PPE69 Family assigned · medium auto-curated
H37Rv Rv3892c · MTBC0 - ·
399 aa · 4374484–4375683 (-) ·
RefSeq YP_178024.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE69 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE69. Pfam: PPE (PF00823.26). |
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 |
P9WHW7
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Uncharacterized PPE family protein PPE69 |
UniProt still lists this protein as Uncharacterized PPE family protein PPE69; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| Preferred name | PPE69 |
| 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 | 0.796 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 13 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.64% of strains (935) · 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 | 1.0e-23 | 6–170 | PPE family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PE36 (PE family protein PE36), high confidence from genomic context alone (score 787 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3893c PE36 |
PE family protein PE36 | 833 | 787 ctx | neighborhood:787 |
Rv3891c esxD |
ESAT-6 like protein EsxD | 571 | 571 ctx | neighborhood:568 |
Rv3890c esxC |
ESAT-6 like protein EsxC | 464 | 464 ctx | neighborhood:457 |
Rv3894c eccC2 |
ESX-2 type VII secretion system protein EccC | 600 | 388 | |
Rv3539 PPE63 |
PPE family protein PPE63 | 440 | 47 | textmining:437 |
Rv2544 lppB |
lipoprotein LppB | 436 | 46 | textmining:434 |
Rv1175c fadH |
NADPH dependent 2,4-dienoyl-CoA reductase FadH | 435 | 46 | textmining:433 |
Rv2543 lppA |
lipoprotein LppA | 435 | 45 | textmining:433 |
Rv3425 PPE57 |
PPE family protein PPE57 | 512 | 44 | textmining:511 |
Rv3429 PPE59 |
PPE family protein PPE59 | 622 | 41 | textmining:622 |
Rv2126c PE_PGRS37 |
PE-PGRS family protein PE_PGRS37 | 511 | 41 | textmining:511 |
Rv2741 PE_PGRS47 |
PE-PGRS family protein PE_PGRS47 | 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 PPE69
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-23)
- (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_178024.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26)
- 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 P9WHW7 (SwissProt, reviewed; Inferred from homology)
- 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 —
12 functional partner(s); context anchor
PE36 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3892c|PPE69 MPDPGWAARTPEANDLLLTAGTGVGTHLANQTAWTTLGASHHASGVASAINTAATAASWLGVGSAASALNVTMLNATLHGLAGWVDVKPAVVSTAIAAFETANAAMRPAPECMENRDEWGVDNAINPSVLWTLTPRIVSLDVEYFGVMWPNNAAVGATYGGVLAALAESLAIPPPVATMGASPAAPAQAAAAVGQAAAEAAAGDGMRSAYQGVQAGSTGAGQSTSAGENFGNQLSTFMQPMQAVMQAAPQALQAPSGLMQAPMSAMQPLQSMVGMFANPGALGMGGAAPGASAASAAGGISAAATEVGAGGGGAALGGGGMPATSFTRPVSAFESGTSGRPVGLRPSGALGADVVRAPTTTVGGTPIGGMPVGHAAGGHRGSHGKSEQAATVRVVDDRR