VIRA_SHIFL
ID VIRA_SHIFL Reviewed; 400 AA.
AC Q7BU69; Q52295; Q6XVV7; Q7BEL1; Q8VSF1;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Cysteine protease-like VirA;
DE EC=3.4.22.-;
DE AltName: Full=Effector protein VirA;
GN Name=virA; OrderedLocusNames=CP0181; ORFNames=pWR501_0191;
OS Shigella flexneri.
OG Plasmid pWR100, Plasmid pCP301, Plasmid pMYSH6000, and
OG Plasmid pINV_F6_M1382.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Shigella.
OX NCBI_TaxID=623;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP REGULATION BY VIRB.
RC STRAIN=YSH6000 / Serotype 2a; PLASMID=pMYSH6000;
RX PubMed=7494473; DOI=10.1111/j.1365-2958.1995.mmi_17020241.x;
RA Uchiya K., Tobe T., Komatsu K., Suzuki T., Watarai M., Fukuda I.,
RA Yoshikawa M., Sasakawa C.;
RT "Identification of a novel virulence gene, virA, on the large plasmid of
RT Shigella, involved in invasion and intercellular spreading.";
RL Mol. Microbiol. 17:241-250(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-10; 40-53 AND
RP 134-144, AND TRANSCRIPTIONAL REGULATION.
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=9582283; DOI=10.1093/emboj/17.10.2894;
RA Demers B., Sansonetti P.J., Parsot C.;
RT "Induction of type III secretion in Shigella flexneri is associated with
RT differential control of transcription of genes encoding secreted
RT proteins.";
RL EMBO J. 17:2894-2903(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-10, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=11115111; DOI=10.1046/j.1365-2958.2000.02179.x;
RA Buchrieser C., Glaser P., Rusniok C., Nedjari H., d'Hauteville H.,
RA Kunst F., Sansonetti P.J., Parsot C.;
RT "The virulence plasmid pWR100 and the repertoire of proteins secreted by
RT the type III secretion apparatus of Shigella flexneri.";
RL Mol. Microbiol. 38:760-771(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=11292750; DOI=10.1128/iai.69.5.3271-3285.2001;
RA Venkatesan M.M., Goldberg M.B., Rose D.J., Grotbeck E.J., Burland V.,
RA Blattner F.R.;
RT "Complete DNA sequence and analysis of the large virulence plasmid of
RT Shigella flexneri.";
RL Infect. Immun. 69:3271-3285(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=M1382 / Serotype 6; PLASMID=pINV_F6_M1382;
RX PubMed=14573649; DOI=10.1128/iai.71.11.6298-6306.2003;
RA Lan R., Stevenson G., Reeves P.R.;
RT "Comparison of two major forms of the Shigella virulence plasmid pINV:
RT positive selection is a major force driving the divergence.";
RL Infect. Immun. 71:6298-6306(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=301 / Serotype 2a; PLASMID=pCP301;
RX PubMed=12384590; DOI=10.1093/nar/gkf566;
RA Jin Q., Yuan Z., Xu J., Wang Y., Shen Y., Lu W., Wang J., Liu H., Yang J.,
RA Yang F., Zhang X., Zhang J., Yang G., Wu H., Qu D., Dong J., Sun L.,
RA Xue Y., Zhao A., Gao Y., Zhu J., Kan B., Ding K., Chen S., Cheng H.,
RA Yao Z., He B., Chen R., Ma D., Qiang B., Wen Y., Hou Y., Yu J.;
RT "Genome sequence of Shigella flexneri 2a: insights into pathogenicity
RT through comparison with genomes of Escherichia coli K12 and O157.";
RL Nucleic Acids Res. 30:4432-4441(2002).
RN [7]
RP TRANSCRIPTIONAL INDUCTION BY MXIE AND IPGC.
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=11971264; DOI=10.1046/j.1365-2958.2002.02836.x;
RA Mavris M., Page A.-L., Tournebize R., Demers B., Sansonetti P.J.,
RA Parsot C.;
RT "Regulation of transcription by the activity of the Shigella flexneri type
RT III secretion apparatus.";
RL Mol. Microbiol. 43:1543-1553(2002).
RN [8]
RP FUNCTION, TUBULIN BINDING, AND SUBUNIT.
RC STRAIN=YSH6000 / Serotype 2a; PLASMID=pMYSH6000;
RX PubMed=12065406; DOI=10.1093/emboj/cdf319;
RA Yoshida S., Katayama E., Kuwae A., Mimuro H., Suzuki T., Sasakawa C.;
RT "Shigella deliver an effector protein to trigger host microtubule
RT destabilization, which promotes Rac1 activity and efficient bacterial
RT internalization.";
RL EMBO J. 21:2923-2935(2002).
