SPTP_SALTY
ID SPTP_SALTY Reviewed; 543 AA.
AC P74873; Q7CPX3;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Secreted effector protein SptP;
DE Includes:
DE RecName: Full=GTPase-activating protein;
DE Short=GAP;
DE Includes:
DE RecName: Full=Tyrosine-protein phosphatase;
DE EC=3.1.3.48;
GN Name=sptP; OrderedLocusNames=STM2878;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ACTIVITY REGULATION, FUNCTION, AND
RP MUTAGENESIS OF CYS-481.
RC STRAIN=SL1344;
RX PubMed=8866485; DOI=10.1111/j.1365-2958.1996.tb02571.x;
RA Kaniga K., Uralil J., Bliska J.B., Galan J.E.;
RT "A secreted protein tyrosine phosphatase with modular effector domains in
RT the bacterial pathogen Salmonella typhimurium.";
RL Mol. Microbiol. 21:633-641(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
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 INTERACTION WITH SICP.
RC STRAIN=SL1344;
RX PubMed=9642193; DOI=10.1128/jb.180.13.3393-3399.1998;
RA Fu Y., Galan J.E.;
RT "Identification of a specific chaperone for SptP, a substrate of the
RT centisome 63 type III secretion system of Salmonella typhimurium.";
RL J. Bacteriol. 180:3393-3399(1998).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-209.
RC STRAIN=SB300;
RX PubMed=10499590; DOI=10.1038/45829;
RA Fu Y., Galan J.E.;
RT "A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell
RT recovery after bacterial invasion.";
RL Nature 401:293-297(1999).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 161-543 IN COMPLEX WITH RAC1,
RP FUNCTION, AND MUTAGENESIS OF THR-213; GLN-246 AND THR-249.
RX PubMed=11163217; DOI=10.1016/s1097-2765(00)00141-6;
RA Stebbins C.E., Galan J.E.;
RT "Modulation of host signaling by a bacterial mimic: structure of the
RT Salmonella effector SptP bound to Rac1.";
RL Mol. Cell 6:1449-1460(2000).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 35-139 IN COMPLEX WITH SICP.
RX PubMed=11689946; DOI=10.1038/35102073;
RA Stebbins C.E., Galan J.E.;
RT "Maintenance of an unfolded polypeptide by a cognate chaperone in bacterial
RT type III secretion.";
RL Nature 414:77-81(2001).
CC -!- FUNCTION: Effector proteins function to alter host cell physiology and
CC promote bacterial survival in host tissues. This protein includes
CC tyrosine phosphatase and GTPase activating protein (GAP) activities.
CC After bacterial internalization, GAP mediates the reversal of the
CC cytoskeletal changes induced by SopE. This function is independent of
CC its tyrosine phosphatase activity, which remains unclear.
CC {ECO:0000269|PubMed:10499590, ECO:0000269|PubMed:11163217,
CC ECO:0000269|PubMed:8866485}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10044};
CC -!- ACTIVITY REGULATION: The tyrosine phosphatase activity is inhibited by
CC sodium vanadate. {ECO:0000269|PubMed:8866485}.
CC -!- SUBUNIT: Forms a complex with SicP. Binds host RAC1.
CC {ECO:0000269|PubMed:11163217, ECO:0000269|PubMed:11689946}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10499590}. Host
CC cytoplasm {ECO:0000269|PubMed:10499590}. Note=Secreted via type III
CC secretion system 1 (SPI-1 TTSS), and delivered into the host cytoplasm.
CC -!- MISCELLANEOUS: Requires SicP as a chaperone for its stability and for
CC secretion. The structure of the SptP-SicP complex contains four
CC molecules of the chaperone SicP, aligned in a linear fashion and
CC arranged in two sets of tightly bound homodimers that bind two SptP
CC molecules. The SicP homodimers do not interact with each other, but are
CC held together by a molecular interface formed between two SptP
CC molecules. The chaperone-binding domain of SptP does not adopt a
CC globular fold for interaction with SicP. Each SptP molecule is wrapped
CC around by three SicP chaperones (two chaperones from one homodimer and
CC a third one from the opposite homodimer pair). SptP interacts with SicP
CC chaperone dimers mainly through four regions of its chaperone-binding
CC domain.
CC -!- SIMILARITY: In the N-terminal section; belongs to the YopE family.
CC {ECO:0000305}.
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DR EMBL; U63293; AAC44349.1; -; Genomic_DNA.
DR EMBL; AE006468; AAL21758.1; -; Genomic_DNA.
DR RefSeq; NP_461799.1; NC_003197.2.
DR RefSeq; WP_000922300.1; NC_003197.2.
DR PDB; 1G4U; X-ray; 2.30 A; S=161-543.
DR PDB; 1G4W; X-ray; 2.20 A; R=161-543.
DR PDB; 1JYO; X-ray; 1.90 A; E/F=35-139.
DR PDBsum; 1G4U; -.
DR PDBsum; 1G4W; -.
DR PDBsum; 1JYO; -.
DR AlphaFoldDB; P74873; -.
DR SMR; P74873; -.
DR IntAct; P74873; 3.
DR STRING; 99287.STM2878; -.
