PPE57 Family assigned · medium auto-curated
H37Rv Rv3425 · MTBC0 - ·
176 aa · 3842239–3842769 (+) ·
RefSeq YP_177971.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE57 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE57. 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 |
Q50703
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE57 |
| Curated function | 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. Induces macrophage activation by augmenting the expression of several cell surface molecules (CD40, CD80, CD86 and MHC class II) and pro-inflammatory cytokines (TNF, IL-6 and IL-12p40) within macrophages. Also participates in adaptive immunity by directing Th1-polarised immune responses. Stimulates specific humoral and cel. |
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) pseudogene candidate
| pN/pS | 0.457 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 25.58% of strains (37143) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
PPE | PF00823.26 | 3.4e-47 | 1–164 | PPE family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE58 (PPE family protein PPE58), high confidence from genomic context alone (score 915 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3426 PPE58 |
PPE family protein PPE58 | 919 | 915 ctx | neighborhood:418 coexpression:860 |
Rv3424c hyp |
hypothetical protein | 533 | 533 ctx | neighborhood:525 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 439 | 51 | textmining:434 |
Rv3875 esxA |
ESAT-6 protein EsxA | 444 | 49 | textmining:440 |
Rv2353c PPE39 |
PPE family protein PPE39 | 513 | 47 | textmining:510 |
Rv1255c |
HTH-type transcriptional regulator | 441 | 47 | textmining:438 |
Rv0310c hyp |
hypothetical protein | 544 | 46 | textmining:542 |
Rv3892c PPE69 |
PPE family protein PPE69 | 512 | 44 | textmining:511 |
Rv2659c |
prophage integrase | 541 | 41 | textmining:541 |
Rv3872 PE35 |
PE family protein PE35 | 444 | 41 | textmining:444 |
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 PPE57
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=3e-47)
- (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_177971.1)
- 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 Q50703 (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 —
10 functional partner(s); context anchor
PPE58 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3425|PPE57 MHPMIPAEYISNIIYEGPGADSLFFASGQLRELAYSVETTAESLEDELDELDENWKGSSSDLLADAVERYLQWLSKHSSQLKHAAWVINGLANAYNDTRRKVVPPEEIAANREERRRLIASNVAGVNTPAIADLDAQYDQYRARNVAVMNAYVSWTRSALSDLPRWREPPQIYRGG