ESXA_MYCTU
ID ESXA_MYCTU Reviewed; 95 AA.
AC P9WNK7; F2GDN6; O84901; P0A564; Q540D8; Q57165;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 48.
DE RecName: Full=6 kDa early secretory antigenic target {ECO:0000303|PubMed:7897219};
DE AltName: Full=ESAT-6;
GN Name=esxA {ECO:0000303|PubMed:19876390}; Synonyms=esaT6;
GN OrderedLocusNames=Rv3875; ORFNames=MTV027.10;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP BIOTECHNOLOGY.
RC STRAIN=H37Rv;
RX PubMed=7897219;
RA Andersen P., Andersen A.B., Sorensen A.L., Nagai S.;
RT "Recall of long-lived immunity to Mycobacterium tuberculosis infection in
RT mice.";
RL J. Immunol. 154:3359-3372(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-11, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=H37Rv;
RX PubMed=7729876; DOI=10.1128/iai.63.5.1710-1717.1995;
RA Soerensen A.L., Nagai S., Houen G., Anderson P., Anderson A.B.;
RT "Purification and characterization of a low-molecular-mass T-cell antigen
RT secreted by Mycobacterium tuberculosis.";
RL Infect. Immun. 63:1710-1717(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Singh B., Siddiqui Z., Singh S., Sharma P.;
RT "ESAT-6 gene of a clinical isolate of Mycobacterium tuberculosis from
RT India.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Lee C.F.;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=1, 2, 3, 4, 5, and 6;
RA Dang D.A., Hoa T.M.T., Tran T.T.H., Nguyen T.N., Ho T.M.L., Nguyen V.H.,
RA Nguyen T.H.H.;
RT "Sequencing and analysis of the gene Esat6 of a Mycobacterium tuberculosis
RT isolate derived from a Vietnamese patient suffering lung tuberculosis.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=7, and 8;
RA Dang D.A., Hoa T.M.T., Tran T.T.H., Nguyen T.N., Ho T.M.L., Nguyen V.H.,
RA Nguyen T.H.H.;
RT "Sequencing and analysis of the gene Esat6 of a Mycobacterium tuberculosis
RT isolate derived from a Vietnamese patient suffering tuberculous
RT meningitis.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9846755; DOI=10.1099/00221287-144-11-3195;
RA Berthet F.-X., Rasmussen P.B., Rosenkrands I., Andersen P., Gicquel B.;
RT "A Mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-
RT molecular-mass culture filtrate protein (CFP-10).";
RL Microbiology 144:3195-3203(1998).
RN [9]
RP PROTEIN SEQUENCE OF 2-95, SUBUNIT, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP ACETYLATION AT THR-2, AND PROTEOLYTIC CLEAVAGE.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=15378760; DOI=10.1002/pmic.200400906;
RA Okkels L.M., Mueller E.C., Schmid M., Rosenkrands I., Kaufmann S.H.,
RA Andersen P., Jungblut P.R.;
RT "CFP10 discriminates between nonacetylated and acetylated ESAT-6 of
RT Mycobacterium tuberculosis by differential interaction.";
RL Proteomics 4:2954-2960(2004).
RN [10]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH ESXB.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11940590; DOI=10.1074/jbc.m201625200;
RA Renshaw P.S., Panagiotidou P., Whelan A., Gordon S.V., Hewinson R.G.,
RA Williamson R.A., Carr M.D.;
RT "Conclusive evidence that the major T-cell antigens of the Mycobacterium
RT tuberculosis complex ESAT-6 and CFP-10 form a tight, 1:1 complex and
RT characterization of the structural properties of ESAT-6, CFP-10, and the
RT ESAT-6*CFP-10 complex. Implications for pathogenesis and virulence.";
RL J. Biol. Chem. 277:21598-21603(2002).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv, and ATCC 35801 / TMC 107 / Erdman;
RX PubMed=14557547; DOI=10.1073/pnas.1635213100;
RA Hsu T., Hingley-Wilson S.M., Chen B., Chen M., Dai A.Z., Morin P.M.,
RA Marks C.B., Padiyar J., Goulding C., Gingery M., Eisenberg D.,
RA Russell R.G., Derrick S.C., Collins F.M., Morris S.L., King C.H.,
RA Jacobs W.R. Jr.;
RT "The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss
RT of secreted lytic function required for invasion of lung interstitial
RT tissue.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12420-12425(2003).
RN [12]
RP FUNCTION, INTERACTION WITH ESXB, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=14557536; DOI=10.1073/pnas.2235593100;
RA Stanley S.A., Raghavan S., Hwang W.W., Cox J.S.;
RT "Acute infection and macrophage subversion by Mycobacterium tuberculosis
RT require a specialized secretion system.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13001-13006(2003).
RN [13]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=14756778; DOI=10.1046/j.1365-2958.2003.03844.x;
RA Guinn K.M., Hickey M.J., Mathur S.K., Zakel K.L., Grotzke J.E.,
RA Lewinsohn D.M., Smith S., Sherman D.R.;
RT "Individual RD1-region genes are required for export of ESAT-6/CFP-10 and
RT for virulence of Mycobacterium tuberculosis.";
RL Mol. Microbiol. 51:359-370(2004).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16030141; DOI=10.1073/pnas.0504922102;
RA Fortune S.M., Jaeger A., Sarracino D.A., Chase M.R., Sassetti C.M.,
RA Sherman D.R., Bloom B.R., Rubin E.J.;
RT "Mutually dependent secretion of proteins required for mycobacterial
RT virulence.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10676-10681(2005).
RN [15]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF THR-2;
RP GLN-4; PHE-8; ALA-14; 28-LEU-LEU-29; TRP-43; GLY-45; 55-GLN-GLN-56;
RP 66-ASN-ASN-67; MET-83; VAL-90; MET-93 AND PHE-94, AND COILED COIL.
RX PubMed=16048998; DOI=10.1074/jbc.m503515200;
RA Brodin P., de Jonge M.I., Majlessi L., Leclerc C., Nilges M., Cole S.T.,
RA Brosch R.;
RT "Functional analysis of early secreted antigenic target-6, the dominant T-
RT cell antigen of Mycobacterium tuberculosis, reveals key residues involved
RT in secretion, complex formation, virulence, and immunogenicity.";
RL J. Biol. Chem. 280:33953-33959(2005).
RN [16]
RP DISRUPTION PHENOTYPE.
