mscL Resolved · high auto-curated

H37Rv Rv0985c · MTBC0 mtbc0_001056 · 151 aa · 1108361–1108816 (-) · RefSeq NP_215500.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)large-conductance ion mechanosensitive channel
MTBC0 PGAP re-annotationlarge-conductance mechanosensitive channel protein MscL
Revised (this work)Large-conductance mechanosensitive channel protein MscL. Pfam: MscL (PF01741.24).

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

Curated reference (UniProt)

UniProt P9WJN5 SwissProt · reviewed · Evidence at protein level
UniProt nameLarge-conductance mechanosensitive channel
Curated functionChannel that opens in response to stretch forces in the membrane lipid bilayer. The force required to trigger channel opening depends on the nature of the membrane lipids; the presence of phosphatidylinositol enhances mechanosensitivity of the channel. May participate in the regulation of osmotic pressure changes within the cell.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namemscL
eggNOG descriptionChannel that opens in response to stretch forces in the membrane lipid bilayer. May participate in the regulation of osmotic pressure changes within the cell
Orthologous groupCOG1970
KEGG orthology K03282
Gene Ontology (43) GO:0003674, GO:0005215, GO:0005488, GO:0005515, GO:0005575, GO:0005623, GO:0005886, GO:0005887, GO:0006810, GO:0006811, GO:0006884, GO:0008150 +31 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 0.701 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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
MscLPF01741.24 6.8e-331–122 Large-conductance mechanosensitive channel, MscL

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

Closest characterised functional partner: Rv0987 (adhesion component ABC transporter permease), medium confidence from genomic context alone (score 406 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1416 ribH 6,7-dimethyl-8-ribityllumazine synthase 988 987 coexpression:987
Rv1392 metK S-adenosylmethionine synthetase 945 945 coexpression:945
Rv3396c guaA GMP synthase 464 465
Rv1380 pyrB aspartate carbamoyltransferase 450 451 coexpression:439
Rv2560 hyp hypothetical protein 407 407 coexpression:407
Rv3853 rraA RNase E regulator RraA 429 406 coexpression:406
Rv0987 adhesion component ABC transporter permease 405 406 ctx neighborhood:400
Rv0986 adhesion component ABC transporter ATP-binding protein 459 403
Rv0984 moaB2 pterin-4-alpha-carbinolamine dehydratase 815 307 textmining:745
Rv2881c cdsA phosphatidate cytidylyltransferase 459 193
Rv0865 mog molybdopterin biosynthesis protein 443 113
Rv3156 nuoL NADH-quinone oxidoreductase subunit L 509 107 textmining:473
Rv3104c transmembrane protein 513 94 textmining:485
Rv0917 betP glycine betaine transport integral membrane protein BetP 491 93 textmining:462
Rv3145 nuoA NADH-quinone oxidoreductase subunit A 530 79 textmining:511

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: large-conductance ion mechanosensitive channel
  • MTBC0 PGAP product: large-conductance mechanosensitive channel protein MscL
  • Pfam (hmmscan --cut_ga): MscL PF01741.24 (E=7e-33)
  • (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_215500.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MscL (PF01741.24)
  • 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 COG1970
  • Curated reference: UniProt P9WJN5 (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 — 24 functional partner(s); context anchor Rv0987
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001056|Rv0985c|mscL
MLKGFKEFLARGNIVDLAVAVVIGTAFTALVTKFTDSIITPLINRIGVNAQSDVGILRIGIGGGQTIDLNVLLSAAINFFLIAFAVYFLVVLPYNTLRKKGEVEQPGDTQVVLLTEIRDLLAQTNGDSPGRHGGRGTPSPTDGPRASTESQ