ppm1 Resolved · high auto-curated

H37Rv Rv2051c · MTBC0 mtbc0_002184 · 874 aa · 2336744–2339368 (-) · RefSeq NP_216567.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)polyprenol-monophosphomannose synthase
MTBC0 PGAP re-annotationapolipoprotein N-acyltransferase
Revised (this work)Apolipoprotein N-acyltransferase. Pfam: LNT_N (PF20154.5), CN_hydrolase (PF00795.28), Glycos_transf_2 (PF00535.33).

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

Curated reference (UniProt)

UniProt O53493 SwissProt · reviewed · Evidence at protein level
UniProt nameBifunctional apolipoprotein N-acyltransferase/polyprenol monophosphomannose synthase [Includes: Apolipoprotein N-acyltransferase
EC (curated) EC 2.3.1.269, EC 2.4.1.-, EC 2.4.1.83
Curated functionCatalyzes the phospholipid dependent N-acylation of the N-terminal cysteine of apolipoprotein, the last step in lipoprotein maturation..; FUNCTION: Transfers mannose from GDP-mannose to lipid acceptors (works best on C20-C95 lipid monophosphate substrates in which the lipid can be modified, tested with the C-terminal domain expressed in M.smegmatis) to form polyprenol monophosphomannose (PPM). PMM is an alkai-stable sugar donor which adds mannose-phosphate residues to triacylated-phosphatidyl-myo-inositol mannosides (PIM2), eventually leading to generation of the cell wall glycolipid lipoglyca.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namelnt
eggNOG descriptionTransfers the fatty acyl group on membrane lipoproteins
Orthologous groupCOG0463
KEGG orthology K03820
CAZy family GT2
Gene Ontology (62) GO:0000030, GO:0003674, GO:0003824, GO:0004582, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006629 +50 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 0.287 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 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
LNT_NPF20154.5 6.6e-3231–182 Apolipoprotein N-acyltransferase N-terminal domain
CN_hydrolasePF00795.28 4.8e-15243–487 Carbon-nitrogen hydrolase
Glycos_transf_2PF00535.33 4.9e-32614–780 Glycosyl transferase family 2

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

Closest characterised functional partner: fxsA (transmembrane protein FxsA), high confidence from genomic context alone (score 870 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2052c hyp hypothetical protein 897 898 ctx neighborhood:510 coexpression:800
Rv2053c fxsA transmembrane protein FxsA 869 870 ctx neighborhood:534 coexpression:732
Rv0983 pepD serine protease PepD 769 759 coexpression:730
Rv0204c transmembrane protein 500 475 ctx cooccurence:408
Rv0112 gca GDP-mannose 4,6-dehydratase 491 475
Rv0236c aftD alpha-(1->3)-arabinofuranosyltransferase 513 448
Rv3784 dTDP-glucose 4,6-dehydratase 503 434
Rv0256c PPE2 PPE family protein PPE2 419 420
Rv3907c pcnA poly(A) polymerase PcnA 422 409
Rv0225 hyp hypothetical protein 432 404
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 484 349
Rv2173 idsA2 geranylgeranyl pyrophosphate synthetase IdsA 406 340
Rv3265c wbbL1 N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase 434 329
Rv2048c pks12 polyketide synthase 513 303
Rv3781 rfbE O-antigen/lipopolysaccharide ABC transporter ATP-binding protein RfbE 450 303

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: polyprenol-monophosphomannose synthase
  • MTBC0 PGAP product: apolipoprotein N-acyltransferase
  • Pfam (hmmscan --cut_ga): LNT_N PF20154.5 (E=7e-32), CN_hydrolase PF00795.28 (E=5e-15), Glycos_transf_2 PF00535.33 (E=5e-32)
  • (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_216567.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LNT_N (PF20154.5), CN_hydrolase (PF00795.28), Glycos_transf_2 (PF00535.33)
  • 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 COG0463
  • Curated reference: UniProt O53493 (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 — 41 functional partner(s); context anchor fxsA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002184|Rv2051c|ppm1
MKLGAWVAAQLPTTRTAVRTRLTRLVVSIVAGLLLYASFPPRNCWWAAVVALALLAWVLTHRATTPVGGLGYGLLFGLVFYVSLLPWIGELVGPGPWLALATTCALFPGIFGLFAVVVRLLPGWPIWFAVGWAAQEWLKSILPFGGFPWGSVAFGQAEGPLLPLVQLGGVALLSTGVALVGCGLTAIALEIEKWWRTGGQGDAPPAVVLPAACICLVLFAAIVVWPQVRHAGSGSGGEPTVTVAVVQGNVPRLGLDFNAQRRAVLDNHVEETLRLAADVHAGLAQQPQFVIWPENSSDIDPFVNPDAGQRISAAAEAIGAPILIGTLMDVPGRPRENPEWTNTAIVWNPGTGPADRHDKAIVQPFGEYLPMPWLFRHLSGYADRAGHFVPGNGTGVVRIAGVPVGVATCWEVIFDRAPRKSILGGAQLLTVPSNNATFNKTMSEQQLAFAKVRAVEHDRYVVVAGTTGISAVIAPDGGELIRTDFFQPAYLDSQVRLKTRLTPATRWGPILQWILVGAAAAVVLVAMRQNGWFPRPRRSEPKGENDDSDAPPGRSEASGPPALSESDDELIQPEQGGRHSSGFGRHRATSRSYMTTGQPAPPAPGNRPSQRVLVIIPTFNERENLPVIHRRLTQACPAVHVLVVDDSSPDGTGQLADELAQADPGRTHVMHRTAKNGLGAAYLAGFAWGLSREYSVLVEMDADGSHAPEQLQRLLDAVDAGADLAIGSRYVAGGTVRNWPWRRLVLSKTANTYSRLALGIGIHDITAGYRAYRREALEAIDLDGVDSKGYCFQIDLTWRTVSNGFVVTEVPITFTERELGVSKMSGSNIREALVKVARWGIEGRLSRSDHARARPDIARPGAGGSRVSRADVTE