rskA Resolved · high auto-curated
H37Rv Rv0444c · MTBC0 mtbc0_000466 ·
232 aa · 536456–537154 (-) ·
RefSeq NP_214958.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | anti-sigma-K factor RskA |
|---|---|
| MTBC0 PGAP re-annotation | anti-sigma-K factor RskA |
| Revised (this work) | Anti-sigma-K factor RskA. Pfam: RskA_N (PF22618.2), RskA_C (PF10099.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WGX5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Anti-sigma-K factor RskA |
| Curated function | An anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigK. 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, Rip1), while cytoplasmic proteases finish degrading the regulatory protein, liberating th. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | rskA |
| eggNOG description | An anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigK. 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, Rip1), while cytoplasmic proteases finish degrading the regulatory protein, liberating the sigma factor |
| Orthologous group | COG5343 |
| Gene Ontology (36) |
GO:0000988, GO:0000989, GO:0003674, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006417, GO:0008150, GO:0009889, GO:0010468, GO:0010556 +24 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 | 1.026 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 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 |
|---|---|---|---|---|
RskA_N | PF22618.2 | 4.5e-23 | 9–56 | Anti-sigma-K factor RskA, N-terminal domain |
RskA_C | PF10099.15 | 3.1e-25 | 94–225 | Anti-sigma-K factor rskA, C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: sigK (ECF RNA polymerase sigma factor SigK), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0445c sigK |
ECF RNA polymerase sigma factor SigK | 999 | 999 ctx | neighborhood:706 cooccurence:636 experimental:987 textmining:906 |
Rv0448c hyp |
hypothetical protein | 674 | 673 ctx | neighborhood:611 |
Rv0446c |
transmembrane protein | 673 | 673 ctx | neighborhood:593 |
Rv2164c hyp |
hypothetical protein | 633 | 633 ctx | cooccurence:628 |
Rv0538 |
membrane protein | 621 | 622 ctx | cooccurence:618 |
Rv0447c ufaA1 |
cyclopropane-fatty-acyl-phospholipid synthase UfaA | 619 | 617 ctx | neighborhood:611 |
Rv0339c iniR |
transcriptional regulator | 608 | 608 ctx | cooccurence:601 |
Rv3903c cpnT hyp |
hypothetical protein | 599 | 600 ctx | cooccurence:594 |
Rv2113 |
integral membrane protein | 592 | 592 ctx | cooccurence:587 |
Rv3909 hyp |
hypothetical protein | 563 | 563 ctx | cooccurence:557 |
Rv3835 hyp |
hypothetical protein | 537 | 538 ctx | cooccurence:533 |
Rv1853 ureD |
urease accessory protein UreD | 523 | 524 ctx | cooccurence:518 |
Rv0449c hyp |
hypothetical protein | 774 | 522 ctx | neighborhood:517 textmining:547 |
Rv1024 |
membrane protein | 481 | 481 ctx | cooccurence:468 |
Rv2843 hyp |
hypothetical protein | 473 | 473 ctx | cooccurence:466 |
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-K factor RskA
- MTBC0 PGAP product: anti-sigma-K factor RskA
- Pfam (hmmscan --cut_ga): RskA_N PF22618.2 (E=4e-23), RskA_C PF10099.15 (E=3e-25)
- (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_214958.1)
- Domains: Pfam-A via hmmscan --cut_ga — RskA_N (PF22618.2), RskA_C (PF10099.15)
- 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
COG5343 - Curated reference: UniProt P9WGX5 (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
sigK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000466|Rv0444c|rskA MTEHTDFELLELATPYALNAVSDDERADIDRRVAAAPSPVAAAFNDEVRAVRETMAVVSAATTAEPPAHLRTAILDATKPEVRRQSRWRTAAFASAAAIAVGLGAFGLGVLTRPSPPPTVAEQVLTAPDVRTVSRPLGAGTATVVFSRDRNTGLLVMNNVAPPSRGTVYQMWLLGGAKGPRSAGTMGTAAVTPSTTATLTDLGASTALAFTVEPGTGSPQPTGTILAELPLG