RX PubMed=16368961; DOI=10.1128/iai.74.1.88-98.2006;
RA Brodin P., Majlessi L., Marsollier L., de Jonge M.I., Bottai D.,
RA Demangel C., Hinds J., Neyrolles O., Butcher P.D., Leclerc C., Cole S.T.,
RA Brosch R.;
RT "Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on
RT immunogenicity and virulence.";
RL Infect. Immun. 74:88-98(2006).
RN [17]
RP INTERACTION WITH ESXB.
RX PubMed=16973880; DOI=10.1126/science.1131167;
RA Champion P.A., Stanley S.A., Champion M.M., Brown E.J., Cox J.S.;
RT "C-terminal signal sequence promotes virulence factor secretion in
RT Mycobacterium tuberculosis.";
RL Science 313:1632-1636(2006).
RN [18]
RP FUNCTION IN APOPTOSIS, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17298391; DOI=10.1111/j.1462-5822.2007.00892.x;
RA Derrick S.C., Morris S.L.;
RT "The ESAT6 protein of Mycobacterium tuberculosis induces apoptosis of
RT macrophages by activating caspase expression.";
RL Cell. Microbiol. 9:1547-1555(2007).
RN [19]
RP FUNCTION IN HOST TLR INHIBITION, INTERACTION WITH HOST TLR2, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF TRP-43; 90-VAL--ALA-95; 90-VAL-PHE-94; VAL-90;
RP MET-93 AND PHE-94.
RX PubMed=17486091; DOI=10.1038/ni1468;
RA Pathak S.K., Basu S., Basu K.K., Banerjee A., Pathak S., Bhattacharyya A.,
RA Kaisho T., Kundu M., Basu J.;
RT "Direct extracellular interaction between the early secreted antigen ESAT-6
RT of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in
RT macrophages.";
RL Nat. Immunol. 8:610-618(2007).
RN [20]
RP ERRATUM OF PUBMED:17486091.
RX PubMed=25689444; DOI=10.1038/ni0315-326b;
RA Pathak S.K., Basu S., Basu K.K., Banerjee A., Pathak S., Bhattacharyya A.,
RA Kaisho T., Kundu M., Basu J.;
RT "Corrigendum: Direct extracellular interaction between the early secreted
RT antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR
RT signaling in macrophages.";
RL Nat. Immunol. 16:326-326(2015).
RN [21]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17604718; DOI=10.1016/j.cell.2007.05.059;
RA van der Wel N., Hava D., Houben D., Fluitsma D., van Zon M., Pierson J.,
RA Brenner M., Peters P.J.;
RT "M. tuberculosis and M. leprae translocate from the phagolysosome to the
RT cytosol in myeloid cells.";
RL Cell 129:1287-1298(2007).
RN [22]
RP FUNCTION, SUBUNIT, AND MEMBRANE-BINDING.
RX PubMed=17557817; DOI=10.1128/jb.00469-07;
RA de Jonge M.I., Pehau-Arnaudet G., Fretz M.M., Romain F., Bottai D.,
RA Brodin P., Honore N., Marchal G., Jiskoot W., England P., Cole S.T.,
RA Brosch R.;
RT "ESAT-6 from Mycobacterium tuberculosis dissociates from its putative
RT chaperone CFP-10 under acidic conditions and exhibits membrane-lysing
RT activity.";
RL J. Bacteriol. 189:6028-6034(2007).
RN [23]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19265145; DOI=10.4049/jimmunol.0803579;
RA Wang X., Barnes P.F., Dobos-Elder K.M., Townsend J.C., Chung Y.T.,
RA Shams H., Weis S.E., Samten B.;
RT "ESAT-6 inhibits production of IFN-gamma by Mycobacterium tuberculosis-
RT responsive human T cells.";
RL J. Immunol. 182:3668-3677(2009).
RN [24]
RP INTERACTION WITH ESPF.
RX PubMed=19682254; DOI=10.1111/j.1365-2958.2009.06821.x;
RA DiGiuseppe Champion P.A., Champion M.M., Manzanillo P., Cox J.S.;
RT "ESX-1 secreted virulence factors are recognized by multiple cytosolic AAA
RT ATPases in pathogenic mycobacteria.";
RL Mol. Microbiol. 73:950-962(2009).
RN [25]
RP NOMENCLATURE.
RX PubMed=19876390; DOI=10.1371/journal.ppat.1000507;
RA Bitter W., Houben E.N., Bottai D., Brodin P., Brown E.J., Cox J.S.,
RA Derbyshire K., Fortune S.M., Gao L.Y., Liu J., Gey van Pittius N.C.,
RA Pym A.S., Rubin E.J., Sherman D.R., Cole S.T., Brosch R.;
RT "Systematic genetic nomenclature for type VII secretion systems.";
RL PLoS Pathog. 5:E1000507-E1000507(2009).
RN [26]
RP INTERACTION WITH HOST TLR2.
RX PubMed=20800577; DOI=10.1016/j.bbrc.2010.08.085;
RA Chambers M.A., Whelan A.O., Spallek R., Singh M., Coddeville B.,
RA Guerardel Y., Elass E.;
RT "Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 and
RT stimulates production of matrix metalloproteinase 9.";
RL Biochem. Biophys. Res. Commun. 400:403-408(2010).
RN [27]
RP SUBUNIT, AND MUTAGENESIS OF GLU-87.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19854905; DOI=10.1128/jb.01032-09;
RA Callahan B., Nguyen K., Collins A., Valdes K., Caplow M., Crossman D.K.,
RA Steyn A.J., Eisele L., Derbyshire K.M.;
RT "Conservation of structure and protein-protein interactions mediated by the
RT secreted mycobacterial proteins EsxA, EsxB, and EspA.";
RL J. Bacteriol. 192:326-335(2010).
RN [28]
RP FUNCTION IN PNEUMOCYTE CYTOTOXICITY, SUBCELLULAR LOCATION, SUBUNIT, AND
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19906174; DOI=10.1111/j.1365-2958.2009.06959.x;
RA Kinhikar A.G., Verma I., Chandra D., Singh K.K., Weldingh K., Andersen P.,
RA Hsu T., Jacobs W.R. Jr., Laal S.;
RT "Potential role for ESAT6 in dissemination of M. tuberculosis via human
RT lung epithelial cells.";
RL Mol. Microbiol. 75:92-106(2010).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=20148899; DOI=10.1111/j.1462-5822.2010.01450.x;
RA Mishra B.B., Moura-Alves P., Sonawane A., Hacohen N., Griffiths G.,
RA Moita L.F., Anes E.;
RT "Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the
RT NLRP3/ASC inflammasome.";
RL Cell. Microbiol. 12:1046-1063(2010).
