esxO Resolved · high auto-curated
H37Rv Rv2346c · MTBC0 mtbc0_002498 ·
94 aa · 2650638–2650922 (-) ·
RefSeq NP_216862.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ESAT-6 like protein EsxO |
|---|---|
| MTBC0 PGAP re-annotation | type VII secretion system effector EsxO |
| Revised (this work) | Type VII secretion system effector EsxO. Pfam: WXG100 (PF06013.19). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNI7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ESAT-6-like protein EsxO |
| Curated function | Plays an important role in mycobacterial pathogenesis in the context of innate immunity. Aids host cell invasion and intracellular bacillary persistence. Increases host oxidative stress response, leading to genomic instability and decrease in macrophage viability. Also induces autophagy and modulates the immune function of macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | esxO |
| eggNOG description | Belongs to the WXG100 family |
| Orthologous group | 2BPBT |
| Gene Ontology (9) |
GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944
|
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 | 0.189 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 synonymous, 6 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 |
|---|---|---|---|---|
WXG100 | PF06013.19 | 2.8e-15 | 3–87 | Proteins of 100 residues with WXG |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxP (ESAT-6 like protein EsxP), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2347c esxP |
ESAT-6 like protein EsxP | 999 | 994 ctx | neighborhood:630 coexpression:860 experimental:900 textmining:929 |
Rv1197 esxK |
ESAT-6 like protein EsxK | 964 | 865 | coexpression:860 textmining:746 |
Rv1038c esxJ |
ESAT-6 like protein EsxJ | 954 | 865 | coexpression:860 textmining:679 |
Rv3620c esxW |
ESAT-6 like protein EsxW | 954 | 865 | coexpression:860 textmining:676 |
Rv1793 esxN |
ESAT-6 like protein EsxN | 912 | 860 | coexpression:860 textmining:400 |
Rv1198 esxL |
ESAT-6 like protein EsxL | 911 | 860 | coexpression:860 |
Rv3619c esxV |
ESAT-6 like protein EsxV | 861 | 860 | coexpression:860 |
Rv1037c esxI |
ESAT-6 like protein EsxI | 829 | 829 | coexpression:829 |
Rv3648c cspA |
cold shock protein A | 841 | 808 | coexpression:806 |
Rv3875 esxA |
ESAT-6 protein EsxA | 921 | 802 | coexpression:802 textmining:621 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 899 | 796 | coexpression:796 textmining:530 |
Rv1196 PPE18 |
PPE family protein PPE18 | 778 | 733 | coexpression:733 |
Rv1872c lldD2 |
L-lactate dehydrogenase | 766 | 733 | coexpression:733 |
Rv0685 tuf |
elongation factor Tu | 731 | 731 | coexpression:731 |
Rv1871c hyp |
hypothetical protein | 730 | 730 | coexpression:730 |
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
- Legacy H37Rv annotation: ESAT-6 like protein EsxO
- MTBC0 PGAP product: type VII secretion system effector EsxO
- Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=3e-15)
- (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 NP_216862.1)
- Domains: Pfam-A via hmmscan --cut_ga — WXG100 (PF06013.19)
- 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
2BPBT - Curated reference: UniProt P9WNI7 (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 —
25 functional partner(s); context anchor
esxP - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002498|Rv2346c|esxO MTINYQFGDVDAHGAMIRAQAGLLEAEHQAIVRDVLAAGDFWGGAGSVACQEFITQLGRNFQVIYEQANAHGQKVQAAGNNMAQTDSAVGSSWA