rsdA Resolved · high auto-curated
H37Rv Rv3413c · MTBC0 mtbc0_003627 ·
299 aa · 3857585–3858484 (-) ·
RefSeq NP_217930.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | anti-sigma-D factor RsdA |
|---|---|
| MTBC0 PGAP re-annotation | anti-sigma D factor RsdA |
| Revised (this work) | Anti-sigma D factor RsdA. Pfam: RsdA_SigD_bd (PF16751.11). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJ71
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Anti-sigma-D factor RsdA |
| Curated function | An anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigD. ECF sigma factors are held in an inactive form by an anti-sigma factor until released by regulated intramembrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. The membrane-spanning regulatory substrate protein is first cut extracytoplasmically (site-1 protease, S1P), then within the membrane itself (site-2 protease, S2P), while cytoplasmic proteases finish degrading the regulatory protein, liberating the sigm. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | rsdA |
| eggNOG description | Anti-sigma-D factor RsdA to sigma factor binding region |
| Orthologous group | 2DVAJ |
| Gene Ontology (2) |
GO:0005575, GO:0005576
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.38% of strains (558) · 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 |
|---|---|---|---|---|
RsdA_SigD_bd | PF16751.11 | 7.0e-17 | 14–58 | Anti-sigma-D factor RsdA to sigma factor binding region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sigD (ECF RNA polymerase sigma factor SigD), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3414c sigD |
ECF RNA polymerase sigma factor SigD | 999 | 1000 ctx | neighborhood:882 cooccurence:488 experimental:999 |
Rv3415c hyp |
hypothetical protein | 868 | 869 ctx | neighborhood:767 cooccurence:459 |
Rv0210 hyp |
hypothetical protein | 746 | 746 ctx | cooccurence:746 |
Rv0556 |
transmembrane protein | 714 | 714 ctx | cooccurence:714 |
Rv2360c hyp |
hypothetical protein | 712 | 712 ctx | cooccurence:712 |
Rv0996 |
transmembrane protein | 711 | 711 ctx | cooccurence:711 |
Rv0481c hyp |
hypothetical protein | 699 | 699 ctx | cooccurence:699 |
Rv2138 lppL |
lipoprotein LppL | 694 | 695 ctx | cooccurence:654 |
Rv3071 hyp |
hypothetical protein | 689 | 689 ctx | cooccurence:689 |
Rv3438 hyp |
hypothetical protein | 681 | 682 ctx | cooccurence:672 |
Rv2474c hyp |
hypothetical protein | 668 | 668 ctx | cooccurence:668 |
Rv2732c |
transmembrane protein | 667 | 667 ctx | cooccurence:667 |
Rv3217c |
integral membrane protein | 665 | 665 ctx | cooccurence:665 |
Rv0431 |
tuberculin-like peptide | 663 | 663 ctx | cooccurence:663 |
Rv3212 hyp |
hypothetical protein | 661 | 661 ctx | cooccurence:660 |
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-sigma-D factor RsdA
- MTBC0 PGAP product: anti-sigma D factor RsdA
- Pfam (hmmscan --cut_ga): RsdA_SigD_bd PF16751.11 (E=7e-17)
- (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_217930.1)
- Domains: Pfam-A via hmmscan --cut_ga — RsdA_SigD_bd (PF16751.11)
- 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
2DVAJ - Curated reference: UniProt P9WJ71 (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 —
95 functional partner(s); context anchor
sigD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003627|Rv3413c|rsdA MREFGNPLGDRPPLDELARTDLLLDALAEREEVDFADPRDDALAALLGQWRDDLRWPPASALVSQDEAVAALRAGVAQRRRARRSLAAVGSVAAALLVLSGFGAVVADARPGDLLYGLHAMMFNRSRVSDDQIVLSAKANLAKVEQMIAQGQWAEAQDELAEVSSTVQAVTDGSRRQDLINEVNLLNTKVETRDPNATLRPGSPSNPAAPGSVGNSWTPLAPVVEPPTPPTPASAAEPSMSAGVSESPMPNSTSTVAASPSTPSSKPEPGSIDPSLEPADEATNPAGQPAPETPVSPTH