MTBC Gene Atlas

rsmA Resolved · high auto-curated

H37Rv Rv3912 · MTBC0 mtbc0_004146 · 254 aa · 4425121–4425885 (+) · RefSeq NP_218429.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)anti-sigma-M factor RsmA
MTBC0 PGAP re-annotationanti-sigma-M factor RsmA
Revised (this work)Anti-sigma-M factor RsmA. Pfam: RsmA_C (PF27063.1).

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

Curated reference (UniProt)

UniProt P9WJ65 SwissProt · reviewed · Inferred from homology
UniProt nameAnti-sigma-M factor RsmA
Curated functionAn anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigM. 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)

Orthologous group2B6VW

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 0.583 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 6 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
RsmA_CPF27063.1 2.9e-11174–249 Anti-sigma factor RsmA, C-terminal extracellular domain

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

Closest characterised functional partner: sigM (ECF RNA polymerase sigma factor SigM), high confidence from genomic context alone (score 878 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3911 sigM ECF RNA polymerase sigma factor SigM 885 878 ctx neighborhood:807
Rv3909 hyp hypothetical protein 821 821 ctx neighborhood:815
Rv3910 murJ peptidoglycan biosynthesis protein 816 816 ctx neighborhood:815
Rv3908 mutT4 mutator protein MutT 812 805 ctx neighborhood:804
Rv3914 trxC thioredoxin TrxC 781 781 ctx neighborhood:776
Rv3913 trxB2 thioredoxin reductase 776 777 ctx neighborhood:776
Rv3604c transmembrane protein 769 770 ctx cooccurence:769
Rv1978 hyp hypothetical protein 760 761 ctx cooccurence:759
Rv0955 integral membrane protein 745 745 ctx cooccurence:745
Rv2687c antibiotic ABC transporter permease 734 734 ctx cooccurence:734
Rv1733c transmembrane protein 731 732 ctx cooccurence:731
Rv2181 alpha-(1-2)-phosphatidylinositol mannoside mannosyltransferase 730 730 ctx cooccurence:708
Rv2686c antibiotic ABC transporter permease 727 728 ctx cooccurence:727
Rv3899c hyp hypothetical protein 683 684 ctx cooccurence:661
Rv1159 pimE polyprenol-phosphate-mannose-dependent alpha-(1-2)-phosphatidylinositol pentamannoside mannosyltransferase 690 679 ctx cooccurence:670

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-M factor RsmA
  • MTBC0 PGAP product: anti-sigma-M factor RsmA
  • Pfam (hmmscan --cut_ga): RsmA_C PF27063.1 (E=3e-11)
  • (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_218429.1)
  • Domains: Pfam-A via hmmscan --cut_ga — RsmA_C (PF27063.1)
  • 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 2B6VW
  • Curated reference: UniProt P9WJ65 (SwissProt, reviewed; Inferred from homology)
  • 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 — 69 functional partner(s); context anchor sigM
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004146|Rv3912|rsmA
MSAADKDPDKHSADADPPLTVELLADLQAGLLDDATAARIRSRVRSDPQAQQILRALNRVRRDVAAMGADPAWGPAARPAVVDSISAALRSARPNSSPGAAHAARPHVHPVRMIAGAAGLCAVATAIGVGAVVDAPPPAPSAPTTAQHITVSKPAPVIPLSRPQVLDLLHHTPDYGPPGGPLGDPSRRTSCLSGLGYPASTPVLGAQPIDIDARPAVLLVIPADTPDKLAVFAVAPHCSAADTGLLASTVVPRA