PPE60 Family assigned · medium auto-curated
H37Rv Rv3478 · MTBC0 - ·
393 aa · 3894426–3895607 (+) ·
RefSeq YP_177976.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE family protein PPE60 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE family protein PPE60. 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 |
Q6MWX1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE60 |
| Curated function | Cell wall-associated antigen that interacts with host Toll-like receptor 2 (TLR2) and induces maturation and activation of dendritic cell (DC) via the MAPK and NF-kappa-B pathways. PPE60-stimulated dendritic cells promote the differentiation of the T-helper Th1 and Th17 cells. PPE60-induced activation of the NLRP3 inflammasome is required for this activity. PPE60 enhances MHC-II expression on the surface of DCs and potentially enables DCs to effectively process antigens and present peptides to CD4(+) T cells for recognition..; FUNCTION: When expressed in M.smegmatis, it up-regulates the produc. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | was demonstrated in lysates by immunodetection (see Dillon et al., 1999) |
| 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 | 0.662 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 11 synonymous, 20 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 | 1.4e-59 | 3–164 | PPE family |
PPE-SVP | PF12484.14 | 4.2e-16 | 309–388 | PPE-SVP subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PE31 (PE family protein PE31), medium confidence from genomic context alone (score 679 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3477 PE31 |
PE family protein PE31 | 919 | 679 ctx | neighborhood:679 textmining:760 |
Rv0178 |
Mce associated membrane protein | 533 | 533 | coexpression:533 |
Rv3479 |
transmembrane protein | 487 | 487 ctx | neighborhood:471 |
Rv1040c PE8 |
PE family protein PE8 | 414 | 291 | |
Rv3875 esxA |
ESAT-6 protein EsxA | 478 | 228 | |
Rv1638A hyp |
hypothetical protein | 438 | 51 | textmining:433 |
Rv2065 cobH |
precorrin-8X methylmutase | 414 | 47 | textmining:411 |
Rv0139 |
oxidoreductase | 512 | 44 | textmining:511 |
Rv1944c hyp |
hypothetical protein | 526 | 41 | textmining:526 |
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 family protein PPE60
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-59), PPE-SVP PF12484.14 (E=4e-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_177976.1)
- 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 Q6MWX1 (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 —
9 functional partner(s); context anchor
PE31 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3478|PPE60 MVDFGALPPEINSARMYAGPGSASLVAAAKMWDSVASDLFSAASAFQSVVWGLTVGSWIGSSAGLMAAAASPYVAWMSVTAGQAQLTAAQVRVAAAAYETAYRLTVPPPVIAENRTELMTLTATNLLGQNTPAIEANQAAYSQMWGQDAEAMYGYAATAATATEALLPFEDAPLITNPGGLLEQAVAVEEAIDTAAANQLMNNVPQALQQLAQPAQGVVPSSKLGGLWTAVSPHLSPLSNVSSIANNHMSMMGTGVSMTNTLHSMLKGLAPAAAQAVETAAENGVWAMSSLGSQLGSSLGSSGLGAGVAANLGRAASVGSLSVPPAWAAANQAVTPAARALPLTSLTSAAQTAPGHMLGGLPLGHSVNAGSGINNALRVPARAYAIPRTPAAG