD |
ECF RNA polymerase sigma factor SigD | 686 | 557 | |
Rv3780 bpa hyp |
hypothetical protein | 538 | 539 ctx | cooccurence:536 |
Rv3412 hyp |
hypothetical protein | 524 | 524 ctx | cooccurence:498 |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 550 | 516 | experimental:500 |
Rv3220c pdtaS |
two component sensor kinase | 533 | 515 ctx | neighborhood:508 |
Rv3605c hyp |
hypothetical protein | 506 | 506 ctx | cooccurence:506 |
Rv0014c pknB |
serine/threonine-protein kinase PknB | 718 | 505 | experimental:500 textmining:454 |
Rv1221 sigE |
ECF RNA polymerase sigma factor SigE | 701 | 492 | textmining:437 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): anti-sigma factor RshA
- Pfam (hmmscan --cut_ga): zf-HC2 PF13490.12 (E=3e-10)
- (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 YP_177945.1)
- Domains: Pfam-A via hmmscan --cut_ga — zf-HC2 (PF13490.12)
- 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
COG5662 - Curated reference: UniProt P9WJ69 (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 —
47 functional partner(s); context anchor
sigH - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3221A|rshA MSENCGPTDAHADHDDSHGGMGCAEVIAEVWTLLDGECTPETRERLRRHLEACPGCLRHYGLEERIKALIGTKCRGDRAPEGLRERLRLEIRRTTIIRGGP