EXOT_PSEAE
ID EXOT_PSEAE Reviewed; 457 AA.
AC Q9I788;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Exoenzyme T;
DE Includes:
DE RecName: Full=GTPase-activating protein;
DE Short=GAP;
DE Includes:
DE RecName: Full=ADP-ribosyltransferase;
DE Short=ADPRT;
DE EC=2.4.2.31 {ECO:0000269|PubMed:11298647, ECO:0000269|PubMed:12807879};
GN Name=exoT; OrderedLocusNames=PA0044;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, MUTAGENESIS OF ARG-149, AND CATALYTIC ACTIVITY.
RC STRAIN=388;
RX PubMed=11298647; DOI=10.1046/j.1462-5822.2001.00108.x;
RA Sundin C., Henriksson M.L., Hallberg B., Forsberg A., Frithz-Lindsten E.;
RT "Exoenzyme T of Pseudomonas aeruginosa elicits cytotoxicity without
RT interfering with Ras signal transduction.";
RL Cell. Microbiol. 3:237-246(2001).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF ARG-149.
RC STRAIN=PA103;
RX PubMed=11895987; DOI=10.1128/iai.70.4.2198-2205.2002;
RA Kazmierczak B.I., Engel J.N.;
RT "Pseudomonas aeruginosa ExoT acts in vivo as a GTPase-activating protein
RT for RhoA, Rac1, and Cdc42.";
RL Infect. Immun. 70:2198-2205(2002).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-149; GLU-383 AND
RP GLU-385.
RC STRAIN=PA103;
RX PubMed=12807879; DOI=10.1074/jbc.m304290200;
RA Sun J., Barbieri J.T.;
RT "Pseudomonas aeruginosa ExoT ADP-ribosylates CT10 regulator of kinase (Crk)
RT proteins.";
RL J. Biol. Chem. 278:32794-32800(2003).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLU-383 AND GLU-385.
RC STRAIN=PA103;
RX PubMed=14688136; DOI=10.1128/iai.72.1.546-558.2004;
RA Garrity-Ryan L., Shafikhani S., Balachandran P., Nguyen L., Oza J.,
RA Jakobsen T., Sargent J., Fang X., Cordwell S., Matthay M.A., Engel J.N.;
RT "The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT
RT contributes to its biological activities.";
RL Infect. Immun. 72:546-558(2004).
RN [6]
RP FUNCTION.
RC STRAIN=PA103;
RX PubMed=26451042; DOI=10.1074/jbc.m115.689950;
RA Wood S.J., Goldufsky J.W., Bello D., Masood S., Shafikhani S.H.;
RT "Pseudomonas aeruginosa ExoT Induces Mitochondrial Apoptosis in Target Host
RT Cells in a Manner That Depends on Its GTPase-activating Protein (GAP)
RT Domain Activity.";
RL J. Biol. Chem. 290:29063-29073(2015).
RN [7]
RP FUNCTION.
RC STRAIN=PA103;
RX PubMed=26020630; DOI=10.1371/journal.ppat.1004934;
RA Wood S., Goldufsky J., Shafikhani S.H.;
RT "Pseudomonas aeruginosa ExoT Induces Atypical Anoikis Apoptosis in Target
RT Host Cells by Transforming Crk Adaptor Protein into a Cytotoxin.";
RL PLoS Pathog. 11:e1004934-e1004934(2015).
RN [8] {ECO:0007744|PDB:4JMF}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 28-77, INTERACTION WITH SPCS, AND
RP SUBCELLULAR LOCATION.
RX PubMed=24387107; DOI=10.1111/febs.12704;
RA Dey S., Datta S.;
RT "Interfacial residues of SpcS chaperone affects binding of effector toxin
RT ExoT in Pseudomonas aeruginosa: novel insights from structural and
RT computational studies.";
RL FEBS J. 281:1267-1280(2014).
RN [9] {ECO:0007744|PDB:6GNN}
RP X-RAY CRYSTALLOGRAPHY (3.79 ANGSTROMS) OF 235-457, INDUCTION BY HOST YWHAB,
RP AND INTERACTION WITH HOST YWHAB.
