ESPB_MYCTU
ID ESPB_MYCTU Reviewed; 460 AA.
AC P9WJD9; L0TH12; Q933K8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=ESX-1 secretion-associated protein EspB {ECO:0000305};
DE AltName: Full=Antigen MTB48 {ECO:0000305};
GN Name=espB {ECO:0000303|PubMed:17676952};
GN Synonyms=mtb48 {ECO:0000303|PubMed:11427558}; OrderedLocusNames=Rv3881c;
GN ORFNames=MTV027.16c;
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].
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=11427558; DOI=10.1128/jcm.39.7.2485-2493.2001;
RA Lodes M.J., Dillon D.C., Mohamath R., Day C.H., Benson D.R., Reynolds L.D.,
RA McNeill P., Sampaio D.P., Skeiky Y.A.W., Badaro R., Persing D.H.,
RA Reed S.G., Houghton R.L.;
RT "Serological expression cloning and immunological evaluation of MTB48, a
RT novel Mycobacterium tuberculosis antigen.";
RL J. Clin. Microbiol. 39:2485-2493(2001).
RN [2]
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 [3]
RP PROTEIN SEQUENCE OF 2-10.
RC STRAIN=NTI-83949;
RX PubMed=12586418; DOI=10.1016/s0378-1097(02)01185-0;
RA Satchidanandam V., Amara R.R., Uchil P.D., Singh V.;
RT "The regulatory elements of the Mycobacterium tuberculosis gene Rv3881c
RT function efficiently in Escherichia coli.";
RL FEMS Microbiol. Lett. 218:365-370(2003).
RN [4]
RP INTERACTION WITH ESPK, SUBCELLULAR LOCATION, CLEAVAGE, AND GENE NAME.
RX PubMed=17676952; DOI=10.1371/journal.ppat.0030105;
RA McLaughlin B., Chon J.S., MacGurn J.A., Carlsson F., Cheng T.L., Cox J.S.,
RA Brown E.J.;
RT "A mycobacterium ESX-1-secreted virulence factor with unique requirements
RT for export.";
RL PLoS Pathog. 3:E105-E105(2007).
RN [5]
RP CLEAVAGE BY MYCP1.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=20227664; DOI=10.1016/j.chom.2010.02.006;
RA Ohol Y.M., Goetz D.H., Chan K., Shiloh M.U., Craik C.S., Cox J.S.;
RT "Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation
RT of ESX-1 secretion and virulence.";
RL Cell Host Microbe 7:210-220(2010).
RN [6]
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 [7]
RP CLEAVAGE BY MYCP1.
RX PubMed=23620593; DOI=10.1074/jbc.m113.462036;
RA Solomonson M., Huesgen P.F., Wasney G.A., Watanabe N., Gruninger R.J.,
RA Prehna G., Overall C.M., Strynadka N.C.;
RT "Structure of the mycosin-1 protease from the mycobacterial ESX-1 protein
RT type VII secretion system.";
RL J. Biol. Chem. 288:17782-17790(2013).
RN [8]
RP CLEAVAGE BY MYCP1.
RX PubMed=24113528; DOI=10.1016/j.jsb.2013.09.022;
RA Wagner J.M., Evans T.J., Chen J., Zhu H., Houben E.N., Bitter W.,
RA Korotkov K.V.;
RT "Understanding specificity of the mycosin proteases in ESX/type VII
RT secretion by structural and functional analysis.";
RL J. Struct. Biol. 184:115-128(2013).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23869560; DOI=10.1111/mmi.12336;
RA Chen J.M., Zhang M., Rybniker J., Boy-Roettger S., Dhar N., Pojer F.,
RA Cole S.T.;
RT "Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-
RT independent virulence.";
RL Mol. Microbiol. 89:1154-1166(2013).
RN [10]
RP FUNCTION IN VIRULENCE.
RC STRAIN=H37Rv;
RX PubMed=25641595; DOI=10.1016/j.jmii.2014.11.008;
RA Huang D., Bao L.;
RT "Mycobacterium tuberculosis EspB protein suppresses interferon-gamma-
RT induced autophagy in murine macrophages.";
RL J. Microbiol. Immunol. Infect. 49:859-865(2016).
