lppX Resolved · high auto-curated

H37Rv Rv2945c · MTBC0 mtbc0_003128 · 233 aa · 3311621–3312322 (-) · RefSeq NP_217461.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipoprotein LppX
MTBC0 PGAP re-annotationLppX_LprAFG lipoprotein
Revised (this work)LppX_LprAFG lipoprotein. Pfam: LppX_LprAFG (PF07161.20).

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

Curated reference (UniProt)

UniProt P9WK65 SwissProt · reviewed · Evidence at protein level
UniProt namePutative phthiocerol dimycocerosate transporter LppX
Curated functionMight be involved in translocating phthiocerol dimycocerosates (PDIM) from the cell membrane to the outer membrane; PDIM forms part of the cell wall.

UniProt still lists this protein as Putative phthiocerol dimycocerosate transporter LppX; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namelppX
eggNOG descriptionMight be involved in translocating phthiocerol dimycocerosates (PDIM) from the cell membrane to the outer membrane
Orthologous group2BPGV
Gene Ontology (40) GO:0003674, GO:0005215, GO:0005319, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0006810, GO:0006869, GO:0008150, GO:0009273 +28 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 0.347 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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
LppX_LprAFGPF07161.20 5.5e-6448–232 LppX_LprAFG lipoprotein

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

Closest characterised functional partner: pks1 (polyketide synthase), high confidence from genomic context alone (score 880 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2946c pks1 polyketide synthase 911 880 ctx neighborhood:469 coexpression:783
Rv2942 mmpL7 transmembrane transport protein MmpL7 953 764 ctx cooccurence:760 textmining:812
Rv2608 PPE42 PPE family protein PPE42 747 747 ctx cooccurence:747
Rv0878c PPE13 PPE family protein PPE13 737 738 ctx cooccurence:734
Rv2939 papA5 phthiocerol/phthiodiolone dimycocerosyl transferase 785 731 ctx cooccurence:587
Rv0442c PPE10 PPE family protein PPE10 720 721 ctx cooccurence:720
Rv0305c PPE6 PPE family protein PPE6 707 708 ctx cooccurence:707
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 717 705 coexpression:703
Rv3343c PPE54 PPE family protein PPE54 704 705 ctx cooccurence:699
Rv0256c PPE2 PPE family protein PPE2 702 703 ctx cooccurence:702
Rv0755c PPE12 PPE family protein PPE12 696 697 ctx cooccurence:696
Rv1548c PPE21 PPE family protein PPE21 695 696 ctx cooccurence:694
Rv1917c PPE34 PPE family protein PPE34 694 695 ctx cooccurence:694
Rv2356c PPE40 Rv2356c, (MTCY98.25), len: 615 aa. PPE40, Member of Mycobacterium tuberculosis PPE_family, highly similar to others e.g. Q10778|MTCY48.17|YF 679 680 ctx cooccurence:676
Rv0355c PPE8 PPE family protein PPE8 675 675 ctx cooccurence:674

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: lipoprotein LppX
  • MTBC0 PGAP product: LppX_LprAFG lipoprotein
  • Pfam (hmmscan --cut_ga): LppX_LprAFG PF07161.20 (E=5e-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_217461.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LppX_LprAFG (PF07161.20)
  • 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 2BPGV
  • Curated reference: UniProt P9WK65 (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 — 91 functional partner(s); context anchor pks1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003128|Rv2945c|lppX
MNDGKRAVTSAVLVVLGACLALWLSGCSSPKPDAEEQGVPVSPTASDPALLAEIRQSLDATKGLTSVHVAVRTTGKVDSLLGITSADVDVRANPLAAKGVCTYNDEQGVPFRVQGDNISVKLFDDWSNLGSISELSTSRVLDPAAGVTQLLSGVTNLQAQGTEVIDGISTTKITGTIPASSVKMLDPGAKSARPATVWIAQDGSHHLVRASIDLGSGSIQLTQSKWNEPVNVD