rslA Resolved · high auto-curated

H37Rv Rv0736 · MTBC0 mtbc0_000778 · 250 aa · 832333–833085 (+) · RefSeq NP_215250.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)anti-sigma-L factor RslA
MTBC0 PGAP re-annotationanti-sigma-L factor RslA
Revised (this work)Anti-sigma-L factor RslA. Pfam: zf-HC2 (PF13490.12).

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

Curated reference (UniProt)

UniProt P9WJ67 SwissProt · reviewed · Evidence at protein level
UniProt nameAnti-sigma-L factor RslA
Curated functionAn anti-sigma factor for extracytoplasmic function (ECF) sigma factor SigL. 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)

COG category K Transcription
eggNOG descriptionPutative zinc-finger
Orthologous groupCOG1595
Gene Ontology (28) GO:0000988, GO:0000989, GO:0003674, GO:0005488, GO:0008150, GO:0008270, GO:0009889, GO:0010556, GO:0016989, GO:0019219, GO:0019222, GO:0031323 +16 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 0.767 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 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
zf-HC2PF13490.12 1.7e-0933–58 Putative zinc-finger

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

Closest characterised functional partner: sigL (ECF RNA polymerase sigma factor SigL), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0735 sigL ECF RNA polymerase sigma factor SigL 999 1000 ctx neighborhood:664 fusion:446 cooccurence:573 coexpression:821 experimental:997 textmining:619
Rv1145 mmpL13a transmembrane transport protein 791 791 coexpression:791
Rv0737 transcriptional regulator 786 778 ctx neighborhood:656
Rv1138c oxidoreductase 791 767 coexpression:767
Rv1660 pks10 chalcone synthase 758 747 coexpression:746
Rv1146 mmpL13b transmembrane transport protein 746 746 coexpression:746
Rv3773c hyp hypothetical protein 711 712 ctx cooccurence:701
Rv0048c membrane protein 624 625 ctx cooccurence:624
Rv2079 hyp hypothetical protein 606 606 ctx cooccurence:588
Rv1189 sigI ECF RNA polymerase sigma factor SigI 622 604
Rv2423 hyp hypothetical protein 585 585 ctx cooccurence:583
Rv3779 transmembrane protein 535 535 ctx cooccurence:534
Rv0142 hyp hypothetical protein 535 535 ctx cooccurence:521
Rv1816 HTH-type transcriptional regulator 531 531 ctx cooccurence:523
Rv0738 hyp hypothetical protein 515 515

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-L factor RslA
  • MTBC0 PGAP product: anti-sigma-L factor RslA
  • Pfam (hmmscan --cut_ga): zf-HC2 PF13490.12 (E=2e-09)
  • (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_215250.1)
  • Domains: Pfam-A via hmmscan --cut_ga — zf-HC2 (PF13490.12)
  • 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 P9WJ67 (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 — 47 functional partner(s); context anchor sigL
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000778|Rv0736|rslA
MTMPLRGLGPPDDTGVREVSTGDDHHYAMWDAAYVLGALSAADRREFEAHLAGCPECRGAVTELCGVPALLSQLDRDEVAAISESAPTVVASGLSPELLPSLLAAVHRRRRRTRLITWVASSAAAAVLAIGVLVGVQGHSAAPQRAAVSALPMAQVGTQLLASTVSISGEPWGTFINLRCVCLAPPYASHDTLAMVVVGRDGSQTRLATWLAEPGHTATPAGSISTPVDQIAAVQVVAADTGQVLLQRSL