PPE33 Family assigned · medium auto-curated

H37Rv Rv1809 · MTBC0 - · 468 aa · 2051282–2052688 (+) · RefSeq YP_177845.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PPE family protein PPE33
MTBC0 PGAP re-annotation
Revised (this work)PPE family protein PPE33. Pfam: PPE (PF00823.26), PPE-SVP (PF12484.14).

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 P9WI03 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized PPE family protein PPE33

UniProt still lists this protein as Uncharacterized PPE family protein PPE33; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category N Cell motility
eggNOG descriptionPolymorphic PE/PPE proteins C terminal
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 1.053 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 10.17% of strains (14774) · 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 1.1e-632–165 PPE family
PPE-SVPPF12484.14 9.2e-12316–384 PPE-SVP subfamily C-terminal region

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

Closest characterised functional partner: PPE32 (PPE family protein PPE32), high confidence from genomic context alone (score 932 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1808 PPE32 PPE family protein PPE32 936 932 ctx neighborhood:544 coexpression:857
Rv1810 hyp hypothetical protein 479 479 ctx neighborhood:455
Rv1811 mgtC Mg2+ transport P-type ATPase MgtC 430 381
Rv1806 PE20 PE family protein PE20 473 270
Rv1175c fadH NADPH dependent 2,4-dienoyl-CoA reductase FadH 412 46 textmining:410
Rv2178c aroG phospho-2-dehydro-3-deoxyheptonate aldolase AroG 417 44 textmining:415
Rv1840c PE_PGRS34 PE-PGRS family protein PE_PGRS34 431 41 textmining:431
Rv2543 lppA lipoprotein LppA 430 41 textmining:431
Rv2544 lppB lipoprotein LppB 412 41 textmining:413

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 PPE33
  • Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-63), PPE-SVP PF12484.14 (E=9e-12)
  • (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_177845.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), PPE-SVP (PF12484.14)
  • 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 P9WI03 (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 — 9 functional partner(s); context anchor PPE32
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1809|PPE33
MDFGLQPPEITSGEMYLGPGAGPMLAAAVAWDGLAAELQSMAASYASIVEGMASESWLGPSSAGMAAAAAPYVTWMSGTSAQAKAAADQARAAVVAYETAFAAVVPPPQIAANRSQLISLVATNIFGQNTAAIAATEAEYGEMWAQDTMAMFGYASSSATASRLTPFTAPPQTTNPSGLAGQAAATGQATALASGTNAVTTALSSAAAQFPFDIIPTLLQGLATLSTQYTQLMGQLINAIFGPTGATTYQNVFVTAANVTKFSTWANDAMSAPNLGMTEFKVFWQPPPAPEIPKSSLGAGLGLRSGLSAGLAHAASAGLGQANLVGDLSVPPSWASATPAVRLVANTLPATSLAAAPATQIPANLLGQMALGSMTGGALGAAAPAIYTGSGARARANGGTPSAEPVKLEAVIAQLQKQPDAVRHWNVDKADLDGLLDRLSKQPGIHAVHVSNGDKPKVALPDTQLGSH