PPE46 Family assigned · medium auto-curated
H37Rv Rv3018c · MTBC0 - ·
434 aa · 3376939–3378243 (-) ·
RefSeq YP_177918.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE46 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE46. 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 |
P9WHY9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized PPE family protein PPE46 |
UniProt still lists this protein as Uncharacterized PPE family protein PPE46; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | Ribulose-phosphate 3-epimerase |
| Orthologous group | COG5651 |
| Gene Ontology (9) |
GO:0008150, GO:0040007, GO:0044110, GO:0044116, GO:0044117, GO:0044119, GO:0044403, GO:0044419, GO:0051704
|
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) pseudogene candidate
| pN/pS | 0.225 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 5 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 1.86% of strains (2699) · 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 | 1.2e-59 | 6–168 | PPE family |
PPE-PPW | PF18878.6 | 2.0e-17 | 373–418 | PPE-PPW subfamily C-terminal region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxQ (ESAT-6 like protein EsxQ), medium confidence from genomic context alone (score 562 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3017c esxQ |
ESAT-6 like protein EsxQ | 638 | 562 ctx | neighborhood:556 |
Rv3018A PE27A |
Rv3018A, len: 28 aa. PE27A, Member of Mycobacterium tuberculosis PE family (see Brennan and Delogu, 2002), most similar to Rv0285 (102 aa), | 771 | 548 ctx | neighborhood:548 textmining:515 |
Rv3020c esxS |
ESAT-6 like protein EsxS | 611 | 531 | |
Rv3019c esxR |
ESAT-6 like protein EsxR | 635 | 453 | |
Rv3022A PE29 |
PE family protein PE29 | 513 | 161 | textmining:444 |
Rv2738c hyp |
hypothetical protein | 521 | 45 | textmining:519 |
Rv0403c mmpS1 |
membrane protein MmpS1 | 512 | 44 | textmining:511 |
Rv1682 hyp |
hypothetical protein | 440 | 43 | textmining:439 |
Rv1840c PE_PGRS34 |
PE-PGRS family protein PE_PGRS34 | 514 | 41 | textmining:514 |
Rv3732 hyp |
hypothetical protein | 439 | 41 | textmining:439 |
Rv1754c hyp |
hypothetical protein | 433 | 41 | textmining:433 |
Rv1818c PE_PGRS33 |
PE-PGRS family protein PE_PGRS33 | 432 | 41 | textmining:432 |
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 PPE46
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-59), PPE-PPW PF18878.6 (E=2e-17)
- (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_177918.1)
- 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 P9WHY9 (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 —
12 functional partner(s); context anchor
esxQ - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3018c|PPE46 MTAPVWLASPPEVHSALLSAGPGPGSLQAAAAGWSALSAEYAAVAQELSVVVAAVGAGVWQGPSAELFVAAYVPYVAWLVQASADSAAAAGEHEAAAAGYVCALAEMPTLPELAANHLTHAVLVATNFFGINTIPIALNEADYVRMWVQAATVMSAYEAVVGAALVATPHTGPAPVIVKPGANEASNAVAAATITPFPWHEIVQFLEETFAAYDQYLSALLSELPAVAWVWFQLFVDILGFNIIGFIITLASNAQLLTEFAINASYVAVGLLYAIAGVIDIVVEWVIGNLFGVVPLLGGPLLGALAAAVVPGVAGLAGVAGLAALPAVGAAAGAPAALVGSVAPVSGGVVSPQARLVSAVEPAPASTSVSVLASDRGAGALGFVGTAGKESVGQPAGLTVLADEFGDGAPVPMLPGSWGPDLVGVAGDGGLVSV