mmpS5 Resolved · high auto-curated

H37Rv Rv0677c · MTBC0 mtbc0_000716 · 142 aa · 782563–782991 (-) · RefSeq NP_215191.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein MmpS5
MTBC0 PGAP re-annotationsiderophore transporter accessory protein MmpS5
Revised (this work)Siderophore transporter accessory protein MmpS5. Pfam: Mycobact_memb (PF05423.19).

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

Curated reference (UniProt)

UniProt P9WJS7 SwissProt · reviewed · Evidence at protein level
UniProt nameSiderophore export accessory protein MmpS5
Curated functionPart of an export system, which is required for biosynthesis and secretion of siderophores. Essential for virulence..; FUNCTION: Overexpression of the system confers non-target based resistance to azoles, clofazimine and bedaquiline, via an efflux mechanism.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namemmpS5
eggNOG descriptionmembrane
Orthologous group2BG05
Gene Ontology (2) GO:0005575, GO:0005576

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 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
Mycobact_membPF05423.19 2.4e-645–142 Mycobacterium membrane protein

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

Closest characterised functional partner: mmpL5 (transmembrane transport protein MmpL5), high confidence from genomic context alone (score 968 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0676c mmpL5 transmembrane transport protein MmpL5 998 968 ctx neighborhood:801 coexpression:848 textmining:951
Rv0678 mmpR5 hyp hypothetical protein 974 814 ctx neighborhood:601 coexpression:553 textmining:870
Rv1219c raaS transcriptional regulator 810 731 coexpression:731
Rv1217c tetronasin ABC transporter integral membrane protein 523 270
Rv0450c mmpL4 transmembrane transport protein MmpL4 879 74 textmining:875
Rv2339 mmpL9 transmembrane transport protein MmpL9 432 68 textmining:416
Rv1049 transcriptional repressor 699 52 textmining:696
Rv0455c hyp hypothetical protein 520 50 textmining:516
Rv0880 HTH-type transcriptional regulator 576 47 textmining:574
Rv0451c mmpS4 membrane protein MmpS4 509 47 textmining:506
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 444 47 textmining:441
Rv1305 atpE ATP synthase subunit C 828 46 textmining:827
Rv0264c hyp hypothetical protein 436 46 textmining:434
Rv2983 cofC 2-phospho-L-lactate guanylyltransferase 520 45 textmining:518
Rv2535c pepQ cytoplasmic peptidase PepQ 642 44 textmining:642

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: membrane protein MmpS5
  • MTBC0 PGAP product: siderophore transporter accessory protein MmpS5
  • Pfam (hmmscan --cut_ga): Mycobact_memb PF05423.19 (E=2e-64)
  • (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_215191.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Mycobact_memb (PF05423.19)
  • 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 2BG05
  • Curated reference: UniProt P9WJS7 (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 — 18 functional partner(s); context anchor mmpL5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000716|Rv0677c|mmpS5
MIGTLKRAWIPLLILVVVAIAGFTVQRIRTFFGSEGILVTPKVFADDPEPFDPKVVEYEVSGSGSYVNINYLDLDAKPQRIDGAALPWSLTLKTTAPSAAPNILAQGDGTSITCRITVDGEVKDERTATGVDALTYCFVKSA