Product Details

Purity

>85% (SDS-PAGE)

Target Names

esxA

Uniprot No.

P9WNK7

Research Area

Others

Alternative Names

esxA; esaT6; Rv3875; MTV027.106 kDa early secretory antigenic target; ESAT-6

Species

Mycobacterium tuberculosis

Expression Region

2-95aa

Target Protein Sequence

TEQQWNFAGIEAAASAIQGNVTSIHSLLDEGKQSLTKLAAAWGGSGSEAYQGVQQKWDAT ATELNNALQNLARTISEAGQAMASTEGNVTGMFA

Protein Length

Partial

Tag Info

Tag type will be determined during the manufacturing process.

The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.

Form

Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer before Lyophilization

Tris/PBS-based buffer, 6% Trehalose, pH 8.0

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet

Please contact us to get it.

Target Background

Function

A secreted protein that plays a number of roles in modulating the host's immune response to infection as well as being responsible for bacterial escape into the host cytoplasm. Acts as a strong host (human) T-cell antigen. Inhibits IL-12 p40 (IL12B) and TNF-alpha expression by infected host (mouse) macrophages, reduces the nitric oxide response by about 75%. In mice previously exposed to the bacterium, elicits high level of IFN-gamma production by T-cells upon subsequent challenge by M.tuberculosis, in the first phase of a protective immune response. Higher levels (1.6-3.3 uM) of recombinant protein inhibit IFN-gamma production by host (human) T-cells and also IL-17 and TNF-alpha production but not IL-2; decreases expression of host ATF-2 and JUN transcription factors by affecting T-cell receptors signaling downstream of ZAP70, without cytotoxicity or apoptosis. EsxA inhibits IFN-gamma production in human T-cells by activating p38 MAPK (MAPK14), p38 MAPK is not responsible for IL-17 decrease. Binds host (mouse) Toll-like receptor 2 (TLR2) and decreases host MYD88-dependent signaling; binding to TLR2 activates host kinase AKT and subsequently inhibits downstream activation of NF-kappa-B; the C-terminal 20 residues (76-95) are necessary and sufficient for the TLR2 inhibitory effect. Required for induction of host (human) IL-1B maturation and release by activating the host NLRP3/ASC inflammasome; may also promote access of other tuberculosis proteins to the host cells cytoplasm. Induces IL-8 (CXCL8) expression in host (human) lung epithelial cells. Exogenously applied protein, or protein expressed in host (human and mouse), binds beta-2-microglobulin (B2M) and decreases its export to the cell surface, probably leading to defects in class I antigen presentation by the host cell. Responsible for mitochondrial fragmention, redistribution around the cell nucleus and decreased mitochondrial mass; this effect is not seen until 48 hours post-infection. Able to disrupt artificial planar bilayers in the absence of EsxB (CFP-10). Native protein binds artificial liposomes in the absence but not presence of EsxB and is able to rigidify and lyse them; the EsxA-EsxB complex dissociates at acidic pH, EsxB might serve as a chaperone to prevent membrane lysis. Recombinant protein induces leakage of phosphocholine liposomes at acidic pH in the absence of ExsB, undergoes conformational change, becoming more alpha-helical at acidic pH. The study using recombinant protein did not find dissociation of EsxA-EsxB complex at acidic pH. Involved in translocation of bacteria from the host (human) phagolysosome to the host cytoplasm. Translocation into host cytoplasm is visible 3 days post-infection using cultured human cells and precedes host cell death. Recombinant protein induces apoptosis in host (human) differentiated cell lines, which is cell-line dependent; bacteria missing the ESX-1 locus do not induce apoptosis. Host (human) cells treated with EsxA become permeable to extracellular dye. EsxA and EsxA-EsxB are cytotoxic to pneumocytes. ESX-1 secretion system-induced host (mouse) cell apoptosis, which is probably responsible for infection of new host cells, might be due to EsxA. EsxA induces necrosis in aged neutrophils. May help regulate assembly and function of the type VII secretion system (T7SS). EsxA disassembles pre-formed EccC-EsxB multimers, possibly by making EccC-EsxA-EsxB trimers instead of EccC-EsxB-EsxB-EccC tetramers.; May be critical in pro-bacteria versus pro-host interactions; ESX-1 mediates DNA mediated export (maybe via EsxA). The DNA interacts with host (human) cGAS, leading to cGAMP production and activation of the host STING-TBK-1-IRF-3 signaling pathway that leads to IFN-beta which is thought to be 'pro-bacteria'. Mycobacterial dsDNA also interacts with AIM2-NLRP3-ASC to activate an inflammasome, leading to the 'pro-host' IL-1-beta.