RN [11]
RP 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 [12] {ECO:0007744|PDB:4XWP, ECO:0007744|PDB:4XXN, ECO:0007744|PDB:4XXX, ECO:0007744|PDB:4XY3}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 7-278, SUBUNIT, AND DOMAIN.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=26051906; DOI=10.1016/j.jsb.2015.06.003;
RA Korotkova N., Piton J., Wagner J.M., Boy-Rottger S., Japaridze A.,
RA Evans T.J., Cole S.T., Pojer F., Korotkov K.V.;
RT "Structure of EspB, a secreted substrate of the ESX-1 secretion system of
RT Mycobacterium tuberculosis.";
RL J. Struct. Biol. 191:236-244(2015).
RN [13] {ECO:0007744|PDB:3J83}
RP STRUCTURE BY ELECTRON MICROSCOPY (30.00 ANGSTROMS) OF 1-348.
RX PubMed=25684576; DOI=10.1016/j.str.2015.01.002;
RA Solomonson M., Setiaputra D., Makepeace K.A., Lameignere E.,
RA Petrotchenko E.V., Conrady D.G., Bergeron J.R., Vuckovic M., DiMaio F.,
RA Borchers C.H., Yip C.K., Strynadka N.C.;
RT "Structure of EspB from the ESX-1 type VII secretion system and insights
RT into its export mechanism.";
RL Structure 23:571-583(2015).
CC -!- FUNCTION: Required for host-cell death and may support an EsxA-
CC independent virulence function (PubMed:23869560). Secreted processed
CC form of EspB binds to phosphatidic acid and phosphatidylserine
CC (PubMed:23869560). Inhibits IFN-gamma-induced autophagy in murine
CC macrophages (PubMed:25641595). {ECO:0000269|PubMed:23869560,
CC ECO:0000269|PubMed:25641595}.
CC -!- SUBUNIT: Mature EspB oligomerizes and forms donut-shaped rings. In
CC contrast, the full-length protein does not oligomerize
CC (PubMed:26051906). Interacts with the C-terminal region of EspK
CC (PubMed:17676952). {ECO:0000269|PubMed:17676952,
CC ECO:0000269|PubMed:26051906}.
CC -!- INTERACTION:
CC P9WJD9; P9WJD9: espB; NbExp=7; IntAct=EBI-16143320, EBI-16143320;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17676952,
CC ECO:0000269|PubMed:23869560}. Note=Secreted via the ESX-1 / type VII
CC secretion system (T7SS) (PubMed:17676952). Secretion requires both EspK
CC and EccCb1, but not EspA, EspC and EspD (PubMed:17676952,
CC PubMed:23869560). {ECO:0000269|PubMed:17676952,
CC ECO:0000269|PubMed:23869560}.
CC -!- DOMAIN: The N-terminal region contains a fused PE/PPE homology domain.
CC The C-terminal region is disordered. {ECO:0000269|PubMed:26051906}.
CC -!- PTM: Cleaved in the C-terminal region by MycP1 (PubMed:17676952,
CC PubMed:20227664, PubMed:23620593, PubMed:24113528). The exact location
CC of the cleavage sites has been the subject of conflicting reports
CC (PubMed:20227664, PubMed:23620593). Further in vitro studies confirmed
CC that Ala-358 is the primary cleavage site and Ala-386 is a secondary
CC cleavage site (PubMed:24113528). Likely translocated as a full-length
CC protein into the periplasm, where it is proteolyzed by MycP1
CC (PubMed:17676952, PubMed:20227664). Proteolysis may serve to limit the
CC secretion of other ESX-1 substrates (PubMed:20227664).
CC {ECO:0000269|PubMed:17676952, ECO:0000269|PubMed:20227664,
CC ECO:0000269|PubMed:23620593, ECO:0000269|PubMed:24113528}.
CC -!- MISCELLANEOUS: BTP15, an inhibitor of ESX-1 secretion, decreases
CC secretion of 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 (PubMed:25299337).
CC {ECO:0000269|PubMed:25299337}.
CC -!- SIMILARITY: Belongs to the EspB family. {ECO:0000305}.
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DR EMBL; AY029285; AAK31576.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP46710.1; -; Genomic_DNA.
DR PIR; G70803; G70803.
DR RefSeq; NP_218398.1; NC_000962.3.
DR RefSeq; WP_003399995.1; NZ_KK339374.1.
