PE_PGRS33 Family assigned · medium auto-curated
H37Rv Rv1818c · MTBC0 - ·
498 aa · 2061178–2062674 (-) ·
RefSeq YP_177846.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE-PGRS family protein PE_PGRS33 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE-PGRS family protein PE_PGRS33. Pfam: PE (PF00934.26), PGRS (PF21526.3). |
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 |
P9WIF5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PE-PGRS family protein PE_PGRS33 |
| Curated function | Induces TNF release through human Toll-like receptor 2 (TLR2) signaling pathway, leading to macrophage apoptosis. The signaling pathway involves TLR2-dependent activation of the mitogen-activated protein kinase kinase kinase 5 (ASK1), which activates the p38 and JNK MAPKs, leading to enhanced expression of TNF and tumor necrosis factor receptor superfamily member 1A (TNFRI) genes. Signals are amplified through classical caspase 8-dependent mitochondrial release of cytochrome c, leading to the activation of caspases 9 and 3. Mediates Ca(2+)-dependent up-regulation of the anti-inflammatory cytok. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| eggNOG description | PE-PGRS family |
| Orthologous group | COG0657 |
| Gene Ontology (46) |
GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0006950, GO:0008150, GO:0009405, GO:0009605, GO:0009607, GO:0009628, GO:0009987 +34 more
|
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 | 0.427 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 7 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 8.41% of strains (12216) · 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 |
|---|---|---|---|---|
PE | PF00934.26 | 1.8e-34 | 4–93 | PE family |
PGRS | PF21526.3 | 1.2e-08 | 118–181 | PGRS repeats |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: bacA (vitamin B12 transport ATP-binding protein BacA), medium confidence from genomic context alone (score 495 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1819c bacA |
vitamin B12 transport ATP-binding protein BacA | 495 | 495 ctx | neighborhood:495 |
Rv1821 secA2 |
accessory Sec system translocase SecA2 | 472 | 355 | |
Rv1381 pyrC |
dihydroorotase | 448 | 160 | |
Rv0774c hyp |
hypothetical protein | 658 | 45 | textmining:657 |
Rv2430c PPE41 |
PPE family protein PPE41 | 668 | 41 | textmining:668 |
Rv1089 PE10 |
PE family protein PE10; Together with PE9, induces macrophage apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Interac | 512 | 41 | textmining:512 |
Rv1196 PPE18 |
PPE family protein PPE18 | 511 | 41 | textmining:511 |
Rv3018c PPE46 |
PPE family protein PPE46 | 432 | 41 | textmining:432 |
Rv0966c hyp |
hypothetical protein | 424 | 41 | textmining:424 |
Rv1383 carA |
carbamoyl-phosphate synthase small subunit | 424 | 41 | textmining:424 |
Rv1787 PPE25 |
PPE family protein PPE25 | 400 | 41 | textmining:401 |
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): PE-PGRS family protein PE_PGRS33
- Pfam (hmmscan --cut_ga): PE PF00934.26 (E=2e-34), PGRS PF21526.3 (E=1e-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_177846.1)
- Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3)
- 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
COG0657 - Curated reference: UniProt P9WIF5 (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 —
11 functional partner(s); context anchor
bacA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1818c|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