ID STXA_SHIDY Reviewed; 315 AA. AC Q9FBI2; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 04-DEC-2007, sequence version 2. DT 02-SEP-2026, entry version 94. DE RecName: Full=Shiga toxin subunit A; DE EC=3.2.2.22; DE Flags: Precursor; GN Name=stxA; OS Shigella dysenteriae. OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Enterobacteriaceae; Shigella. OX NCBI_TaxID=622; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Kozlov Y.V., Kabishev A.A., Fedchenko V.I., Bayev A.A.; RT "Cloning and primary structure of Shigella toxin genes."; RL Dokl. Biochem. 295:744-749(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2830229; DOI=10.1128/jb.170.3.1116-1122.1988; RA Strockbine N.A., Jackson M.P., Sung L.M., Holmes R.K., O'Brien A.D.; RT "Cloning and sequencing of the genes for Shiga toxin from Shigella RT dysenteriae type 1."; RL J. Bacteriol. 170:1116-1122(1988). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3049254; DOI=10.1016/0378-1119(88)90398-8; RA Kozlov Y.V., Kabishev A.A., Lukyanov E.V., Bayev A.A.; RT "The primary structure of the operons coding for Shigella dysenteriae toxin RT and temperature phage H30 shiga-like toxin."; RL Gene 67:213-221(1988). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=H2765-39/81 / Type 1; RX PubMed=10948097; DOI=10.1128/iai.68.9.4856-4864.2000; RA Unkmeir A., Schmidt H.; RT "Structural analysis of phage-borne stx genes and their flanking sequences RT in shiga toxin-producing Escherichia coli and Shigella dysenteriae type 1 RT strains."; RL Infect. Immun. 68:4856-4864(2000). RN [5] RP EFFECT ON EUKARYOTIC RIBOSOME. RX PubMed=3276522; DOI=10.1111/j.1432-1033.1988.tb13756.x; RA Endo Y., Tsurugi K., Yutsudo T., Takeda Y., Ogasawara T., Igarashi K.; RT "Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of RT Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the RT toxins."; RL Eur. J. Biochem. 171:45-50(1988). RN [6] RP CLEAVAGE BY FURIN. RX PubMed=7738018; DOI=10.1074/jbc.270.18.10817; RA Garred O., van Deurs B., Sandvig K.; RT "Furin-induced cleavage and activation of Shiga toxin."; RL J. Biol. Chem. 270:10817-10821(1995). RN [7] RP MUTAGENESIS OF TRP-299; ASP-300; ARG-310 AND ARG-311. RX PubMed=7768810; DOI=10.1128/jb.177.11.3128-3132.1995; RA Jemal C., Haddad J.E., Begum D., Jackson M.P.; RT "Analysis of Shiga toxin subunit association by using hybrid A polypeptides RT and site-specific mutagenesis."; RL J. Bacteriol. 177:3128-3132(1995). RN [8] RP MUTAGENESIS OF PHE-248; ALA-253; ILE-254; LEU-255 AND GLY-256. RX PubMed=9784530; DOI=10.1128/iai.66.11.5252-5259.1998; RA Suhan M.L., Hovde C.J.; RT "Disruption of an internal membrane-spanning region in Shiga toxin 1 RT reduces cytotoxicity."; RL Infect. Immun. 66:5252-5259(1998). RN [9] RP CRYSTALLIZATION. RX PubMed=8345529; DOI=10.1006/jmbi.1993.1421; RA Kozlov Y.V., Chernaia M.M., Fraser M.E., James M.N.G.; RT "Purification and crystallization of Shiga toxin from Shigella RT dysenteriae."; RL J. Mol. Biol. 232:704-706(1993). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-315. RX PubMed=7656009; DOI=10.1038/nsb0194-59; RA Fraser M.E., Chernaia M.M., Kozlov Y.V., James M.N.G.; RT "Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A RT resolution."; RL Nat. Struct. Biol. 1:59-64(1994). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-315. 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 toxin contains a single subunit A and five copies of CC subunit B. CC -!- SIMILARITY: Belongs to the ribosome-inactivating protein family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07903; CAA30741.1; -; Genomic_DNA. DR EMBL; M19437; AAA98347.1; -; Genomic_DNA. DR EMBL; M24352; AAA26538.1; -; Genomic_DNA. DR EMBL; AJ271153; CAC05622.1; -; Genomic_DNA. DR RefSeq; WP_000691354.1; NZ_CP024466.1. DR PDB; 1DM0; X-ray; 2.50 A; A/L=23-309. DR PDB; 1R4Q; X-ray; 2.50 A; A/L=23-315. DR AlphaFoldDB; Q9FBI2; -. DR SMR; Q9FBI2; -. DR BindingDB; Q9FBI2; -. DR ChEMBL; CHEMBL3879822; -. DR DrugCentral; Q9FBI2; -. DR UniLectin; Q9FBI2; -. DR OMA; CNMKIII; -. DR BioCyc; MetaCyc:MONOMER-18743; -. DR EvolutionaryTrace; Q9FBI2; -. DR GO; GO:0030598; F:rRNA N-glycosylase activity; IEA:UniProtKB-EC. DR GO; GO:0017148; P:negative regulation of translation; IEA:InterPro. 