ID   STXA_BP933              Reviewed;         319 AA.
AC   P09385; Q9R398;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   27-MAR-2024, entry version 125.
DE   RecName: Full=Shiga-like toxin 2 subunit A;
DE            Short=SLT-2 A subunit;
DE            Short=SLT-2a;
DE            Short=SLT-IIa;
DE            EC=3.2.2.22;
DE   AltName: Full=Verocytotoxin 2 subunit A;
DE   AltName: Full=Verotoxin 2 subunit A;
DE   AltName: Full=rRNA N-glycosidase 2;
DE   Flags: Precursor;
GN   Name=stxA2; Synonyms=stx2A; OrderedLocusNames=L0103;
OS   Escherichia phage 933W (Bacteriophage 933W).
OC   Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC   Sepvirinae; Traversvirus; Traversvirus tv933W.
OX   NCBI_TaxID=10730;
OH   NCBI_TaxID=83334; Escherichia coli O157:H7.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Jackson M.P., Neill R.J., O'Brien A.D., Holmes R.K., Newland J.W.;
RT   "Nucleotide sequence analysis and comparison of the structural genes for
RT   Shiga-like toxin I and Shiga-like toxin II encoded by bacteriophages from
RT   Escherichia coli 933.";
RL   FEMS Microbiol. Lett. 44:109-114(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=E32511;
RX   PubMed=1997410; DOI=10.1128/iai.59.3.1065-1073.1991;
RA   Schmitt C.K., McKee M.L., O'Brien A.D.;
RT   "Two copies of Shiga-like toxin II-related genes common in
RT   enterohemorrhagic Escherichia coli strains are responsible for the
RT   antigenic heterogeneity of the O157:H-strain E32511.";
RL   Infect. Immun. 59:1065-1073(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=OX3:H21;
RX   PubMed=8412629; DOI=10.1006/mpat.1993.1058;
RA   Paton A.W., Paton J.C., Manning P.A.;
RT   "Polymerase chain reaction amplification, cloning and sequencing of variant
RT   Escherichia coli Shiga-like toxin type II operons.";
RL   Microb. Pathog. 15:77-82(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9103976; DOI=10.1111/j.1574-6968.1997.tb10305.x;
RA   Schmidt H., Scheef J., Janetzki-Mittmann C., Datz M., Karch H.;
RT   "An ileX tRNA gene is located close to the Shiga toxin II operon in
RT   enterohemorrhagic Escherichia coli O157 and non-O157 strains.";
RL   FEMS Microbiol. Lett. 149:39-44(1997).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=16232431; DOI=10.1016/s1389-1723(99)80014-0;
RA   Kusumoto M., Nishiya Y., Kawamura Y., Shinagawa K.;
RT   "Identification of an insertion sequence, IS1203 variant, in a Shiga toxin
RT   2 gene of Escherichia coli O157:H7.";
RL   J. Biosci. Bioeng. 87:93-96(1999).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=FLY16;
RX   PubMed=10071501; DOI=10.1093/jmedent/36.1.108;
RA   Iwasa M., Makino S., Asakura H., Kobori H., Morimoto Y.;
RT   "Detection of Escherichia coli O157:H7 from Musca domestica (Diptera:
RT   Muscidae) at a cattle farm in Japan.";
RL   J. Med. Entomol. 36:108-112(1999).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=CS1718;
RA   Yu J.Y., Jeon H.G., Kang Y.H., Kim E.C., Sohn C.K., Lee B.K.;
RT   "Characterization of Shiga toxin genes in Shiga toxin-producing Escherichia
RT   coli isolated in Korea.";
RL   Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=11561972; DOI=10.1017/s0950268801005635;
RA   Asakura H., Makino S., Kobori H., Watarai M., Shirahata T., Ikeda T.,
RA   Takeshi K.;
RT   "Phylogenetic diversity and similarity of active sites of Shiga toxin (stx)
RT   in Shiga toxin-producing Escherichia coli (STEC) isolates from humans and
RT   animals.";
RL   Epidemiol. Infect. 127:27-36(2001).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=15466582; DOI=10.1128/aem.70.10.6309-6314.2004;
RA   De Baets L., Van der Taelen I., De Filette M., Pierard D., Allison L.,
RA   De Greve H., Hernalsteens J.P., Imberechts H.;
RT   "Genetic typing of shiga toxin 2 variants of Escherichia coli by PCR-
RT   restriction fragment length polymorphism analysis.";
RL   Appl. Environ. Microbiol. 70:6309-6314(2004).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10074068; DOI=10.1128/jb.181.6.1767-1778.1999;
RA   Plunkett G. III, Rose D.J., Durfee T.J., Blattner F.R.;
RT   "Sequence of Shiga toxin 2 phage 933W from Escherichia coli O157:H7: Shiga
RT   toxin as a phage late-gene product.";
RL   J. Bacteriol. 181:1767-1778(1999).
