ETXA_STAAU
ID ETXA_STAAU Reviewed; 257 AA.
AC P0A0L2; P13163;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Enterotoxin type A;
DE AltName: Full=SEA;
DE Flags: Precursor;
GN Name=entA;
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=FRI337;
RX PubMed=3335483; DOI=10.1128/jb.170.1.34-41.1988;
RA Betley M.J., Mekalanos J.J.;
RT "Nucleotide sequence of the type A staphylococcal enterotoxin gene.";
RL J. Bacteriol. 170:34-41(1988).
RN [2]
RP PROTEIN SEQUENCE OF 25-257.
RX PubMed=3584106; DOI=10.1016/s0021-9258(18)48194-x;
RA Huang I.-Y., Hughes J.L., Bergdoll M.S., Schantz E.J.;
RT "Complete amino acid sequence of staphylococcal enterotoxin A.";
RL J. Biol. Chem. 262:7006-7013(1987).
RN [3]
RP FUNCTION, AND INTERACTION WITH MHC CLASS II ANTIGEN DR1/HLA-DRB1 AND
RP HLA-DRA.
RX PubMed=2658055; DOI=10.1126/science.2658055;
RA Mollick J.A., Cook R.G., Rich R.R.;
RT "Class II MHC molecules are specific receptors for staphylococcus
RT enterotoxin A.";
RL Science 244:817-820(1989).
RN [4]
RP REVIEW ON FUNCTION.
RX PubMed=22069659; DOI=10.3390/toxins2071751;
RA Argudin M.A., Mendoza M.C., Rodicio M.R.;
RT "Food poisoning and Staphylococcus aureus enterotoxins.";
RL Toxins 2:1751-1773(2010).
RN [5]
RP FUNCTION.
RX PubMed=23321986; DOI=10.1038/mi.2012.138;
RA Kumar S., Colpitts S.L., Menoret A., Budelsky A.L., Lefrancois L.,
RA Vella A.T.;
RT "Rapid alphabeta T-cell responses orchestrate innate immunity in response
RT to Staphylococcal enterotoxin A.";
RL Mucosal Immunol. 6:1006-1015(2013).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=7628431; DOI=10.1002/j.1460-2075.1995.tb07336.x;
RA Schad E.M., Zaitseva I., Zaitsev V.N., Dohlsten M., Kalland T.,
RA Schlievert P.M., Ohlendorf D.H., Svensson L.A.;
RT "Crystal structure of the superantigen staphylococcal enterotoxin type A.";
RL EMBO J. 14:3292-3301(1995).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH ZINC.
RX PubMed=8943278; DOI=10.1074/jbc.271.50.32212;
RA Sundstroem M., Hallen D., Svensson A., Schad E., Dohlsten M., Abrahmsen L.;
RT "The Co-crystal structure of staphylococcal enterotoxin type A with Zn2+ at
RT 2.7-A resolution. Implications for major histocompatibility complex class
RT II binding.";
RL J. Biol. Chem. 271:32212-32216(1996).
RN [8]
RP 3D-STRUCTURE MODELING.
RX PubMed=7552730; DOI=10.1038/nsb0895-680;
RA Swaminathan S., Furey W.F. Jr., Pletcher J., Sax M.;
RT "Residues defining V beta specificity in staphylococcal enterotoxins.";
RL Nat. Struct. Biol. 2:680-686(1995).
RN [9]
RP COMPARISON OF STRUCTURE OF SEA AND SEC2.
RX PubMed=9191070; DOI=10.1006/jmbi.1997.1023;
RA Schad E.M., Papageorgiou A.C., Svensson L.A., Acharya K.R.;
RT "A structural and functional comparison of staphylococcal enterotoxins A
RT and C2 reveals remarkable similarity and dissimilarity.";
RL J. Mol. Biol. 269:270-280(1997).
RN [10] {ECO:0007744|PDB:1I4G, ECO:0007744|PDB:1I4H}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH ZINC, AND
RP MUTAGENESIS OF HIS-211.
RX PubMed=11713682; DOI=10.1007/s007750100251;
RA Haakansson M., Antonsson P., Bjoerk P., Svensson L.A.;
RT "Cooperative zinc binding in a staphylococcal enterotoxin A mutant mimics
RT the SEA-MHC class II interaction.";
RL J. Biol. Inorg. Chem. 6:757-762(2001).
