lppD Resolved · high auto-curated

H37Rv Rv1899c · MTBC0 - · 343 aa · 2145214–2146245 (-) · RefSeq NP_216415.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipoprotein LppD
MTBC0 PGAP re-annotation
Revised (this work)Lipoprotein LppD. Pfam: Macro (PF01661.28).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P9WK29 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1899c

UniProt still lists this protein as Uncharacterized protein Rv1899c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namelppD
eggNOG descriptionAppr-1'-p processing enzyme
Orthologous groupCOG2110
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944

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) pseudogene candidate

pN/pS 0.45 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.06% of strains (1544) · 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
MacroPF01661.28 1.4e-29193–302 Macro domain

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

Closest characterised functional partner: lipJ (lignin peroxidase LipJ), high confidence from genomic context alone (score 788 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1900c lipJ lignin peroxidase LipJ 789 788 ctx neighborhood:780
Rv1151c cobB NAD-dependent protein deacylase 775 765 ctx cooccurence:586
Rv1901 cinA competence damage-inducible protein CinA 592 593 ctx neighborhood:580
Rv2972c hyp hypothetical protein 423 419
Rv0143c transmembrane protein 403 403
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 426 384
Rv2116 lppK lipoprotein LppK 690 151 textmining:650
Rv0805 cpdA 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA 462 91 textmining:433
Rv3623 lpqG lipoprotein LpqG 529 75 textmining:512
Rv0619 galTb Rv0619, (MTCY19H5.02c), len: 181 aa (probable partial CDS). Probable galTb, second part of galactose-1-phosphate uridylyltransferase, highly 452 75 textmining:433
Rv3390 lpqD lipoprotein LpqD 534 62 textmining:524
Rv2080 lppJ lipoprotein LppJ 486 55 textmining:479
Rv3905c esxF ESAT-6 like protein EsxF 478 52 textmining:473
Rv0604 lpqO lipoprotein LpqO 653 51 textmining:650
Rv3904c esxE ESAT-6 like protein EsxE 404 50

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): lipoprotein LppD
  • Pfam (hmmscan --cut_ga): Macro PF01661.28 (E=1e-29)
  • (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_216415.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Macro (PF01661.28)
  • 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 COG2110
  • Curated reference: UniProt P9WK29 (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 — 29 functional partner(s); context anchor lipJ
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1899c|lppD
MSRAAGLPRLSWFAGLTWFAGGSTGAGCAAHPALAGLTAGARCPAYAAISASTARPAATAGTTPATGASGSARPTDAAGMADLARPGVVATHAVRTLGTTGSRAIGLCPCQPLDCPRSPQATLNLGSMGRSLDGPQWRRARVRLCGRWWRRSNTTRGASPRPPSTCRGDNVSMIELEVHQADVTKLELDAITNAANTRLRHAGGVAAAIARAGGPELQRESTEKAPIGLGEAVETTAGDMPARYVIHAATMELGGPTSGEIITAATAATLRKADELGCRSLALVAFGTGVGGFPLDDAARLMVGAVRRHRPGSLQRVVFAVHGDAAERAFSAAIQAGEDTARR