SPVC_SALTY
ID SPVC_SALTY Reviewed; 241 AA.
AC P0A2M9; P21456;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=MAPK phosphothreonine lyase;
DE EC=4.2.3.-;
DE AltName: Full=27.5 kDa virulence protein;
DE AltName: Full=Secreted effector protein SpvC;
GN Name=spvC; Synonyms=mkaD, vsdD; OrderedLocusNames=PSLT038;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OG Plasmid pSLT, and Plasmid pEX102.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC PLASMID=pEX102;
RX PubMed=2227425; DOI=10.1016/0378-1119(90)90150-p;
RA Taira S., Rhen M.;
RT "Nucleotide sequence of mkaD, a virulence-associated gene of Salmonella
RT typhimurium containing variable and constant regions.";
RL Gene 93:147-150(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720; PLASMID=pSLT;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP PROTEIN SEQUENCE OF 2-10.
RC PLASMID=pEX102;
RX PubMed=2037236; DOI=10.1016/0378-1097(91)90573-s;
RA Taira S., Baumann M., Riikonen P., Sukupolvi S., Rhen M.;
RT "Amino-terminal sequence analysis of four plasmid-encoded virulence-
RT associated proteins of Salmonella typhimurium.";
RL FEMS Microbiol. Lett. 77:319-323(1991).
RN [4]
RP FUNCTION, AND SUBSTRATES.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720; PLASMID=pSLT;
RX PubMed=17303758; DOI=10.1126/science.1138960;
RA Li H., Xu H., Zhou Y., Zhang J., Long C., Li S., Chen S., Zhou J.-M.,
RA Shao F.;
RT "The phosphothreonine lyase activity of a bacterial type III effector
RT family.";
RL Science 315:1000-1003(2007).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ROLE IN VIRULENCE, SUBCELLULAR LOCATION,
RP SECRETION VIA TYPE III SECRETION SYSTEM, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 14028 / SGSC 2980 / CDC 6516-60 / NCTC 12023;
RX PubMed=18284579; DOI=10.1111/j.1365-2958.2008.06134.x;
RA Mazurkiewicz P., Thomas J., Thompson J.A., Liu M., Arbibe L.,
RA Sansonetti P., Holden D.W.;
RT "SpvC is a Salmonella effector with phosphothreonine lyase activity on host
RT mitogen-activated protein kinases.";
RL Mol. Microbiol. 67:1371-1383(2008).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF APOENZYME AND MUTANT ALA-136 IN
RP COMPLEX WITH A PHOSPHOPEPTIDE SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, REACTION MECHANISM, ACTIVE SITES, AND
RP MUTAGENESIS OF PHE-100; LYS-104; HIS-106; LYS-134; LYS-136; ARG-148;
RP TYR-158; LYS-160; ASP-201; ARG-213 AND ARG-220.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720; PLASMID=pSLT;
RX PubMed=18060821; DOI=10.1016/j.molcel.2007.11.011;
RA Zhu Y., Li H., Long C., Hu L., Xu H., Liu L., Chen S., Wang D.C., Shao F.;
RT "Structural insights into the enzymatic mechanism of the pathogenic MAPK
RT phosphothreonine lyase.";
RL Mol. Cell 28:899-913(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF APOENZYME AND MUTANT ALA-136 IN
RP COMPLEX WITH A PHOSPHOPEPTIDE SUBSTRATE, FUNCTION, ACTIVE SITES, AND
RP MUTAGENESIS OF PHE-86; ARG-90; PHE-100; LYS-104; HIS-106; LYS-134; LYS-136;
RP ARG-148; VAL-149; TYR-158; LYS-160; ARG-213; GLU-215 AND ARG-220.
RX PubMed=18084305; DOI=10.1038/nsmb1329;
RA Chen L., Wang H., Zhang J., Gu L., Huang N., Zhou J.M., Chai J.;
RT "Structural basis for the catalytic mechanism of phosphothreonine lyase.";
RL Nat. Struct. Mol. Biol. 15:101-102(2008).