RN [9]
RP REGULATION BY MXIE, AND INDUCTION.
RC STRAIN=ATCC 700930 / 2457T / Serotype 2a; PLASMID=pWR100;
RX PubMed=12142411; DOI=10.1128/jb.184.16.4409-4419.2002;
RA Kane C.D., Schuch R., Day W.A. Jr., Maurelli A.T.;
RT "MxiE regulates intracellular expression of factors secreted by the
RT Shigella flexneri 2a type III secretion system.";
RL J. Bacteriol. 184:4409-4419(2002).
RN [10]
RP REGULATION BY MXIE AND IPGC.
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=12446624; DOI=10.1128/jb.184.24.6751-6759.2002;
RA Mavris M., Sansonetti P.J., Parsot C.;
RT "Identification of the cis-acting site involved in activation of promoters
RT regulated by activity of the type III secretion apparatus in Shigella
RT flexneri.";
RL J. Bacteriol. 184:6751-6759(2002).
RN [11]
RP REGULATION BY MXIE AND VIRB, AND INDUCTION.
RC STRAIN=M90T / Serotype 5a; PLASMID=pWR100;
RX PubMed=15758240; DOI=10.1099/mic.0.27639-0;
RA Le Gall T., Mavris M., Martino M.C., Bernardini M.L., Denamur E.,
RA Parsot C.;
RT "Analysis of virulence plasmid gene expression defines three classes of
RT effectors in the type III secretion system of Shigella flexneri.";
RL Microbiology 151:951-962(2005).
RN [12]
RP FUNCTION, CYSTEINE PROTEASE ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS
RP OF CYS-34.
RC STRAIN=YSH6000 / Serotype 2a; PLASMID=pMYSH6000;
RX PubMed=17095701; DOI=10.1126/science.1133174;
RA Yoshida S., Handa Y., Suzuki T., Ogawa M., Suzuki M., Tamai A., Abe A.,
RA Katayama E., Sasakawa C.;
RT "Microtubule-severing activity of Shigella is pivotal for intercellular
RT spreading.";
RL Science 314:985-989(2006).
CC -!- FUNCTION: Alpha-tubulin-specific protease that is required for entry
CC into epithelial cells and for subsequent intra- and intercellular
CC spreading. Contributes to bacterial entry into epithelial cells by
CC inducing microtubule (MT) destabilization and the formation of membrane
CC ruffles. The membrane ruffling evoked by VirA results from the
CC activation of host rac1, which is associated with the destruction of MT
CC networks. Creates a tunnel inside the host cell cytoplasm by breaking
CC down the microtubule infrastructure. This facilitates the bacterium's
CC movement through the cytoplasm and also helps other bacteria move
CC faster during the invasion of the eukaryotic cell. Is absolutely
CC required for virulence. {ECO:0000269|PubMed:12065406,
CC ECO:0000269|PubMed:17095701, ECO:0000269|PubMed:7494473}.
CC -!- ACTIVITY REGULATION: Inhibited by the cysteine protease inhibitors
CC leupeptin and cystatin-C. {ECO:0000269|PubMed:17095701}.
CC -!- SUBUNIT: Monomer. Interacts specifically with alpha tubulin, a major
CC component of microtubule. {ECO:0000269|PubMed:12065406}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11115111,
CC ECO:0000269|PubMed:7494473}. Note=Translocated into the host cell via
CC the type III secretion system (TTSS). Localizes in the cytoplasm of the
CC infected cell.
CC -!- INDUCTION: Transcriptionally activated by VirB and MxiE, in association
CC with IpgC, upon invasion of the eukaryotic cell. Induced at 37 degrees
CC Celsius. {ECO:0000269|PubMed:12142411, ECO:0000269|PubMed:15758240,
CC ECO:0000269|PubMed:9582283}.
CC -!- SIMILARITY: Belongs to the protease EspG/VirA family. {ECO:0000305}.
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DR EMBL; D26468; BAA05480.1; -; Genomic_DNA.
DR EMBL; AF047364; AAC23713.1; -; Genomic_DNA.
DR EMBL; AL391753; CAC05836.1; -; Genomic_DNA.
DR EMBL; AF348706; AAK18501.1; -; Genomic_DNA.
