SOPE_SALTM
ID SOPE_SALTM Reviewed; 240 AA.
AC O52623;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 100.
DE RecName: Full=Guanine nucleotide exchange factor SopE;
DE AltName: Full=Effector protein SopE;
DE AltName: Full=Toxin SopE;
GN Name=sopE;
OS Salmonella typhimurium.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=90371;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-24; 58-68; 112-121
RP AND 159-173, AND SUBCELLULAR LOCATION.
RC STRAIN=SL1344;
RX PubMed=9482928; DOI=10.1073/pnas.95.5.2574;
RA Hardt W.-D., Urlaub H., Galan J.E.;
RT "A substrate of the centisome 63 type III protein secretion system of
RT Salmonella typhimurium is encoded by a cryptic bacteriophage.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2574-2579(1998).
RN [2]
RP FUNCTION.
RC STRAIN=SL1344;
RX PubMed=9630225; DOI=10.1016/s0092-8674(00)81442-7;
RA Hardt W.-D., Chen L.-M., Schuebel K.E., Bustelo X.R., Galan J.E.;
RT "S. typhimurium encodes an activator of Rho GTPases that induces membrane
RT ruffling and nuclear responses in host cells.";
RL Cell 93:815-826(1998).
RN [3]
RP PROPHAGE-RELATED REGION.
RC STRAIN=SL1344;
RX PubMed=10449782; DOI=10.1073/pnas.96.17.9845;
RA Mirold S., Rabsch W., Rohde M., Stender S., Tschaepe H., Ruessmann H.,
RA Igwe E., Hardt W.-D.;
RT "Isolation of a temperate bacteriophage encoding the type III effector
RT protein SopE from an epidemic Salmonella typhimurium strain.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9845-9850(1999).
RN [4]
RP INDUCTION.
RC STRAIN=SL1344;
RX PubMed=11296219; DOI=10.1093/emboj/20.8.1850;
RA Darwin K.H., Miller V.L.;
RT "Type III secretion chaperone-dependent regulation: activation of virulence
RT genes by SicA and InvF in Salmonella typhimurium.";
RL EMBO J. 20:1850-1862(2001).
RN [5]
RP FUNCTION.
RC STRAIN=SL1344;
RX PubMed=11440999; DOI=10.1074/jbc.m100609200;
RA Friebel A., Ilchmann H., Aepfelbacher M., Ehrbar K., Machleidt W.,
RA Hardt W.-D.;
RT "SopE and SopE2 from Salmonella typhimurium activate different sets of
RT RhoGTPases of the host cell.";
RL J. Biol. Chem. 276:34035-34040(2001).
RN [6]
RP INTERACTION WITH CHAPERONE INVB.
RC STRAIN=SL1344;
RX PubMed=14617659; DOI=10.1128/jb.185.23.6950-6967.2003;
RA Ehrbar K., Friebel A., Miller S.I., Hardt W.-D.;
RT "Role of the Salmonella pathogenicity island 1 (SPI-1) protein InvB in type
RT III secretion of SopE and SopE2, two Salmonella effector proteins encoded
RT outside of SPI-1.";
RL J. Bacteriol. 185:6950-6967(2003).
RN [7]
RP INTERACTION WITH CHAPERONE INVB.
RC STRAIN=SL1344;
RX PubMed=14645290; DOI=10.1128/jb.185.24.7279-7284.2003;
RA Lee S.H., Galan J.E.;
RT "InvB is a type III secretion-associated chaperone for the Salmonella
RT enterica effector protein SopE.";
RL J. Bacteriol. 185:7279-7284(2003).
RN [8]
RP MUTAGENESIS OF ASP-103; GLN-109; ASP-124; GLY-168 AND LYS-198.
RC STRAIN=SL1344;
RX PubMed=12719429; DOI=10.1074/jbc.m302475200;
RA Schlumberger M.C., Friebel A., Buchwald G., Scheffzek K., Wittinghofer A.,
RA Hardt W.-D.;
RT "Amino acids of the bacterial toxin SopE involved in G nucleotide exchange
RT on Cdc42.";
RL J. Biol. Chem. 278:27149-27159(2003).
RN [9]
RP EPIDEMICS.
RX PubMed=15150335; DOI=10.1099/jmm.0.05510-0;
RA Hopkins K.L., Threlfall E.J.;
RT "Frequency and polymorphism of sopE in isolates of Salmonella enterica
RT belonging to the ten most prevalent serotypes in England and Wales.";
RL J. Med. Microbiol. 53:539-543(2004).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF GLY-168.
RX PubMed=31285585; DOI=10.1038/s41564-019-0484-8;
RA Yuki K.E., Marei H., Fiskin E., Eva M.M., Gopal A.A.,
RA Schwartzentruber J.A., Majewski J., Cellier M., Mandl J.N., Vidal S.M.,
RA Malo D., Dikic I.;
RT "CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and
RT protects against bacterial infection.";
RL Nat. Microbiol. 4:1516-1531(2019).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 78-240 IN COMPLEX WITH CDC42.
RC STRAIN=SL1344;
RX PubMed=12093730; DOI=10.1093/emboj/cdf329;
RA Buchwald G., Friebel A., Galan J.E., Hardt W.-D., Wittinghofer A.,
RA Scheffzek K.;
RT "Structural basis for the reversible activation of a Rho protein by the
RT bacterial toxin SopE.";
RL EMBO J. 21:3286-3295(2002).
CC -!- FUNCTION: Activator for both CDC42 and RAC1 by directly engaging these
CC Rho GTPases and acting as potent guanine nucleotide exchange factor
CC (GEF). This activation results in actin cytoskeleton rearrangements and
CC stimulates membrane ruffling, promoting bacterial entry into non-
CC phagocytic cells. Also activates MAPK8, indicating that it is capable
CC of stimulating signaling pathways that can lead to nuclear responses.
