PPE17 Family assigned · medium auto-curated
H37Rv Rv1168c · MTBC0 - ·
346 aa · 1298764–1299804 (-) ·
RefSeq YP_177791.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE17 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE17. Pfam: PPE (PF00823.26), EspB_PPE (PF21856.3), 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 |
P9WI27
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE17 |
| Curated function | Induces pro-inflammatory responses. Induces host TLR1/2 heterodimerization, which causes an increased recruitment of IRAK1, MYD88, and protein kinase C epsilon (PRKCE) to the downstream TLR-signaling complex that translocates PRKCE into the nucleus in an IRAK1-dependent manner. PRKCE-mediated phosphorylation allowed the nuclear IRAK3 to be exported to the cytoplasm, leading to increased activation of ERK1/2, stabilization of MAPK phosphatase 1 (MKP1), and induction of TNF with concomitant down-regulation of MAP kinase p38..; FUNCTION: During M.tuberculosis and HIV-1 co-infection, can stimulate. |
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) pseudogene candidate
| pN/pS | 1.1 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 10.32% of strains (14979) · 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 | 1.5e-48 | 2–161 | PPE family |
EspB_PPE | PF21856.3 | 3.5e-08 | 24–168 | ESX-1 secretion-associated protein EspB, PPE domain |
PPE-SVP | PF12484.14 | 8.3e-07 | 270–337 | PPE-SVP subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lipX (lipase LipX), high confidence from genomic context alone (score 762 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1169c lipX |
lipase LipX | 914 | 762 ctx | neighborhood:762 textmining:656 |
Rv1170 mshB |
1D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase | 599 | 599 ctx | neighborhood:498 |
Rv1167c |
transcriptional regulator | 595 | 596 ctx | neighborhood:593 |
Rv2431c PE25 |
PE family protein PE25 | 604 | 155 | textmining:551 |
Rv0265c |
iron ABC transporter substrate-binding lipoprotein | 447 | 51 | textmining:442 |
Rv2558 hyp |
hypothetical protein | 522 | 50 | textmining:518 |
Rv2660c hyp |
hypothetical protein | 514 | 50 | textmining:510 |
Rv3891c esxD |
ESAT-6 like protein EsxD | 488 | 46 | textmining:486 |
Rv3288c usfY hyp |
hypothetical protein | 514 | 44 | textmining:513 |
Rv2107 PE22 |
PE family protein PE22 | 431 | 41 | textmining:431 |
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 PPE17
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-48), EspB_PPE PF21856.3 (E=4e-08), PPE-SVP PF12484.14 (E=8e-07)
- (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_177791.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), EspB_PPE (PF21856.3), 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 P9WI27 (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
lipX - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1168c|PPE17 MDFTIFPPEFNSLNIQGSARPFLVAANAWKNLSNELSYAASRFESEINGLITSWRGPSSTIMAAAVAPFRAWIVTTASLAELVADHISVVAGAYEAAHAAHVPLPVIETNRLTRLALATTNIFGIHTPAIFALDALYAQYWSQDGEAMNLYATMAAAAARLTPFSPPAPIANPGALARLYELIGSVSETVGSFAAPATKNLPSKLWTLLTKGTYPLTAARISSIPVEYVLAFVEGSNMGQMMGNLAMRSLTPTLKGPLELLPNAVRPAVSATLGNADTIGGLSVPPSWVADKSITPLAKAVPTSAPGGPSGTSWAQLGLASLAGGAVGAVAARTRSGVILRSPAAG