RN   [11]
RP   INDUCTION.
RX   PubMed=8550198; DOI=10.1128/iai.64.2.495-502.1996;
RA   Muhldorfer I., Hacker J., Keusch G.T., Acheson D.W., Tschape H., Kane A.V.,
RA   Ritter A., Olschlager T., Donohue-Rolfe A.;
RT   "Regulation of the Shiga-like toxin II operon in Escherichia coli.";
RL   Infect. Immun. 64:495-502(1996).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 23-319.
RX   PubMed=15075327; DOI=10.1074/jbc.m401939200;
RA   Fraser M.E., Fujinaga M., Cherney M.M., Melton-Celsa A.R., Twiddy E.M.,
RA   O'Brien A.D., James M.N.G.;
RT   "Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7.";
RL   J. Biol. Chem. 279:27511-27517(2004).
CC   -!- FUNCTION: The A subunit is responsible for inhibiting protein synthesis
CC       through the catalytic inactivation of 60S ribosomal subunits. After
CC       endocytosis, the A subunit is cleaved by furin in two fragments, A1 and
CC       A2: A1 is the catalytically active fragment, and A2 is essential for
CC       holotoxin assembly with the B subunits.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Endohydrolysis of the N-glycosidic bond at one specific
CC         adenosine on the 28S rRNA.; EC=3.2.2.22;
CC   -!- SUBUNIT: Shiga-like toxin contains a single A subunit and multiple
CC       copies of a B subunit.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the ribosome-inactivating protein family.
CC       {ECO:0000305}.
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DR   EMBL; X07865; CAA30714.1; -; Genomic_DNA.
DR   EMBL; M59432; AAA19623.1; -; Unassigned_DNA.
DR   EMBL; L11079; AAA16362.1; -; Unassigned_DNA.
DR   EMBL; Y10775; CAA71747.1; -; Genomic_DNA.
DR   EMBL; AB017524; BAA33759.1; -; Genomic_DNA.
DR   EMBL; AB015057; BAA34372.1; -; Genomic_DNA.
DR   EMBL; AF461167; AAM70033.1; -; Genomic_DNA.
DR   EMBL; AB048239; BAB83026.1; -; Genomic_DNA.
DR   EMBL; AB048240; BAB83028.1; -; Genomic_DNA.
DR   EMBL; AY443052; AAS07596.1; -; Genomic_DNA.
DR   EMBL; AF125520; AAD25445.1; -; Genomic_DNA.
DR   PIR; I76713; I76713.
DR   PIR; S01032; S01032.
DR   RefSeq; NP_049500.1; NC_000924.1.
DR   PDB; 1R4P; X-ray; 1.77 A; A=23-319.
DR   PDB; 2GA4; X-ray; 1.80 A; A=23-319.
DR   PDB; 7UJJ; EM; 6.50 A; A=23-319.
DR   PDBsum; 1R4P; -.
DR   PDBsum; 2GA4; -.
DR   PDBsum; 7UJJ; -.
DR   EMDB; EMD-26563; -.
DR   SMR; P09385; -.
DR   IntAct; P09385; 1.
DR   ChEMBL; CHEMBL4662932; -.
