PE6 Family assigned · medium auto-curated
H37Rv Rv0335c · MTBC0 - ·
171 aa · 399535–400050 (-) ·
RefSeq YP_177717.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE family protein PE6 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE family protein PE6. Pfam: PE (PF00934.26). |
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 |
L7N648
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PE family protein PE6 |
| Curated function | Essential virulence factor involved in regulating host-pathogen interactions by regulating multiple host cell functions. Interacts with host TLR4 receptor at the macrophage cell surface and promotes activation of the canonical NF-kappa-B signaling pathway to stimulate secretion of the proinflammatory cytokines TNF, IL-12 and IL-6. Strongly induces apoptosis by inducing pro-apoptotic factors and efficiently activating the reticulum endoplasmic stress-mediated UPR pathway. Probably induces apoptosis of macrophages late in the infection cycle after excessive mycobacterial burden to aid in the apo. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversionO Post-translational modification, protein turnover, chaperones
|
|---|---|
| eggNOG description | amine dehydrogenase activity |
| Orthologous group | COG3391 |
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 | 0.757 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 2 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 17.44% of strains (25319) · 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 |
|---|---|---|---|---|
PE | PF00934.26 | 1.8e-16 | 70–126 | PE family |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0336 hyp |
hypothetical protein | 527 | 527 ctx | neighborhood:527 |
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): PE family protein PE6
- Pfam (hmmscan --cut_ga): PE PF00934.26 (E=2e-16)
- (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_177717.1)
- Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26)
- 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
COG3391 - Curated reference: UniProt L7N648 (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 — 1 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0335c|PE6 MRSMGFLHRACRAPSSLPAPLMARPGRSVLARPAATPPGPLCATTRPRPPQGNQPPASRISNFPPKRHKTRVLAAAEDEVSAAVAALISAHGRRHHSLNNQAAAFHGQFAQNLNVGAGSCASAETTADAPTQALLGPADRQRRQRRAVRQWLVRWAAHPGRATRGFHNHRQ