OSPC3_SHIFL
ID OSPC3_SHIFL Reviewed; 484 AA.
AC A0A0H2US87; R4X5L7;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-SEP-2015, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Arginine ADP-riboxanase OspC3 {ECO:0000305};
DE EC=4.3.99.- {ECO:0000269|PubMed:34671164};
GN Name=ospC3 {ECO:0000303|PubMed:23684308};
GN ORFNames=SF_p0115 {ECO:0000312|EMBL:AAL72321.1};
OS Shigella flexneri.
OG Plasmid pCP301, and Plasmid pMYSH6000.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Shigella.
OX NCBI_TaxID=623;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 333-LEU--ASN-337; 456-LEU--ALA-459
RP AND LEU-471.
RC STRAIN=YSH6000 / Serotype 2a; PLASMID=pMYSH6000;
RX PubMed=23684308; DOI=10.1016/j.chom.2013.04.012;
RA Kobayashi T., Ogawa M., Sanada T., Mimuro H., Kim M., Ashida H.,
RA Akakura R., Yoshida M., Kawalec M., Reichhart J.M., Mizushima T.,
RA Sasakawa C.;
RT "The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory
RT cell death, and promotes epithelial infection.";
RL Cell Host Microbe 13:570-583(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=301 / Serotype 2a {ECO:0000312|Proteomes:UP000001006};
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 [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=34409271; DOI=10.1016/j.isci.2021.102910;
RA Oh C., Verma A., Hafeez M., Hogland B., Aachoui Y.;
RT "Shigella OspC3 suppresses murine cytosolic LPS sensing.";
RL IScience 24:102910-102910(2021).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-141; ASP-177; PHE-186;
RP GLU-192; GLU-326 AND HIS-328.
RC STRAIN=ATCC 700930 / 2457T / Serotype 2a;
RX PubMed=34671164; DOI=10.1038/s41586-021-04020-1;
RA Li Z., Liu W., Fu J., Cheng S., Xu Y., Wang Z., Liu X., Shi X., Liu Y.,
RA Qi X., Liu X., Ding J., Shao F.;
RT "Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11.";
RL Nature 599:290-295(2021).
CC -!- FUNCTION: ADP-riboxanase effector that inhibits host cell pyroptosis
CC (PubMed:23684308, PubMed:34409271, PubMed:34671164). Acts by mediating
CC arginine ADP-riboxanation of host CASP4/CASP11, blocking CASP4/CASP11
CC autoprocessing (PubMed:34671164). This prevents CASP4 activation and
CC ability to recognize and cleave GSDMD, thereby inhibiting LPS-induced
CC pyroptosis (PubMed:34671164). ADP-riboxanation takes place in two
CC steps: OspC3 first catalyzes ADP-ribosylation of target Arg, and then
CC initiates a deamination to remove one N-omega group (PubMed:34671164).
CC {ECO:0000269|PubMed:23684308, ECO:0000269|PubMed:34409271,
CC ECO:0000269|PubMed:34671164}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + NAD(+) = ADP-riboxanated L-argininyl-
CC [protein] + H(+) + NH4(+) + nicotinamide; Xref=Rhea:RHEA:69500,
CC Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:17719, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:28938, ChEBI:CHEBI:29965,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:184300;
CC Evidence={ECO:0000269|PubMed:34671164};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69501;
CC Evidence={ECO:0000269|PubMed:34671164};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:23684308}. Host
CC cytoplasm {ECO:0000305|PubMed:34409271}. Note=Secreted via the type III
CC secretion system (TTSS). {ECO:0000269|PubMed:23684308}.
CC -!- DISRUPTION PHENOTYPE: Host cells display increased pyroptosis.
CC {ECO:0000269|PubMed:23684308}.
CC -!- SIMILARITY: Belongs to the OspC family. {ECO:0000305}.
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DR EMBL; AB819724; BAN28452.1; -; Genomic_DNA.
DR EMBL; AF386526; AAL72321.1; -; Genomic_DNA.
DR RefSeq; NP_858248.1; NC_004851.1.
DR SMR; A0A0H2US87; -.
DR STRING; 198214.CP0115; -.
DR EnsemblBacteria; AAL72321; AAL72321; SF_p0115.
DR GeneID; 1238024; -.
DR KEGG; sfl:CP0115; -.
DR PATRIC; fig|198214.7.peg.5367; -.
DR HOGENOM; CLU_053336_0_0_6; -.
DR Proteomes; UP000001006; Plasmid pCP301.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0140740; F:ADP-riboxanase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0052041; P:negative regulation by symbiont of host programmed cell death; IDA:UniProtKB.
