ESXB_MYCTU
ID ESXB_MYCTU Reviewed; 100 AA.
AC P9WNK5; L0TDT9; O69739; P0A566;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=ESAT-6-like protein EsxB;
DE AltName: Full=10 kDa culture filtrate antigen CFP-10 {ECO:0000303|PubMed:9846755};
DE Short=CFP-10;
DE AltName: Full=Secreted antigenic protein MTSA-10;
GN Name=esxB {ECO:0000303|PubMed:19876390};
GN Synonyms=cfp10, lhp {ECO:0000303|PubMed:9846755},
GN mtsA10 {ECO:0000303|Ref.2}; OrderedLocusNames=Rv3874; ORFNames=MTV027.09;
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], PROTEIN SEQUENCE OF 2-16, SUBCELLULAR
RP LOCATION, 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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Singh B., Siddiqui Z., Singh S., Sharma P.;
RT "Rv3874 (mtsa-10) gene of a clinical isolate of Mycobacterium tuberculosis
RT from India.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH ESXA.
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 [5]
RP FUNCTION, 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 [6]
RP INTERACTION WITH ESXA AND ECCCB1, AND SUBCELLULAR LOCATION.
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 [7]
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 [8]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
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 [9]
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 [10]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DOMAIN, 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 [11]
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 [12]
RP INTERACTION WITH ESXA AND ECCCB1, DOMAIN, AND MUTAGENESIS OF LEU-94;
RP SER-96; MET-98; GLY-99 AND PHE-100.
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 [13]
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 [14]
RP FUNCTION, AND SUBUNIT.
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 [15]
RP INTERACTION WITH PPE68.
RX PubMed=17433643; DOI=10.1016/j.micres.2006.11.016;
RA Teutschbein J., Schumann G., Mollmann U., Grabley S., Cole S.T., Munder T.;
RT "A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of
RT Mycobacterium tuberculosis.";
RL Microbiol. Res. 164:253-259(2009).
RN [16]
RP 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 [17]
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 [18]
RP SUBUNIT, AND MUTAGENESIS OF GLN-42; ALA-62 AND SER-95.
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 [19]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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 [21]
RP 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 [22]
RP INTERACTION WITH HOST B2M, AND SUBCELLULAR LOCATION.
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 [23]
RP FUNCTION IN NEUTROPHIL ACTIVATION.
RX PubMed=25332123; DOI=10.1128/iai.02493-14;
RA Welin A., Bjoernsdottir H., Winther M., Christenson K., Oprea T.,
RA Karlsson A., Forsman H., Dahlgren C., Bylund J.;
RT "CFP-10 from Mycobacterium tuberculosis selectively activates human
RT neutrophils through a pertussis toxin-sensitive chemotactic receptor.";
RL Infect. Immun. 83:205-213(2015).
RN [24]
RP POSSIBLE FUNCTION, AND INTERACTION WITH ECCCB1.
RX PubMed=25865481; DOI=10.1016/j.cell.2015.03.040;
RA Rosenberg O.S., Dovala D., Li X., Connolly L., Bendebury A.,
RA Finer-Moore J., Holton J., Cheng Y., Stroud R.M., Cox J.S.;
RT "Substrates control multimerization and activation of the multi-domain
RT ATPase motor of type VII secretion.";
RL Cell 161:501-512(2015).
RN [25]
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 [26]
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 [27]
RP STRUCTURE BY NMR OF 2-100 IN COMPLEX WITH ESAT-6 (ESXA), SUBUNIT, AND
RP SUBCELLULAR LOCATION.
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 [28]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH ESAT-6 (ESXA).
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. Acts as a strong host (human) T-cell
CC antigen (PubMed:11940590). Involved in translocation of bacteria from
CC the host (human) phagolysosome to the host cytoplasm (PubMed:17604718).
CC Might serve as a chaperone to prevent uncontrolled membrane lysis by
CC its partner EsxA; native protein binds poorly to artificial liposomes
CC in the absence or presence of EsxA (PubMed:17557817, PubMed:26260636).
CC EsxA and EsxA-EsxB are cytotoxic to pneumocytes (PubMed:19906174). EsxB
CC (and EsxA-EsxB but not EsxA alone) activates human neutrophils; EsxB
CC transiently induces host (human) intracellular Ca(2+) mobility in a
CC dose-dependent manner, monocytes and lymphocytes do not respond
CC (PubMed:25332123). Neutrophils respond to EsxB by chemotaxis and primed
CC neutrophils treated with EsxB produce reactive oxygen species (ROS);
CC Ca(2+) release and the ROS burst via are induced by an unidentified G-
CC protein coupled receptor (PubMed:25332123). May help regulate assembly
CC and function of the type VII secretion system (T7SS) (PubMed:25865481).
CC {ECO:0000269|PubMed:11940590, ECO:0000269|PubMed:17557817,
CC ECO:0000269|PubMed:17604718, ECO:0000269|PubMed:19906174,
CC ECO:0000269|PubMed:25332123, ECO:0000269|PubMed:25865481,
CC ECO:0000305|PubMed:26260636}.
