PPE63 Family assigned · medium auto-curated

H37Rv Rv3539 · MTBC0 - · 479 aa · 3978059–3979498 (+) · RefSeq YP_177987.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PPE family protein PPE63
MTBC0 PGAP re-annotation
Revised (this work)PPE family protein PPE63. Pfam: PPE (PF00823.26), PE-PPE (PF08237.18).

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 P9WHX5 SwissProt · reviewed · Evidence at protein level
UniProt nameEsterase PPE63
EC (curated) EC 3.1.1.-
Curated functionExhibits esterase activity with p-nitrophenyl esters as substrates, whose carbon chains range from C2 to C16 (pNPC2 to pNPC16). It shows maximum activity with p-nitrophenyl butyrate (pNPC4)..; FUNCTION: It may promote survival in host cells via cell wall modulation and altered immune response of host. Expression in M.smegmatis alters its colony morphology, lipid composition and integrity of the cell wall. It provides resistance to multiple hostile environmental stress conditions and several antibiotics. The recombinant M.smegmatis expressing PPE63 demonstrates higher infection and intracellula.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category N Cell motility
eggNOG descriptiondomain protein
Orthologous groupCOG5651
Gene Ontology (6) GO:0005575, 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)

pN/pS 0.519 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 8 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 0.49% of strains (710) · convergent

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
PPEPF00823.26 2.9e-603–166 PPE family
PE-PPEPF08237.18 1.9e-75240–462 PE-PPE domain

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

Closest characterised functional partner: kstD (3-oxosteroid 1-dehydrogenase), medium confidence from genomic context alone (score 545 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3537 kstD 3-oxosteroid 1-dehydrogenase 545 545 ctx neighborhood:536
Rv3538 dehydrogenase 543 543 ctx neighborhood:536
Rv2431c PE25 PE family protein PE25 623 155 textmining:573
Rv3892c PPE69 PPE family protein PPE69 440 47 textmining:437
Rv3893c PE36 PE family protein PE36 630 41 textmining:630
Rv3097c lipY triacylglycerol lipase Lip 510 41 textmining:511

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): PPE family protein PPE63
  • Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=3e-60), PE-PPE PF08237.18 (E=2e-75)
  • (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 YP_177987.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), PE-PPE (PF08237.18)
  • 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 COG5651
  • Curated reference: UniProt P9WHX5 (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 — 6 functional partner(s); context anchor kstD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3539|PPE63
MADFLTLSPEVNSARMYAGGGPGSLSAAAAAWDELAAELWLAAASFESVCSGLADRWWQGPSSRMMAAQAARHTGWLAAAATQAEGAASQAQTMALAYEAAFAATVHPALVAANRALVAWLAGSNVFGQNTPAIAAAEAIYEQMWAQDVVAMLNYHAVASAVGARLRPWQQLLHELPRRLGGEHSDSTNTELANPSSTTTRITVPGASPVHAATLLPFIGRLLAARYAELNTAIGTNWFPGTTPEVVSYPATIGVLSGSLGAVDANQSIAIGQQMLHNEILAATASGQPVTVAGLSMGSMVIDRELAYLAIDPNAPPSSALTFVELAGPERGLAQTYLPVGTTIPIAGYTVGNAPESQYNTSVVYSQYDIWADPPDRPWNLLAGANALMGAAYFHDLTAYAAPQQGIEIAAVTSSLGGTTTTYMIPSPTLPLLLPLKQIGVPDWIVGGLNNVLKPLVDAGYSQYAPTAGPYFSHGNLVW