PE35 Family assigned · medium auto-curated
H37Rv Rv3872 · MTBC0 - ·
99 aa · 4350745–4351044 (+) ·
RefSeq YP_178021.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | PE family protein PE35 |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | PE family protein PE35. 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 |
P9WIG7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | PE family immunomodulator PE35 |
| Curated function | Plays a major role in RD1-associated pathogenesis, and may contribute to the establishment and maintenance of M.tuberculosis infection. Together with PPE68, stimulates the secretion of IL-10 and MCP-1 from human macrophages, via the interaction with human Toll-like receptor 2 (TLR2). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PE family |
| Orthologous group | 2AXVZ |
| Gene Ontology (2) |
GO:0005575, GO:0005576
|
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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 97.72% of strains (141903) · reference-fixed |
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 | 2.0e-11 | 25–90 | PE family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: PPE68 (PPE family protein PPE68), high confidence from genomic context alone (score 834 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3873 PPE68 |
PPE family protein PPE68 | 988 | 834 ctx | neighborhood:681 experimental:500 textmining:933 |
Rv3871 eccCb1 |
ESX-1 secretion system protein EccCb | 906 | 546 ctx | neighborhood:546 textmining:803 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 907 | 475 ctx | neighborhood:475 textmining:831 |
Rv3870 eccCa1 |
ESX-1 secretion system protein EccCa | 656 | 420 ctx | neighborhood:420 textmining:431 |
Rv3869 eccB1 |
ESX-1 secretion system protein EccB | 570 | 420 ctx | neighborhood:420 |
Rv3868 eccA1 |
ESX-1 secretion system protein EccA1 | 506 | 420 ctx | neighborhood:420 |
Rv3875 esxA |
ESAT-6 protein EsxA | 859 | 415 ctx | neighborhood:415 textmining:770 |
Rv3867 espH |
ESX-1 secretion-associated protein EspH | 452 | 357 | |
Rv3866 espG1 |
ESX-1 secretion-associated protein EspG | 534 | 325 | |
Rv3877 eccD1 |
ESX-1 secretion system protein EccD1 | 746 | 298 | textmining:653 |
Rv3876 espI |
ESX-1 secretion-associated protein EspI | 726 | 298 | textmining:626 |
Rv3864 espE |
ESX-1 secretion-associated protein EspE | 530 | 255 | |
Rv3878 espJ |
ESX-1 secretion-associated protein EspJ | 745 | 223 | textmining:685 |
Rv0285 PE5 |
PE family protein PE5 | 664 | 41 | textmining:665 |
Rv3879c espK |
ESX-1 secretion-associated protein EspK | 655 | 41 | textmining:655 |
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 PE35
- Pfam (hmmscan --cut_ga): PE PF00934.26 (E=2e-11)
- (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_178021.1)
- 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
2AXVZ - Curated reference: UniProt P9WIG7 (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 —
24 functional partner(s); context anchor
PPE68 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3872|PE35 MEKMSHDPIAADIGTQVSDNALHGVTAGSTALTSVTGLVPAGADEVSAQAATAFTSEGIQLLASNASAQDQLHRAGEAVQDVARTYSQIDDGAAGVFAE