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 27-MAR-2024, entry version 144. 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; Pseudomonadota; 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 T3SS), 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 99287-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-MONOMER; -. 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; IEA:UniProtKB-EC. DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro. DR CDD; cd14559; PTP_YopH-like; 1. DR CDD; cd00219; ToxGAP; 1. DR Gene3D; 4.10.1330.10; non globular Virulence effector SptP domain; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR Gene3D; 1.20.120.260; Virulence factor YopE uncharacterised domain; 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 PANTHER; PTHR19134; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE; 1. DR PANTHER; PTHR19134:SF449; RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE GAMMA; 1. 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; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR SUPFAM; SSF47233; Bacterial GAP domain; 1. DR SUPFAM; SSF56568; Non-globular alpha+beta subunits of globular proteins; 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 //