RN [30]
RP FUNCTION.
RX PubMed=21586573; DOI=10.1074/jbc.m111.234062;
RA Peng H., Wang X., Barnes P.F., Tang H., Townsend J.C., Samten B.;
RT "The Mycobacterium tuberculosis early secreted antigenic target of 6 kDa
RT inhibits T cell interferon-gamma production through the p38 mitogen-
RT activated protein kinase pathway.";
RL J. Biol. Chem. 286:24508-24518(2011).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [32]
RP FUNCTION IN HOST PHAGOSOME LYSIS, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 84-ALA--ALA-95.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=22319448; DOI=10.1371/journal.ppat.1002507;
RA Simeone R., Bobard A., Lippmann J., Bitter W., Majlessi L., Brosch R.,
RA Enninga J.;
RT "Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and
RT host cell death.";
RL PLoS Pathog. 8:E1002507-E1002507(2012).
RN [33]
RP FUNCTION, AND MUTAGENESIS OF 84-ALA--ALA-95.
RX PubMed=22524898; DOI=10.1111/j.1462-5822.2012.01799.x;
RA Houben D., Demangel C., van Ingen J., Perez J., Baldeon L., Abdallah A.M.,
RA Caleechurn L., Bottai D., van Zon M., de Punder K., van der Laan T.,
RA Kant A., Bossers-de Vries R., Willemsen P., Bitter W., van Soolingen D.,
RA Brosch R., van der Wel N., Peters P.J.;
RT "ESX-1-mediated translocation to the cytosol controls virulence of
RT mycobacteria.";
RL Cell. Microbiol. 14:1287-1298(2012).
RN [34]
RP FUNCTION, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=23150662; DOI=10.1074/jbc.m112.420869;
RA De Leon J., Jiang G., Ma Y., Rubin E., Fortune S., Sun J.;
RT "Mycobacterium tuberculosis ESAT-6 exhibits a unique membrane-interacting
RT activity that is not found in its ortholog from non-pathogenic
RT Mycobacterium smegmatis.";
RL J. Biol. Chem. 287:44184-44191(2012).
RN [35]
RP POSSIBLE FUNCTION IN APOPTOSIS AND HOST INFECTION, AND INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv, and MT103;
RX PubMed=23848406; DOI=10.1111/cmi.12169;
RA Aguilo J.I., Alonso H., Uranga S., Marinova D., Arbues A., de Martino A.,
RA Anel A., Monzon M., Badiola J., Pardo J., Brosch R., Martin C.;
RT "ESX-1-induced apoptosis is involved in cell-to-cell spread of
RT Mycobacterium tuberculosis.";
RL Cell. Microbiol. 15:1994-2005(2013).
RN [36]
RP FUNCTION.
RX PubMed=23867456; DOI=10.1074/jbc.m112.448217;
RA Boggaram V., Gottipati K.R., Wang X., Samten B.;
RT "Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium
RT tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial
RT cells via protein kinase signaling and reactive oxygen species.";
RL J. Biol. Chem. 288:25500-25511(2013).
RN [37]
RP SECRETION INDUCTION BY ZINC, AND SECRETION INHIBITION.
RX PubMed=25299337; DOI=10.1016/j.chom.2014.09.008;
RA Rybniker J., Chen J.M., Sala C., Hartkoorn R.C., Vocat A., Benjak A.,
RA Boy-Roettger S., Zhang M., Szekely R., Greff Z., Orfi L., Szabadkai I.,
RA Pato J., Keri G., Cole S.T.;
RT "Anticytolytic screen identifies inhibitors of mycobacterial virulence
RT protein secretion.";
RL Cell Host Microbe 16:538-548(2014).
RN [38]
RP FUNCTION IN NEUTROPHIL NECROSIS.
RX PubMed=25321481; DOI=10.1038/cddis.2014.394;
RA Francis R.J., Butler R.E., Stewart G.R.;
RT "Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx,
RT necrosis and neutrophil extracellular trap formation.";
RL Cell Death Dis. 5:E1474-E1474(2014).
RN [39]
RP FUNCTION, INTERACTION WITH HOST B2M, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF 90-VAL--ALA-95.
RX PubMed=25356553; DOI=10.1371/journal.ppat.1004446;
RA Sreejit G., Ahmed A., Parveen N., Jha V., Valluri V.L., Ghosh S.,
RA Mukhopadhyay S.;
RT "The ESAT-6 protein of Mycobacterium tuberculosis interacts with beta-2-
RT microglobulin (beta2M) affecting antigen presentation function of
RT macrophage.";
RL PLoS Pathog. 10:E1004446-E1004446(2014).
RN [40]
RP FUNCTION IN PORE FORMATION, SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS
RP OF 1-MET--GLY-10; ASN-21; GLN-34; SER-35; THR-37; GLY-45; GLN-55; TRP-58;
RP ALA-60 AND 86-THR--ALA-95.
RX PubMed=25645924; DOI=10.1074/jbc.m114.622076;
RA Ma Y., Keil V., Sun J.;
RT "Characterization of Mycobacterium tuberculosis EsxA membrane insertion:
RT roles of N- and C-terminal flexible arms and central helix-turn-helix
RT motif.";
RL J. Biol. Chem. 290:7314-7322(2015).
RN [41]
RP FUNCTION.
RC STRAIN=H37Rv;
RX PubMed=26048138; DOI=10.1016/j.chom.2015.05.003;
RA Wassermann R., Gulen M.F., Sala C., Perin S.G., Lou Y., Rybniker J.,
RA Schmid-Burgk J.L., Schmidt T., Hornung V., Cole S.T., Ablasser A.;
RT "Mycobacterium tuberculosis differentially activates cGAS- and
RT inflammasome-dependent intracellular immune responses through ESX-1.";
RL Cell Host Microbe 17:799-810(2015).
