PPE2 Family assigned · medium auto-curated
H37Rv Rv0256c · MTBC0 - ·
556 aa · 307877–309547 (-) ·
RefSeq YP_177704.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE2 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE2. Pfam: PPE (PF00823.26), PPE-PPW (PF18878.6). |
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 |
P9WI47
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE2 |
| Curated function | Inhibits nitric oxide (NO) production in activated macrophages. Acts by inhibiting expression of the host inducible nitric oxide synthase (iNOS). PPE2 is translocated into the host macrophage nucleus, where it interacts with a GATA-binding site overlapping with the TATA box of NOS2 (iNOS) promoter, and strongly inhibits NOS2 gene transcription. Reduction in NO production in turn facilitates intracellular survival of the bacilli inside the macrophage. In addition, disrupts the assembly of NADPH oxidase complex, which inhibits NADPH oxidase-mediated reactive oxygen species (ROS) generation in ma. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | PPE family |
| Orthologous group | COG5651 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.871 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 11 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (253) · 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 | 3.3e-58 | 6–168 | PPE family |
PPE-PPW | PF18878.6 | 7.0e-16 | 502–547 | PPE-PPW subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cobQ1 (cobyric acid synthase), high confidence from genomic context alone (score 765 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0255c cobQ1 |
cobyric acid synthase | 915 | 765 ctx | neighborhood:759 textmining:656 |
Rv3810 pirG |
cell surface protein | 761 | 762 ctx | cooccurence:758 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 758 | 759 ctx | cooccurence:757 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 754 | 755 ctx | cooccurence:754 |
Rv3446c hyp |
hypothetical protein | 752 | 753 ctx | cooccurence:751 |
Rv0479c |
membrane protein | 749 | 749 ctx | cooccurence:746 |
Rv3899c hyp |
hypothetical protein | 748 | 749 ctx | cooccurence:747 |
Rv3604c |
transmembrane protein | 745 | 745 ctx | cooccurence:744 |
Rv0955 |
integral membrane protein | 738 | 738 ctx | cooccurence:737 |
Rv2082 hyp |
hypothetical protein | 736 | 736 ctx | cooccurence:729 |
Rv3558 PPE64 |
PPE family protein PPE64 | 720 | 721 ctx | cooccurence:718 |
Rv3887c eccD2 |
ESX-2 secretion system protein EccD | 712 | 713 ctx | cooccurence:711 |
Rv2945c lppX |
lipoprotein LppX | 702 | 703 ctx | cooccurence:702 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 694 | 694 ctx | cooccurence:694 |
Rv0254c cobU |
bifunctional cobinamide kinase/cobinamide phosphate guanylyltransferase | 891 | 693 ctx | neighborhood:690 textmining:660 |
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 PPE2
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=3e-58), PPE-PPW PF18878.6 (E=7e-16)
- (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_177704.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), PPE-PPW (PF18878.6)
- 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 P9WI47 (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 —
120 functional partner(s); context anchor
cobQ1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0256c|PPE2 MTAPIWMASPPEVHSALLSSGPGPGPLLVSAEGWHSLSIAYAETADELAALLAAVQAGTWDGPTAAVYVAAHTPYLAWLVQASANSAAMATRQETAATAYGTALAAMPTLAELGANHALHGVLMATNFFGINTIPIALNESDYARMWIQAATTMASYQAVSTAAVAAAPQTTPAPQIVKANAPTAASDEPNQVQEWLQWLQKIGYTDFYNNVIQPFINWLTNLPFLQAMFSGFDPWLPSLGNPLTFLSPANIAFALGYPMDIGSYVAFLSQTFAFIGADLAAAFASGNPATIAFTLMFTTVEAIGTIITDTIALVKTLLEQTLALLPAALPLLAAPLAPLTLAPASAAGGFAGLSGLAGLVGIPPSAPPVIPPVAAIAPSIPTPTPTPAPAPAPTAVTAPTPPPGPPPPPVTAPPPVTGAGIQSFGYLVGDLNSAAQARKAVGTGVRKKTPEPDSAEAPAAAAAPEEQVQPQRRRRPKIKQLGRGYEYLDLDPETGHDPTGSPQGAGTLGFAGTTHKASPGQVAGLITLPNDAFGGSPRTPMMPGTWDTDSATRVE