PPE4 Family assigned · medium auto-curated
H37Rv Rv0286 · MTBC0 - ·
513 aa · 349935–351476 (+) ·
RefSeq YP_177711.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE4 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE4. 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 |
P9WI43
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PPE family protein PPE4 |
| Curated function | Important for the siderophore-mediated iron-acquisition function of ESX-3. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | PPE family |
| Orthologous group | COG5651 |
| Gene Ontology (2) |
GO:0008150, GO:0040007
|
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 | 0.214 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 6 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-62 | 6–168 | PPE family |
PPE-PPW | PF18878.6 | 8.9e-21 | 440–487 | PPE-PPW subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: eccC3 (ESX-3 secretion system protein EccC3), high confidence from genomic context alone (score 958 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0284 eccC3 |
ESX-3 secretion system protein EccC3 | 968 | 958 ctx | neighborhood:801 coexpression:799 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 962 | 947 ctx | neighborhood:801 coexpression:746 |
Rv0289 espG3 |
ESX-3 secretion-associated protein EspG3 | 954 | 936 ctx | neighborhood:564 coexpression:860 |
Rv0292 eccE3 |
ESX-3 secretion system protein EccE | 933 | 904 ctx | neighborhood:457 coexpression:831 |
Rv0291 mycP3 |
membrane-anchored mycosin MycP | 904 | 904 ctx | neighborhood:469 coexpression:827 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 936 | 898 ctx | neighborhood:469 coexpression:815 textmining:405 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA | 929 | 895 ctx | neighborhood:801 coexpression:494 |
Rv0285 PE5 |
PE family protein PE5 | 990 | 801 ctx | neighborhood:801 textmining:954 |
Rv0287 esxG |
ESAT-6 like protein EsxG | 932 | 755 ctx | neighborhood:644 textmining:736 |
Rv0288 esxH |
ESAT-6-like protein EsxH | 940 | 620 ctx | neighborhood:561 textmining:850 |
Rv0281 |
S-adenosylmethionine-dependent methyltransferase | 581 | 581 ctx | neighborhood:451 |
Rv0280 PPE3 |
PPE family protein PPE3 | 469 | 437 ctx | neighborhood:401 |
Rv1794 espG5 hyp |
hypothetical protein | 454 | 295 | |
Rv2431c PE25 |
PE family protein PE25 | 536 | 155 | textmining:474 |
Rv3020c esxS |
ESAT-6 like protein EsxS | 441 | 118 |
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 PPE4
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-62), PPE-PPW PF18878.6 (E=9e-21)
- (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_177711.1)
- 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 P9WI43 (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 —
17 functional partner(s); context anchor
eccC3 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0286|PPE4 MAAPIWMASPPEVHSALLSNGPGPGSLVAAATAWSQLSAEYASTAAELSGLLGAVPGWAWQGPSAEWYVAAHLPYVAWLTQASADAAGAAAQHEAAAAAYTTALAAMPTLAELAANHVIHTVLVATNFFGINTIPITLNEADYVRMWLQAAAVMGLYQAASGAALASAPRTVPAPTVMNPGGGAASTVGAVNPWQWLLALLQQLWNAYTGFYGWMLQLIWQFLQDPIGNSIKIIIAFLTNPIQALITYGPLLFALGYQIFFNLVGWPTWGMILSSPFLLPAGLGLGLAAIAFLPIVLAPAVIPPASTPLAAAAVAAGSVWPAVSMAVTGAGTAGAATPAAGAAPSAGAAPAPAAPATASFAYAVGGSGDWGPSLGPTVGGRGGIKAPAATVPAAAAAAATRGQSRARRRRRSELRDYGDEFLDMDSDSGFGPSTGDHGAQASERGAGTLGFAGTATKERRVRAVGLTALAGDEFGNGPRMPMVPGTWEQGSNEPEAPDGSGRGGGDGLPHDSK