ID   ESXA_MYCS2              Reviewed;          95 AA.
AC   A0QNJ6;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2007, sequence version 1.
DT   25-MAY-2022, entry version 102.
DE   RecName: Full=ESAT-6-like protein EsxA {ECO:0000303|PubMed:19854905};
GN   Name=esxA {ECO:0000303|PubMed:19854905};
GN   OrderedLocusNames=MSMEG_0066, MSMEI_0067;
OS   Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS   smegmatis).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycolicibacterium.
OX   NCBI_TaxID=246196;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RA   Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA   Fraser C.M.;
RL   Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA   Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA   Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT   "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT   mutations or sequencing errors?";
RL   Genome Biol. 8:R20.1-R20.9(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=18955433; DOI=10.1101/gr.081901.108;
RA   Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA   Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT   "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT   and a new MS-based protocol.";
RL   Genome Res. 19:128-135(2009).
RN   [4]
RP   SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=15687187; DOI=10.1128/jb.187.4.1238-1245.2005;
RA   Converse S.E., Cox J.S.;
RT   "A protein secretion pathway critical for Mycobacterium tuberculosis
RT   virulence is conserved and functional in Mycobacterium smegmatis.";
RL   J. Bacteriol. 187:1238-1245(2005).
RN   [5]
RP   SUBUNIT.
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   [6]
RP   SUBUNIT.
RC   STRAIN=ATCC 700084 / mc(2)155;
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   [7]
RP   FUNCTION, AND SUBUNIT.
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   [8]
RP   FUNCTION, AND MUTAGENESIS OF 25-THR-ALA-26 AND ALA-26.
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).
CC   -!- FUNCTION: An exported protein. Unlike its M.tuberculosis counterpart
CC       has poor pore forming ability in artificial liposomes, does not undergo
CC       conformational change at acidic pH (PubMed:23150662). Mutation of 2
CC       residues to those found in M.tuberculosis (25-TA-26 to IH) alters the
CC       properties of this protein so that it inserts into liposomes at acidic
CC       pH, forming pores, like its M.tuberculosis counterpart
CC       (PubMed:26801203). {ECO:0000269|PubMed:23150662,
CC       ECO:0000269|PubMed:26801203}.
CC   -!- SUBUNIT: Forms a tight 1:1 complex with EsxB (PubMed:19854905,
CC       PubMed:20085764, PubMed:23150662). An artificial EsxA-EsxB heterodimer
CC       interacts with EspA (PubMed:19854905). {ECO:0000269|PubMed:19854905,
CC       ECO:0000269|PubMed:20085764, ECO:0000269|PubMed:23150662}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15687187}.
CC       Note=Probably secreted via the ESX-1 / type VII secretion system
CC       (T7SS). Accumulates in the cell and is secreted when grown in Saunton's
CC       medium, when grown in 7H9 medium protein only accumulates
CC       intracellularly (PubMed:15687187). {ECO:0000269|PubMed:15687187,
CC       ECO:0000305}.
CC   -!- DISRUPTION PHENOTYPE: No secretion of EsxB, very little EsxB protein
CC       accumulates intracellularly (PubMed:15687187).
CC       {ECO:0000269|PubMed:15687187}.
CC   -!- MISCELLANEOUS: To improve over-expression in E.coli the proteins were
CC       cloned as a single protein in the (non-native) order esxA-esxB with a
CC       cleavable thrombin tag (PubMed:19854905).
CC       {ECO:0000269|PubMed:19854905}.
CC   -!- SIMILARITY: Belongs to the WXG100 family. ESAT-6 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; CP000480; ABK75559.1; -; Genomic_DNA.
DR   EMBL; CP001663; AFP36549.1; -; Genomic_DNA.
DR   RefSeq; WP_003891394.1; NZ_SIJM01000058.1.
DR   RefSeq; YP_884484.1; NC_008596.1.
DR   AlphaFoldDB; A0QNJ6; -.
DR   SMR; A0QNJ6; -.
DR   STRING; 246196.MSMEI_0067; -.
DR   EnsemblBacteria; ABK75559; ABK75559; MSMEG_0066.
DR   EnsemblBacteria; AFP36549; AFP36549; MSMEI_0067.
DR   GeneID; 66738256; -.
DR   KEGG; msg:MSMEI_0067; -.
DR   KEGG; msm:MSMEG_0066; -.
DR   PATRIC; fig|246196.19.peg.64; -.
DR   eggNOG; COG4842; Bacteria.
DR   OMA; QAVQMRW; -.
DR   OrthoDB; 1930308at2; -.
DR   Proteomes; UP000000757; Chromosome.
DR   Proteomes; UP000006158; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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   Reference proteome; Secreted.
FT   CHAIN           1..95
FT                   /note="ESAT-6-like protein EsxA"
FT                   /id="PRO_0000437932"
FT   MUTAGEN         25..26
FT                   /note="TA->IH: Forms pores in liposomes, responds to pH
FT                   changes, changes residues to resemble M.tuberculosis
FT                   protein."
FT                   /evidence="ECO:0000269|PubMed:26801203"
FT   MUTAGEN         26
FT                   /note="A->H: Does not form pores in liposomes, like wild-
FT                   type protein."
FT                   /evidence="ECO:0000269|PubMed:26801203"
SQ   SEQUENCE   95 AA;  9738 MW;  471E3F67D3AAB7ED CRC64;
     MTEQVWNFAG IEGGASEIHG AVSTTAGLLD EGKASLTTLA SAWGGTGSEA YQAVQARWDS
     TSNELNLALQ NLAQTISEAG QTMAQTEAGV TGMFA