Rv3104c Family assigned · medium auto-curated

H37Rv Rv3104c · MTBC0 mtbc0_003300 · 308 aa · 3493216–3494142 (-) · RefSeq NP_217620.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationmechanosensitive ion channel family protein
Revised (this work)Mechanosensitive ion channel family protein. Pfam: MS_channel_1st (PF21088.3), MS_channel_2nd (PF00924.25), MS_channel_3rd (PF21082.3).

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

Curated reference (UniProt)

UniProt O05781 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namemscS
eggNOG descriptionmechanosensitive ion channel
Orthologous groupCOG0668
KEGG orthology K22044

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 0.239 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 3 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (146) · clonal

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
MS_channel_1stPF21088.3 8.6e-0989–129 Mechanosensitive ion channel, transmembrane helices 2/3
MS_channel_2ndPF00924.25 2.9e-18131–200 Mechanosensitive ion channel, beta-domain
MS_channel_3rdPF21082.3 1.8e-11207–292 Mechanosensitive ion channel MscS, C-terminal

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

Closest characterised functional partner: prfB (peptide chain release factor PrfB), high confidence from genomic context alone (score 892 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3105c prfB peptide chain release factor PrfB 892 892 ctx neighborhood:881
Rv3103c hyp hypothetical protein 883 882 ctx neighborhood:882
Rv3106 fprA NADPH-ferredoxin reductase FprA 780 780 ctx neighborhood:780
Rv3102c ftsE cell division ATP-binding protein FtsE 716 716 ctx neighborhood:706
Rv3101c ftsX cell division protein FtsX 706 706 ctx neighborhood:702
Rv3100c smpB SsrA-binding protein 686 685 ctx neighborhood:682
Rv3099c hyp hypothetical protein 637 637 ctx neighborhood:635
Rv1832 gcvB glycine dehydrogenase 617 618 coexpression:618
Rv0260c transcriptional regulator 425 189
Rv3412 hyp hypothetical protein 557 169 textmining:489
Rv0985c mscL large-conductance ion mechanosensitive channel 513 94 textmining:485
Rv3665c dppB dipeptide ABC transporter permease DppB 504 77 textmining:485
Rv0067c transcriptional regulator 489 53 textmining:483

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: transmembrane protein
  • MTBC0 PGAP product: mechanosensitive ion channel family protein
  • Pfam (hmmscan --cut_ga): MS_channel_1st PF21088.3 (E=9e-09), MS_channel_2nd PF00924.25 (E=3e-18), MS_channel_3rd PF21082.3 (E=2e-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_217620.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MS_channel_1st (PF21088.3), MS_channel_2nd (PF00924.25), MS_channel_3rd (PF21082.3)
  • 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 COG0668
  • Curated reference: UniProt O05781 (TrEMBL, unreviewed; 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 — 13 functional partner(s); context anchor prfB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003300|Rv3104c|
MTTSGTVLATSIAQHWHNFWRGEIGDWILNRGLRIVMLLIAAVLAARFVTWLANRVTRRLDLGFTESDALVRSEATKHRQAVASVISWVSIVLIYVVVVYEVIDVLPVPVGALVGPAAVLGAALGFGAQRLVQDLLAGFFIIVEKQYGFGDLVELSMVGSPENAAGTVEDVTLRVTKLRSSEGEVFTVPNGNIVKSVNLSKDWARAVVDIPVPTSADLGRVNEVLHQECEHARHDSLLGELLLDEPTVMGVERIEVDTVTLRLVARTLPGKQFEAGRQLRVLVIRALTRAGIVTAADARAAVAESPEQ