Gene References into Functions

The authors conclude that Mycobacterium tuberculosis ESAT-6 stimulates macrophage IL-6 production through STAT3 activation. PMID: 28106119
Rv1057 deletion reduced ESAT-6 secretion and modulated the interactions between M. tuberculosis and macrophages. PMID: 29134265
Mycobacterium tuberculosis ESAT-6 induces dose-dependent activation of caspase-1, and cytotoxicity in mouse retinal pigment epithelium cells. PMID: 29180292
Here we engineer the sequence of EsxA to add desirable tryptic properties aimed at improving complex MS analysis. We demonstrate that EsxA variants are amenable to MS analysis and remain functional in established in vitro and ex vivo assays of Esx-1-function. PMID: 27625110
EsxA contributes to mycobacterial virulence with its membrane-permeabilizing activity that is required for cytosolic translocation. PMID: 27600772
that ESX-1 [6-kDa early secretory antigenic target (ESAT-6) secretion system 1] dependent cell membrane lysis is contact dependent and accompanied by gross membrane disruptions rather than discrete pores. PMID: 28119503
ESAT6 may induce renal injury by promoting miR-155 expression through the TLR-4/MyD88 signaling pathway in MTB-infected mice. PMID: 28655852
This is the first report proclaiming that the ESAT-6 regulates Prdx-1 which is involved in the increase of mycobacterial uptake and survival. The intermediate mechanisms involve the increased Prdx-1 production in macrophages through the activation of p38 and NRF-2 dependent signaling. PMID: 29032183
ESAT-6, an essential virulence factor of Mycobacterium tuberculosis, may contribute to the abnormal hematopoiesis of tuberculosis patients by inhibiting the proliferation and differentiation of CD34-positive hematopoietic cells via apoptosis. PMID: 27745787
Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine-induced protection was lost in the absence of ESAT-6-dependent cytosolic contact. PMID: 27111234
ESAT6 can inhibit the autophagy and promote the growth of Mycobacterium tuberculosis. PMID: 28274307
Mycobacterium tuberculosis activates inflammatory and stromal cells to secrete MMP-10, and this is partly driven by the virulence factor early secretory antigenic target-6. PMID: 27654284
Furthermore, in both Raw264.7 and ACM cells, MTOR inhibition significantly suppressed the survival of BCG. In conclusion, our study highlights how ESAT6 blocks autophagy and promotes BCG survival in a way that activates MTOR. PMID: 27317487
This study suggests I25-H26 as the pH-sensor essential for Mycobacterium smegmatis ESAT-6 to fully acquire the activity, while multiple residues contributed to Mycobacterium tuberculosis ESAT-6 pore-forming activity. PMID: 26801203
ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters beta2M to inhibit cell surface expression of MHC-I-beta2M complexes, resulting in downregulation of class I-mediated antigen presentation. PMID: 25356553
ESAT-6 forms dimers/multimers with higher molecular weight, which disappeared under the action of the detergent amidosulfobetaine-14, giving rise to another conformational state of the protein. PMID: 26260636
MicroRNA profiling of Mtb-infected macrophages revealed the downregulation of miR-let-7f in a manner dependent on the Mtb secreted effector ESAT-6 leading to A20 increase, a feedback inhibitor of the NF-kappaB pathway. PMID: 25683052
ESAT-6 significantly increased miR-155 expression, which was dependent on TLR2/NF-kappaB activation in macrophages. PMID: 25721573
ESAT-6 has a leukocidin function, which may facilitate bacterial avoidance of the antimicrobial action of the neutrophil. PMID: 25321481
Both the N- and C-terminal flexible arms are required for membrane disruption, and the central helix-turn-helix motif of EsxA inserts into the membrane. PMID: 25645924
Assessment of T cell response to novel Mycobacterium tuberculosis synthetic overlapping peptides mixtures (Rv2659 and Rv2660) and ESAT-6 in Egyptian patients. PMID: 25812354
Further, activation of nuclear factor-kappaB (NF-kappaB) and the NF-kappaB-regulated genes encoding tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) participated in esxT-induced apoptosis. PMID: 25242740
These data show Mycobacterium tuberculosis ESAT6-induced down-regulation of IFN-gamma / SOCS1 expression to be induced only in active tuberculosis cases, distinguishing them from healthy individuals likely to have latent tuberculosis. PMID: 24423713
Two lines of transgenic carrot plants producing Mycobacterium tuberculosis proteins (ESAT6 and CFP10) have been constructed... the proteins in question are appropriate as a candidate edible vaccine against tuberculosis. PMID: 24455687
MtbESAT-6 possesses a unique membrane-interacting activity that is not found in MsESAT-6. PMID: 23150662
