PE_PGRS18 Family assigned · medium auto-curated
H37Rv Rv0980c · MTBC0 - ·
457 aa · 1095078–1096451 (-) ·
RefSeq YP_177775.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE-PGRS family protein PE_PGRS18 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE-PGRS family protein PE_PGRS18. Pfam: PE (PF00934.26), PGRS (PF21526.3), NHL (PF01436.28). |
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 |
Q79FU0
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | PE-PGRS family protein PE_PGRS18 |
| Curated function | Enhances mycobacterial intracellular survival, probably via altering host macrophage cytokine profiling and attenuating the cell apoptosis. Could be required for host endothelial-cell invasion..; FUNCTION: Expression in Mycobacterium smegmatis, a nonpathogenic species naturally deficient in PE_PGRS genes, results in alteration of the production of host cytokines, including IL-6, IL-1beta, IL-10 and IL-12p40, as well as enhanced survival within macrophages largely via attenuating the apoptosis of macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Large extracellular alpha-helical protein |
| 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 | 0.381 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 11 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.44% of strains (635) · 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 | 6.2e-28 | 4–92 | PE family |
PGRS | PF21526.3 | 1.7e-11 | 117–192 | PGRS repeats |
NHL | PF01436.28 | 2.5e-06 | 291–317 | NHL repeat |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0318c (integral membrane protein), medium confidence from genomic context alone (score 461 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1057 hyp |
hypothetical protein | 743 | 743 ctx | cooccurence:743 |
Rv2383c mbtB |
phenyloxazoline synthase | 668 | 668 | coexpression:657 |
Rv2194 qcrC |
ubiquinol-cytochrome C reductase cytochrome subunit C | 670 | 650 | experimental:622 |
Rv1157c hyp |
hypothetical protein | 561 | 562 | coexpression:417 |
Rv0318c |
integral membrane protein | 461 | 461 ctx | cooccurence:460 |
Rv1753c PPE24 |
PPE family protein PPE24 | 572 | 442 ctx | cooccurence:442 |
Rv3403c hyp |
hypothetical protein | 428 | 429 ctx | cooccurence:411 |
Rv3350c PPE56 |
PPE family protein PPE56 | 428 | 428 ctx | cooccurence:428 |
Rv3800c pks13 |
polyketide synthase | 426 | 426 | coexpression:400 |
Rv2384 mbtA |
2,3-dihydroxybenzoate-AMP ligase | 420 | 420 | coexpression:409 |
Rv2082 hyp |
hypothetical protein | 416 | 416 | |
Rv3347c PPE55 |
PPE family protein PPE55 | 414 | 414 ctx | cooccurence:414 |
Rv2737A |
Rv2737A, len: 57 aa. Conserved hypothetical cys-rich protein (possibly gene fragment), similar to central part of AJ243803_1|glgA from Strep | 414 | 414 | coexpression:414 |
Rv0355c PPE8 |
PPE family protein PPE8 | 414 | 414 ctx | cooccurence:414 |
Rv2209 |
integral membrane protein | 412 | 412 ctx | cooccurence:412 |
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_PGRS18
- Pfam (hmmscan --cut_ga): PE PF00934.26 (E=6e-28), PGRS PF21526.3 (E=2e-11), NHL PF01436.28 (E=3e-06)
- (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_177775.1)
- Domains: Pfam-A via hmmscan --cut_ga — PE (PF00934.26), PGRS (PF21526.3), NHL (PF01436.28)
- 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 Q79FU0 (SwissProt, reviewed; Evidence at transcript 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 —
29 functional partner(s); context anchor
Rv0318c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0980c|PE_PGRS18 MSFVNVAPQLVSTAAADAARIGSAINTANTAAAATTQVLAAAHDEVSTAIAALFGSHGQHYQAISAQVAAYQERFVLALSQASSTYAVAEAASATPLQNVLDAINAPVQSLTGRPLIGDGANGIDGTGQAGGNGGWLWGNGGNGGSGAPGQAGGAGGAAGLIGNGGAGGAGGQGLPFEAGANGGAGGAGGWLFGNGGAGGVGGAGGAGTTFGVAGGDGGTGGVGGHGGLIGVGGHGGDGGTGGTGGAVSLARAGTAGGAGGGPAGGIGGAGGVGGAGGAAGAVTTITHASFNDPHGVAVNPGGNIYVTNQGSNTVSVIDPVTNTVTGSITDGNGPSGVAVSPVTGLVFVTNFDSNTVSVIDPNTNTVTGSIPVGTGAYGVAVNPGGNIYVTNQFSNTVSVIDPATNTVTGSPIPVGLDPTGVAVNPVTGVVYVTNSLDDTVSVITGEPARSVCSAAI