RN [42]
RP FUNCTION.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=26048136; DOI=10.1016/j.chom.2015.05.004;
RA Watson R.O., Bell S.L., MacDuff D.A., Kimmey J.M., Diner E.J., Olivas J.,
RA Vance R.E., Stallings C.L., Virgin H.W., Cox J.S.;
RT "The cytosolic sensor cGAS detects Mycobacterium tuberculosis DNA to induce
RT type I interferons and activate autophagy.";
RL Cell Host Microbe 17:811-819(2015).
RN [43]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv, and ATCC 35801 / TMC 107 / Erdman;
RX PubMed=26092385; DOI=10.1016/j.micinf.2015.06.003;
RA Fine-Coulson K., Giguere S., Quinn F.D., Reaves B.J.;
RT "Infection of A549 human type II epithelial cells with Mycobacterium
RT tuberculosis induces changes in mitochondrial morphology, distribution and
RT mass that are dependent on the early secreted antigen, ESAT-6.";
RL Microbes Infect. 17:689-697(2015).
RN [44]
RP FUNCTION, AND SUBUNIT.
RX PubMed=26260636; DOI=10.1111/febs.13408;
RA Refai A., Haoues M., Othman H., Barbouche M.R., Moua P., Bondon A.,
RA Mouret L., Srairi-Abid N., Essafi M.;
RT "Two distinct conformational states of Mycobacterium tuberculosis virulent
RT factor early secreted antigenic target 6 kDa are behind the discrepancy
RT around its biological functions.";
RL FEBS J. 282:4114-4129(2015).
RN [45]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ALA-17; 25-ILE-HIS-26;
RP HIS-26; LYS-38; ASN-67 AND ARG-74.
RX PubMed=26801203; DOI=10.1002/1873-3468.12072;
RA Peng X., Jiang G., Liu W., Zhang Q., Qian W., Sun J.;
RT "Characterization of differential pore-forming activities of ESAT-6
RT proteins from Mycobacterium tuberculosis and Mycobacterium smegmatis.";
RL FEBS Lett. 590:509-519(2016).
RN [46]
RP REVIEW.
RX PubMed=26456678; DOI=10.1016/j.toxicon.2015.10.003;
RA Peng X., Sun J.;
RT "Mechanism of ESAT-6 membrane interaction and its roles in pathogenesis of
RT Mycobacterium tuberculosis.";
RL Toxicon 116:29-34(2016).
RN [47]
RP PRELIMINARY X-RAY CRYSTALLOGRAPHY, AND SUBUNIT.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20085764; DOI=10.1016/j.febslet.2009.12.057;
RA Poulsen C., Holton S., Geerlof A., Wilmanns M., Song Y.H.;
RT "Stoichiometric protein complex formation and over-expression using the
RT prokaryotic native operon structure.";
RL FEBS Lett. 584:669-674(2010).
RN [48]
RP STRUCTURE BY NMR IN COMPLEX WITH CFP-10 (ESXB), SUBUNIT, SUBCELLULAR
RP LOCATION, AND DOMAIN.
RX PubMed=15973432; DOI=10.1038/sj.emboj.7600732;
RA Renshaw P.S., Lightbody K.L., Veverka V., Muskett F.W., Kelly G.,
RA Frenkiel T.A., Gordon S.V., Hewinson R.G., Burke B., Norman J.,
RA Williamson R.A., Carr M.D.;
RT "Structure and function of the complex formed by the tuberculosis virulence
RT factors CFP-10 and ESAT-6.";
RL EMBO J. 24:2491-2498(2005).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 2-95 IN COMPLEX WITH CFP-10
RP (ESXB).
RC STRAIN=H37Rv;
RX PubMed=24586681; DOI=10.1371/journal.pone.0089313;
RA Poulsen C., Panjikar S., Holton S.J., Wilmanns M., Song Y.H.;
RT "WXG100 protein superfamily consists of three subfamilies and exhibits an
RT alpha-helical C-terminal conserved residue pattern.";
RL PLoS ONE 9:E89313-E89313(2014).
CC -!- FUNCTION: A secreted protein that plays a number of roles in modulating
CC the host's immune response to infection as well as being responsible
CC for bacterial escape into the host cytoplasm. Acts as a strong host
CC (human) T-cell antigen (PubMed:7729876, PubMed:11940590). Inhibits IL-
CC 12 p40 (IL12B) and TNF-alpha expression by infected host (mouse)
CC macrophages, reduces the nitric oxide response by about 75%
CC (PubMed:14557536). In mice previously exposed to the bacterium, elicits
CC high level of IFN-gamma production by T-cells upon subsequent challenge
CC by M.tuberculosis, in the first phase of a protective immune response
CC (PubMed:7897219, PubMed:7729876). Higher levels (1.6-3.3 uM) of
CC recombinant protein inhibit IFN-gamma production by host (human) T-
CC cells and also IL-17 and TNF-alpha production but not IL-2; decreases
CC expression of host ATF-2 and JUN transcription factors by affecting T-
CC cell receptors signaling downstream of ZAP70, without cytotoxicity or
CC apoptosis (PubMed:19265145). EsxA inhibits IFN-gamma production in
CC human T-cells by activating p38 MAPK (MAPK14), p38 MAPK is not
CC responsible for IL-17 decrease (PubMed:21586573). Binds host (mouse)
CC Toll-like receptor 2 (TLR2) and decreases host MYD88-dependent
CC signaling; binding to TLR2 activates host kinase AKT and subsequently
CC inhibits downstream activation of NF-kappa-B; the C-terminal 20
CC residues (76-95) are necessary and sufficient for the TLR2 inhibitory
CC effect (PubMed:17486091). Required for induction of host (human) IL-1B
CC maturation and release by activating the host NLRP3/ASC inflammasome;
CC may also promote access of other tuberculosis proteins to the host
CC cells cytoplasm (PubMed:20148899). Induces IL-8 (CXCL8) expression in
CC host (human) lung epithelial cells (PubMed:23867456). Exogenously
CC applied protein, or protein expressed in host (human and mouse), binds
CC beta-2-microglobulin (B2M) and decreases its export to the cell
CC surface, probably leading to defects in class I antigen presentation by
CC the host cell (PubMed:25356553). Responsible for mitochondrial
CC fragmention, redistribution around the cell nucleus and decreased
CC mitochondrial mass; this effect is not seen until 48 hours post-
CC infection (PubMed:26092385). Able to disrupt artificial planar bilayers
CC in the absence of EsxB (CFP-10) (PubMed:14557547). Native protein binds
CC artificial liposomes in the absence but not presence of EsxB and is
CC able to rigidify and lyse them; the EsxA-EsxB complex dissociates at
CC acidic pH, EsxB might serve as a chaperone to prevent membrane lysis
CC (PubMed:17557817). Recombinant protein induces leakage of
CC phosphocholine liposomes at acidic pH in the absence of ExsB, undergoes
CC conformational change, becoming more alpha-helical at acidic pH
CC (PubMed:23150662, PubMed:25645924). The study using recombinant protein
CC did not find dissociation of EsxA-EsxB complex at acidic pH
CC (PubMed:23150662). Involved in translocation of bacteria from the host
CC (human) phagolysosome to the host cytoplasm (PubMed:17604718,
CC PubMed:22319448). Translocation into host cytoplasm is visible 3 days
CC post-infection using cultured human cells and precedes host cell death
CC (PubMed:22319448). Recombinant protein induces apoptosis in host
CC (human) differentiated cell lines, which is cell-line dependent;
CC bacteria missing the ESX-1 locus do not induce apoptosis
CC (PubMed:17298391). Host (human) cells treated with EsxA become
CC permeable to extracellular dye (PubMed:17298391). EsxA and EsxA-EsxB
CC are cytotoxic to pneumocytes (PubMed:19906174). ESX-1 secretion system-
CC induced host (mouse) cell apoptosis, which is probably responsible for
CC infection of new host cells, might be due to EsxA (PubMed:23848406).