The virulence-associated secreted protein ESAT-6 plays a key role in miR-155 induction and its subsequent effects on Bach1 and SHIP1 repression. PMID: 22712528
Mycobacterium tuberculosis-derived protein ESAT-6 (Rv3875) induced transient increase in the expression and release of BAT3 in macrophages. PMID: 22808273
Hepatitis B virus core particles were capable of enhancing ESAT-6-specific immune responses in a mouse model PMID: 21689705
ESAT-6 directly inhibits human T-cell responses by affecting TCR signaling pathways downstream of ZAP70. PMID: 20006311
As virulent Mycobacterium tuberculosis reaches a threshold number of bacilli inside the human macrophageESAT-6-dependent necrosis occurs, activating caspase-1 in the process. PMID: 21637850
ESAT-6 inhibits T cell IFN-gamma production in a p38 MAPK-dependent manner. PMID: 21586573
Data show that ESAT-6 test may be the most appropriate for diagnosis of childhood TB, both LTBI and TB disease. PMID: 21039742
The authors show that recognition of Mycobacterium tuberculosis infection by the NLRP3 inflammasome requires the activity of the bacterial virulence factor ESAT-6, and the subsequent IL-1beta response is regulated by NLR/CARD proteins such as ASC. PMID: 20148899
Phenylalanine-rich peptides potently bind ESAT6, a virulence determinant of Mycobacterium tuberculosis, which may have a role in the pathogen's growth PMID: 19901982
These studies demonstrate that ESAT6 causes cytolysis of type 1 and type 2 pneumocytes. PMID: 19906174
study identified mechanism by which mycobacteria induce granulomas: ESAT-6 induced MMP9 in epithelial cells neighboring infected macrophages; MMP9 enhanced recruitment of macrophages, which contributed to nascent granuloma maturation & bacterial growth PMID: 20007864
role in pathogenicity and antigenicity of Mycobacterium tuberculosis [review] PMID: 15488391
treatment of J774 macrophages with ESAT-6 also enhanced IFN-gamma-induced expression of the surface molecules B7.1, Class II Antigen, and Intercellular Adhesion Molecule-1 PMID: 15860216
The surface features of the ESAT-6.CFP10 complex, together with observed binding to specific host cells, strongly suggest a key signalling role for the complex PMID: 15973432
A strict correlation has been found between ESAT-6 export and the generation of ESAT-6 specific T-cell responses in mice. PMID: 16368961
findings demonstrate that ESAT6 induces apoptosis in THP-1 human macrophages; induction of apoptosis by ESAT6 is dependent on the dose of the protein and the expression of caspase genes PMID: 17298391
Direct binding of ESAT-6 to toll-like receptor 2 activated Akt and prevented interaction between the adaptor MyD88 and 'downstream' kinase IRAK4 PMID: 17486091
ESAT-6 induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the cytoplasm but not in the nucleus, which normally is the case for MAP kinases. ESAT-6 also antagonized LPS-induced ERK1/2 phosphorylation in the nucleus. PMID: 17915024
Results demonstrate that ESAT-6-specific Th1 cells can provide protection against inhaled M. tuberculosis, but only after the first week of infection. PMID: 18779346
ESAT-6 directly inhibits human T cell responses to mycobacterial antigens by affecting T cell receptor signaling pathways downstream of ZAP70 protein tyrosine kinase. PMID: 19265145
positive correlation between ESAT6-induced IFNgamma and CXCL9 was present in all tuberculosis patients, but IFNgamma and CCL2 was only correlated in limited disease PMID: 19340290

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Subcellular Location

Secreted. Secreted, cell wall. Host cell surface. Host cytoplasm. Host endoplasmic reticulum. Host cell membrane.

Protein Families

WXG100 family, ESAT-6 subfamily

Database Links

KEGG: mtu:Rv3875

STRING: 83332.Rv3875

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Code	CSB-EP358627MVZ
MSDS	MSDS
Size	Pls inquire
Source	E.coli
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Code	CSB-EP358627MVZ-B
MSDS	MSDS
Size	Pls inquire
Source	E.coli
Conjugate	Avi-tag Biotinylated E. coli biotin ligase (BirA) is highly specific in covalently attaching biotin to the 15 amino acid AviTag peptide. This recombinant protein was biotinylated in vivo by AviTag-BirA technology, which method is BriA catalyzes amide linkage between the biotin and the specific lysine of the AviTag.
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Code	CSB-BP358627MVZ
MSDS	MSDS
Size	Pls inquire
Source	Baculovirus
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Code	CSB-MP358627MVZ
MSDS	MSDS
Size	Pls inquire
Source	Mammalian cell
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Recombinant Mycobacterium tuberculosis 6 kDa early secretory antigenic target (esxA), partial

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