sigC Resolved · high auto-curated

H37Rv Rv2069 · MTBC0 mtbc0_002203 · 185 aa · 2355557–2356114 (+) · RefSeq NP_216585.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ECF RNA polymerase sigma factor SigC
MTBC0 PGAP re-annotationRNA polymerase sigma factor SigC
Revised (this work)RNA polymerase sigma factor SigC. Pfam: Sigma70_r2 (PF04542.21), Sigma70_ECF (PF07638.18), 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 P9WGH1 SwissProt · reviewed · Evidence at protein level
UniProt nameECF RNA polymerase sigma factor SigC
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 usually held in an inactive form by an anti-sigma factor until released by regulated intramembrane proteolysis; this sigma factor does not seem to have a cognate anti-sigma factor however. It has been suggested that the sigma domains 2 and 4 may interact via polar residues in this protein to autoregulate. Positively regulates expression of a small regulon of genes.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namesigC
eggNOG descriptionBelongs to the sigma-70 factor family. ECF subfamily
Orthologous groupCOG1595
KEGG orthology K03088
Gene Ontology (36) GO:0001101, GO:0001666, GO:0006355, GO:0006950, GO:0008150, GO:0009266, GO:0009405, GO:0009408, GO:0009410, GO:0009415, GO:0009628, GO:0009889 +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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 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 6.4e-1530–93 Sigma-70 region 2
Sigma70_ECFPF07638.18 8.6e-0553–174 ECF sigma factor
Sigma70_r4_2PF08281.19 4.7e-16122–174 Sigma-70, region 4
Sigma70_r4PF04545.23 8.9e-06128–174 Sigma-70, region 4

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

Closest characterised functional partner: Rv0093c (membrane protein), high confidence from genomic context alone (score 891 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0093c membrane protein 891 891 ctx fusion:734 cooccurence:462
Rv3223c sigH ECF RNA polymerase sigma factor SigH 939 752 ctx cooccurence:752 textmining:766
Rv3911 sigM ECF RNA polymerase sigma factor SigM 903 704 ctx cooccurence:702 textmining:687
Rv2068c blaC beta-lactamase 663 655 ctx neighborhood:589
Rv0735 sigL ECF RNA polymerase sigma factor SigL 945 628 ctx cooccurence:627 textmining:859
Rv2067c hyp hypothetical protein 556 556 ctx neighborhood:550
Rv3221A rshA anti-sigma factor RshA 580 484
Rv0736 rslA anti-sigma-L factor RslA 515 484
Rv1222 rseA anti-sigma E factor RseA 558 473
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 486 457 experimental:456
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 482 454 experimental:451
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 465 436 experimental:431
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 462 433 experimental:431
Rv3909 hyp hypothetical protein 417 418
Rv3372 otsB2 trehalose 6-phosphate phosphatase 412 413 coexpression:413

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 SigC
  • MTBC0 PGAP product: RNA polymerase sigma factor SigC
  • Pfam (hmmscan --cut_ga): Sigma70_r2 PF04542.21 (E=6e-15), Sigma70_ECF PF07638.18 (E=9e-05), Sigma70_r4_2 PF08281.19 (E=5e-16), Sigma70_r4 PF04545.23 (E=9e-06)
  • (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_216585.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sigma70_r2 (PF04542.21), Sigma70_ECF (PF07638.18), 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 P9WGH1 (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 — 28 functional partner(s); context anchor Rv0093c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002203|Rv2069|sigC
MTATASDDEAVTALALSAAKGNGRALEAFIKATQQDVWRFVAYLSDVGSADDLTQETFLRAIGAIPRFSARSSARTWLLAIARHVVADHIRHVRSRPRTTRGARPEHLIDGDRHARGFEDLVEVTTMIADLTTDQREALLLTQLLGLSYADAAAVCGCPVGTIRSRVARARDALLADAEPDDLTG