RX PubMed=30224724; DOI=10.1038/s41467-018-06194-1;
RA Karlberg T., Hornyak P., Pinto A.F., Milanova S., Ebrahimi M., Lindberg M.,
RA Pullen N., Nordstrom A., Loverli E., Caraballo R., Wong E.V., Nareoja K.,
RA Thorsell A.G., Elofsson M., De La Cruz E.M., Bjorkegren C., Schuler H.;
RT "14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a
RT hydrophobic surface.";
RL Nat. Commun. 9:3785-3785(2018).
RN [10] {ECO:0007744|PDB:6JNP}
RP X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 23-79.
RA Datta S., Mondal A.;
RT "Structure of ExoT-SpcS Complex from Pseudomonas aeruginosa.";
RL Submitted (MAR-2019) to the PDB data bank.
CC -!- FUNCTION: Bifunctional effector protein that is secreted and delivered
CC by the type III secretion system into eukaryotic target cells. The N-
CC terminus encodes a GTPase-activating protein activity, whereas the C-
CC terminus encodes an ADP-ribosyltransferase activity (PubMed:11298647).
CC ADP-ribosylates several eukaryotic proteins including CT10 regulator of
CC kinase (Crk) proteins (PubMed:12807879). In turn, induces atypical
CC anoikis apoptosis by transforming Crk adaptor protein into a cytotoxin
CC (PubMed:26020630). Affects host cell morphology by disrupting the actin
CC cytoskeleton (PubMed:14688136). In addition to this activity, acts via
CC its N-terminal region as a GTPase-activating protein (GAP) for host Rho
CC GTPases including RhoA, Rac1, Cdc42 and Ras (PubMed:11895987). The GAP
CC domain activity induces mitochondrial disruption in the target host
CC cell by activating host caspases 3 and 9 that execute cellular death
CC (PubMed:26451042). This activity also causes stress fiber disassembly
CC (PubMed:11895987). {ECO:0000269|PubMed:11298647,
CC ECO:0000269|PubMed:11895987, ECO:0000269|PubMed:12807879,
CC ECO:0000269|PubMed:14688136, ECO:0000269|PubMed:26020630,
CC ECO:0000269|PubMed:26451042}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D-
CC ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149,
CC Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:142554; EC=2.4.2.31;
CC Evidence={ECO:0000269|PubMed:11298647, ECO:0000269|PubMed:12807879};
CC -!- SUBUNIT: Interacts with chaperone protein SpcS; this interaction
CC maintains ExoT in a secretion competent state within the cytoplasm
CC (PubMed:24387107). Interacts with host YWHAB (PubMed:30224724).
CC {ECO:0000269|PubMed:24387107, ECO:0000269|PubMed:30224724}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:24387107}.
CC Note=Secreted via type III secretion system (T3SS) and delivered into
CC the host cytoplasm. {ECO:0000305}.
CC -!- INDUCTION: By host YWHAB. {ECO:0000269|Ref.10}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the YopE family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the Arg-specific ADP-
CC ribosyltransferase family. {ECO:0000305}.
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DR EMBL; AE004091; AAG03434.1; -; Genomic_DNA.
DR PIR; G83639; G83639.
DR RefSeq; NP_248734.1; NC_002516.2.
DR RefSeq; WP_003114583.1; NZ_QZGE01000015.1.
DR PDB; 4JMF; X-ray; 2.10 A; A=28-77.
DR PDB; 6GNN; X-ray; 3.79 A; C=235-457.
DR PDB; 6JNP; X-ray; 2.26 A; A/D=23-79.
DR PDBsum; 4JMF; -.
DR PDBsum; 6GNN; -.
DR PDBsum; 6JNP; -.
DR AlphaFoldDB; Q9I788; -.
DR SMR; Q9I788; -.
DR STRING; 287.DR97_3001; -.
DR TCDB; 1.C.106.4.2; the bacillus thuringiensis vegetative insecticidal protein-2 (vip2) family.
DR PaxDb; Q9I788; -.
DR DNASU; 878350; -.
