mmpL7 Resolved · high auto-curated

H37Rv Rv2942 · MTBC0 mtbc0_003125 · 920 aa · 3306067–3308829 (+) · RefSeq NP_217458.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane transport protein MmpL7
MTBC0 PGAP re-annotationphthiocerol dimycocerosate RND transporter MmpL7
Revised (this work)Phthiocerol dimycocerosate RND transporter MmpL7. Pfam: MMPL (PF03176.22).

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

Curated reference (UniProt)

UniProt P9WJU7 SwissProt · reviewed · Evidence at protein level
UniProt namePhthiocerol dimycocerosate exporter MmpL7
Curated functionRequired for export of phthiocerol dimycocerosate (PDIM) to the cell wall. Essential for normal replication during the active-growth phase of the murine tuberculosis model..; FUNCTION: Confers a high level of resistance to isoniazid (INH) when overexpressed in M.smegmatis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category N Cell motility
T Signal transduction mechanisms
Preferred namemmpL7
eggNOG descriptioninvolved in translocation of phthiocerol dimycocerosate (DIM) in the cell wall
Orthologous groupCOG2409
KEGG orthology K06994
Gene Ontology (44) GO:0005575, GO:0005623, GO:0005886, GO:0005887, GO:0006810, GO:0006855, GO:0006869, GO:0008150, GO:0009605, GO:0009607, GO:0010876, GO:0015893 +32 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 0.234 · purifying
Polymorphic sites (≥ 0.1% of strains) 13 synonymous, 8 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
MMPLPF03176.22 4.7e-7075–382 MMPL family

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

Closest characterised functional partner: fadD28 (long-chain-fatty-acid--AMP ligase FadD28), high confidence from genomic context alone (score 818 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2941 fadD28 long-chain-fatty-acid--AMP ligase FadD28 937 818 ctx neighborhood:801 textmining:669
Rv2608 PPE42 PPE family protein PPE42 769 769 ctx cooccurence:768
Rv3343c PPE54 PPE family protein PPE54 764 765 ctx cooccurence:758
Rv2945c lppX lipoprotein LppX 953 764 ctx cooccurence:760 textmining:812
Rv1917c PPE34 PPE family protein PPE34 760 761 ctx cooccurence:759
Rv0355c PPE8 PPE family protein PPE8 758 759 ctx cooccurence:756
Rv0442c PPE10 PPE family protein PPE10 758 758 ctx cooccurence:756
Rv3347c PPE55 PPE family protein PPE55 757 758 ctx cooccurence:754
Rv2209 integral membrane protein 757 758 ctx cooccurence:741
Rv3350c PPE56 PPE family protein PPE56 755 755 ctx cooccurence:753
Rv0305c PPE6 PPE family protein PPE6 753 754 ctx cooccurence:753
Rv0878c PPE13 PPE family protein PPE13 753 754 ctx cooccurence:749
Rv1004c membrane protein 742 743 ctx cooccurence:742
Rv1753c PPE24 PPE family protein PPE24 739 740 ctx cooccurence:738
Rv1548c PPE21 PPE family protein PPE21 739 740 ctx cooccurence:738

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 transport protein MmpL7
  • MTBC0 PGAP product: phthiocerol dimycocerosate RND transporter MmpL7
  • Pfam (hmmscan --cut_ga): MMPL PF03176.22 (E=5e-70)
  • (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_217458.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MMPL (PF03176.22)
  • 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 COG2409
  • Curated reference: UniProt P9WJU7 (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 — 125 functional partner(s); context anchor fadD28
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003125|Rv2942|mmpL7
MPSPAGRLHRIRYIRLKKSSPDCRATITSGSADGQRRSPRLTNLLVVAAWVAAAVIANLLLTFTQAEPHDTSPALLPQDAKTAAATSRIAQAFPGTGSNAIAYLVVEGGSTLEPQDQPYYDAAVGALRADTRHVGSVLDWWSDPVTAPLGTSPDGRSATAMVWLRGEAGTTQAAESLDAVRSVLRQLPPSEGLRASIVVPAITNDMPMQITAWQSATIVTVAAVIAVLLLLRARLSVRAAAIVLLTADLSLAVAWPLAAVVRGHDWGTDSVFSWTLAAVLTIGTITAATMLAARLGSDAGHSAAPTYRDSLPAFALPGACVAIFTGPLLLARTPALHGVGTAGLGVFVALAASLTVLPALIALAGASRQLPAPTTGAGWTGRLSLPVSSASALGTAAVLAICMLPIIGMRWGVAENPTRQGGAQVLPGNALPDVVVIKSARDLRDPAALIAINQVSHRLVEVPGVRKVESAAWPAGVPWTDASLSSAAGRLADQLGQQAGSFVPAVTAIKSMKSIIEQMSGAVDQLDSTVNVTLAGARQAQQYLDPMLAAARNLKNKTTELSEYLETIHTWIVGFTNCPDDVLCTAMRKVIEPYDIVVTGMNELSTGADRISAISTQTMSALSSAPRMVAQMRSALAQVRSFVPKLETTIQDAMPQIAQASAMLKNLSADFADTGEGGFHLSRKDLADPSYRHVRESMFSSDGTATRLFLYSDGQLDLAAAARAQQLEIAAGKAMKYGSLVDSQVTVGGAAQIAAAVRDALIHDAVLLAVILLTVVALASMWRGAVHGAAVGVGVLASYLAALGVSIALWQHLLDRELNALVPLVSFAVLASCGVPYLVAGIKAGRIADEATGARSKGAVSGRGAVAPLAALGGVFGAGLVLVSGGSFSVLSQIGTVVVLGLGVLITVQRAWLPTTPGRR