PPE3 Family assigned · medium auto-curated
H37Rv Rv0280 · MTBC0 - ·
536 aa · 339364–340974 (+) ·
RefSeq YP_177709.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE3 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE3. 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 |
P9WI45
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized PPE family protein PPE3 |
UniProt still lists this protein as Uncharacterized PPE family protein PPE3; the revised annotation above is ahead of the current UniProt record.
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 | 1.4 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 12 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 | 1.1e-60 | 4–166 | PPE family |
PPE-PPW | PF18878.6 | 4.0e-20 | 473–520 | PPE-PPW subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccA3 (ESX-3 secretion system protein EccA), high confidence from genomic context alone (score 845 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2990c hyp |
hypothetical protein | 971 | 860 | coexpression:860 textmining:803 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA | 876 | 845 ctx | neighborhood:416 coexpression:746 |
Rv0106 hyp |
hypothetical protein | 888 | 804 | coexpression:804 textmining:457 |
Rv2058c rpmB2 |
50S ribosomal protein L28 | 897 | 798 | coexpression:798 textmining:514 |
Rv0281 |
S-adenosylmethionine-dependent methyltransferase | 826 | 773 ctx | neighborhood:713 |
Rv2059 hyp |
hypothetical protein | 778 | 732 | coexpression:732 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 688 | 584 ctx | neighborhood:416 |
Rv0284 eccC3 |
ESX-3 secretion system protein EccC3 | 636 | 535 ctx | neighborhood:416 |
Rv0286 PPE4 |
PPE family protein PPE4 | 469 | 437 ctx | neighborhood:401 |
Rv0285 PE5 |
PE family protein PE5 | 450 | 416 ctx | neighborhood:416 |
Rv0279c PE_PGRS4 |
PE-PGRS family protein PE_PGRS4 | 413 | 413 ctx | neighborhood:413 |
Rv0287 esxG |
ESAT-6 like protein EsxG | 580 | 354 | |
Rv0289 espG3 |
ESX-3 secretion-associated protein EspG3 | 464 | 333 | |
Rv0288 esxH |
ESAT-6-like protein EsxH | 512 | 320 | |
Rv0291 mycP3 |
membrane-anchored mycosin MycP | 672 | 299 | textmining:551 |
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 PPE3
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-60), PPE-PPW PF18878.6 (E=4e-20)
- (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_177709.1)
- 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 P9WI45 (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
eccA3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0280|PPE3 MTLWMASPPEVHSALLSSGPGPGSVLSAAGVWSSLSAEYAAVADELIGLLGAVQTGAWQGPSAAAYVAAHAPYLAWLMRASETSAEAAARHETVAAAYTTAVAAMPTLVELAANHTLHGVLVATNFFGINTIPIALNEADYARMWTQAASTMATYQAVAEAAVASAPQTTPAPPILAAEAADDDHDHDHDHGGEPTPLDYLVAEILRIISGGRLIWDPAEGTMNGIPFEDYTDAAQPIWWVVRAIEFSKDFETFVQELFVNPVEAFQFYFELLLFDYPTHIVQIVEALSQSPQLLAVALGSVISNLGAVTGFAGLSGLAGMQPAAIPALAPVAAAPSTLPAVAMAPTMAAPGAAVASAAAPASAPAASTVASATPAPPPAPGAAGFGYPYAIAPPGIGFGSGMSASASAQRKAPQPDSAAAAAAAAAVRDQARARRRRRVTRRGYGDEFMDMNIDVDPDWGPPPGEDPVTSTVASDRGAGHLGFAGTARREAVADAAGMTTLAGDDFGDGPTTPMVPGSWDPDRDAPGSAEPGDRG