sigA Resolved · high auto-curated

H37Rv Rv2703 · MTBC0 mtbc0_002877 · 528 aa · 3040250–3041836 (+) · RefSeq NP_217219.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)RNA polymerase sigma factor SigA
MTBC0 PGAP re-annotationRNA polymerase sigma factor
Revised (this work)RNA polymerase sigma factor. Pfam: Sigma70_r1_2 (PF00140.26), Sigma70_r2 (PF04542.21), Sigma70_r3 (PF04539.23), 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 P9WGI1 SwissProt · reviewed · Evidence at protein level
UniProt nameRNA polymerase sigma factor SigA
Curated functionSigma factors are initiation factors that promote the attachment of RNA polymerase (RNAP) to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth (Probable). RNAP reconstituted with SigA or SigB is equally susceptible to rifampicin.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namesigA
eggNOG descriptionSigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor is the primary sigma factor during exponential growth
Orthologous groupCOG0568
KEGG orthology K03086
Gene Ontology (52) GO:0000988, GO:0000990, GO:0001101, GO:0003674, GO:0003676, GO:0003677, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006355 +40 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 0.651 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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_r1_2PF00140.26 1.7e-15226–259 Sigma-70 factor, region 1.2
Sigma70_r2PF04542.21 6.5e-24295–365 Sigma-70 region 2
Sigma70_r3PF04539.23 1.0e-28374–450 Sigma-70 region 3
Sigma70_r4PF04545.23 2.8e-18463–516 Sigma-70, region 4

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

Closest characterised functional partner: rpoA (DNA-directed RNA polymerase subunit alpha), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 999 1000 experimental:999 textmining:514
Rv3457c rpoA DNA-directed RNA polymerase subunit alpha 999 1000 ctx cooccurence:508 experimental:999
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 999 999 experimental:999
Rv3197A whiB7 transcriptional regulator WhiB7 999 999 experimental:999
Rv3219 whiB1 transcriptional regulator WhiB1 999 999 experimental:999 textmining:504
Rv0668 rpoC DNA-directed RNA polymerase subunit beta' 999 999 experimental:999
Rv2050 rbpA RNA polymerase-binding protein RbpA 995 995 experimental:995
Rv3583c carD RNA polymerase-binding transcription factor CarD 974 973 experimental:971
Rv2095c pafC proteasome accessory factor C 871 871 experimental:870
Rv2359 zur zinc uptake regulation protein 852 820 experimental:767
Rv2704 hyp hypothetical protein 900 819 ctx neighborhood:815 textmining:469
Rv2343c dnaG DNA primase 833 811 ctx cooccurence:426 coexpression:646
Rv2702 ppgK polyphosphate glucokinase 752 742 ctx neighborhood:741
Rv3833 AraC family transcriptional regulator 766 732 experimental:722
Rv2841c nusA transcription termination/antitermination protein NusA 723 689 experimental:446

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: RNA polymerase sigma factor SigA
  • MTBC0 PGAP product: RNA polymerase sigma factor
  • Pfam (hmmscan --cut_ga): Sigma70_r1_2 PF00140.26 (E=2e-15), Sigma70_r2 PF04542.21 (E=6e-24), Sigma70_r3 PF04539.23 (E=1e-28), Sigma70_r4 PF04545.23 (E=3e-18)
  • (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_217219.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sigma70_r1_2 (PF00140.26), Sigma70_r2 (PF04542.21), Sigma70_r3 (PF04539.23), 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 COG0568
  • Curated reference: UniProt P9WGI1 (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 — 114 functional partner(s); context anchor rpoA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002877|Rv2703|sigA
MAATKASTATDEPVKRTATKSPAASASGAKTGAKRTAAKSASGSPPAKRATKPAARSVKPASAPQDTTTSTIPKRKTRAAAKSAAAKAPSARGHATKPRAPKDAQHEAATDPEDALDSVEELDAEPDLDVEPGEDLDLDAADLNLDDLEDDVAPDADDDLDSGDDEDHEDLEAEAAVAPGQTADDDEEIAEPTEKDKASGDFVWDEDESEALRQARKDAELTASADSVRAYLKQIGKVALLNAEEEVELAKRIEAGLYATQLMTELSERGEKLPAAQRRDMMWICRDGDRAKNHLLEANLRLVVSLAKRYTGRGMAFLDLIQEGNLGLIRAVEKFDYTKGYKFSTYATWWIRQAITRAMADQARTIRIPVHMVEVINKLGRIQRELLQDLGREPTPEELAKEMDITPEKVLEIQQYAREPISLDQTIGDEGDSQLGDFIEDSEAVVAVDAVSFTLLQDQLQSVLDTLSEREAGVVRLRFGLTDGQPRTLDEIGQVYGVTRERIRQIESKTMSKLRHPSRSQVLRDYLD