CC -!- SUBUNIT: Able to form a homodimer (By similarity). Forms a tight 1:1
CC complex with EsxA (ESAT-6) (PubMed:11940590, PubMed:14557536,
CC PubMed:16048998, PubMed:16973880, PubMed:19854905, PubMed:19906174,
CC PubMed:23150662, PubMed:26260636, PubMed:20085764, PubMed:15973432,
CC PubMed:24586681). The complex persists even after secretion
CC (PubMed:16048998). In vitro EsxB only interacts with non-acetylated
CC EsxA; it interacts with C-terminally truncated EsxA (missing the last
CC 10 residues) (PubMed:15378760). The native EsxA-EsxB complex
CC dissociates at pH 4.0, and EsxA may then be freed to then lyse
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 EccCb1 (PubMed:14557536,
CC PubMed:16973880, PubMed:25865481). Interacts with PPE68
CC (PubMed:17433643). Interacts with EccCa1, EccCb1, EsxA, EspI and EspJ
CC (PubMed:19854905). An artificial EsxB-EsxA heterodimer interacts with
CC EspA, EccB1, EccCa1, EccCb1, EspI, EspJ, EccA2 and EccE2; the latter 2
CC are from the adjacent ESX-2 locus (PubMed:19854905). Interacts with
CC host (human) beta-2-microglobulin (B2M) in complex with EsxA; only
CC binds free B2M and not B2M in complex with HLA-I (PubMed:25356553).
CC {ECO:0000250|UniProtKB:D1A4H0, ECO:0000269|PubMed:11940590,
CC ECO:0000269|PubMed:14557536, ECO:0000269|PubMed:15973432,
CC ECO:0000269|PubMed:16048998, ECO:0000269|PubMed:16973880,
CC ECO:0000269|PubMed:17433643, ECO:0000269|PubMed:17557817,
CC ECO:0000269|PubMed:19854905, ECO:0000269|PubMed:19906174,
CC ECO:0000269|PubMed:20085764, ECO:0000269|PubMed:23150662,
CC ECO:0000269|PubMed:24586681, ECO:0000269|PubMed:25356553,
CC ECO:0000269|PubMed:25865481, ECO:0000269|PubMed:26260636}.
CC -!- INTERACTION:
CC P9WNK5; P9WPC9: clpC1; NbExp=3; IntAct=EBI-1253936, EBI-1254029;
CC P9WNK5; P9WNB1: eccCb1; NbExp=3; IntAct=EBI-1253936, EBI-6514882;
CC P9WNK5; P9WNK7: esxA; NbExp=22; IntAct=EBI-1253936, EBI-1253925;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14557536,
CC ECO:0000269|PubMed:15378760, ECO:0000269|PubMed:16048998,
CC ECO:0000269|PubMed:9846755}. Secreted, cell wall
CC {ECO:0000269|PubMed:19906174}. Host cell surface
CC {ECO:0000269|PubMed:15973432, ECO:0000269|PubMed:19265145}. Host
CC endoplasmic reticulum {ECO:0000269|PubMed:25356553}. Note=Probably
CC secreted via the ESX-1 / type VII secretion system (T7SS)
CC (PubMed:19876390). Binds to CD14+ and CD19+ host (human) cells
CC (PubMed:19265145). Localized on the cell surface of host (human) cell
CC 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 (PubMed:25356553).
CC {ECO:0000269|PubMed:15973432, ECO:0000269|PubMed:19265145,
CC ECO:0000269|PubMed:19876390, ECO:0000269|PubMed:25356553}.
CC -!- INDUCTION: Constitutively expressed, part of the esxB-esxA operon
CC (PubMed:9846755). {ECO:0000269|PubMed:9846755}.
CC -!- DOMAIN: May be secreted as a 4 coiled-coil complex with EsxA
CC (PubMed:16048998). The C-terminal domain is required for interaction
CC with both EsxA and EccCb1; the last 7 amino acids are necessary and
CC sufficient for EccCb1 binding and secretion (PubMed:16973880).
CC {ECO:0000269|PubMed:16048998, ECO:0000269|PubMed:16973880}.
CC -!- DISRUPTION PHENOTYPE: Bacteria no longer translocate from the
CC phagolysosome to the cytosol of host (human) cells probably due to
CC polar effects on the downstream esxA gene; bacteria replicate in
CC phagolysosome, decreased apoptosis of infected host (human) dendritic
CC cells (PubMed:17604718). Loss of ability to lyse host (human) lung
CC epithelial cells, possibly due to polar effects on the downstream esxA
CC gene; in BALB/c-infected mice bacteria are not as invasive and cause
CC decreased lung disease (PubMed:14557547). No growth in the human
CC macrophage-like cell line THP-1, no cytotoxicity (PubMed:14756778).
CC Inactivation leads to absence of EsxA and EsxB from cell lysates
CC (PubMed:14756778, PubMed:16368961). No secretion of EspA
CC (PubMed:16030141). {ECO:0000269|PubMed:14557547,
CC ECO:0000269|PubMed:14756778, ECO:0000269|PubMed:16030141,
CC ECO:0000269|PubMed:16368961}.