RN [11] {ECO:0007744|PDB:1DYQ}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEX WITH ZINC, AND
RP INTERACTION WITH MHC CLASS II ANTIGEN DR1/HLA-DRB1 AND HLA-DRA.
RX PubMed=11847286; DOI=10.1110/ps.39702;
RA Krupka H.I., Segelke B.W., Ulrich R.G., Ringhofer S., Knapp M., Rupp B.;
RT "Structural basis for abrogated binding between staphylococcal enterotoxin
RT A superantigen vaccine and MHC-IIalpha.";
RL Protein Sci. 11:642-651(2002).
RN [12] {ECO:0007744|PDB:1LO5}
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS), MUTAGENESIS OF ASP-251, INTERACTION
RP WITH HOST HLA-DRA, AND FUNCTION.
RX PubMed=12467569; DOI=10.1016/s0969-2126(02)00895-x;
RA Petersson K., Thunnissen M., Forsberg G., Walse B.;
RT "Crystal structure of a SEA variant in complex with MHC class II reveals
RT the ability of SEA to crosslink MHC molecules.";
RL Structure 10:1619-1626(2002).
RN [13] {ECO:0007744|PDB:5FK9}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS), FUNCTION, INTERACTION WITH HOST T
RP CELL RECEPTOR BETA VARIABLE 7-9/TRBV7-9, AND DISULFIDE BOND.
RX PubMed=27180909; DOI=10.1038/srep25796;
RA Rodstrom K.E., Regenthal P., Bahl C., Ford A., Baker D.,
RA Lindkvist-Petersson K.;
RT "Two common structural motifs for TCR recognition by staphylococcal
RT enterotoxins.";
RL Sci. Rep. 6:25796-25796(2016).
CC -!- FUNCTION: Staphylococcal enterotoxin that activates the host immune
CC system by binding as unprocessed molecules to major histocompatibility
CC (MHC) complex class II and T-cell receptor (TCR) molecules
CC (PubMed:2658055, PubMed:12467569). In turn, waves of cellular
CC activation, cytokine production, and migration into the lung tissue and
CC airways occur via alphabeta T-cells (PubMed:23321986). Causes also the
CC intoxication staphylococcal food poisoning syndrome. The illness is
CC characterized by high fever, hypotension, diarrhea, shock, and in some
CC cases death (Probable). {ECO:0000269|PubMed:12467569,
CC ECO:0000269|PubMed:23321986, ECO:0000269|PubMed:2658055,
CC ECO:0000305|PubMed:22069659}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit. The zinc ion is necessary for the
CC toxin interaction with MHC class II.;
CC -!- SUBUNIT: Monomer. Interacts with MHC class II molecules alpha/HLA-DRB1
CC and beta/HLA-DRA chains (PubMed:2658055, PubMed:12467569,
CC PubMed:11847286). The interaction with MHC-II molecules occurs at both
CC zinc-dependent and zinc-independent sites (PubMed:2658055,
CC PubMed:12467569). Interacts with T-cell receptor beta variable 7-
CC 9/TRBV7-9 (PubMed:27180909). {ECO:0000269|PubMed:11847286,
CC ECO:0000269|PubMed:12467569, ECO:0000269|PubMed:2658055,
CC ECO:0000269|PubMed:27180909}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- MISCELLANEOUS: This toxin seems to be coded by a bacteriophage.
CC -!- SIMILARITY: Belongs to the staphylococcal/streptococcal toxin family.
CC {ECO:0000305}.
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DR EMBL; M18970; AAA26681.1; -; Genomic_DNA.
DR PIR; A28664; A28664.
DR RefSeq; WP_000750412.1; NZ_WOFG01000001.1.
DR PDB; 1DYQ; X-ray; 1.50 A; A=25-257.
DR PDB; 1ESF; X-ray; 1.90 A; A/B=25-257.
DR PDB; 1I4G; X-ray; 2.10 A; A/B=25-257.
DR PDB; 1I4H; X-ray; 2.90 A; A/B=25-257.
DR PDB; 1LO5; X-ray; 3.20 A; D=25-257.
DR PDB; 1SXT; X-ray; 2.70 A; A/B=25-257.
DR PDB; 5FK9; X-ray; 3.10 A; C=25-257.
DR PDBsum; 1DYQ; -.
DR PDBsum; 1ESF; -.
DR PDBsum; 1I4G; -.
DR PDBsum; 1I4H; -.
