MTBC Gene Atlas

PPE64 Family assigned · medium auto-curated

H37Rv Rv3558 · MTBC0 - · 552 aa · 3997980–3999638 (+) · RefSeq YP_177988.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PPE family protein PPE64
MTBC0 PGAP re-annotation—
Revised (this work)PPE family protein PPE64. Pfam: PPE (PF00823.26), Pentapeptide_2 (PF01469.25).

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 Q6MWW0 TrEMBL · unreviewed · Inferred from homology
UniProt namePPE family protein PPE64

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category N Cell motility
eggNOG descriptionPentapeptide repeats (8 copies)
Orthologous groupCOG5651

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 1.231 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 11 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 5.76% of strains (8359) · 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
PPEPF00823.26 2.8e-593–167 PPE family
Pentapeptide_2PF01469.25 1.3e-08405–443 Pentapeptide repeats (8 copies)

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

Closest characterised functional partner: PE_PGRS28 (PE-PGRS family protein PE_PGRS28), high confidence from genomic context alone (score 773 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2082 hyp hypothetical protein 774 774 ctx cooccurence:771
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 773 773 ctx cooccurence:773
Rv1004c membrane protein 772 773 ctx cooccurence:772
Rv2853 PE_PGRS48 PE-PGRS family protein PE_PGRS48 772 772 ctx cooccurence:772
Rv0124 PE_PGRS2 PE-PGRS family protein PE_PGRS2 772 772 ctx cooccurence:772
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 771 771 ctx cooccurence:771
Rv1243c PE_PGRS23 PE-PGRS family protein PE_PGRS23 771 771 ctx cooccurence:771
Rv0872c PE_PGRS15 PE-PGRS family protein PE_PGRS15 771 771 ctx cooccurence:771
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 770 770 ctx cooccurence:770
Rv2209 integral membrane protein 768 769 ctx cooccurence:768
Rv3864 espE ESX-1 secretion-associated protein EspE 766 767 ctx cooccurence:764
Rv0341 iniB isoniazid inducible protein IniB 761 762 ctx cooccurence:760
Rv0305c PPE6 PPE family protein PPE6 760 761 coexpression:730
Rv3903c cpnT hyp hypothetical protein 800 758 ctx cooccurence:728
Rv0977 PE_PGRS16 PE-PGRS family protein PE_PGRS16 758 758 ctx cooccurence:758

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 PPE64
  • Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=3e-59), Pentapeptide_2 PF01469.25 (E=1e-08)
  • (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_177988.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), Pentapeptide_2 (PF01469.25)
  • 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 Q6MWW0 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 101 functional partner(s); context anchor PE_PGRS28
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3558|PPE64
MAHFSVLPPEINSLRMYLGAGSAPMLQAAAAWDGLAAELGTAASSFSSVTTGLTGQAWQGPASAAMAAAAAPYAGFLTTASAQAQLAAGQAKAVASVFEAAKAAIVPPAAVAANREAFLALIRSNWLGLNAPWIAAVESLYEEYWAADVAAMTGYHAGASQAAAQLPLPAGLQQFLNTLPNLGIGNQGNANLGGGNTGSGNIGNGNKGSSNLGGGNIGNNNIGSGNRGSDNFGAGNVGTGNIGFGNQGPIDVNLLATPGQNNVGLGNIGNNNMGFGNTGDANTGGGNTGNGNIGGGNTGNNNFGFGNTGNNNIGIGLTGNNQMGINLAGLLNSGSGNIGIGNSGTNNIGLFNSGSGNIGVFNTGANTLVPGDLNNLGVGNSGNANIGFGNAGVLNTGFGNASILNTGLGNAGELNTGFGNAGFVNTGFDNSGNVNTGNGNSGNINTGSWNAGNVNTGFGIITDSGLTNSGFGNTGTDVSGFFNTPTGPLAVDVSGFFNTASGGTVINGQTSGIGNIGVPGTLFGSVRSGLNTGLFNMGTAISGLFNLRQLLG