CC Chaperone InvB is required for secretion and translocation of SopE.
CC {ECO:0000269|PubMed:11440999, ECO:0000269|PubMed:31285585,
CC ECO:0000269|PubMed:9630225}.
CC -!- INTERACTION:
CC O52623; P60953: CDC42; Xeno; NbExp=2; IntAct=EBI-602254, EBI-81752;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9482928}.
CC Note=Secreted via the type III secretion system 1 (SPI-1 TTSS).
CC -!- INDUCTION: Transcriptionally activated by InvF in association with
CC SicA. {ECO:0000269|PubMed:11296219}.
CC -!- MISCELLANEOUS: Encoded within a prophage region, which is only present
CC in very few Salmonella isolates. SopE-expressing S.typhimurium strains
CC are associated with severe epidemics.
CC -!- SIMILARITY: Belongs to the GEF (guanine exchange factor) SopE family.
CC {ECO:0000305}.
CC -!- CAUTION: SopE is not present in the complete genome strain LT2.
CC {ECO:0000305}.
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DR EMBL; AF043239; AAC02071.1; -; Genomic_DNA.
DR RefSeq; WP_000161707.1; NZ_WIDF01000016.1.
DR PDB; 1GZS; X-ray; 2.30 A; B/D=78-240.
DR PDBsum; 1GZS; -.
DR AlphaFoldDB; O52623; -.
DR SMR; O52623; -.
DR IntAct; O52623; 1.
DR PATRIC; fig|90371.1188.peg.2871; -.
DR OMA; YATIYSE; -.
DR EvolutionaryTrace; O52623; -.
DR PHI-base; PHI:6799; -.
DR PHI-base; PHI:7923; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IEA:InterPro.
DR GO; GO:0090630; P:activation of GTPase activity; IEA:InterPro.
DR Gene3D; 1.10.4120.10; -; 1.
DR InterPro; IPR005414; SopE.
DR InterPro; IPR035949; SopE-like_GEF_dom_sf.
DR InterPro; IPR016019; SopE_GEF_dom.
DR InterPro; IPR016018; SopE_N_dom.
DR Pfam; PF05364; SecIII_SopE_N; 1.
DR Pfam; PF07487; SopE_GEF; 1.
DR PIRSF; PIRSF034781; SecIII_sopE; 1.
DR PRINTS; PR01593; SOPEPROTEIN.
DR SUPFAM; SSF81832; SSF81832; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; GTPase activation;
KW Guanine-nucleotide releasing factor; Secreted; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9482928"
FT CHAIN 2..240
FT /note="Guanine nucleotide exchange factor SopE"
FT /id="PRO_0000220740"
FT REGION 15..78
FT /note="Interaction with InvB"
FT REGION 78..240
FT /note="GEF catalytic domain"
FT REGION 165..172
FT /note="Catalytic loop involved in contact with CDC42"
FT REGION 166..169
FT /note="Core-loop involved in conformational changes in
FT complex with CDC42"
FT SITE 103
FT /note="Helps stabilization of SopE-CDC42"
FT SITE 109
FT /note="Helps stabilization of SopE-CDC42"
FT SITE 124
FT /note="Helps stabilization of SopE-CDC42"
FT SITE 131
FT /note="Helps stabilization of SopE-CDC42"
FT SITE 174
FT /note="Helps stabilization of SopE-CDC42"
FT SITE 194
FT /note="Helps stabilization of SopE-CDC42"
FT SITE 198
FT /note="Helps stabilization of SopE-CDC42"
FT MUTAGEN 103
FT /note="D->A: 4-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 103
FT /note="D->E: 2-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 109
FT /note="Q->A: 700-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 109
FT /note="Q->N: 160-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 124
FT /note="D->A,E: 160-800-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 168
FT /note="G->A: 5000-fold reduction in GEF activity. Fails to
FT reduce CYRIB protein levels."
FT /evidence="ECO:0000269|PubMed:12719429,
FT ECO:0000269|PubMed:31285585"
FT MUTAGEN 168
FT /note="G->V: 20000-fold reduction in GEF activity. Fails to
FT reduce CYRIB protein levels."
FT /evidence="ECO:0000269|PubMed:12719429,
FT ECO:0000269|PubMed:31285585"
FT MUTAGEN 168
FT /note="Missing: 800-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 198
FT /note="K->A,R: No effect."
FT /evidence="ECO:0000269|PubMed:12719429"
FT MUTAGEN 198
FT /note="K->E: More than 20-fold reduction in GEF activity."
FT /evidence="ECO:0000269|PubMed:12719429"
FT HELIX 80..94
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 96..102
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 104..132
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 138..150
FT /evidence="ECO:0007829|PDB:1GZS"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:1GZS"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 173..183
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 185..188
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 191..209
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:1GZS"
FT HELIX 221..236
FT /evidence="ECO:0007829|PDB:1GZS"
SQ SEQUENCE 240 AA; 26636 MW; F636F6C437018D03 CRC64;
MTKITLSPQN FRIQKQETTL LKEKSTEKNS LAKSILAVKN HFIELRSKLS ERFISHKNTE
SSATHFHRGS ASEGRAVLTN KVVKDFMLQT LNDIDIRGSA SKDPAYASQT REAILSAVYS
KNKDQCCNLL ISKGINIAPF LQEIGEAAKN AGLPGTTKND VFTPSGAGAN PFITPLISSA
NSKYPRMFIN QHQQASFKIY AEKIIMTEVA PLFNECAMPT PQQFQLILEN IANKYIQNTP