DR EnsemblBacteria; AAG03434; AAG03434; PA0044.
DR GeneID; 878350; -.
DR KEGG; pae:PA0044; -.
DR PATRIC; fig|208964.12.peg.45; -.
DR PseudoCAP; PA0044; -.
DR HOGENOM; CLU_603900_0_0_6; -.
DR OMA; MHIQSSQ; -.
DR BioCyc; PAER208964:G1FZ6-46-MON; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro.
DR GO; GO:0106274; F:NAD+-protein-arginine ADP-ribosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd00219; ToxGAP; 1.
DR Gene3D; 1.20.120.260; -; 1.
DR InterPro; IPR003540; ADP-ribosyltransferase.
DR InterPro; IPR003537; YopE-like.
DR InterPro; IPR014773; YopE_GAP_dom.
DR InterPro; IPR037168; YopE_GAP_dom_sf.
DR Pfam; PF03496; ADPrib_exo_Tox; 1.
DR Pfam; PF03545; YopE; 1.
DR PRINTS; PR01372; YERSINIAYOPE.
DR SUPFAM; SSF47233; SSF47233; 1.
DR PROSITE; PS51996; TR_MART; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycosyltransferase; Nucleotidyltransferase;
KW Reference proteome; Secreted; Toxin; Transferase; Virulence.
FT CHAIN 1..457
FT /note="Exoenzyme T"
FT /id="PRO_0000451080"
FT DOMAIN 242..418
FT /note="TR mART core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT REGION 1..237
FT /note="GTPase-activating protein (GAP) domain"
FT /evidence="ECO:0000250|UniProtKB:G3XDA1"
FT REGION 238..457
FT /note="ADP-ribosyltransferase domain"
FT /evidence="ECO:0000250|UniProtKB:G3XDA1"
FT ACT_SITE 322
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 346
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 385
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT MUTAGEN 149
FT /note="R->K: Loss of GAP activity."
FT /evidence="ECO:0000269|PubMed:11298647,
FT ECO:0000269|PubMed:11895987, ECO:0000269|PubMed:12807879"
FT MUTAGEN 383
FT /note="E->D: Loss of ADP-ribosyltransferase activity; when
FT associated with D-385."
FT /evidence="ECO:0000269|PubMed:12807879,
FT ECO:0000269|PubMed:14688136"
FT MUTAGEN 385
FT /note="E->D: Loss of ADP-ribosyltransferase activity; when
FT associated with D-383."
FT /evidence="ECO:0000269|PubMed:12807879,
FT ECO:0000269|PubMed:14688136"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:4JMF"
FT HELIX 36..41
FT /evidence="ECO:0007829|PDB:4JMF"
FT HELIX 53..57
FT /evidence="ECO:0007829|PDB:4JMF"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:4JMF"
FT HELIX 66..76
FT /evidence="ECO:0007829|PDB:4JMF"
SQ SEQUENCE 457 AA; 48515 MW; 6516FD2152E5CD6A CRC64;
MHIQSSQQNP SFVAELSQAV AGRLGQVEAR QVATPREAQQ LAQRQEAPKG EGLLSRLGAA
LARPFVAIIE WLGKLLGSRA HAATQAPLSR QDAPPAASLS AAEIKQMMLQ KALPLTLGGL
GKASELATLT AERLAKDHTR LASGDGALRS LATALVGIRD GSRIEASRTQ AARLLEQSVG
GIALQQWGTA GGAASQHVLS ASPEQLREIA VQLHAVMDKV ALLRHAVESE VKGEPVDKAL
ADGLVEHFGL EAEQYLGEHP DGPYSDAEVM ALGLYTNGEY QHLNRSLRQG RELDAGQALI
DRGMSAAFEK SGPAEQVVKT FRGTQGRDAF EAVKEGQVGH DAGYLSTSRD PGVARSFAGQ
GTITTLFGRS GIDVSEISIE GDEQEILYDK GTDMRVLLSA KDGQGVTRRV LEEATLGERS
GHGEGLLDAL DLATGTDRSG KPQEQDLRLR MRGLDLA