CC -!- FUNCTION: Secreted effector that irreversibly inactivates host MAP
CC kinases by catalyzing the dephosphorylation of the phosphothreonine
CC residue in the pT-X-pY motif in MAPK2/ERK2, MAPK3/ERK1, and p38, via a
CC beta-elimination reaction leading to a dehydrobutyrine residue. Is also
CC able to remove the phosphate group from phospho-JNK in vitro, but JNK
CC may not be a substrate in vivo. Could help suppress localized pro-
CC inflammatory responses at infection foci in the spleen and liver, and
CC thereby facilitate bacterial growth. {ECO:0000269|PubMed:17303758,
CC ECO:0000269|PubMed:18060821, ECO:0000269|PubMed:18084305,
CC ECO:0000269|PubMed:18284579}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=52.2 uM for the Erk2 phosphopeptide DHTGFL-pT-E-pY-VATR
CC {ECO:0000269|PubMed:18060821};
CC Vmax=22.72 umol/min/mg enzyme with the Erk2 phosphopeptide DHTGFL-pT-
CC E-pY-VATR as substrate {ECO:0000269|PubMed:18060821};
CC Note=kcat is 10.60 sec(-1) with the Erk2 phosphopeptide DHTGFL-pT-E-
CC pY-VATR as substrate.;
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:18060821};
CC -!- INTERACTION:
CC P0A2M9; P28482: MAPK1; Xeno; NbExp=3; IntAct=EBI-15676035, EBI-959949;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18284579}. Note=Can
CC be secreted in vitro by either the SPI-1 or SPI-2 type III secretion
CC systems (T3SS). Translocation of the protein into the cytosol of
CC infected macrophages by intracellular bacteria is dependent on the SPI-
CC 2 T3SS. Translocated SpvC proteins appear to be distributed evenly in
CC the cytoplasm of infected cells, and neither colocalize with the SCV
CC membrane nor accumulate in the nucleus of infected cells.
CC -!- DISRUPTION PHENOTYPE: Strains lacking this gene are attenuated for
CC systemic virulence in mice. {ECO:0000269|PubMed:18284579}.
CC -!- SIMILARITY: Belongs to the phosphothreonine lyase family.
CC {ECO:0000305}.
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DR EMBL; M34355; AAA27162.1; -; Genomic_DNA.
DR EMBL; AE006471; AAL23529.1; -; Genomic_DNA.
DR PIR; JQ0747; JQ0747.
DR RefSeq; NP_490528.1; NC_003277.2.
DR RefSeq; WP_001122242.1; NC_003277.2.
DR PDB; 2P1W; X-ray; 2.30 A; A=1-241.
DR PDB; 2Q8Y; X-ray; 2.00 A; A=1-241.
DR PDB; 2Z8M; X-ray; 2.00 A; A/B=1-241.
DR PDB; 2Z8N; X-ray; 1.80 A; A/B=1-241.
DR PDB; 2Z8O; X-ray; 2.40 A; A/B=1-241.
DR PDB; 2Z8P; X-ray; 1.80 A; A=1-241.
DR PDB; 4H43; X-ray; 2.30 A; A/B=1-241.
DR PDB; 4HAH; X-ray; 1.80 A; A/B=1-241.
DR PDBsum; 2P1W; -.
DR PDBsum; 2Q8Y; -.
DR PDBsum; 2Z8M; -.
DR PDBsum; 2Z8N; -.
DR PDBsum; 2Z8O; -.
DR PDBsum; 2Z8P; -.
DR PDBsum; 4H43; -.
DR PDBsum; 4HAH; -.
DR AlphaFoldDB; P0A2M9; -.
DR SMR; P0A2M9; -.
DR DIP; DIP-46403N; -.
DR IntAct; P0A2M9; 2.
DR MINT; P0A2M9; -.
DR EnsemblBacteria; AAL23529; AAL23529; PSLT038.
DR GeneID; 1256201; -.
DR KEGG; stm:PSLT038; -.
DR PATRIC; fig|99287.12.peg.4889; -.
