PE_PGRS35 Family assigned · medium auto-curated
H37Rv Rv1983 · MTBC0 - ·
558 aa · 2226244–2227920 (+) ·
RefSeq YP_177854.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE-PGRS family protein PE_PGRS35 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE-PGRS family protein PE_PGRS35. Pfam: PE (PF00934.26), PGRS (PF21526.3), PE-PGRS_C (PF20729.3). |
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 |
P9WIF1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PE cleavage protein A |
| Curated function | Aspartic protease that processes the lipase LipY and other PE_PGRS proteins. Can also cleave itself. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolism
|
|---|---|
| eggNOG description | acetylesterase activity |
| Orthologous group | COG0657 |
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 | 1.136 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 | 5.7e-34 | 4–93 | PE family |
PGRS | PF21526.3 | 1.6e-16 | 122–191 | PGRS repeats |
PE-PGRS_C | PF20729.3 | 4.2e-103 | 269–552 | PE-PGRS C-terminal aspartyl peptidase-like domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: vapC36 (ribonuclease VapC36), medium confidence from genomic context alone (score 535 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1982c vapC36 |
ribonuclease VapC36 | 637 | 535 ctx | neighborhood:535 |
Rv1982A vapB36 |
antitoxin VapB36 | 535 | 535 ctx | neighborhood:535 |
Rv1981c nrdF1 |
ribonucleoside-diphosphate reductase subunit beta NrdF1 | 493 | 318 | |
Rv1979c |
permease | 419 | 180 | |
Rv1988 erm(37) |
23S rRNA (adenine(2058)-N(6))-methyltransferase Erm(37) | 438 | 50 | textmining:433 |
Rv1987 |
chitinase | 510 | 41 | textmining:510 |
Rv1978 hyp |
hypothetical protein | 439 | 41 | textmining:439 |
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_PGRS35
- Pfam (hmmscan --cut_ga): PE PF00934.26 (E=6e-34), PGRS PF21526.3 (E=2e-16), PE-PGRS_C PF20729.3 (E=4e-103)
- (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_177854.1)
- Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3), PE-PGRS_C (PF20729.3)
- 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
COG0657 - Curated reference: UniProt P9WIF1 (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 —
7 functional partner(s); context anchor
vapC36 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1983|PE_PGRS35 MSFLVVVPEFLTSAAADVENIGSTLRAANAAAAASTTALAAAGADEVSAAVAALFARFGQEYQAVSAQASAFHQQFVQTLNSASGSYAAAEATIASQLQTAQHDLLGAVNAPTETLLGRPLIGDGAPGTATSPNGGAGGLLYGNGGNGYSATASGVGGGAGGSAGLIGNGGAGGAGGPNAPGGAGGNGGWLLGNGGIGGPGGASSIPGMSGGAGGTGGAAGLLGWGANGGAGGLGDGVGVDRGTGGAGGRGGLLYGGYGVSGPGGDGRTVPLEIIHVTEPTVHANVNGGPTSTILVDTGSAGLVVSPEDVGGILGVLHMGLPTGLSISGYSGGLYYIFATYTTTVDFGNGIVTAPTAVNVVLLSIPTSPFAISTYFSALLADPTTTPFEAYFGAVGVDGVLGVGPNAVGPGPSIPTMALPGDLNQGVLIDAPAGELVFGPNPLPAPNVEVVGSPITTLYVKIDGGTPIPVPSIIDSGGVTGTIPSYVIGSGTLPANTNIEVYTSPGGDRLYAFNTNDYRPTVISSGLMNTGFLPFRFQPVYIDYSPSGIGTTVFDHPA