sigK Family assigned · medium auto-curated

H37Rv Rv0445c · MTBC0 mtbc0_000467 · 187 aa · 537198–537761 (-) · RefSeq NP_214959.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ECF RNA polymerase sigma factor SigK
MTBC0 PGAP re-annotationsigma-70 family RNA polymerase sigma factor SigK
Revised (this work)Sigma-70 family RNA polymerase sigma factor SigK. Pfam: Sigma70_r2 (PF04542.21), Sigma70_r4_2 (PF08281.19), Sigma70_r4 (PF04545.23).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WGH7 SwissProt · reviewed · Evidence at protein level
UniProt nameECF RNA polymerase sigma factor SigK
Curated functionSigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma factors are held in an inactive form by an anti-sigma factor until released by regulated intramembrane proteolysis. Sigma-K controls genes such as mpt70 and mpt83.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namesigK
eggNOG descriptionBelongs to the sigma-70 factor family. ECF subfamily
Orthologous groupCOG1595
KEGG orthology K03088
Gene Ontology (21) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0010468, GO:0010565, GO:0016020, GO:0019216, GO:0019217, GO:0019222, GO:0030312 +9 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 0.343 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 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)

PfamAccessioni-EvalueResiduesDescription
Sigma70_r2PF04542.21 1.2e-1430–96 Sigma-70 region 2
Sigma70_r4_2PF08281.19 1.2e-10128–180 Sigma-70, region 4
Sigma70_r4PF04545.23 1.3e-13133–182 Sigma-70, region 4

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: rskA (anti-sigma-K factor RskA), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0444c rskA anti-sigma-K factor RskA 999 999 ctx neighborhood:706 cooccurence:636 experimental:987 textmining:906
Rv0448c hyp hypothetical protein 828 827 ctx neighborhood:726
Rv0446c transmembrane protein 763 763 ctx neighborhood:694
Rv0447c ufaA1 cyclopropane-fatty-acyl-phospholipid synthase UfaA 749 738 ctx neighborhood:696
Rv0449c hyp hypothetical protein 897 712 ctx neighborhood:586 textmining:657
Rv3911 sigM ECF RNA polymerase sigma factor SigM 884 524 ctx cooccurence:506 textmining:768
Rv2873 mpt83 cell surface lipoprotein 911 501 ctx cooccurence:429 textmining:831
Rv2875 mpt70 major secreted immunogenic protein Mpt70 914 490 ctx cooccurence:413 textmining:840
Rv0736 rslA anti-sigma-L factor RslA 634 489
Rv3221A rshA anti-sigma factor RshA 516 486
Rv1222 rseA anti-sigma E factor RseA 605 471
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 489 461 experimental:456
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 487 458 experimental:451
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 477 448 experimental:431
Rv0451c mmpS4 membrane protein MmpS4 440 440 ctx neighborhood:436

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: ECF RNA polymerase sigma factor SigK
  • MTBC0 PGAP product: sigma-70 family RNA polymerase sigma factor SigK
  • Pfam (hmmscan --cut_ga): Sigma70_r2 PF04542.21 (E=1e-14), Sigma70_r4_2 PF08281.19 (E=1e-10), Sigma70_r4 PF04545.23 (E=1e-13)
  • (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_214959.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sigma70_r2 (PF04542.21), Sigma70_r4_2 (PF08281.19), Sigma70_r4 (PF04545.23)
  • 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 COG1595
  • Curated reference: UniProt P9WGH7 (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 — 36 functional partner(s); context anchor rskA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000467|Rv0445c|sigK
MTGPPRLSSDLDALLRRVAGHDQAAFAEFYDHTKSRVYGLVMRVLRDTGYSEETTQEIYLEVWRNASEFDSAKGSALAWLLTMAHRRAVDRVRCEQAGNQREVRYGAANVDPASDVVADLAIAGDERRRVTECLKALTDTQRQCIELAYYGGLTYVEVSRRLAANLSTIKSRMRDALRSLRNCLDVS