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 NCBIfam; NF041694; Shig_StxA_1a; 1. DR NCBIfam; NF033658; Shiga_Stx1A; 1. DR PANTHER; PTHR33453; -; 1. DR PANTHER; PTHR33453:SF34; RIBOSOME-INACTIVATING PROTEIN; 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. DR PDBsum; 1DM0; -. DR PDBsum; 1R4Q; -. PE 1: Evidence at protein level; KW 3D-structure; Disulfide bond; Hydrolase; Protein synthesis inhibitor; KW Signal; Toxin; Virulence. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..315 FT /note="Shiga toxin subunit A" FT /id="PRO_0000312302" FT REGION 23..273 FT /note="A1" FT REGION 274..315 FT /note="A2" FT ACT_SITE 189 FT SITE 273..274 FT /note="Cleavage; by furin" FT DISULFID 264..283 FT /evidence="ECO:0000250" FT MUTAGEN 248 FT /note="F->Y: No effect on enzymatic activity; 10-fold FT decrease in cytotoxicity." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 253 FT /note="A->D: 225-fold decrease in cytotoxicity, probably FT due to reduced translocation across the ER membrane; when FT associated with E-256." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 253 FT /note="A->D: No effect on enzymatic activity; slight FT decrease in cytotoxicity." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 254 FT /note="I->E: No effect on enzymatic activity or FT cytotoxicity." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 255 FT /note="L->E: No effect on enzymatic activity or FT cytotoxicity." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 256 FT /note="G->E: 225-fold decrease in cytotoxicity, probably FT due to reduced translocation across the ER membrane; when FT associated with D-253." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 256 FT /note="G->E: No effect on enzymatic activity; slight FT decrease in cytotoxicity." FT /evidence="ECO:0000269|PubMed:9784530" FT MUTAGEN 299 FT /note="W->F,G: No effect on cytotoxicity." FT /evidence="ECO:0000269|PubMed:7768810" FT MUTAGEN 300 FT /note="D->K: Reduced subunit association and cytotoxicity." FT /evidence="ECO:0000269|PubMed:7768810" FT MUTAGEN 310 FT /note="R->E: Reduced subunit association and cytotoxicity." FT /evidence="ECO:0000269|PubMed:7768810" FT MUTAGEN 311 FT /note="R->E: Reduced subunit association and cytotoxicity." FT /evidence="ECO:0000269|PubMed:7768810" FT CONFLICT 190 FT /note="A -> P (in Ref. 2; CAA30741)" FT /evidence="ECO:0000305" FT STRAND 24..28 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 32..46 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 47..55 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 58..63 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 71..77 FT /evidence="ECO:0007829|PDB:1DM0" FT TURN 81..83 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 90..94 FT /evidence="ECO:0007829|PDB:1DM0" FT TURN 95..98 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 99..105 FT /evidence="ECO:0007829|PDB:1DM0" FT TURN 106..109 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 115..117 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 126..129 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 136..143 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 154..165 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 169..171 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 174..184 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 185..189 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 194..201 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 216..222 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 225..231 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 239..243 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 246..250 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 251..257 FT /evidence="ECO:0007829|PDB:1DM0" FT TURN 286..288 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:1DM0" FT STRAND 295..300 FT /evidence="ECO:0007829|PDB:1DM0" FT HELIX 301..307 FT /evidence="ECO:0007829|PDB:1DM0" SQ SEQUENCE 315 AA; 34814 MW; 8A423DF7ABF58F30 CRC64; MKIIIFRVLT FFFVIFSVNV VAKEFTLDFS TAKTYVDSLN VIRSAIGTPL QTISSGGTSL LMIDSGTGDN LFAVDVRGID PEEGRFNNLR LIVERNNLYV TGFVNRTNNV FYRFADFSHV TFPGTTAVTL SGDSSYTTLQ RVAGISRTGM QINRHSLTTS YLDLMSHSGT SLTQSVARAM LRFVTVTAEA LRFRQIQRGF RTTLDDLSGR SYVMTAEDVD LTLNWGRLSS VLPDYHGQDS VRVGRISFGS INAILGSVAL ILNCHHHASR VARMASDEFP SMCPADGRVR GITHNKILWD SSTLGAILMR RTISS //