mmpS4 Resolved · high auto-curated

H37Rv Rv0451c · MTBC0 mtbc0_000473 · 140 aa · 544853–545275 (-) · RefSeq NP_214965.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein MmpS4
MTBC0 PGAP re-annotationsiderophore RND transporter accessory protein MmpS4
Revised (this work)Siderophore RND transporter accessory protein MmpS4. 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 P9WJS9 SwissProt · reviewed · Evidence at protein level
UniProt nameSiderophore export accessory protein MmpS4
Curated functionPart of an export system, which is required for biosynthesis and secretion of siderophores. Essential for virulence.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namemmpS4
eggNOG descriptionMycobacterium membrane protein
Orthologous group2BG05

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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 1.3e-742–140 Mycobacterium membrane protein

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

Closest characterised functional partner: mmpL4 (transmembrane transport protein MmpL4), high confidence from genomic context alone (score 909 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0450c mmpL4 transmembrane transport protein MmpL4 984 909 ctx neighborhood:882 textmining:831
Rv0449c hyp hypothetical protein 660 659 ctx neighborhood:659
Rv0447c ufaA1 cyclopropane-fatty-acyl-phospholipid synthase UfaA 509 510 ctx neighborhood:508
Rv0446c transmembrane protein 509 510 ctx neighborhood:508
Rv0448c hyp hypothetical protein 509 509 ctx neighborhood:509
Rv0452 transcriptional regulator 821 508 ctx neighborhood:508 textmining:652
Rv0445c sigK ECF RNA polymerase sigma factor SigK 440 440 ctx neighborhood:436
Rv0676c mmpL5 transmembrane transport protein MmpL5 911 133 textmining:902
Rv1501 hyp hypothetical protein 419 55 textmining:411
Rv3592 mhuD heme-degrading monooxygenase 516 51 textmining:511
Rv3533c PPE62 PPE family protein PPE62 443 50 textmining:438
Rv1348 irtA iron ABC transporter ATP-binding protein/permease IrtA 654 47 textmining:652
Rv0677c mmpS5 membrane protein MmpS5 509 47 textmining:506
Rv0203 hyp hypothetical protein 437 47 textmining:434
Rv3424c hyp hypothetical protein 414 47 textmining:411

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 MmpS4
  • MTBC0 PGAP product: siderophore RND transporter accessory protein MmpS4
  • Pfam (hmmscan --cut_ga): Mycobact_memb PF05423.19 (E=1e-74)
  • (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_214965.1)
  • 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 P9WJS9 (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 — 23 functional partner(s); context anchor mmpL4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000473|Rv0451c|mmpS4
MLMRTWIPLVILVVVIVGGFTVHRIRGFFGSENRPSYSDTNLENSKPFNPKHLTYEIFGPPGTVADISYFDVNSEPQRVDGAVLPWSLHITTNDAAVMGNIVAQGNSDSIGCRITVDGKVRAERVSNEVNAYTYCLVKSA