Reviewed, UniProtKB/Swiss-Prot Q9FBI2 (STXA_SHIDY)

Names and origin

Protein names

Recommended name:
    Shiga toxin subunit A
    EC=3.2.2.22

Gene names

Name:

stxA

Organism

Shigella dysenteriae

Taxonomic identifier

622 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Shigella

Protein attributes

Sequence length	315 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The A subunit is responsible for inhibiting protein synthesis through the catalytic inactivation of 60S ribosomal subunits. After endocytosis, the A subnit is cleaved by furin in two fragments, A1 and A2: A1 is the catalytically active fragment, and A2 is essential for holotoxin assembly with the B subunits.
Catalytic activity	Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
Subunit structure	Shiga toxin contains a single subunit A and five copies of subunit B.
Sequence similarities	Belongs to the ribosome-inactivating protein family.

Ontologies

Keywords
Domain	Signal
Molecular function	Hydrolase Protein synthesis inhibitor Toxin
PTM	Disulfide bond
Technical term	3D-structure
Gene Ontology (GO)
Biological process	negative regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	rRNA N-glycosylase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 315

293

Shiga toxin subunit A

PRO_0000312302

Regions

Region

23 – 273

251

A1

Region

274 – 315

42

A2

Sites

Active site

189

1

Site

273 – 274

2

Cleavage; by furin

Amino acid modifications

Disulfide bond

264 ↔ 283

By similarity

Experimental info

Mutagenesis

248

1

F → Y: No effect on enzymatic activity; 10-fold decrease in cytotoxicity. Ref.8

Mutagenesis

253

1

A → D: 225-fold decrease in cytotoxicity, probably due to reduced translocation across the ER membrane; when associated with E-256. Ref.8

Mutagenesis

253

1

A → D: No effect on enzymatic activity; slight decrease in cytotoxicity. Ref.8

Mutagenesis

254

1

I → E: No effect on enzymatic activity or cytotoxicity. Ref.8

Mutagenesis

255

1

L → E: No effect on enzymatic activity or cytotoxicity. Ref.8

Mutagenesis

256

1

G → E: 225-fold decrease in cytotoxicity, probably due to reduced translocation across the ER membrane; when associated with D-253. Ref.8

Mutagenesis

256

1

G → E: No effect on enzymatic activity; slight decrease in cytotoxicity. Ref.8

Mutagenesis

299

1

W → F or G: No effect on cytotoxicity. Ref.7

Mutagenesis

300

1

D → K: Reduced subunit association and cytotoxicity. Ref.7

Mutagenesis

310

1

R → E: Reduced subunit association and cytotoxicity. Ref.7

Mutagenesis

311

1

R → E: Reduced subunit association and cytotoxicity. Ref.7

Sequence conflict

190

1

A → P in CAA30741. Ref.2

Secondary structure

1

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315

Helix Strand Turn

Details...

Beta strand

24 – 28

5

Helix

32 – 45

14

Beta strand

49 – 54

6

Beta strand

59 – 62

4

Beta strand

71 – 77

7

Beta strand

90 – 94

5

Turn

95 – 98

4

Turn

106 – 108

3

Beta strand

110 – 113

4

Helix

115 – 117

3

Beta strand

126 – 129

4

Helix

136 – 142

7

Helix

154 – 165

12

Helix

174 – 192

19

Helix

194 – 197

4

Helix

201 – 204

4

Helix

216 – 222

7

Helix

228 – 231

4

Helix

232 – 234

3

Beta strand

240 – 242

3

Helix

251 – 254

4

Beta strand

295 – 299

5

Turn

301 – 303

3

Sequences

	Sequence		Length	Mass (Da)
	Q9FBI2-1 [UniParc]. Last modified December 4, 2007. Version 2. Checksum: 8A423DF7ABF58F30	FASTA	315	34,814
	10 20 30 40 50 60 MKIIIFRVLT FFFVIFSVNV VAKEFTLDFS TAKTYVDSLN VIRSAIGTPL QTISSGGTSL 70 80 90 100 110 120 LMIDSGTGDN LFAVDVRGID PEEGRFNNLR LIVERNNLYV TGFVNRTNNV FYRFADFSHV 130 140 150 160 170 180 TFPGTTAVTL SGDSSYTTLQ RVAGISRTGM QINRHSLTTS YLDLMSHSGT SLTQSVARAM 190 200 210 220 230 240 LRFVTVTAEA LRFRQIQRGF RTTLDDLSGR SYVMTAEDVD LTLNWGRLSS VLPDYHGQDS 250 260 270 280 290 300 VRVGRISFGS INAILGSVAL ILNCHHHASR VARMASDEFP SMCPADGRVR GITHNKILWD 310 SSTLGAILMR RTISS