CC EsxA induces necrosis in aged neutrophils (PubMed:25321481). May help
CC regulate assembly and function of the type VII secretion system (T7SS)
CC (By similarity). EsxA disassembles pre-formed EccC-EsxB multimers,
CC possibly by making EccC-EsxA-EsxB trimers instead of EccC-EsxB-EsxB-
CC EccC tetramers (By similarity). {ECO:0000250|UniProtKB:D1A4H1,
CC ECO:0000269|PubMed:11940590, ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:14557547, ECO:0000269|PubMed:17298391,
CC ECO:0000269|PubMed:17486091, ECO:0000269|PubMed:17557817,
CC ECO:0000269|PubMed:17604718, ECO:0000269|PubMed:19265145,
CC ECO:0000269|PubMed:19906174, ECO:0000269|PubMed:20148899,
CC ECO:0000269|PubMed:21586573, ECO:0000269|PubMed:22319448,
CC ECO:0000269|PubMed:23867456, ECO:0000269|PubMed:25321481,
CC ECO:0000269|PubMed:25356553, ECO:0000269|PubMed:26092385,
CC ECO:0000269|PubMed:26260636, ECO:0000269|PubMed:7729876,
CC ECO:0000269|PubMed:7897219, ECO:0000305|PubMed:23848406}.
CC -!- FUNCTION: May be critical in pro-bacteria versus pro-host interactions;
CC ESX-1 mediates DNA mediated export (maybe via EsxA). The DNA interacts
CC with host (human) cGAS, leading to cGAMP production and activation of
CC the host STING-TBK-1-IRF-3 signaling pathway that leads to IFN-beta
CC which is thought to be 'pro-bacteria'. Mycobacterial dsDNA also
CC interacts with AIM2-NLRP3-ASC to activate an inflammasome, leading to
CC the 'pro-host' IL-1-beta (PubMed:26048138, PubMed:26048136).
CC {ECO:0000269|PubMed:26048136, ECO:0000269|PubMed:26048138}.
CC -!- SUBUNIT: Forms a tight 1:1 complex with EsxB (CFP-10) (PubMed:11940590,
CC PubMed:14557536, PubMed:16048998, PubMed:16973880, PubMed:19854905,
CC PubMed:19906174, PubMed:23150662, PubMed:26260636, PubMed:20085764,
CC PubMed:15973432, PubMed:24586681). The complex persists even after
CC secretion (PubMed:16048998). Recombinant His-tagged protein forms
CC dimers and higher order multimers; how the protein is prepared
CC influences its multimerization and its subsequent properties in vitro
CC (PubMed:26260636). In vitro EsxB only interacts with non-acetylated
CC EsxA; it also interacts with C-terminally truncated EsxA (missing the
CC last 10 residues) (PubMed:15378760). The native EsxA-EsxB complex
CC dissociates at pH 4.0, and EsxA may then be freed to lyse (host)
CC membranes (PubMed:17557817). Another study using recombinant protein
CC did not find dissociation at acidic pH (PubMed:23150662). Recombinant
CC heterodimer (with a His tag on EsxB) can be dissociated by the
CC detergents amidosulfobetaine-14 and lauryldimethylamine N-oxide
CC (PubMed:26260636). Interacts with EspF (PubMed:19682254). An artificial
CC EsxB-EsxA heterodimer interacts with EspA, EccB1, EccCa1, EccCb1, EspI,
CC EspJ, EccA2 and EccE2; the latter 2 are from the adjacent ESX-2 locus
CC (PubMed:19854905). Contributes to the heterodimer's interaction with
CC EccCb1 (PubMed:19854905). Interacts with host (mouse and human) TLR2
CC (PubMed:17486091, PubMed:20800577). Interacts with host (human) beta-2-
CC microglobulin (B2M) alone and in complex with EsxB; only binds free B2M
CC and not B2M in complex with HLA-I (PubMed:25356553). The EsxA-EsxB-B2M
CC complex can be detected in the host endoplasmic reticulum
CC (PubMed:25356553). The B2M-EsxA complex can be detected in patients
CC with pleural tuberculosis and is stable from pH 4.0 to 8.0 and in the
CC presence of 2M NaCl (PubMed:25356553). {ECO:0000269|PubMed:11940590,
CC ECO:0000269|PubMed:14557536, ECO:0000269|PubMed:15378760,
CC ECO:0000269|PubMed:15973432, ECO:0000269|PubMed:16048998,
CC ECO:0000269|PubMed:16973880, ECO:0000269|PubMed:17486091,
CC ECO:0000269|PubMed:17557817, ECO:0000269|PubMed:19682254,
CC ECO:0000269|PubMed:19854905, ECO:0000269|PubMed:19906174,
CC ECO:0000269|PubMed:20085764, ECO:0000269|PubMed:20800577,
CC ECO:0000269|PubMed:23150662, ECO:0000269|PubMed:24586681,
CC ECO:0000269|PubMed:25356553, ECO:0000269|PubMed:26260636}.
