PE8 Family assigned · medium auto-curated

H37Rv Rv1040c · MTBC0 - · 275 aa · 1162549–1163376 (-) · RefSeq YP_177779.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)PE family protein PE8
MTBC0 PGAP re-annotation
Revised (this work)PE family protein PE8. Pfam: PE (PF00934.26), 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 L7N667 SwissProt · reviewed · Evidence at protein level
UniProt namePE family protein PE8
Curated functionPromotes the intracellular survival of recombinant Mycobacterium within macrophages by regulating host inflammatory cytokines production and inhibiting cell late apoptosis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPolymorphic PE/PPE proteins C terminal
Orthologous group29WFN

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 0.502 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 4 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
PEPF00934.26 1.0e-265–93 PE family
PPE-SVPPF12484.14 6.0e-20192–272 PPE-SVP subfamily C-terminal region

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

Closest characterised functional partner: PPE15 (PPE family protein PPE15), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1039c PPE15 PPE family protein PPE15 999 1000 ctx neighborhood:594 experimental:999 textmining:437
Rv2768c PPE43 PPE family protein PPE43 907 899 experimental:891
Rv2770c PPE44 PPE family protein PPE44 904 899 experimental:891
Rv1794 espG5 hyp hypothetical protein 898 898 experimental:898
Rv1038c esxJ ESAT-6 like protein EsxJ 477 366
Rv1037c esxI ESAT-6 like protein EsxI 484 340
Rv3621c PPE65 PPE family protein PPE65 559 291 textmining:404
Rv0355c PPE8 PPE family protein PPE8 475 291
Rv3478 PPE60 PE family protein PPE60 414 291
Rv2352c PPE38 PPE family protein PPE38 409 291
Rv2633c hyp hypothetical protein 519 41 textmining:519
Rv1004c membrane protein 515 41 textmining:515
Rv3289c transmembrane protein 515 41 textmining:515
Rv2632c hyp hypothetical protein 511 41 textmining:511
Rv2442c rplU 50S ribosomal protein L21 510 41 textmining:510

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): PE family protein PE8
  • Pfam (hmmscan --cut_ga): PE PF00934.26 (E=1e-26), PPE-SVP PF12484.14 (E=6e-20)
  • (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_177779.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), 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 29WFN
  • Curated reference: UniProt L7N667 (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 — 20 functional partner(s); context anchor PPE15
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1040c|PE8
MSFLKTVPEELTAAAAQLGTIGAAMAAQNAAAAAPTTAIAPAALDEVSALQAALFTAYGTFYQQVSAEAQAMHDMFVNTLGISAGTYGVTESLNSSAAASPLSGITGEASAIIQATTGLFPPELSGGIGNILNIGAGNWASATSTLIGLAGGGLLPAEEAAEAASALGGEAALGELGALGAAEAALGEAGIAAGLGSASAIGMLSVPPAWAGQATLVSTTSTLPGAGWTAAAPQAAAGTFIPGMPGVASAARNSAGFGAPRYGVKPIVMPKPATV