DR InterPro; IPR010366; OspC1-3.
DR Pfam; PF06128; Shigella_OspC; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Host cytoplasm; Lyase; Plasmid; Reference proteome; Repeat;
KW Secreted; Toxin; Virulence.
FT CHAIN 1..484
FT /note="Arginine ADP-riboxanase OspC3"
FT /id="PRO_0000455086"
FT REPEAT 369..398
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 413..444
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 451..480
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT MUTAGEN 141
FT /note="F->A: Abolished arginine ADP-riboxanation of host
FT CASP4/CASP11."
FT /evidence="ECO:0000269|PubMed:34671164"
FT MUTAGEN 177
FT /note="D->A: Abolished deamination step without affecting
FT the arginine ADP-ribosylation step."
FT /evidence="ECO:0000269|PubMed:34671164"
FT MUTAGEN 186
FT /note="F->A: Abolished arginine ADP-riboxanation of host
FT CASP4/CASP11."
FT /evidence="ECO:0000269|PubMed:34671164"
FT MUTAGEN 192
FT /note="E->A: In EH/AA mutant; abolished arginine ADP-
FT riboxanation of host CASP4/CASP11; when associated with A-
FT 328."
FT /evidence="ECO:0000269|PubMed:34671164"
FT MUTAGEN 326
FT /note="E->A: Abolished arginine ADP-riboxanation of host
FT CASP4/CASP11."
FT /evidence="ECO:0000269|PubMed:34671164"
FT MUTAGEN 328
FT /note="H->A: In EH/AA mutant; abolished arginine ADP-
FT riboxanation of host CASP4/CASP11; when associated with A-
FT 192."
FT /evidence="ECO:0000269|PubMed:34671164"
FT MUTAGEN 333..337
FT /note="LSTDN->AAAAA: Abolished interaction with host
FT CASP4/CASP11 and ability to prevent host pyroptosis; when
FT associated with 456-A--A-459 and A-471."
FT /evidence="ECO:0000269|PubMed:23684308"
FT MUTAGEN 456..459
FT /note="LDNA->ADNG: In delta-Ank; impaired interaction with
FT host CASP4/CASP11; when associated with A-471. Abolished
FT interaction with host CASP4/CASP11 and ability to prevent
FT host pyroptosis; when associated with 333-A--A-337 and A-
FT 471."
FT /evidence="ECO:0000269|PubMed:23684308"
FT MUTAGEN 471
FT /note="L->A: In delta-Ank; impaired interaction with host
FT CASP4/CASP11; when associated with 456-A--A-459. Abolished
FT interaction with host CASP4/CASP11 and ability to prevent
FT host pyroptosis; when associated with 333-A--A-337 and 456-
FT A--A-459."
FT /evidence="ECO:0000269|PubMed:23684308"
FT CONFLICT 23
FT /note="I -> T (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="D -> A (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 36..38
FT /note="ISC -> VLR (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 57..61
FT /note="DTVKS -> NTVKN (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="I -> L (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="L -> I (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="T -> V (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="D -> N (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="A -> S (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="T -> I (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="K -> Q (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 170..182
FT /note="YKNTFSEDIEEIA -> HKNTYSEDIKEIS (in Ref. 1;
FT BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="T -> K (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="R -> G (in Ref. 1; BAN28452)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 484 AA; 55651 MW; F12AB9300AA00182 CRC64;
MKIPEAVNHI NVQNNIDLVD GKINPNKDTK ALQKNISCVT NSSSSGISEK HLDHCADTVK
SFLRKSIAAQ SYSKMFSQGT SFKSLNLSIE APSGARSSFR SLEHLDKVSR HYLSEIIQKT
HPLSSDERHL LSIIINSDFN FRHQSNANLS NNTLNIKSFD KIKSENIQTY KNTFSEDIEE
IANHDFVFFG VEISNHQETL PLNKTHHTVD FGANAYIIDH DSPYGYMTLT DHFDNAIPPV
FYHEHQSFFL DNFKEVVDEV SRYVHGNQGK TDVPIFNTKD MRLGIGLHLI DFIRKSKDQR
FREFCYNKNI DPVSLDRIIN FVFQLEYHIP RMLSTDNFKK IKLRDISLED AIKASNYEEI
NNKVTDKKMA HQALAYSLGN KKADIALYLL SKFNFTKQDV AEMEKMKNNR YCNLYDVEYL
LSKDGANYKV LEYFINNGLV DVNKKFQKVN SGDTMLDNAM KSKDSKMIDF LLKNGAILGK
RFEI
