PPE32 Family assigned · medium auto-curated
H37Rv Rv1808 · MTBC0 - ·
409 aa · 2049921–2051150 (+) ·
RefSeq YP_177844.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE32 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE32. 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 |
P9WI05
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE32 |
| Curated function | Virulence factor that modulates the production of host cytokines. Interacts with host TLR2 receptor at the macrophage cell surface and induces the secretion of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokines TNF and interleukin-6 (IL-6), via coactivation of MAPK and NF-kappa-B signaling pathways. Also increases the expression of IL-12p40 and IL-32 through activation of the ERK1/2 signaling pathway. Can induce cell apotopsis in macrophages via activation of caspases and increase reticulum endoplasmic stress response. When expressed in M.smegmatis, it enh. |
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 | 0.455 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 | 4.6e-69 | 2–164 | PPE family |
PPE-SVP | PF12484.14 | 2.1e-08 | 312–382 | PPE-SVP subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE33 (PPE family protein PPE33), high confidence from genomic context alone (score 932 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1809 PPE33 |
PPE family protein PPE33 | 936 | 932 ctx | neighborhood:544 coexpression:857 |
Rv1807 PPE31 |
Rv1807, (MTV049.29), len: 399 aa. PPE31, Member of the Mycobacterium tuberculosis PPE family of glycine-rich proteins, most similar to Rv178 | 509 | 496 ctx | neighborhood:406 |
Rv1810 hyp |
hypothetical protein | 403 | 403 | |
Rv1806 PE20 |
PE family protein PE20 | 629 | 366 | textmining:440 |
Rv1862 adhA |
alcohol dehydrogenase A | 522 | 53 | textmining:516 |
Rv1147 hyp |
hypothetical protein | 626 | 47 | textmining:624 |
Rv1352 hyp |
hypothetical protein | 513 | 47 | textmining:510 |
Rv0774c hyp |
hypothetical protein | 629 | 46 | textmining:628 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 440 | 45 | textmining:438 |
Rv2985 mutT1 |
8-oxo-dGTP diphosphatase | 437 | 44 | textmining:436 |
Rv3095 |
HTH-type transcriptional regulator | 539 | 41 | textmining:539 |
Rv2303c |
antibiotic-resistance protein | 511 | 41 | textmining:511 |
Rv0187 |
O-methyltransferase | 438 | 41 | textmining:438 |
Rv1840c PE_PGRS34 |
PE-PGRS family protein PE_PGRS34 | 437 | 41 | textmining:437 |
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 PPE32
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=5e-69), PPE-SVP PF12484.14 (E=2e-08)
- (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_177844.1)
- 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 P9WI05 (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 —
14 functional partner(s); context anchor
PPE33 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1808|PPE32 MDFGALPPEINSGRMYAGPGSGPLLAAAAAWDALAAELYSAAASYGSTIEGLTVAPWMGPSSITMAAAVAPYVAWISVTAGQAEQAGAQAKIAAGVYETAFAATVPPPVIEANRALLMSLVATNIFGQNTPAIAATEAHYAEMWAQDAAAMYGYAGSSATASQLAPFSEPPQTTNPSATAAQSAVVAQAAGAAASSDITAQLSQLISLLPSTLQSLATTATATSASAGWDTVLQSITTILANLTGPYSIIGLGAIPGGWWLTFGQILGLAQNAPGVAALLGPKAAAGALSPLAPLRGGYIGDITPLGGGATGGIARAIYVGSLSVPQGWAEAAPVMRAVASVLPGTGAAPALAAEAPGALFGEMALSSLAGRALAGTAVRSGAGAARVAGGSVTEDVASTTTIIVIPAD