PPE18 Family assigned · medium auto-curated
H37Rv Rv1196 · MTBC0 - ·
391 aa · 1339349–1340524 (+) ·
RefSeq YP_177795.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE18 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE18. 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 |
L7N675
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE18 |
| Curated function | Could be a crucial virulence factor for intracellular survival of M.tuberculosis. Favors development of Th2-type response, and down-regulates the pro-inflammatory and Th1-type response. Specifically interacts with the human Toll-like receptor 2 (TLR2), leading to an early and sustained activation of p38 MAPK, which induces IL-10 production and activates Th2-type immune response. Also inhibits pro-inflammatory cytokines IL-12p40 and TNF production. Acts by up-regulating the expression as well as tyrosine phosphorylation of suppressor of cytokine signaling 3 (SOCS-3), leading to the inhibition o. |
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)
| pN/pS | 0.597 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 15 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 | 9.8e-63 | 3–164 | PPE family |
PPE-SVP | PF12484.14 | 7.7e-19 | 306–386 | PPE-SVP subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxK (ESAT-6 like protein EsxK), high confidence from genomic context alone (score 892 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1197 esxK |
ESAT-6 like protein EsxK | 964 | 892 ctx | neighborhood:488 coexpression:798 textmining:685 |
Rv1198 esxL |
ESAT-6 like protein EsxL | 941 | 878 ctx | neighborhood:419 coexpression:799 textmining:535 |
Rv3619c esxV |
ESAT-6 like protein EsxV | 858 | 803 | coexpression:803 |
Rv3620c esxW |
ESAT-6 like protein EsxW | 882 | 799 | coexpression:799 textmining:438 |
Rv2347c esxP |
ESAT-6 like protein EsxP | 802 | 774 | coexpression:774 |
Rv1793 esxN |
ESAT-6 like protein EsxN | 840 | 772 | coexpression:772 |
Rv1038c esxJ |
ESAT-6 like protein EsxJ | 787 | 744 | coexpression:744 |
Rv2346c esxO |
ESAT-6 like protein EsxO | 778 | 733 | coexpression:733 |
Rv1361c PPE19 |
PPE family protein PPE19 | 732 | 731 | coexpression:731 |
Rv1195 PE13 |
PE family protein PE13 | 908 | 647 ctx | neighborhood:647 textmining:751 |
Rv1794 espG5 hyp |
hypothetical protein | 463 | 309 | |
Rv3881c espB |
ESX-1 secretion-associated protein EspB | 577 | 154 | textmining:521 |
Rv3477 PE31 |
PE family protein PE31 | 827 | 93 | textmining:817 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 441 | 90 | textmining:411 |
Rv3875 esxA |
ESAT-6 protein EsxA | 658 | 86 | textmining:642 |
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 PPE18
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-62), PPE-SVP PF12484.14 (E=8e-19)
- (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_177795.1)
- 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 L7N675 (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 —
23 functional partner(s); context anchor
esxK - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1196|PPE18 MVDFGALPPEINSARMYAGPGSASLVAAAQMWDSVASDLFSAASAFQSVVWGLTVGSWIGSSAGLMVAAASPYVAWMSVTAGQAELTAAQVRVAAAAYETAYGLTVPPPVIAENRAELMILIATNLLGQNTPAIAVNEAEYGEMWAQDAAAMFGYAAATATATATLLPFEEAPEMTSAGGLLEQAAAVEEASDTAAANQLMNNVPQALQQLAQPTQGTTPSSKLGGLWKTVSPHRSPISNMVSMANNHMSMTNSGVSMTNTLSSMLKGFAPAAAAQAVQTAAQNGVRAMSSLGSSLGSSGLGGGVAANLGRAASVGSLSVPQAWAAANQAVTPAARALPLTSLTSAAERGPGQMLGGLPVGQMGARAGGGLSGVLRVPPRPYVMPHSPAAG