DR PDB; 3J83; EM; 30.00 A; A/B/C/D/E/F/G=1-348.
DR PDB; 4XWP; X-ray; 1.82 A; A=7-278.
DR PDB; 4XXN; X-ray; 2.14 A; A=7-278.
DR PDB; 4XXX; X-ray; 1.50 A; A=7-278.
DR PDB; 4XY3; X-ray; 3.04 A; A=1-460.
DR PDB; 6XZC; EM; 3.37 A; A/B/C/D/E/F/G=1-460.
DR PDB; 7P13; EM; 2.29 A; A/B/C/D/E/F/G=2-287.
DR PDBsum; 3J83; -.
DR PDBsum; 4XWP; -.
DR PDBsum; 4XXN; -.
DR PDBsum; 4XXX; -.
DR PDBsum; 4XY3; -.
DR PDBsum; 6XZC; -.
DR PDBsum; 7P13; -.
DR AlphaFoldDB; P9WJD9; -.
DR SMR; P9WJD9; -.
DR STRING; 83332.Rv3881c; -.
DR iPTMnet; P9WJD9; -.
DR PaxDb; P9WJD9; -.
DR DNASU; 886214; -.
DR GeneID; 45427884; -.
DR GeneID; 886214; -.
DR KEGG; mtu:Rv3881c; -.
DR TubercuList; Rv3881c; -.
DR eggNOG; ENOG50341Q7; Bacteria.
DR OMA; MAPMHGA; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0051701; P:biological process involved in interaction with host; IMP:MTBBASE.
DR GO; GO:0044315; P:protein secretion by the type VII secretion system; IMP:MTBBASE.
DR Gene3D; 1.20.1260.20; -; 1.
DR InterPro; IPR041275; EspB_PE.
DR InterPro; IPR038332; PPE_sf.
DR Pfam; PF18625; EspB_PE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Reference proteome;
KW Secreted; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12586418,
FT ECO:0007744|PubMed:21969609"
FT CHAIN 2..460
FT /note="ESX-1 secretion-associated protein EspB"
FT /id="PRO_0000096612"
FT REGION 92..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..441
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 358..359
FT /note="Cleavage; by MycP1"
FT /evidence="ECO:0000269|PubMed:23620593,
FT ECO:0000269|PubMed:24113528"
FT SITE 386..387
FT /note="Cleavage; by MycP1"
FT /evidence="ECO:0000269|PubMed:23620593,
FT ECO:0000269|PubMed:24113528"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:4XXX"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:4XXX"
FT HELIX 40..88
FT /evidence="ECO:0007829|PDB:4XXX"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:7P13"
FT HELIX 133..141
FT /evidence="ECO:0007829|PDB:4XXX"
FT HELIX 147..164
FT /evidence="ECO:0007829|PDB:4XXX"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:4XXX"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:4XY3"
FT HELIX 179..222
FT /evidence="ECO:0007829|PDB:4XXX"
FT HELIX 226..238
FT /evidence="ECO:0007829|PDB:4XXX"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:4XXX"
FT HELIX 243..267
FT /evidence="ECO:0007829|PDB:4XXX"
SQ SEQUENCE 460 AA; 47594 MW; 7528743226AD7A71 CRC64;
MTQSQTVTVD QQEILNRANE VEAPMADPPT DVPITPCELT AAKNAAQQLV LSADNMREYL
AAGAKERQRL ATSLRNAAKA YGEVDEEAAT ALDNDGEGTV QAESAGAVGG DSSAELTDTP
RVATAGEPNF MDLKEAARKL ETGDQGASLA HFADGWNTFN LTLQGDVKRF RGFDNWEGDA
ATACEASLDQ QRQWILHMAK LSAAMAKQAQ YVAQLHVWAR REHPTYEDIV GLERLYAENP
SARDQILPVY AEYQQRSEKV LTEYNNKAAL EPVNPPKPPP AIKIDPPPPP QEQGLIPGFL
MPPSDGSGVT PGTGMPAAPM VPPTGSPGGG LPADTAAQLT SAGREAAALS GDVAVKAASL
GGGGGGGVPS APLGSAIGGA ESVRPAGAGD IAGLGQGRAG GGAALGGGGM GMPMGAAHQG
QGGAKSKGSQ QEDEALYTED RAWTEAVIGN RRRQDSKESK