CC -!- INTERACTION:
CC P9WNK7; P9WNK5: esxB; NbExp=22; IntAct=EBI-1253925, EBI-1253936;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:14557547, ECO:0000269|PubMed:15378760,
CC ECO:0000269|PubMed:16030141, ECO:0000269|PubMed:16048998,
CC ECO:0000269|PubMed:7729876, ECO:0000269|PubMed:7897219}. Secreted, cell
CC wall {ECO:0000269|PubMed:19906174}. Host cell surface
CC {ECO:0000269|PubMed:15973432, ECO:0000269|PubMed:17486091,
CC ECO:0000269|PubMed:19265145}. Host cytoplasm
CC {ECO:0000269|PubMed:20148899}. Host endoplasmic reticulum
CC {ECO:0000269|PubMed:25356553}. Host cell membrane
CC {ECO:0000305|PubMed:25645924, ECO:0000305|PubMed:26801203}.
CC Note=Probably secreted via the ESX-1 / type VII secretion system (T7SS)
CC (PubMed:19876390). Secreted protein binds to bacterial cell wall
CC (PubMed:19906174). Binds to host (mouse) TLR2 on the cell surface
CC (PubMed:17486091). Binds to CD4+, CD8+, CD14+ and CD19+ host (human)
CC cells (PubMed:19265145). Localized on the cell surface of host (human)
CC cell monocytes and macrophages (often in patches), but not fibroblasts
CC (PubMed:15973432). Exogenous EsxA and EsxA-EsxB complex can enter host
CC (human and mouse) endoplasmic reticulum, where they bind beta-2-
CC microglobulin (PubMed:25356553). At acidic pH able to form pores in
CC artificial membranes, might form pores in host phagosome membranes in
CC absence of EsxB, allowing escape of bacteria into the host cytoplasm
CC (PubMed:25645924, PubMed:26801203). The central pair of alpha helices
CC probably insert into the membrane while the N- and C-terminal arms do
CC not, but may rest on the membrane surface as they are required for
CC membrane insertion (PubMed:25645924). {ECO:0000269|PubMed:15973432,
CC ECO:0000269|PubMed:17486091, ECO:0000269|PubMed:19265145,
CC ECO:0000269|PubMed:19876390, ECO:0000269|PubMed:19906174,
CC ECO:0000269|PubMed:25356553, ECO:0000269|PubMed:25645924,
CC ECO:0000305|PubMed:25645924, ECO:0000305|PubMed:26801203}.
CC -!- INDUCTION: Constitutively expressed in culture (at protein level)
CC (PubMed:9846755, PubMed:23848406). Up-regulated in infected human
CC pneumonocytes (PubMed:19906174). Zinc increases secreted levels of this
CC protein; 0.5 mM Zn(2+), the physiological concentration in macrophages,
CC induces 6-fold more secreted protein (PubMed:25299337). Part of the
CC esxB-esxA operon (PubMed:9846755). {ECO:0000269|PubMed:19906174,
CC ECO:0000269|PubMed:23848406, ECO:0000269|PubMed:25299337,
CC ECO:0000269|PubMed:9846755}.
CC -!- DOMAIN: May be secreted as a 4 coiled-coil complex with EsxB
CC (PubMed:16048998). {ECO:0000269|PubMed:16048998}.
CC -!- PTM: Upon purification from strain ATCC 27294 a C-terminally truncated
CC peptide (missing residues 85-95) has been found; it is not clear if
CC this is physiologically relevant (PubMed:15378760). An additional
CC unknown modification on peptide Thr-86-Ala-95 has also been seen
CC (PubMed:15378760). {ECO:0000269|PubMed:15378760}.
CC -!- DISRUPTION PHENOTYPE: Bacteria no longer translocate from the
CC phagolysosome to the cytosol of host (human) cells; bacteria replicate
CC only in host phagolysosome rather than cytoplasm, decreased apoptosis
CC of infected host (human) dendritic cells (PubMed:17604718). Bacteria
CC missing the RD1 locus do not gain access to host (human) cytoplasm;
CC complementation with the RD1 locus restores access, but if EsxA is
CC missing the last 12 residues cytoplasmic access is not restored
CC although truncated EsxA is secreted by bacteria (PubMed:22319448). Loss
CC of ability to lyse host (human) lung epithelial cells, possibly due to
CC polar effects from the upstream esxB gene; in BALB/c-infected mice
CC bacteria are not as invasive and cause decreased lung disease
CC (PubMed:14557547). No growth in the human macrophage-like cell line
CC THP-1, no cytotoxicity (PubMed:14756778). Severely attenutated
CC infection in mice, nearly 1000-fold less bacteria in lung and spleen of
CC C57BL/6 (PubMed:14557536, PubMed:14756778). Inactivation leads to
CC absence of EsxA and EsxB from cell lysates (PubMed:14756778,
CC PubMed:16368961). No secretion of EspA (PubMed:16030141). No longer
CC decreases expression of IL-12 p40 and TNF-alpha by infected murine
CC macrophages, while the nitric oxide response is only partially reduced
CC (PubMed:14557536). Significantly decreased production of IL-1 beta
CC (IL1B), decreased activation of host (human) CASP-1 in response to
CC bacterial infection (PubMed:20148899). Mitochondrial morphology is no
CC longer perturbed in human alveolar epithelial cell line A549
CC (PubMed:26092385). {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:14557547, ECO:0000269|PubMed:14756778,
CC ECO:0000269|PubMed:16030141, ECO:0000269|PubMed:16368961,
CC ECO:0000269|PubMed:17604718, ECO:0000269|PubMed:20148899,
CC ECO:0000269|PubMed:22319448, ECO:0000269|PubMed:26092385}.
CC -!- BIOTECHNOLOGY: A good candiate for vaccine development
CC (PubMed:7897219). It has been tested in a number of experimental
CC situations. {ECO:0000305|PubMed:7897219}.
CC -!- MISCELLANEOUS: Genes esxA and esxB are part of RD1 (part of a 15-gene
CC locus known as ESX-1), a section of DNA deleted in the M.bovis BCG
CC strain used for vaccination. Deletion of this region is thought to be
CC largely responsible for the attenuation of BCG, and esxA and esxB in
CC particular are very important in this effect (PubMed:14557547,
CC PubMed:14756778, PubMed:16368961, PubMed:17298391, PubMed:22319448,
CC PubMed:22524898). {ECO:0000269|PubMed:14557547,
CC ECO:0000269|PubMed:14756778, ECO:0000269|PubMed:16368961,
CC ECO:0000269|PubMed:17298391, ECO:0000269|PubMed:22319448,
CC ECO:0000269|PubMed:22524898}.
