sigM Resolved · high auto-curated

H37Rv Rv3911 · MTBC0 - · 222 aa · 4400186–4400854 (+) · RefSeq NP_218428.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ECF RNA polymerase sigma factor SigM
MTBC0 PGAP re-annotation
Revised (this work)ECF RNA polymerase sigma factor SigM. Pfam: Sigma70_r2 (PF04542.21).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O53590 SwissProt · reviewed · Evidence at transcript level
UniProt nameECF RNA polymerase sigma factor SigM
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 (RsaM, AC L7N5D7) until released by regulated intramembrane proteolysis (Probable). This sigma factor is required for the synthesis of surface or secreted molecules.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
Preferred namesigM
eggNOG descriptionBelongs to the sigma-70 factor family. ECF subfamily
Orthologous groupCOG1595
KEGG orthology K03088
Gene Ontology (48) GO:0001101, GO:0005575, GO:0005623, GO:0005886, GO:0006355, GO:0008150, GO:0009410, GO:0009415, GO:0009628, GO:0009889, GO:0009891, GO:0009893 +36 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 0.613 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 5 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 98.21% of strains (142603) · reference-fixed

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 2.6e-1639–105 Sigma-70 region 2

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

Closest characterised functional partner: rsmA (anti-sigma-M factor RsmA), high confidence from genomic context alone (score 878 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3912 rsmA anti-sigma-M factor RsmA 885 878 ctx neighborhood:807
Rv3909 hyp hypothetical protein 827 828 ctx neighborhood:724
Rv3910 murJ peptidoglycan biosynthesis protein 746 737 ctx neighborhood:724
Rv3908 mutT4 mutator protein MutT 730 731 ctx neighborhood:724
Rv2069 sigC ECF RNA polymerase sigma factor SigC 903 704 ctx cooccurence:702 textmining:687
Rv3913 trxB2 thioredoxin reductase 722 612 ctx neighborhood:603
Rv3914 trxC thioredoxin TrxC 704 605 ctx neighborhood:603
Rv0735 sigL ECF RNA polymerase sigma factor SigL 914 560 ctx cooccurence:498 textmining:814
Rv0445c sigK ECF RNA polymerase sigma factor SigK 884 524 ctx cooccurence:506 textmining:768
Rv3414c sigD ECF RNA polymerase sigma factor SigD 894 513 ctx cooccurence:510 textmining:792
Rv0736 rslA anti-sigma-L factor RslA 673 506
Rv0182c sigG ECF RNA polymerase sigma factor SigG 748 503 ctx cooccurence:492 textmining:515
Rv3915 cwlM peptidoglycan hydrolase 522 500 ctx neighborhood:482
Rv2181 alpha-(1-2)-phosphatidylinositol mannoside mannosyltransferase 495 495
Rv3221A rshA anti-sigma factor RshA 558 486

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): ECF RNA polymerase sigma factor SigM
  • Pfam (hmmscan --cut_ga): Sigma70_r2 PF04542.21 (E=3e-16)
  • (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_218428.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Sigma70_r2 (PF04542.21)
  • 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 O53590 (SwissProt, reviewed; Evidence at transcript 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 — 40 functional partner(s); context anchor rsmA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3911|sigM
MPPPIGYCPAVGFGGRHERSDAELLAAHVAGDRYAFDQLFRRHHRQLHRLARLTSRTSEDADDALQDAMLSAHRGAGSFRYDAAVSSWLHRIVVNACLDRLRRAKAHPTAPLEDVYPVADRTAQVETAIAVQRALMRLPVEQRAAVVAVDMQGYSIADTRPDAGRGRGHRQEPLRPGAGPPSAAAGLSQHRGEHPALTPLPVRRSIDPRARRYPTSGYCHRA