DR EMBL; AY206441; AAP79023.1; -; Genomic_DNA.
DR EMBL; AF386526; AAL72296.2; -; Genomic_DNA.
DR PIR; S70187; S70187.
DR RefSeq; NP_085345.1; NC_002698.1.
DR RefSeq; NP_858314.2; NC_004851.1.
DR RefSeq; WP_001195004.1; NZ_WPGT01000147.1.
DR RefSeq; YP_009062518.1; NC_024996.1.
DR PDB; 3EB8; X-ray; 2.40 A; A/B=45-400.
DR PDB; 3EE1; X-ray; 3.01 A; A/B=14-400.
DR PDB; 4FMB; X-ray; 3.20 A; A/C/E=45-400.
DR PDBsum; 3EB8; -.
DR PDBsum; 3EE1; -.
DR PDBsum; 4FMB; -.
DR AlphaFoldDB; Q7BU69; -.
DR SMR; Q7BU69; -.
DR IntAct; Q7BU69; 2.
DR STRING; 198214.CP0181; -.
DR PRIDE; Q7BU69; -.
DR EnsemblBacteria; AAL72296; AAL72296; SF_p0181.
DR GeneID; 1237992; -.
DR KEGG; sfl:CP0181; -.
DR PATRIC; fig|198214.7.peg.5432; -.
DR HOGENOM; CLU_688663_0_0_6; -.
DR OMA; KCEIDEM; -.
DR EvolutionaryTrace; Q7BU69; -.
DR Proteomes; UP000001006; Plasmid pCP301.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.10.450.460; -; 1.
DR InterPro; IPR009669; Cys_protease_VirA/EspG.
DR InterPro; IPR043098; Cys_protease_VirA/EspG_N.
DR Pfam; PF06872; EspG; 1.
DR PIRSF; PIRSF011515; EspG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hydrolase; Plasmid; Protease;
KW Reference proteome; Secreted; Thiol protease; Virulence.
FT CHAIN 1..400
FT /note="Cysteine protease-like VirA"
FT /id="PRO_0000297842"
FT REGION 224..315
FT /note="Tubulin-binding domain"
FT ACT_SITE 34
FT /evidence="ECO:0000255"
FT VARIANT 36
FT /note="I -> V (in plasmid pINV_F6_M1382)"
FT VARIANT 56
FT /note="H -> Y (in plasmid pINV_F6_M1382)"
FT VARIANT 173
FT /note="H -> P (in plasmid pINV_F6_M1382)"
FT VARIANT 239
FT /note="V -> L (in plasmid pINV_F6_M1382)"
FT MUTAGEN 34
FT /note="C->S: Decreases alpha-tubulin degradation, bacterial
FT motility, and virulence."
FT /evidence="ECO:0000269|PubMed:17095701"
FT CONFLICT 8
FT /note="Missing (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 54..63
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:3EE1"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:3EE1"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 126..129
FT /evidence="ECO:0007829|PDB:4FMB"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:3EB8"
FT TURN 176..181
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 182..191
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3EE1"
FT HELIX 209..218
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:3EE1"
FT HELIX 236..246
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 252..263
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 268..276
FT /evidence="ECO:0007829|PDB:3EB8"
FT TURN 280..283
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 287..307
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 315..325
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 342..354
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 357..369
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 377..383
FT /evidence="ECO:0007829|PDB:3EB8"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:3EB8"
FT STRAND 390..399
FT /evidence="ECO:0007829|PDB:3EB8"
SQ SEQUENCE 400 AA; 44735 MW; DDA0422BF215688F CRC64;
MQTSNITNHE RNDSSWMSTV KSTTEVSWNK LSFCDILLKI ITFGIYSPHE TLAEKHSEKK
LMDSFSPSLS QDKMDGEFAH ANIDGISIRL CLNKGICSVF YLDGDKIQST QLSSKEYNNL
LSSLPPKQFN LGKVHTITAP VSGNFKTHKP APEVIETAIN CCTSIIPNDD YFHVKDTDFN
SVWHDIYRDI RASDSNSTKI YFNNIEIPLK LIADLINELG INEFIDSKKE LQMLSYNQVN
KIINSNFPQQ DLCFQTEKLL FTSLFQDPAF ISALTSAFWQ SLHITSSSVE HIYAQIMSEN
IENRLNFMPE QRVINNCGHI IKINAVVPKN DTAISASGGR AYEVSSSILP SHITCNGVGI
NKIETSYLVH AGTLPSSEGL RNAIPPESRQ VSFAIISPDV