DR PDBsum; 1LO5; -.
DR PDBsum; 1SXT; -.
DR PDBsum; 5FK9; -.
DR AlphaFoldDB; P0A0L2; -.
DR SMR; P0A0L2; -.
DR DIP; DIP-58974N; -.
DR IntAct; P0A0L2; 1.
DR Allergome; 2139; Sta a SEA.
DR OMA; NGNKHES; -.
DR EvolutionaryTrace; P0A0L2; -.
DR PRO; PR:P0A0L2; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042289; F:MHC class II protein binding; IPI:BHF-UCL.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR InterPro; IPR008992; Enterotoxin.
DR InterPro; IPR006126; Staph/Strept_toxin_CS.
DR InterPro; IPR006173; Staph_tox_OB.
DR InterPro; IPR016091; SuperAg_toxin_C.
DR InterPro; IPR013307; Superantigen_bac.
DR InterPro; IPR006123; Toxin_b-grasp_Staph/Strep.
DR InterPro; IPR006177; Toxin_bac.
DR Pfam; PF02876; Stap_Strp_tox_C; 1.
DR Pfam; PF01123; Stap_Strp_toxin; 1.
DR PRINTS; PR00279; BACTRLTOXIN.
DR PRINTS; PR01898; SAGSUPRFAMLY.
DR SUPFAM; SSF50203; SSF50203; 1.
DR SUPFAM; SSF54334; SSF54334; 1.
DR PROSITE; PS00277; STAPH_STREP_TOXIN_1; 1.
DR PROSITE; PS00278; STAPH_STREP_TOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Enterotoxin;
KW Metal-binding; Secreted; Signal; Superantigen; Toxin; Zinc.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:3584106"
FT CHAIN 25..257
FT /note="Enterotoxin type A"
FT /id="PRO_0000035604"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:11847286,
FT ECO:0007744|PDB:1DYQ"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:11713682,
FT ECO:0000269|PubMed:11847286, ECO:0007744|PDB:1DYQ,
FT ECO:0007744|PDB:1I4G, ECO:0007744|PDB:1I4H"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:11713682,
FT ECO:0000269|PubMed:11847286, ECO:0007744|PDB:1DYQ,
FT ECO:0007744|PDB:1I4G, ECO:0007744|PDB:1I4H"
FT DISULFID 120..130
FT /evidence="ECO:0000269|PubMed:27180909,
FT ECO:0007744|PDB:5FK9"
FT MUTAGEN 211
FT /note="H->A: Almost 10-fold reduction of the binding to
FT major histocompatibility complex (MHC) class II."
FT /evidence="ECO:0000269|PubMed:11713682"
FT MUTAGEN 251
FT /note="D->A: Loss of interaction with the beta chain of
FT HLA-DR1 through the zinc-dependent site."
FT /evidence="ECO:0000269|PubMed:12467569"
FT CONFLICT 242
FT /note="T -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 28..31
FT /evidence="ECO:0007829|PDB:1ESF"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:1DYQ"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:1DYQ"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:5FK9"
FT HELIX 46..55
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 84..87
FT /evidence="ECO:0007829|PDB:1SXT"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:1DYQ"
FT HELIX 98..104
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:1DYQ"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 122..124
FT /evidence="ECO:0007829|PDB:1ESF"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1SXT"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1DYQ"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:1SXT"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 166..175
FT /evidence="ECO:0007829|PDB:1DYQ"
FT HELIX 176..191
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:5FK9"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 205..211
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 218..221
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:1ESF"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:1DYQ"
FT HELIX 233..237
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:1DYQ"
FT STRAND 249..255
FT /evidence="ECO:0007829|PDB:1DYQ"
SQ SEQUENCE 257 AA; 29669 MW; ADEBF5BCA1F14677 CRC64;
MKKTAFTLLL FIALTLTTSP LVNGSEKSEE INEKDLRKKS ELQGTALGNL KQIYYYNEKA
KTENKESHDQ FLQHTILFKG FFTDHSWYND LLVDFDSKDI VDKYKGKKVD LYGAYYGYQC
AGGTPNKTAC MYGGVTLHDN NRLTEEKKVP INLWLDGKQN TVPLETVKTN KKNVTVQELD
LQARRYLQEK YNLYNSDVFD GKVQRGLIVF HTSTEPSVNY DLFGAQGQYS NTLLRIYRDN
KTINSENMHI DIYLYTS