DR HOGENOM; CLU_100525_0_0_6; -.
DR OMA; RVDQQSR; -.
DR PhylomeDB; P0A2M9; -.
DR BioCyc; SENT99287:PSLT038-MON; -.
DR SABIO-RK; P0A2M9; -.
DR EvolutionaryTrace; P0A2M9; -.
DR PRO; PR:P0A2M9; -.
DR Proteomes; UP000001014; Plasmid pSLT.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.2430.10; -; 1.
DR InterPro; IPR003519; OspF/SpvC.
DR InterPro; IPR038498; OspF/SpvC_sf.
DR Pfam; PF03536; VRP3; 1.
DR PRINTS; PR01342; SALVRPPROT.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Lyase; Plasmid;
KW Reference proteome; Secreted; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2037236"
FT CHAIN 2..241
FT /note="MAPK phosphothreonine lyase"
FT /id="PRO_0000221668"
FT ACT_SITE 106
FT /note="Proton donor"
FT ACT_SITE 136
FT /note="Proton acceptor"
FT MUTAGEN 86
FT /note="F->D: Marked decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18084305"
FT MUTAGEN 90
FT /note="R->E: Slight decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18084305"
FT MUTAGEN 100
FT /note="F->E: Marked decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 100
FT /note="F->L: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 104
FT /note="K->A,R: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 106
FT /note="H->A: Marked decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 106
FT /note="H->K: 7-fold decrease in enzymatic activity, but no
FT effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 106
FT /note="H->N: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 134
FT /note="K->A: 2-fold decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 134
FT /note="K->E: Slight decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 134
FT /note="K->R: No effect on enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 136
FT /note="K->A,R: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 148
FT /note="R->A: Marked decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 148
FT /note="R->Q: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 149
FT /note="V->D: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18084305"
FT MUTAGEN 158
FT /note="Y->E: Marked decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 158
FT /note="Y->F: 20-fold decrease in enzymatic activity, but no
FT effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 160
FT /note="K->A: More than 5-fold decrease in substrate
FT affinity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 160
FT /note="K->E: Slight decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 160
FT /note="K->R: 2-fold decrease in enzymatic activity, but no
FT effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 201
FT /note="D->N: 47-fold decrease in enzymatic activity, but no
FT effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:18060821"
FT MUTAGEN 213
FT /note="R->A,Q: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 215
FT /note="E->A: Nearly no decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18084305"
FT MUTAGEN 220
FT /note="R->A: Marked decrease in enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT MUTAGEN 220
FT /note="R->Q: Loss of enzymatic activity."
FT /evidence="ECO:0000269|PubMed:18060821,
FT ECO:0000269|PubMed:18084305"
FT HELIX 29..35
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:2Z8N"
FT TURN 66..69
FT /evidence="ECO:0007829|PDB:4HAH"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:2Z8N"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:2Z8N"
FT STRAND 82..93
FT /evidence="ECO:0007829|PDB:2Z8N"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 114..125
FT /evidence="ECO:0007829|PDB:2Z8N"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:2Z8N"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:2Z8N"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 170..189
FT /evidence="ECO:0007829|PDB:2Z8N"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:2Z8N"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 224..230
FT /evidence="ECO:0007829|PDB:2Z8N"
FT HELIX 234..240
FT /evidence="ECO:0007829|PDB:2Z8N"
SQ SEQUENCE 241 AA; 27646 MW; 77625271D78F8814 CRC64;
MPINRPNLNL NIPPLNIVAA YDGAEIPSTN KHLKNNFNSL HNQMRKMPVS HFKEALDVPD
YSGMRQSGFF AMSQGFQLNN HGYDVFIHAR RESPQSQGKF AGDKFHISVL RDMVPQAFQA
LSGLLFSEDS PVDKWKVTDM EKVVQQARVS LGAQFTLYIK PDQENSQYSA SFLHKTRQFI
ECLESRLSEN GVISGQCPES DVHPENWKYL SYRNELRSGR DGGEMQRQAL REEPFYRLMT
E
