PPE42 Family assigned · medium auto-curated
H37Rv Rv2608 · MTBC0 - ·
580 aa · 2935046–2936788 (+) ·
RefSeq YP_177893.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PPE family protein PPE42 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PPE family protein PPE42. Pfam: PPE (PF00823.26), PE-PPE (PF08237.18). |
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 |
P9WHZ5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized PPE family protein PPE42 |
| Curated function | Elicits a high humoral and a low T-cell response. Could be involved in directing the host toward development of a more humoral type of immune response. |
UniProt still lists this protein as Uncharacterized PPE family protein PPE42; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
N Cell motility
|
|---|---|
| eggNOG description | PFAM PE-PPE, C-terminal |
| Orthologous group | COG5651 |
| Gene Ontology (33) |
GO:0002682, GO:0002684, GO:0008150, GO:0009605, GO:0009607, GO:0035821, GO:0043207, GO:0044003, GO:0044403, GO:0044419, GO:0048518, GO:0048583 +21 more
|
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 | 0.498 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 6 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.10% of strains (148) · 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 | 1.3e-62 | 2–165 | PPE family |
PE-PPE | PF08237.18 | 1.5e-84 | 300–525 | PE-PPE domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2209 (integral membrane protein), high confidence from genomic context alone (score 773 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2209 |
integral membrane protein | 772 | 773 ctx | cooccurence:770 |
Rv1004c |
membrane protein | 771 | 772 ctx | cooccurence:769 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 802 | 771 ctx | cooccurence:771 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 779 | 771 ctx | cooccurence:771 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 778 | 770 ctx | cooccurence:770 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 777 | 769 ctx | cooccurence:769 |
Rv2942 mmpL7 |
transmembrane transport protein MmpL7 | 769 | 769 ctx | cooccurence:768 |
Rv3879c espK |
ESX-1 secretion-associated protein EspK | 768 | 768 ctx | cooccurence:768 |
Rv2082 hyp |
hypothetical protein | 766 | 767 ctx | cooccurence:764 |
Rv0341 iniB |
isoniazid inducible protein IniB | 760 | 760 ctx | cooccurence:760 |
Rv2853 PE_PGRS48 |
PE-PGRS family protein PE_PGRS48 | 765 | 757 ctx | cooccurence:757 |
Rv2954c hyp |
hypothetical protein | 755 | 756 ctx | cooccurence:754 |
Rv0977 PE_PGRS16 |
PE-PGRS family protein PE_PGRS16 | 779 | 753 ctx | cooccurence:753 |
Rv3864 espE |
ESX-1 secretion-associated protein EspE | 814 | 752 ctx | cooccurence:751 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 750 | 751 ctx | cooccurence:749 |
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 PPE42
- Pfam (hmmscan --cut_ga): PPE PF00823.26 (E=1e-62), PE-PPE PF08237.18 (E=2e-84)
- (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_177893.1)
- Domains: Pfam-A via hmmscan --cut_ga — PPE (PF00823.26), PE-PPE (PF08237.18)
- 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 P9WHZ5 (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 —
123 functional partner(s); context anchor
Rv2209 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2608|PPE42 MNFAVLPPEVNSARIFAGAGLGPMLAAASAWDGLAEELHAAAGSFASVTTGLAGDAWHGPASLAMTRAASPYVGWLNTAAGQAAQAAGQARLAASAFEATLAATVSPAMVAANRTRLASLVAANLLGQNAPAIAAAEAEYEQIWAQDVAAMFGYHSAASAVATQLAPIQEGLQQQLQNVLAQLASGNLGSGNVGVGNIGNDNIGNANIGFGNRGDANIGIGNIGDRNLGIGNTGNWNIGIGITGNGQIGFGKPANPDVLVVGNGGPGVTALVMGGTDSLLPLPNIPLLEYAARFITPVHPGYTATFLETPSQFFPFTGLNSLTYDVSVAQGVTNLHTAIMAQLAAGNEVVVFGTSQSATIATFEMRYLQSLPAHLRPGLDELSFTLTGNPNRPDGGILTRFGFSIPQLGFTLSGATPADAYPTVDYAFQYDGVNDFPKYPLNVFATANAIAGILFLHSGLIALPPDLASGVVQPVSSPDVLTTYILLPSQDLPLLVPLRAIPLLGNPLADLIQPDLRVLVELGYDRTAHQDVPSPFGLFPDVDWAEVAADLQQGAVQGVNDALSGLGLPPPWQPALPRLF