UniProtKB - P9WJE1 (ESPA_MYCTU)
Protein
ESX-1 secretion-associated protein EspA
Gene
espA
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Functioni
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 (PubMed:17604718).3 Publications
Miscellaneous
Maintenance of wild-type levels of EspA requires both EspC and EspD.1 Publication
Has been postulated to mediate virulence through maintenance of mycobacterial cell surface integrity (PubMed:20585630), but studies of detergent sensitivity of various strains and mutants indicate that EspACD and ESX-1 deficiency does not impact the cell surface integrity (PubMed:24078612).2 Publications
GO - Biological processi
- Actinobacterium-type cell wall biogenesis Source: MTBBASE
- pathogenesis Source: MTBBASE
- protein secretion by the type VII secretion system Source: MTBBASE
Keywordsi
Biological process | Virulence |
Enzyme and pathway databases
BioCyci | MTBH37RV:G185E-7895-MONOMER |
Names & Taxonomyi
Protein namesi | Recommended name: ESX-1 secretion-associated protein EspACurated |
Gene namesi | Name:espA1 Publication Ordered Locus Names:Rv3616c |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv3616c |
Subcellular locationi
GO - Cellular componenti
- extracellular region Source: MTBBASE
- extracellular space Source: MTBBASE
- plasma membrane Source: MTBBASE
Keywords - Cellular componenti
SecretedPathology & Biotechi
Disruption phenotypei
Deletion mutants fail to secrete EsxA and EsxB, and are as attenuated as ESX-1 mutants in virulence assays (PubMed:16030141). Bacteria no longer translocate from the phagolysosome to the cytosol of host (human) cells; bacteria replicate in phagolysosome (PubMed:17604718). Host (human) cells no longer produce cytokine IP-10 (CXCL10) upon infection, but continue to produce IL-1 beta (IL1B) (PubMed:26048138).3 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 5 | F → R: Severely destabilizes EspA and blocks ESX-1 secretion in vitro, but does not impact the cytotoxicity in cellular models of infection. Can induce proinflammatory responses in THP-1 cells and is as virulent as wild-type during the acute phase of infection in mice. 1 Publication | 1 | |
Mutagenesisi | 41 | K → A: Severely destabilizes EspA and blocks ESX-1 secretion in vitro, but does not impact the cytotoxicity in cellular models of infection. Can induce proinflammatory responses in THP-1 cells and is as virulent as wild-type during the acute phase of infection in mice. 1 Publication | 1 | |
Mutagenesisi | 50 | F → R: Severely destabilizes EspA and blocks ESX-1 secretion in vitro. Attenuated in cellular models of tuberculosis infection. 1 Publication | 1 | |
Mutagenesisi | 55 | W → R: Impairs EsxA and EsxB secretion in vitro. Modest impact on EspD stability and secretion. Attenuated in cellular models of tuberculosis infection. 1 Publication | 1 | |
Mutagenesisi | 57 | G → R: Impairs EsxA and EsxB secretion in vitro. Modest impact on EspD stability and secretion. Attenuated in cellular models of tuberculosis infection. 1 Publication | 1 | |
Mutagenesisi | 62 | K → A: Severely destabilizes EspA and blocks ESX-1 secretion in vitro. Attenuated in cellular models of tuberculosis infection. 1 Publication | 1 | |
Mutagenesisi | 138 | C → A: Does not affect secretion, but inhibits disulfide bond formation. Alters mycobacterial cell wall integrity and significantly attenuates virulence. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000393903 | 1 – 392 | ESX-1 secretion-associated protein EspAAdd BLAST | 392 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 138 | Interchain1 Publication |
Keywords - PTMi
Disulfide bondProteomic databases
PaxDbi | P9WJE1 |
Expressioni
Inductioni
Transcriptionally activated by EspR (PubMed:18685700, PubMed:22389481, PubMed:25536998). Repressed by the MprB/MprA two-component system, by direct regulation and via EspR (PubMed:23104803, PubMed:25536998). Up-regulated by the PhoP/PhoR two-component system, via EspR (PubMed:16573683, PubMed:25536998).5 Publications
Interactioni
Subunit structurei
Protein-protein interaction databases
IntActi | P9WJE1, 1 interactor |
STRINGi | 83332.Rv3616c |
i Sequence
Sequence statusi: Complete.
P9WJE1-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSRAFIIDPT ISAIDGLYDL LGIGIPNQGG ILYSSLEYFE KALEELAAAF
60 70 80 90 100
PGDGWLGSAA DKYAGKNRNH VNFFQELADL DRQLISLIHD QANAVQTTRD
110 120 130 140 150
ILEGAKKGLE FVRPVAVDLT YIPVVGHALS AAFQAPFCAG AMAVVGGALA
160 170 180 190 200
YLVVKTLINA TQLLKLLAKL AELVAAAIAD IISDVADIIK GTLGEVWEFI
210 220 230 240 250
TNALNGLKEL WDKLTGWVTG LFSRGWSNLE SFFAGVPGLT GATSGLSQVT
260 270 280 290 300
GLFGAAGLSA SSGLAHADSL ASSASLPALA GIGGGSGFGG LPSLAQVHAA
310 320 330 340 350
STRQALRPRA DGPVGAAAEQ VGGQSQLVSA QGSQGMGGPV GMGGMHPSSG
360 370 380 390
ASKGTTTKKY SEGAAAGTED AERAPVEADA GGGQKVLVRN VV
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46439.1 |
PIRi | A70957 |
RefSeqi | NP_218133.1, NC_000962.3 WP_003912265.1, NZ_NVQJ01000056.1 |
Genome annotation databases
EnsemblBacteriai | CCP46439; CCP46439; Rv3616c |
GeneIDi | 885377 |
KEGGi | mtu:Rv3616c mtv:RVBD_3616c |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AL123456 Genomic DNA Translation: CCP46439.1 |
PIRi | A70957 |
RefSeqi | NP_218133.1, NC_000962.3 WP_003912265.1, NZ_NVQJ01000056.1 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
IntActi | P9WJE1, 1 interactor |
STRINGi | 83332.Rv3616c |
Proteomic databases
PaxDbi | P9WJE1 |
Genome annotation databases
EnsemblBacteriai | CCP46439; CCP46439; Rv3616c |
GeneIDi | 885377 |
KEGGi | mtu:Rv3616c mtv:RVBD_3616c |
Organism-specific databases
TubercuListi | Rv3616c |
Phylogenomic databases
OMAi | LEEVWEF |
Enzyme and pathway databases
BioCyci | MTBH37RV:G185E-7895-MONOMER |
Family and domain databases
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ESPA_MYCTU | |
Accessioni | P9WJE1Primary (citable) accession number: P9WJE1 Secondary accession number(s): L0TDB5, O06267, Q7D572 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | September 18, 2019 | |
This is version 24 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names