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 quite important in this effect (PubMed:14557547,
CC PubMed:14756778, PubMed:16368961). {ECO:0000269|PubMed:14557547,
CC ECO:0000269|PubMed:14756778, ECO:0000269|PubMed:16368961}.
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 -!- SIMILARITY: Belongs to the WXG100 family. CFP-10 subfamily.
CC {ECO:0000305|PubMed:19876390}.
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DR EMBL; AF004671; AAC83445.1; -; Genomic_DNA.
DR EMBL; AF419854; AAL14999.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46703.1; -; Genomic_DNA.
DR PIR; H70802; H70802.
DR RefSeq; NP_218391.1; NC_000962.3.
DR RefSeq; WP_003399940.1; NZ_NVQJ01000074.1.
DR PDB; 1WA8; NMR; -; A=2-100.
DR PDB; 3FAV; X-ray; 2.15 A; A/C=1-100.
DR PDB; 6J19; X-ray; 1.98 A; B=1-100.
DR PDBsum; 1WA8; -.
DR PDBsum; 3FAV; -.
DR PDBsum; 6J19; -.
DR AlphaFoldDB; P9WNK5; -.
DR BMRB; P9WNK5; -.
DR SMR; P9WNK5; -.
DR IntAct; P9WNK5; 13.
DR MINT; P9WNK5; -.
DR STRING; 83332.Rv3874; -.
DR iPTMnet; P9WNK5; -.
DR PaxDb; P9WNK5; -.
DR DNASU; 886194; -.
DR GeneID; 45427878; -.
DR GeneID; 886194; -.
DR KEGG; mtu:Rv3874; -.
DR TubercuList; Rv3874; -.
DR eggNOG; COG4842; Bacteria.
DR OMA; DISANIH; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0044228; C:host cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0046812; F:host cell surface binding; IDA:MTBBASE.
DR GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
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; Cell wall; Chaperone; Coiled coil;
KW Direct protein sequencing; Host endoplasmic reticulum; Reference proteome;
KW Secreted; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9846755,
FT ECO:0007744|PubMed:21969609"
FT CHAIN 2..100
FT /note="ESAT-6-like protein EsxB"
FT /id="PRO_0000167796"
FT REGION 81..100
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..100
FT /note="Required for ESAT-6/CFP-10 complex to bind to host
FT macrophage and monocytes"
FT /evidence="ECO:0000269|PubMed:15973432"
FT COILED 7..42
FT /evidence="ECO:0000305|PubMed:16048998"
FT COILED 49..86
FT /evidence="ECO:0000255, ECO:0000305|PubMed:16048998"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT MUTAGEN 42
FT /note="Q->P: Abolishes EsxB-EsxA heterodimer interaction
FT with EccCb1 and EspA, maintains interaction with EccA2 and
FT EccE2."
FT /evidence="ECO:0000269|PubMed:19854905"
FT MUTAGEN 62
FT /note="A->S: Abolishes EsxB-EsxA heterodimer interaction
FT with EccCb1, weaker interaction with EspA, maintains
FT interaction with EccA2 and EccE2."
FT /evidence="ECO:0000269|PubMed:19854905"
FT MUTAGEN 94
FT /note="L->A: Abolishes interaction with EccCb1, but not
FT with EsxA."
FT /evidence="ECO:0000269|PubMed:16973880"
FT MUTAGEN 95
FT /note="S->T: Abolishes EsxB-EsxA heterodimer interaction
FT with EccCb1, maintains interaction with EspA, EccA2 and
FT EccE2."
FT /evidence="ECO:0000269|PubMed:19854905"
FT MUTAGEN 96
FT /note="S->A: No change in stability."
FT /evidence="ECO:0000269|PubMed:16973880"
FT MUTAGEN 98
FT /note="M->A: Abolishes interaction with EccCb1, but not
FT with EsxA. No change in stability, but loss of secretion."
FT /evidence="ECO:0000269|PubMed:16973880"
FT MUTAGEN 99
FT /note="G->A: Abolishes interaction with EccCb1, but not
FT with EsxA."
FT /evidence="ECO:0000269|PubMed:16973880"
FT MUTAGEN 100
FT /note="F->A: Abolishes interaction with EccCb1, but not
FT with EsxA. No change in stability, but loss of secretion."
FT /evidence="ECO:0000269|PubMed:16973880"
FT HELIX 2..10
FT /evidence="ECO:0007829|PDB:3FAV"
FT HELIX 12..37
FT /evidence="ECO:0007829|PDB:3FAV"
FT TURN 38..41
FT /evidence="ECO:0007829|PDB:3FAV"
FT HELIX 45..83
FT /evidence="ECO:0007829|PDB:3FAV"
FT TURN 89..94
FT /evidence="ECO:0007829|PDB:6J19"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:6J19"
SQ SEQUENCE 100 AA; 10794 MW; 285F4FC96F55D194 CRC64;
MAEMKTDAAT LAQEAGNFER ISGDLKTQID QVESTAGSLQ GQWRGAAGTA AQAAVVRFQE
AANKQKQELD EISTNIRQAG VQYSRADEEQ QQALSSQMGF