CC -!- MISCELLANEOUS: Secretion of EspA, EsxA and EsxB is mutually dependent
CC (PubMed:16030141). {ECO:0000269|PubMed:16030141}.
CC -!- MISCELLANEOUS: To improve expression in E.coli the proteins were cloned
CC as a single protein in the order esxB-esxA with a cleavable thrombin
CC tag (PubMed:19854905). {ECO:0000269|PubMed:19854905}.
CC -!- MISCELLANEOUS: 2 inhibitors of ESX-1 secretion decrease secretion of
CC this protein, without being bacteriocidal. BTP15 inhibits
CC autophosphorylation of MprB with subsequent up-regulation of espA and
CC decreased secretion of EspB and EsxA. BBH7 also inhibits TAT-dependent
CC secretion of (at least) Ag85C (fbpC) and up-regulates members of the
CC ESX-5 locus as well as other genes that are involved in cell wall
CC biogenesis and metal ion homeostasis (PubMed:25299337).
CC {ECO:0000269|PubMed:25299337}.
CC -!- SIMILARITY: Belongs to the WXG100 family. ESAT-6 subfamily.
CC {ECO:0000305|PubMed:19876390}.
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DR EMBL; X79562; CAA56099.1; -; Genomic_DNA.
DR EMBL; AF420491; AAL16896.1; -; Genomic_DNA.
DR EMBL; AY207398; AAO62007.1; -; Genomic_DNA.
DR EMBL; DQ451152; ABD98021.1; -; Genomic_DNA.
DR EMBL; DQ451153; ABD98022.1; -; Genomic_DNA.
DR EMBL; DQ451154; ABD98023.1; -; Genomic_DNA.
DR EMBL; DQ451155; ABD98024.1; -; Genomic_DNA.
DR EMBL; DQ451156; ABD98025.1; -; Genomic_DNA.
DR EMBL; DQ451157; ABD98026.1; -; Genomic_DNA.
DR EMBL; DQ451158; ABD98027.1; -; Genomic_DNA.
DR EMBL; DQ451159; ABD98028.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46704.1; -; Genomic_DNA.
DR EMBL; AF004671; AAC83446.1; -; Genomic_DNA.
DR PIR; A70803; A70803.
DR RefSeq; WP_003399963.1; NZ_NVQJ01000074.1.
DR RefSeq; YP_178023.1; NC_000962.3.
DR PDB; 1WA8; NMR; -; B=1-95.
DR PDB; 3FAV; X-ray; 2.15 A; B/D=2-95.
DR PDBsum; 1WA8; -.
DR PDBsum; 3FAV; -.
DR AlphaFoldDB; P9WNK7; -.
DR BMRB; P9WNK7; -.
DR SMR; P9WNK7; -.
DR DIP; DIP-61227N; -.
DR IntAct; P9WNK7; 2.
DR MINT; P9WNK7; -.
DR STRING; 83332.Rv3875; -.
DR iPTMnet; P9WNK7; -.
DR PaxDb; P9WNK7; -.
DR ABCD; P9WNK7; 2 sequenced antibodies.
DR DNASU; 886209; -.
DR GeneID; 45427879; -.
DR GeneID; 886209; -.
DR KEGG; mtu:Rv3875; -.
DR TubercuList; Rv3875; -.
DR eggNOG; COG4842; Bacteria.
DR OMA; QAVQMRW; -.
DR PhylomeDB; P9WNK7; -.
DR Reactome; R-HSA-9636667; Manipulation of host energy metabolism.
DR Reactome; R-HSA-9637628; Modulation by Mtb of host immune system.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IDA:MTBBASE.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044228; C:host cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; IDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0046812; F:host cell surface binding; IDA:MTBBASE.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:MTBBASE.
DR GO; GO:0052027; P:modulation by symbiont of host signal transduction pathway; IDA:MTBBASE.
DR GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
DR GO; GO:0052083; P:suppression by symbiont of host cell-mediated immune response; IDA:MTBBASE.
DR GO; GO:0052085; P:suppression by symbiont of host T-cell mediated immune response; IDA:CACAO.
DR InterPro; IPR036689; ESAT-6-like_sf.
DR InterPro; IPR010310; T7SS_ESAT-6-like.
DR Pfam; PF06013; WXG100; 1.
DR SUPFAM; SSF140453; SSF140453; 1.
DR TIGRFAMs; TIGR03930; WXG100_ESAT6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Cell wall; Coiled coil;
KW Direct protein sequencing; Host cell membrane; Host cytoplasm;
KW Host endoplasmic reticulum; Host membrane; Membrane; Reference proteome;
KW Secreted; Transmembrane; Transmembrane helix; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15378760,
FT ECO:0000269|PubMed:7729876, ECO:0007744|PubMed:21969609"
FT CHAIN 2..95
FT /note="6 kDa early secretory antigenic target"
FT /id="PRO_0000167793"
FT TRANSMEM 11..43
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25645924"
FT TRANSMEM 49..85
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:25645924"
FT REGION 85..95
FT /note="Not required for ESAT-6/CFP-10 complex to bind to
FT host macrophage and monocytes"
FT /evidence="ECO:0000269|PubMed:15973432"
FT COILED 8..39
FT /evidence="ECO:0000305|PubMed:16048998"
FT COILED 56..87
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16048998"
FT MOD_RES 2
FT /note="N-acetylthreonine; partial"
FT /evidence="ECO:0000269|PubMed:15378760,
FT ECO:0007744|PubMed:21969609"
FT MUTAGEN 2..10
FT /note="Missing: 40% reduction in liposome disruption. 80%
FT reduction; when associated with 86-T--A-95."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 2
FT /note="T->H: Wild-type virulence in an esxA deletion
FT strain; protein should not be acetylated."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 4
FT /note="Q->L: Wild-type virulence in an esxA deletion
FT strain."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 8
FT /note="F->I: Wild-type virulence in an esxA deletion
FT strain."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 14
FT /note="A->R: Wild-type virulence in an esxA deletion
FT strain."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 17
FT /note="A->E: 88% reduction in liposome disruption; when
FT associated with 25-T-A-26."