DR   GeneID; 1261950; -.
DR   KEGG; vg:1261950; -.
DR   OrthoDB; 4295at10239; -.
DR   EvolutionaryTrace; P09385; -.
DR   Proteomes; UP000002135; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0030598; F:rRNA N-glycosylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0098676; P:modulation of host virulence by virus; IEA:UniProtKB-KW.
DR   GO; GO:0017148; P:negative regulation of translation; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.420.10; Ricin (A subunit), domain 1; 1.
DR   Gene3D; 4.10.470.10; Ricin (A Subunit), domain 2; 1.
DR   InterPro; IPR036041; Ribosome-inact_prot_sf.
DR   InterPro; IPR001574; Ribosome_inactivat_prot.
DR   InterPro; IPR017988; Ribosome_inactivat_prot_CS.
DR   InterPro; IPR016138; Ribosome_inactivat_prot_sub1.
DR   InterPro; IPR016139; Ribosome_inactivat_prot_sub2.
DR   InterPro; IPR016331; Shiga-like_toxin_subunit_A.
DR   PANTHER; PTHR33453; -; 1.
DR   PANTHER; PTHR33453:SF48; RRNA N-GLYCOSYLASE; 1.
DR   Pfam; PF00161; RIP; 1.
DR   PIRSF; PIRSF001924; Shigella_toxin_subunit_A; 1.
DR   SUPFAM; SSF56371; Ribosome inactivating proteins (RIP); 1.
DR   PROSITE; PS00275; SHIGA_RICIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Hydrolase;
KW   Modulation of host virulence by virus; Protein synthesis inhibitor;
KW   Reference proteome; Secreted; Signal; Toxin; Viral exotoxin; Virulence.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   CHAIN           23..319
FT                   /note="Shiga-like toxin 2 subunit A"
FT                   /id="PRO_0000030792"
FT   REGION          23..272
FT                   /note="A1"
FT                   /evidence="ECO:0000250"
FT   REGION          273..314
FT                   /note="A2"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        189
FT                   /evidence="ECO:0000250"
FT   SITE            272..273
FT                   /note="Cleavage; by furin"
FT                   /evidence="ECO:0000250"
FT   DISULFID        263..282
FT   VARIANT         17
FT                   /note="S -> P (in strain: OX3:H21)"
FT   VARIANT         26
FT                   /note="T -> M (in strain: OX3:H21)"
FT   VARIANT         277
FT                   /note="E -> D (in strain: FLY16 and CS1718)"
FT   STRAND          24..28
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           32..46
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          47..55
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          58..63
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          71..77
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          89..94
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   TURN            95..97
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          100..105
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   TURN            106..109
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          110..113
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           115..117
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          125..129
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           136..143
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           154..166
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          169..171
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           174..186
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           188..192
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           194..201
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           202..204
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           215..222
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           224..230
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           231..233
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          240..242
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          245..247
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           250..256
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          284..287
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          290..293
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   STRAND          296..299
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           300..306
FT                   /evidence="ECO:0007829|PDB:1R4P"
FT   HELIX           312..317
FT                   /evidence="ECO:0007829|PDB:1R4P"
SQ   SEQUENCE   319 AA;  35714 MW;  98F73319ACAE48D6 CRC64;
     MKCILFKWVL CLLLGFSSVS YSREFTIDFS TQQSYVSSLN SIRTEISTPL EHISQGTTSV
     SVINHTPPGS YFAVDIRGLD VYQARFDHLR LIIEQNNLYV AGFVNTATNT FYRFSDFTHI
     SVPGVTTVSM TTDSSYTTLQ RVAALERSGM QISRHSLVSS YLALMEFSGN TMTRDASRAV
     LRFVTVTAEA LRFRQIQREF RQALSETAPV YTMTPGDVDL TLNWGRISNV LPEYRGEDGV
     RVGRISFNNI SAILGTVAVI LNCHHQGARS VRAVNEESQP ECQITGDRPV IKINNTLWES
     NTAAAFLNRK SQFLYTTGK
//