esxH Resolved · high auto-curated
H37Rv Rv0288 · MTBC0 mtbc0_000307 ·
96 aa · 355142–355432 (+) ·
RefSeq NP_214802.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ESAT-6-like protein EsxH |
|---|---|
| MTBC0 PGAP re-annotation | type VII secretion system effector EsxH |
| Revised (this work) | Type VII secretion system effector EsxH. 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 |
P9WNK3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ESAT-6-like protein EsxH |
| Curated function | EsxH, in complex with EsxG, disrupts ESCRT function and impairs host phagosome maturation, thereby promoting intracellular bacterial growth. The complex acts by interacting, via EsxH, with the host hepatocyte growth factor-regulated tyrosine kinase substrate (HGS/HRS), a component of the ESCRT machinery. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | esxH |
| eggNOG description | Belongs to the WXG100 family |
| Orthologous group | COG4842 |
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, 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 | 3.2e-18 | 3–87 | Proteins of 100 residues with WXG |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxG (ESAT-6 like protein EsxG), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0287 esxG |
ESAT-6 like protein EsxG | 999 | 1000 ctx | neighborhood:727 coexpression:860 experimental:993 textmining:993 |
Rv0289 espG3 |
ESX-3 secretion-associated protein EspG3 | 980 | 963 ctx | neighborhood:859 coexpression:751 textmining:484 |
Rv3020c esxS |
ESAT-6 like protein EsxS | 939 | 834 | experimental:822 textmining:650 |
Rv0290 eccD3 |
ESX-3 secretion system protein EccD | 874 | 789 ctx | neighborhood:658 coexpression:409 textmining:429 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 976 | 734 | coexpression:734 textmining:915 |
Rv0284 eccC3 |
ESX-3 secretion system protein EccC3 | 803 | 729 ctx | neighborhood:588 |
Rv0291 mycP3 |
membrane-anchored mycosin MycP | 737 | 721 ctx | neighborhood:658 |
Rv0292 eccE3 |
ESX-3 secretion system protein EccE | 835 | 711 ctx | neighborhood:658 textmining:451 |
Rv1038c esxJ |
ESAT-6 like protein EsxJ | 836 | 703 | coexpression:703 textmining:473 |
Rv0286 PPE4 |
PPE family protein PPE4 | 940 | 620 ctx | neighborhood:561 textmining:850 |
Rv0283 eccB3 |
ESX-3 secretion system protein EccB3 | 700 | 614 ctx | neighborhood:588 |
Rv0282 eccA3 |
ESX-3 secretion system protein EccA | 723 | 605 ctx | neighborhood:588 |
Rv0285 PE5 |
PE family protein PE5 | 854 | 578 ctx | neighborhood:578 textmining:669 |
Rv3875 esxA |
ESAT-6 protein EsxA | 944 | 392 | textmining:912 |
Rv0281 |
S-adenosylmethionine-dependent methyltransferase | 587 | 372 |
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 EsxH
- MTBC0 PGAP product: type VII secretion system effector EsxH
- Pfam (hmmscan --cut_ga): WXG100 PF06013.19 (E=3e-18)
- (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_214802.1)
- 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
COG4842 - Curated reference: UniProt P9WNK3 (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 —
50 functional partner(s); context anchor
esxG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000307|Rv0288|esxH MSQIMYNYPAMLGHAGDMAGYAGTLQSLGAEIAVEQAALQSAWQGDTGITYQAWQAQWNQAMEDLVRAYHAMSSTHEANTMAMMARDTAEAAKWGG