DR PaxDb; P74873; -.
DR EnsemblBacteria; AAL21758; AAL21758; STM2878.
DR GeneID; 1254401; -.
DR KEGG; stm:STM2878; -.
DR PATRIC; fig|99287.12.peg.3034; -.
DR HOGENOM; CLU_039619_0_0_6; -.
DR OMA; WIDKAST; -.
DR BioCyc; SENT99287:STM2878-MON; -.
DR EvolutionaryTrace; P74873; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR CDD; cd00219; ToxGAP; 1.
DR Gene3D; 1.20.120.260; -; 1.
DR Gene3D; 3.90.190.10; -; 1.
DR Gene3D; 4.10.1330.10; -; 1.
DR InterPro; IPR011070; Globular_prot_asu/bsu.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR015203; SptP_N.
DR InterPro; IPR044899; SptP_N_sf.
DR InterPro; IPR016130; Tyr_Pase_AS.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR003546; Tyr_Pase_SptP/YopH.
DR InterPro; IPR014773; YopE_GAP_dom.
DR InterPro; IPR037168; YopE_GAP_dom_sf.
DR Pfam; PF09119; SicP-binding; 1.
DR Pfam; PF00102; Y_phosphatase; 1.
DR Pfam; PF03545; YopE; 1.
DR PRINTS; PR01371; BACYPHPHTASE.
DR SMART; SM00194; PTPc; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF47233; SSF47233; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR SUPFAM; SSF56568; SSF56568; 1.
DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50055; TYR_PHOSPHATASE_PTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; GTPase activation; Host cytoplasm; Hydrolase;
KW Protein phosphatase; Reference proteome; Secreted; Virulence.
FT CHAIN 1..543
FT /note="Secreted effector protein SptP"
FT /id="PRO_0000094866"
FT DOMAIN 280..543
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT REGION 35..139
FT /note="Chaperone-binding"
FT REGION 167..290
FT /note="GAP"
FT ACT_SITE 481
FT /note="Phosphocysteine intermediate"
FT MUTAGEN 209
FT /note="R->A: Loss of GAP activity."
FT /evidence="ECO:0000269|PubMed:10499590"
FT MUTAGEN 213
FT /note="T->A: Loss of RAC1 binding and GAP activity."
FT /evidence="ECO:0000269|PubMed:11163217"
FT MUTAGEN 246
FT /note="Q->A: Loss of RAC1 binding and GAP activity."
FT /evidence="ECO:0000269|PubMed:11163217"
FT MUTAGEN 249
FT /note="T->A: Loss of RAC1 binding and GAP activity."
FT /evidence="ECO:0000269|PubMed:11163217"
FT MUTAGEN 481
FT /note="C->S: Loss of phosphatase activity."
FT /evidence="ECO:0000269|PubMed:8866485"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 62..71
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 77..89
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 93..105
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:1JYO"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 122..127
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:1JYO"
FT HELIX 172..180
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:1G4U"
FT HELIX 208..218
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:1G4U"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:1G4U"
FT HELIX 254..258
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 263..288
FT /evidence="ECO:0007829|PDB:1G4W"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 330..338
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 341..347
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 354..367
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 372..374
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:1G4W"
FT TURN 382..385
FT /evidence="ECO:0007829|PDB:1G4W"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 392..396
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 399..405
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 415..424
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 427..436
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 448..459
FT /evidence="ECO:0007829|PDB:1G4W"
FT STRAND 478..485
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 486..499
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 505..515
FT /evidence="ECO:0007829|PDB:1G4W"
FT TURN 518..521
FT /evidence="ECO:0007829|PDB:1G4W"
FT HELIX 524..538
FT /evidence="ECO:0007829|PDB:1G4W"
SQ SEQUENCE 543 AA; 60048 MW; 060D2113EB5B5429 CRC64;
MLKYEERKLN NLTLSSFSKV GVSNDARLYI AKENTDKAYV APEKFSSKVL TWLGKMPLFK
NTEVVQKHTE NIRVQDQKIL QTFLHALTEK YGETAVNDAL LMSRINMNKP LTQRLAVQIT
ECVKAADEGF INLIKSKDNV GVRNAALVIK GGDTKVAEKN NDVGAESKQP LLDIALKGLK
RTLPQLEQMD GNSLRENFQE MASGNGPLRS LMTNLQNLNK IPEAKQLNDY VTTLTNIQVG
VARFSQWGTC GGEVERWVDK ASTHELTQAV KKIHVIAKEL KNVTAELEKI EAGAPMPQTM
SGPTLGLARF AVSSIPINQQ TQVKLSDGMP VPVNTLTFDG KPVALAGSYP KNTPDALEAH
MKMLLEKECS CLVVLTSEDQ MQAKQLPPYF RGSYTFGEVH TNSQKVSSAS QGEAIDQYNM
QLSCGEKRYT IPVLHVKNWP DHQPLPSTDQ LEYLADRVKN SNQNGAPGRS SSDKHLPMIH
CLGGVGRTGT MAAALVLKDN PHSNLEQVRA DFRDSRNNRM LEDASQFVQL KAMQAQLLMT
TAS
