PPE26 Family assigned · medium auto-curated
H37Rv Rv1789 · MTBC0 - ·
393 aa · 2026790–2027971 (+) ·
RefSeq YP_177835.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE26 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE26. 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 |
Q79FK6
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE26 |
| Curated function | Probably plays a key role in regulating innate and adaptive immune responses through human Toll-like receptor 2 (TLR2). Interacts with TLR2, leading to the subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kappa-B) signaling pathways. Stimulates macrophage activation by augmenting pro-inflammatory cytokine production (TNF, IL-6 and IL-12p40) and the expression of cell surface molecules (CD80, CD86, MHC class I and II). Also participates in adaptive immunity by directing Th1-polarised immune responses. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | Polymorphic PE/PPE proteins C terminal |
| 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 | 0.734 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 6 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 | 9.7e-68 | 2–164 | PPE family |
PPE-SVP | PF12484.14 | 4.0e-19 | 312–389 | PPE-SVP subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PE18 (PE family protein PE18), high confidence from genomic context alone (score 812 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1788 PE18 |
PE family protein PE18 | 961 | 812 ctx | neighborhood:812 textmining:804 |
Rv1787 PPE25 |
PPE family protein PPE25 | 634 | 611 ctx | neighborhood:590 |
Rv1862 adhA |
alcohol dehydrogenase A | 531 | 83 | textmining:510 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 445 | 64 | textmining:432 |
Rv1352 hyp |
hypothetical protein | 443 | 52 | textmining:437 |
Rv3095 |
HTH-type transcriptional regulator | 517 | 51 | textmining:512 |
Rv1147 hyp |
hypothetical protein | 549 | 49 | textmining:546 |
Rv0187 |
O-methyltransferase | 435 | 49 | textmining:431 |
Rv2303c |
antibiotic-resistance protein | 440 | 44 | textmining:439 |
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 PPE26
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-67), PPE-SVP PF12484.14 (E=4e-19)
- (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_177835.1)
- 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 Q79FK6 (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
PE18 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1789|PPE26 MDFGALPPEVNSVRMYAGPGSAPMVAAASAWNGLAAELSSAATGYETVITQLSSEGWLGPASAAMAEAVAPYVAWMSAAAAQAEQAATQARAAAAAFEAAFAATVPPPLIAANRASLMQLISTNVFGQNTSAIAAAEAQYGEMWAQDSAAMYAYAGSSASASAVTPFSTPPQIANPTAQGTQAAAVATAAGTAQSTLTEMITGLPNALQSLTSPLLQSSNGPLSWLWQILFGTPNFPTSISALLTDLQPYASFFYNTEGLPYFSIGMGNNFIQSAKTLGLIGSAAPAAVAAAGDAAKGLPGLGGMLGGGPVAAGLGNAASVGKLSVPPVWSGPLPGSVTPGAAPLPVSTVSAAPEAAPGSLLGGLPLAGAGGAGAGPRYGFRPTVMARPPFAG