espA Resolved · high auto-curated
H37Rv Rv3616c · MTBC0 mtbc0_003833 ·
392 aa · 4078901–4080079 (-) ·
RefSeq NP_218133.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ESX-1 secretion-associated protein EspA |
|---|---|
| MTBC0 PGAP re-annotation | type VII secretion system ESX-1 target EspA |
| Revised (this work) | Type VII secretion system ESX-1 target EspA. Pfam: EspA_EspE (PF18879.7). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJE1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ESX-1 secretion-associated protein EspA |
| Curated function | Required for secretion of EsxA (ESAT-6) and EsxB (CFP-10) and for virulence. Involved in translocation of bacteria from the host (human) phagolysosome to the host cytoplasm. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Preferred name | espA |
|---|---|
| Orthologous group | 2AP1K |
| Gene Ontology (38) |
GO:0002790, GO:0005575, GO:0005576, GO:0005615, GO:0005623, GO:0005886, GO:0006810, GO:0008104, GO:0008150, GO:0009273, GO:0009306, GO:0009405 +26 more
|
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 | 0.56 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 8 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 |
|---|---|---|---|---|
EspA_EspE | PF18879.7 | 7.9e-27 | 21–103 | EspA/EspE family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: espC (ESX-1 secretion-associated protein EspC), high confidence from genomic context alone (score 945 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3615c espC |
ESX-1 secretion-associated protein EspC | 996 | 945 ctx | neighborhood:621 coexpression:860 textmining:946 |
Rv3614c espD |
ESX-1 secretion-associated protein EspD | 991 | 916 ctx | neighborhood:423 coexpression:860 textmining:902 |
Rv3613c hyp |
hypothetical protein | 843 | 810 | coexpression:735 |
Rv3612c hyp |
hypothetical protein | 868 | 630 | coexpression:514 textmining:658 |
Rv3874 esxB |
ESAT-6-like protein EsxB | 942 | 431 | textmining:902 |
Rv0198c zmp1 |
zinc metalloprotease | 411 | 411 | coexpression:400 |
Rv1084 hyp |
hypothetical protein | 401 | 400 | |
Rv3870 eccCa1 |
ESX-1 secretion system protein EccCa | 711 | 365 | textmining:564 |
Rv1795 eccD5 |
ESX-5 type VII secretion system protein EccD | 510 | 364 | |
Rv3871 eccCb1 |
ESX-1 secretion system protein EccCb | 754 | 336 | textmining:646 |
Rv1783 eccC5 |
ESX-5 type VII secretion system protein EccC5 | 414 | 289 | |
Rv2748c ftsK |
DNA translocase FtsK | 442 | 284 | |
Rv0284 eccC3 |
ESX-3 secretion system protein EccC3 | 403 | 284 | |
Rv3882c eccE1 |
ESX-1 secretion system protein EccE1 | 493 | 240 | |
Rv1797 eccE5 |
ESX-5 type VII secretion system protein EccE | 504 | 239 |
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: ESX-1 secretion-associated protein EspA
- MTBC0 PGAP product: type VII secretion system ESX-1 target EspA
- Pfam (hmmscan --cut_ga): EspA_EspE PF18879.7 (E=8e-27)
- (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_218133.1)
- Domains: Pfam-A via hmmscan --cut_ga — EspA_EspE (PF18879.7)
- 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
2AP1K - Curated reference: UniProt P9WJE1 (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 —
30 functional partner(s); context anchor
espC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003833|Rv3616c|espA MSRAFIIDPTISAIDGLYDLLGIGIPNQGGILYSSLEYFEKALEELAAAFPGDGWLGSAADKYAGKNRNHVNFFQELADLDRQLISLIHDQANAVQTTRDILEGAKKGLEFVRPVAVDLTYIPVVGHALSAAFQAPFCAGAMAVVGGALAYLVVKTLINATQLLKLLAKLAELVAAAIADIISDVADIIKGILGEVWEFITNALNGLKELWDKLTGWVTGLFSRGWSNLESFFAGVPGLTGATSGLSQVTGLFGAAGLSASSGLAHADSLASSASLPALAGIGGGSGFGGLPSLAQVHAASTRQALRPRADGPVGAAAEQVGGQSQLVSAQGSQGMGGPVGMGGMHPSSGASKGTTTKKYSEGAAAGTEDAERAPVEADAGGGQKVLVRNVV