FT /evidence="ECO:0000269|PubMed:26801203"
FT MUTAGEN 21
FT /note="N->C: Cannot be overproduced and purified."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 25..26
FT /note="IH->TA: 40% reduction in liposome disruption. 88%
FT reduction in liposome disruption; when associated with E-
FT 17. Reduced liposome disruption; when associated with T-
FT 38."
FT /evidence="ECO:0000269|PubMed:26801203"
FT MUTAGEN 26
FT /note="H->A: 16% reduction in liposome disruption."
FT /evidence="ECO:0000269|PubMed:26801203"
FT MUTAGEN 28..29
FT /note="LL->AS: Does not restore virulence in an esxA
FT deletion strain, decreased secretion of EsxA and EsxB."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 34
FT /note="Q->C: NBD-linked protein does not fluoresce at
FT acidic pH in presence of liposomes, this residue may face
FT inwards in membranes away from lipids."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 35
FT /note="S->C: NBD-linked protein fluoresces at acidic pH in
FT presence of liposomes, suggests this residue faces lipids."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 37
FT /note="T->C: NBD-linked protein does not fluoresce at
FT acidic pH in presence of liposomes, this residue may face
FT inwards in membranes away from lipids."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 38
FT /note="K->T: Reduced liposome disruption; when associated
FT with 25-T-A-26."
FT /evidence="ECO:0000269|PubMed:26801203"
FT MUTAGEN 43
FT /note="W->R: Does not restore virulence in an esxA deletion
FT strain, wild-type secretion of EsxA and EsxB but no complex
FT formed (PubMed:16048998). No effect on host TLR2-
FT signaling."
FT /evidence="ECO:0000269|PubMed:16048998,
FT ECO:0000269|PubMed:17486091"
FT MUTAGEN 45
FT /note="G->C: NBD-linked protein moderately fluoresces at
FT acidic pH in presence of liposomes, suggests this residue
FT is partially within membrane."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 45
FT /note="G->T: Does not restore virulence in an esxA deletion
FT strain, wild-type secretion of EsxA and EsxB."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 55..56
FT /note="QQ->IA: Wild-type virulence in an esxA deletion
FT strain."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 55
FT /note="Q->C: NBD-linked protein does not fluoresce at
FT acidic pH in presence of liposomes, this residue may face
FT inwards in membranes away from lipids."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 58
FT /note="W->C: Cannot be overproduced and purified."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 60
FT /note="A->C: NBD-linked protein fluoresces at acidic pH in
FT presence of liposomes, suggests this residue faces lipids."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 66..67
FT /note="NN->IA: Wild-type virulence in an esxA deletion
FT strain."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 67
FT /note="N->L: Reduced liposome disruption; when associated
FT with 25-T-A-26."
FT /evidence="ECO:0000269|PubMed:26801203"
FT MUTAGEN 74
FT /note="R->Q: Reduced liposome disruption; when associated
FT with 25-T-A-26."
FT /evidence="ECO:0000269|PubMed:26801203"
FT MUTAGEN 83
FT /note="M->I: Wild-type virulence in an esxA deletion
FT strain."
FT /evidence="ECO:0000269|PubMed:16048998"
FT MUTAGEN 84..95
FT /note="Missing: Bacteria no longer gain access to host
FT cytoplasm via phagosomal rupture."
FT /evidence="ECO:0000269|PubMed:22319448,
FT ECO:0000269|PubMed:22524898"
FT MUTAGEN 86..95
FT /note="Missing: 40% reduction in liposome disruption. 80%
FT reduction; when associated with 2-T--G-10."
FT /evidence="ECO:0000269|PubMed:25645924"
FT MUTAGEN 87
FT /note="E->K: Abolishes EsxB-EsxA heterodimer interaction
FT with EccCb1, maintains interaction with EspA, EccA2 and
FT EccE2."
FT /evidence="ECO:0000269|PubMed:19854905"
FT MUTAGEN 90..95
FT /note="Missing: No longer inhibits host TLR2-signaling
FT (PubMed:17486091). Does not interact with host B2M, does
FT not decrease B2M cell surface expression, no defects in
FT antigen presentation (PubMed:25356553)."
FT /evidence="ECO:0000269|PubMed:17486091,
FT ECO:0000269|PubMed:25356553"
FT MUTAGEN 90..94
FT /note="VTGMF->RTGTQ: No longer inhibits host TLR2-
FT signaling."
FT /evidence="ECO:0000269|PubMed:17486091"
FT MUTAGEN 90
FT /note="V->R: Does not restore virulence in an esxA deletion
FT strain, wild-type secretion of EsxA and EsxB
FT (PubMed:16048998). Partially inhibits host TLR2-signaling
FT (PubMed:17486091)."
FT /evidence="ECO:0000269|PubMed:16048998,
FT ECO:0000269|PubMed:17486091"
FT MUTAGEN 93
FT /note="M->T: Partially restores virulence in an esxA
FT deletion strain, wild-type secretion of EsxA and EsxB
FT (PubMed:16048998). Partially inhibits host TLR2-signaling
FT (PubMed:17486091)."
FT /evidence="ECO:0000269|PubMed:16048998,
FT ECO:0000269|PubMed:17486091"
FT MUTAGEN 94
FT /note="F->Q: Does not restore virulence in an esxA deletion
FT strain, wild-type secretion of EsxA and EsxB
FT (PubMed:16048998). Partially inhibits host TLR2-signaling
FT (PubMed:17486091)."
FT /evidence="ECO:0000269|PubMed:16048998,
FT ECO:0000269|PubMed:17486091"
FT HELIX 11..38
FT /evidence="ECO:0007829|PDB:3FAV"
FT HELIX 39..43
FT /evidence="ECO:0007829|PDB:3FAV"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1WA8"
FT HELIX 49..80
FT /evidence="ECO:0007829|PDB:3FAV"
FT TURN 82..85
FT /evidence="ECO:0007829|PDB:1WA8"
FT TURN 91..93
FT /evidence="ECO:0007829|PDB:1WA8"
SQ SEQUENCE 95 AA; 9904 MW; 79BD529E3D88F519 CRC64;
MTEQQWNFAG IEAAASAIQG NVTSIHSLLD EGKQSLTKLA AAWGGSGSEA YQGVQQKWDA
TATELNNALQ NLARTISEAG QAMASTEGNV TGMFA
