ID   ETXD_STAAU              Reviewed;         258 AA.
AC   P20723;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   03-MAY-2023, entry version 98.
DE   RecName: Full=Enterotoxin type D;
DE   AltName: Full=SED;
DE   Flags: Precursor;
GN   Name=entD;
OS   Staphylococcus aureus.
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=1280;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2549000; DOI=10.1128/jb.171.9.4799-4806.1989;
RA   Bayles K.W., Iandolo J.J.;
RT   "Genetic and molecular analyses of the gene encoding staphylococcal
RT   enterotoxin D.";
RL   J. Bacteriol. 171:4799-4806(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN
RP   COMPLEX WITH ZINC, SUBUNIT, AND INTERACTION WITH HOST HLA-DRA AND HLA-DRB1.
RC   STRAIN=ATCC 23235 / NCTC 10656;
RX   PubMed=9003758; DOI=10.1002/j.1460-2075.1996.tb01074.x;
RA   Sundstroem M., Abrahmsen L., Antonsson P., Mehindate K., Mourad W.,
RA   Dohlsten M.;
RT   "The crystal structure of staphylococcal enterotoxin type D reveals Zn2+-
RT   mediated homodimerization.";
RL   EMBO J. 15:6832-6840(1996).
RN   [3]
RP   FUNCTION.
RX   PubMed=8621894;
RA   Domiati-Saad R., Attrep J.F., Brezinschek H.P., Cherrie A.H., Karp D.R.,
RA   Lipsky P.E.;
RT   "Staphylococcal enterotoxin D functions as a human B cell superantigen by
RT   rescuing VH4-expressing B cells from apoptosis.";
RL   J. Immunol. 156:3608-3620(1996).
RN   [4]
RP   FUNCTION, SUBUNIT, MUTAGENESIS OF PHE-72; ASP-212; HIS-248 AND ASP-252, AND
RP   INTERACTION WITH HOST HLA-DRB1.
RX   PubMed=9551975;
RA   Al-Daccak R., Mehindate K., Damdoumi F., Etongue-Mayer P., Nilsson H.,
RA   Antonsson P., Sundstroem M., Dohlsten M., Sekaly R.P., Mourad W.;
RT   "Staphylococcal enterotoxin D is a promiscuous superantigen offering
RT   multiple modes of interactions with the MHC class II receptors.";
RL   J. Immunol. 160:225-232(1998).
RN   [5]
RP   FUNCTION.
RX   PubMed=17306397; DOI=10.1016/j.ijfoodmicro.2006.10.050;
RA   Kerouanton A., Hennekinne J.A., Letertre C., Petit L., Chesneau O.,
RA   Brisabois A., De Buyser M.L.;
RT   "Characterization of Staphylococcus aureus strains associated with food
RT   poisoning outbreaks in France.";
RL   Int. J. Food Microbiol. 115:369-375(2007).
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. In turn,
CC       this ternary complex activates a large number of T-lymphocytes
CC       initiating a systemic release of pro-inflammatory cytokines
CC       (PubMed:9551975). In addition, induces B-cell proliferation and
CC       differentiation in the presence of T-cells (PubMed:8621894). Causes
CC       also the intoxication staphylococcal food poisoning syndrome
CC       (PubMed:17306397). {ECO:0000269|PubMed:17306397,
CC       ECO:0000269|PubMed:8621894, ECO:0000269|PubMed:9551975}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=A zinc-binding site contributes directly to formation of the
CC       homodimer. {ECO:0000269|PubMed:9003758};
CC   -!- SUBUNIT: Homodimer; zinc-dependent (PubMed:9003758). Interacts with MHC
CC       class II molecules composed of alpha/HLA-DRA and beta/HLA-DRB1 chains
CC       (PubMed:9003758, PubMed:9551975). {ECO:0000269|PubMed:9003758,
CC       ECO:0000269|PubMed:9551975}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the staphylococcal/streptococcal toxin family.
CC       {ECO:0000305}.
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DR   EMBL; M28521; AAB06195.1; -; Genomic_DNA.
DR   PIR; A33953; A33953.
DR   AlphaFoldDB; P20723; -.
DR   SMR; P20723; -.
DR   Allergome; 2142; Sta a SED.
DR   PRO; PR:P20723; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR   Gene3D; 2.40.50.110; -; 1.
DR   Gene3D; 3.10.20.120; -; 1.
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; Bacterial enterotoxins; 1.
DR   SUPFAM; SSF54334; Superantigen toxins, C-terminal domain; 1.
DR   PROSITE; PS00277; STAPH_STREP_TOXIN_1; 1.
DR   PROSITE; PS00278; STAPH_STREP_TOXIN_2; 1.
PE   1: Evidence at protein level;
KW   Enterotoxin; Metal-binding; Secreted; Signal; Superantigen; Toxin;
KW   Virulence; Zinc.
FT   SIGNAL          1..25
FT   CHAIN           26..258
FT                   /note="Enterotoxin type D"
FT                   /id="PRO_0000035612"
FT   BINDING         212
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000269|PubMed:9003758"
FT   BINDING         248
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /evidence="ECO:0000269|PubMed:9003758"
FT   BINDING         250
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000269|PubMed:9003758"
FT   BINDING         252
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared between two neighboring
FT                   subunits"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000269|PubMed:9003758"
FT   VARIANT         114
FT                   /note="P -> A (in strain: ATCC 23235)"
FT   MUTAGEN         72
FT                   /note="F->A: Complete loss of host cytokine gene
FT                   expression."
FT                   /evidence="ECO:0000269|PubMed:9551975"
FT   MUTAGEN         212
FT                   /note="D->A: Complete loss of host cytokine gene
FT                   expression."
FT                   /evidence="ECO:0000269|PubMed:9551975"
FT   MUTAGEN         248
FT                   /note="H->A: Complete loss of host cytokine gene
FT                   expression."
FT                   /evidence="ECO:0000269|PubMed:9551975"
FT   MUTAGEN         252
FT                   /note="D->A: Complete loss of host cytokine gene
FT                   expression."
FT                   /evidence="ECO:0000269|PubMed:9551975"
SQ   SEQUENCE   258 AA;  29746 MW;  4F7C6A28D42597FD CRC64;
     MKKFNILIAL LFFTSLVISP LNVKANENID SVKEKELHKK SELSSTALNN MKHSYADKNP
     IIGENKSTGD QFLENTLLYK KFFTDLINFE DLLINFNSKE MAQHFKSKNV DVYPIRYSIN
     CYGGEIDRTA CTYGGVTPHE GNKLKERKKI PINLWINGVQ KEVSLDKVQT DKKNVTVQEL
     DAQARRYLQK DLKLYNNDTL GGKIQRGKIE FDSSDGSKVS YDLFDVKGDF PEKQLRIYSD
     NKTLSTEHLH IDIYLYEK
//