PE_PGRS5 Family assigned · medium auto-curated
H37Rv Rv0297 · MTBC0 - ·
591 aa · 361334–363109 (+) ·
RefSeq YP_177713.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE-PGRS family protein PE_PGRS5 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE-PGRS family protein PE_PGRS5. Pfam: PE (PF00934.26), PGRS (PF21526.3). |
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 |
Q6MX50
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PE-PGRS family protein PE_PGRS5 |
| Curated function | Involved in endoplasmic reticulum (ER) stress-mediated apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Localizes to the host ER, leading to ER stress, disruption of intracellular Ca(2+) homeostasis and increase of nitric oxide (NO) and reactive oxygen species (ROS) levels. Stress response results in caspase-8 activation and apoptosis of macrophage cells. Apoptosis may lead to dissemination of the bacteria, thereby spreading the disease. |
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)
| pN/pS | 0.891 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 9 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 |
|---|---|---|---|---|
PE | PF00934.26 | 3.1e-31 | 4–94 | PE family |
PGRS | PF21526.3 | 2.7e-13 | 116–184 | PGRS repeats |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0296c (sulfatase), medium confidence from genomic context alone (score 524 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3354 hyp |
hypothetical protein | 693 | 674 | experimental:470 |
Rv3103c hyp |
hypothetical protein | 618 | 594 | experimental:512 |
Rv2564 glnQ |
glutamine ABC transporter ATP-binding protein | 614 | 578 | |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 614 | 578 | |
Rv0986 |
adhesion component ABC transporter ATP-binding protein | 598 | 578 | |
Rv0296c |
sulfatase | 524 | 524 ctx | neighborhood:524 |
Rv0295c stf0 hyp |
hypothetical protein | 524 | 524 ctx | neighborhood:524 |
Rv0298 |
antitoxin | 499 | 498 ctx | neighborhood:498 |
Rv0299 |
toxin | 499 | 498 ctx | neighborhood:498 |
Rv0301 vapC2 |
ribonuclease VapC2 | 417 | 417 ctx | neighborhood:417 |
Rv0300 vapB2 |
antitoxin VapB2 | 417 | 417 ctx | neighborhood:417 |
Rv0354c PPE7 |
PPE family protein PPE7 | 527 | 41 | textmining:528 |
Rv3621c PPE65 |
PPE family protein PPE65 | 453 | 41 | textmining:453 |
Rv1089 PE10 |
PE family protein PE10; Together with PE9, induces macrophage apoptosis through human Toll-like receptor 4 (TLR4) signaling pathway. Interac | 435 | 41 | textmining:435 |
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-PGRS family protein PE_PGRS5
- Pfam (hmmscan --cut_ga): PE PF00934.26 (E=3e-31), PGRS PF21526.3 (E=3e-13)
- (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_177713.1)
- Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3)
- 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 Q6MX50 (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 —
14 functional partner(s); context anchor
Rv0296c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0297|PE_PGRS5 MSFVIAQPEMIAAAAGELASIRSAINAANAAAAAQTTGVMSAAADEVSTAVAALFSSHAQAYQAASAQAAAFHAQVVRTLTVDAGAYASAEAANAGPNMLAAVNAPAQALLGRPLIGNGANGAPGTGQAGGDGGLLFGNGGNGGSGAPGQAGGAGGAAGFFGNGGNGGDGGAGANGGAGGTAGWFFGFGGNGGAGGIGVAGINGGLGGAGGDGGNAGFFGNGGNGGMGGAGAAGVNAVNPGLATPVTPAANGGNGLNLVGVPGTAGGGADGANGSAIGQAGGAGGDGGNASTSGGIGIAQTGGAGGAGGAGGDGAPGGNGGNGGSVEHTGATGSSASGGNGATGGNGGVGAPGGAGGNGGHVSGGSVNTAGAGGKGGNGGTGGAGGPGGHGGSVLSGPVGDSGNGGAGGDGGAGVSATDIAGTGGRGGNGGHGGLWIGNGGDGGAGGVGGVGGAGAAGAIGGHGGDGGSVNTPIGGSEAGDGGKGGLGGDGGGRGIFGQFGAGGAGGAGGVGGAGGAGGTGGGGGNGGAIFNAGTPGAAGTGGDGGVGGTGAAGGKGGAGGSGGVNGATGADGAKGLDGATGGKGNNGNPG