ID   ESXO_MYCTU              Reviewed;          94 AA.
AC   P9WNI7; L0T9C9; P95242;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 34.
DE   RecName: Full=ESAT-6-like protein EsxO {ECO:0000305};
GN   Name=esxO {ECO:0000303|PubMed:19876390, ECO:0000303|PubMed:24312350};
GN   OrderedLocusNames=Rv2346c; ORFNames=MTCY98.15c;
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 [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   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX   PubMed=12919853; DOI=10.1016/s1286-4579(03)00179-5;
RA   He X.Y., Zhuang Y.H., Zhang X.G., Li G.L.;
RT   "Comparative proteome analysis of culture supernatant proteins of
RT   Mycobacterium tuberculosis H37Rv and H37Ra.";
RL   Microbes Infect. 5:851-856(2003).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX   PubMed=17443846; DOI=10.1002/pmic.200600853;
RA   Malen H., Berven F.S., Fladmark K.E., Wiker H.G.;
RT   "Comprehensive analysis of exported proteins from Mycobacterium
RT   tuberculosis H37Rv.";
RL   Proteomics 7:1702-1718(2007).
RN   [4]
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   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [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   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=26786654; DOI=10.1016/j.tube.2015.11.006;
RA   Mohanty S., Dal Molin M., Ganguli G., Padhi A., Jena P., Selchow P.,
RA   Sengupta S., Meuli M., Sander P., Sonawane A.;
RT   "Mycobacterium tuberculosis EsxO (Rv2346c) promotes bacillary survival by
RT   inducing oxidative stress mediated genomic instability in macrophages.";
RL   Tuberculosis 96:44-57(2016).
RN   [7] {ECO:0007744|PDB:3OGI, ECO:0007744|PDB:4GZR}
RP   X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS), AND INTERACTION WITH ESXP.
RX   PubMed=24312350; DOI=10.1371/journal.pone.0081753;
RA   Arbing M.A., Chan S., Harris L., Kuo E., Zhou T.T., Ahn C.J., Nguyen L.,
RA   He Q., Lu J., Menchavez P.T., Shin A., Holton T., Sawaya M.R., Cascio D.,
RA   Eisenberg D.;
RT   "Heterologous expression of mycobacterial Esx complexes in Escherichia coli
RT   for structural studies is facilitated by the use of maltose binding protein
RT   fusions.";
RL   PLoS ONE 8:E81753-E81753(2013).
CC   -!- FUNCTION: Plays an important role in mycobacterial pathogenesis in the
CC       context of innate immunity. Aids host cell invasion and intracellular
CC       bacillary persistence. Increases host oxidative stress response,
CC       leading to genomic instability and decrease in macrophage viability.
CC       Also induces autophagy and modulates the immune function of
CC       macrophages. {ECO:0000269|PubMed:26786654}.
CC   -!- SUBUNIT: Forms a complex with EsxP. {ECO:0000269|PubMed:24312350}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12919853,
CC       ECO:0000269|PubMed:17443846}. Note=Probably secreted via the ESX-5 /
CC       type VII secretion system (T7SS). {ECO:0000305|PubMed:19876390}.
CC   -!- DISRUPTION PHENOTYPE: Deletion mutant does not show any difference in
CC       intracellular survival and oxidative stress responses.
CC       {ECO:0000269|PubMed:26786654}.
CC   -!- SIMILARITY: Belongs to the WXG100 family. ESAT-6 subfamily.
CC       {ECO:0000305|PubMed:19876390}.
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DR   EMBL; AL123456; CCP45134.1; -; Genomic_DNA.
DR   PIR; C70662; C70662.
DR   RefSeq; NP_216862.1; NC_000962.3.
DR   RefSeq; WP_003899283.1; NZ_NVQJ01000012.1.
DR   PDB; 3OGI; X-ray; 2.55 A; A/C=1-94.
DR   PDB; 4GZR; X-ray; 2.55 A; A/C=1-94.
DR   PDBsum; 3OGI; -.
DR   PDBsum; 4GZR; -.
DR   AlphaFoldDB; P9WNI7; -.
DR   SMR; P9WNI7; -.
DR   IntAct; P9WNI7; 8.
DR   MINT; P9WNI7; -.
DR   STRING; 83332.Rv2346c; -.
DR   PaxDb; P9WNI7; -.
DR   DNASU; 888956; -.
DR   GeneID; 888956; -.
DR   KEGG; mtu:Rv2346c; -.
DR   TubercuList; Rv2346c; -.
DR   eggNOG; ENOG5032I3T; Bacteria.
DR   OMA; CQEFISQ; -.
DR   PhylomeDB; P9WNI7; -.
DR   PHI-base; PHI:5581; -.
DR   PHI-base; PHI:8519; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR   GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   InterPro; IPR009416; ESAT-6-like_Myco.
DR   InterPro; IPR036689; ESAT-6-like_sf.
DR   InterPro; IPR010310; T7SS_ESAT-6-like.
DR   Pfam; PF06013; WXG100; 1.
DR   PIRSF; PIRSF037656; DUF1066; 1.
DR   SUPFAM; SSF140453; SSF140453; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Reference proteome; Secreted; Virulence.
FT   CHAIN           1..94
FT                   /note="ESAT-6-like protein EsxO"
FT                   /id="PRO_0000167814"
FT   HELIX           14..37
FT                   /evidence="ECO:0007829|PDB:3OGI"
FT   HELIX           39..42
FT                   /evidence="ECO:0007829|PDB:4GZR"
FT   HELIX           51..66
FT                   /evidence="ECO:0007829|PDB:3OGI"
SQ   SEQUENCE   94 AA;  9954 MW;  C740622D0BB7C8CA CRC64;
     MTINYQFGDV DAHGAMIRAQ AGLLEAEHQA IVRDVLAAGD FWGGAGSVAC QEFITQLGRN
     FQVIYEQANA HGQKVQAAGN NMAQTDSAVG SSWA