References

[1]	"Cloning and primary structure of Shigella toxin genes." Kozlov Y.V., Kabishev A.A., Fedchenko V.I., Bayev A.A. Dokl. Biochem. 295:744-749(1987) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning and sequencing of the genes for Shiga toxin from Shigella dysenteriae type 1." Strockbine N.A., Jackson M.P., Sung L.M., Holmes R.K., O'Brien A.D. J. Bacteriol. 170:1116-1122(1988) [PubMed: 2830229] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The primary structure of the operons coding for Shigella dysenteriae toxin and temperature phage H30 shiga-like toxin." Kozlov Y.V., Kabishev A.A., Lukyanov E.V., Bayev A.A. Gene 67:213-221(1988) [PubMed: 3049254] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Structural analysis of phage-borne stx genes and their flanking sequences in shiga toxin-producing Escherichia coli and Shigella dysenteriae type 1 strains." Unkmeir A., Schmidt H. Infect. Immun. 68:4856-4864(2000) [PubMed: 10948097] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: H2765-39/81 / Type 1.
[5]	"Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins." Endo Y., Tsurugi K., Yutsudo T., Takeda Y., Ogasawara T., Igarashi K. Eur. J. Biochem. 171:45-50(1988) [PubMed: 3276522] [Abstract] Cited for: EFFECT ON EUKARYOTIC RIBOSOME.
[6]	"Furin-induced cleavage and activation of Shiga toxin." Garred O., van Deurs B., Sandvig K. J. Biol. Chem. 270:10817-10821(1995) [PubMed: 7738018] [Abstract] Cited for: CLEAVAGE BY FURIN.
[7]	"Analysis of Shiga toxin subunit association by using hybrid A polypeptides and site-specific mutagenesis." Jemal C., Haddad J.E., Begum D., Jackson M.P. J. Bacteriol. 177:3128-3132(1995) [PubMed: 7768810] [Abstract] Cited for: MUTAGENESIS OF TRP-299; ASP-300; ARG-310 AND ARG-311.
[8]	"Disruption of an internal membrane-spanning region in Shiga toxin 1 reduces cytotoxicity." Suhan M.L., Hovde C.J. Infect. Immun. 66:5252-5259(1998) [PubMed: 9784530] [Abstract] Cited for: MUTAGENESIS OF PHE-248; ALA-253; ILE-254; LEU-255 AND GLY-256.
[9]	"Purification and crystallization of Shiga toxin from Shigella dysenteriae." Kozlov Y.V., Chernaia M.M., Fraser M.E., James M.N.G. J. Mol. Biol. 232:704-706(1993) [PubMed: 8345529] [Abstract] Cited for: CRYSTALLIZATION.
[10]	"Crystal structure of the holotoxin from Shigella dysenteriae at 2.5 A resolution." Fraser M.E., Chernaia M.M., Kozlov Y.V., James M.N.G. Nat. Struct. Biol. 1:59-64(1994) [PubMed: 7656009] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-315.
[11]	"Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7." Fraser M.E., Fujinaga M., Cherney M.M., Melton-Celsa A.R., Twiddy E.M., O'Brien A.D., James M.N.G. J. Biol. Chem. 279:27511-27517(2004) [PubMed: 15075327] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-315.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X07903 Genomic DNA. Translation: CAA30741.1.
M19437 Genomic DNA. Translation: AAA98347.1.
M24352 Genomic DNA. Translation: AAA26538.1.
AJ271153 Genomic DNA. Translation: CAC05622.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DM0	X-ray	2.50	A/L	23-309	[»]
1R4Q	X-ray	2.50	A/L	23-315	[»]

ModBase

Search...

Enzyme and pathway databases

BRENDA

3.2.2.22. 118928.

Family and domain databases

InterPro

IPR001574. Ribosome_inactivat_prot.
IPR017988. Ribosome_inactivat_prot_CS.
IPR016138. Ribosome_inactivat_prot_sub1.
IPR016139. Ribosome_inactivat_prot_sub2.
IPR016331. Shiga-like_toxin_subunit_A.
[Graphical view]

Gene3D

G3DSA:3.40.420.10. Ribosome_inactivat_prot_sub1. 1 hit.
G3DSA:4.10.470.10. Ribosome_inactivat_prot_sub2. 1 hit.

Pfam

PF00161. RIP. 1 hit.
[Graphical view]

PIRSF

PIRSF001924. Shigella_toxin_subunit_A. 1 hit.

PROSITE

PS00275. SHIGA_RICIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

STXA_SHIDY

Accession

Primary (citable) accession number: Q9FBI2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 4, 2007
Last sequence update:	December 4, 2007
Last modified:	January 19, 2010
This is version 40 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)