PPE68 Family assigned · medium auto-curated
H37Rv Rv3873 · MTBC0 - ·
368 aa · 4351075–4352181 (+) ·
RefSeq YP_178022.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE68 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE68. Pfam: PPE (PF00823.26). |
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 |
P9WHW9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family immunomodulator PPE68 |
| Curated function | Plays a major role in RD1-associated pathogenesis, and may contribute to the establishment and maintenance of M.tuberculosis infection. Together with PE35, stimulates the secretion of IL-10 and MCP-1 from human macrophages, via the interaction with human Toll-like receptor 2 (TLR2). Stimulates high levels of gamma interferon secretion in peripheral blood mononuclear cells isolated from tuberculosis patients, as well as from healthy tuberculin purified protein derivative-positive donors. Does not interfere with the secretion and immunogenicity of EsxA (ESAT-6) and EsxB (CFP-10). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | PPE family |
| Orthologous group | COG5651 |
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 3 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PPE | PF00823.26 | 3.7e-51 | 3–159 | PPE family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: espG1 (ESX-1 secretion-associated protein EspG), high confidence from genomic context alone (score 935 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3866 espG1 |
ESX-1 secretion-associated protein EspG | 957 | 935 ctx | neighborhood:571 coexpression:855 |
Rv3864 espE |
ESX-1 secretion-associated protein EspE | 894 | 883 | coexpression:850 |
Rv3872 PE35 |
PE family protein PE35 | 988 | 834 ctx | neighborhood:681 experimental:500 textmining:933 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 963 | 788 ctx | neighborhood:776 textmining:834 |
Rv3878 espJ |
ESX-1 secretion-associated protein EspJ | 939 | 782 | coexpression:716 textmining:735 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 | 798 | 709 ctx | neighborhood:628 |
Rv3870 eccCa1 |
ESX-1 secretion system protein EccCa | 705 | 691 ctx | neighborhood:672 |
Rv3869 eccB1 |
ESX-1 secretion system protein EccB | 723 | 689 ctx | neighborhood:672 |
Rv3871 eccCb1 |
ESX-1 secretion system protein EccCb | 868 | 660 ctx | neighborhood:643 textmining:628 |
Rv3875 esxA |
ESAT-6 protein EsxA | 931 | 631 ctx | neighborhood:609 textmining:823 |
Rv3876 espI |
ESX-1 secretion-associated protein EspI | 811 | 627 | coexpression:449 textmining:515 |
Rv3867 espH |
ESX-1 secretion-associated protein EspH | 590 | 590 | |
Rv3881c espB |
ESX-1 secretion-associated protein EspB | 648 | 531 | coexpression:474 |
Rv3877 eccD1 |
ESX-1 secretion system protein EccD1 | 528 | 396 | |
Rv3865 espF |
ESX-1 secretion-associated protein EspF | 569 | 373 |
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 PPE68
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=4e-51)
- (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_178022.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26)
- 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 P9WHW9 (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 —
25 functional partner(s); context anchor
espG1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3873|PPE68 MLWHAMPPELNTARLMAGAGPAPMLAAAAGWQTLSAALDAQAVELTARLNSLGEAWTGGGSDKALAAATPMVVWLQTASTQAKTRAMQATAQAAAYTQAMATTPSLPEIAANHITQAVLTATNFFGINTIPIALTEMDYFIRMWNQAALAMEVYQAETAVNTLFEKLEPMASILDPGASQSTTNPIFGMPSPGSSTPVGQLPPAATQTLGQLGEMSGPMQQLTQPLQQVTSLFSQVGGTGGGNPADEEAAQMGLLGTSPLSNHPLAGGSGPSAGAGLLRAESLPGAGGSLTRTPLMSQLIEKPVAPSVMPAAAAGSSATGGAAPVGAGAMGQGAQSGGSTRPGLVAPAPLAQEREEDDEDDWDEEDDW