EXOS_PSEAE
ID EXOS_PSEAE Reviewed; 453 AA.
AC G3XDA1;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Secreted exoenzyme S;
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:15252013, ECO:0000269|PubMed:9516428};
GN Name=exoS; OrderedLocusNames=PA3841;
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, AND CATALYTIC ACTIVITY.
RC STRAIN=PA103;
RX PubMed=9516428; DOI=10.1074/jbc.273.13.7332;
RA Ganesan A.K., Frank D.W., Misra R.P., Schmidt G., Barbieri J.T.;
RT "Pseudomonas aeruginosa exoenzyme S ADP-ribosylates Ras at multiple
RT sites.";
RL J. Biol. Chem. 273:7332-7337(1998).
RN [3]
RP FUNCTION.
RC STRAIN=PA103;
RX PubMed=10419499; DOI=10.1074/jbc.274.31.21823;
RA Ganesan A.K., Vincent T.S., Olson J.C., Barbieri J.T.;
RT "Pseudomonas aeruginosa exoenzyme S disrupts Ras-mediated signal
RT transduction by inhibiting guanine nucleotide exchange factor-catalyzed
RT nucleotide exchange.";
RL J. Biol. Chem. 274:21823-21829(1999).
RN [4]
RP FUNCTION, MUTAGENESIS OF ARG-137 AND ARG-146, AND DOMAIN.
RC STRAIN=PA103;
RX PubMed=10593930; DOI=10.1074/jbc.274.51.36369;
RA Goehring U.M., Schmidt G., Pederson K.J., Aktories K., Barbieri J.T.;
RT "The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-
RT activating protein for Rho GTPases.";
RL J. Biol. Chem. 274:36369-36372(1999).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=15252013; DOI=10.1074/jbc.m405707200;
RA Maresso A.W., Baldwin M.R., Barbieri J.T.;
RT "Ezrin/radixin/moesin proteins are high affinity targets for ADP-
RT ribosylation by Pseudomonas aeruginosa ExoS.";
RL J. Biol. Chem. 279:38402-38408(2004).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=PA99;
RX PubMed=26090668; DOI=10.1371/journal.ppat.1004945;
RA Rangel S.M., Diaz M.H., Knoten C.A., Zhang A., Hauser A.R.;
RT "The Role of ExoS in Dissemination of Pseudomonas aeruginosa during
RT Pneumonia.";
RL PLoS Pathog. 11:e1004945-e1004945(2015).
RN [7]
RP FUNCTION.
RX PubMed=28494242; DOI=10.1016/j.chom.2017.04.001;
RA Vareechon C., Zmina S.E., Karmakar M., Pearlman E., Rietsch A.;
RT "Pseudomonas aeruginosa Effector ExoS Inhibits ROS Production in Human
RT Neutrophils.";
RL Cell Host Microbe 21:611-618(2017).
RN [8]
RP FUNCTION.
RC STRAIN=PA103;
RX PubMed=30232373; DOI=10.1038/s41598-018-32491-2;
RA Kaminski A., Gupta K.H., Goldufsky J.W., Lee H.W., Gupta V.,
RA Shafikhani S.H.;
RT "Pseudomonas aeruginosa ExoS Induces Intrinsic Apoptosis in Target Host
RT Cells in a Manner That is Dependent on its GAP Domain Activity.";
RL Sci. Rep. 8:14047-14047(2018).
CC -!- FUNCTION: Bifunctional effector protein that is secreted and delivered
CC by the type III secretion system into eukaryotic target cells
CC (PubMed:15252013). The N-terminus encodes a GTPase-activating protein
CC activity, whereas the C-terminus encodes an ADP-ribosyltransferase
CC activity. ADP-ribosylates several eukaryotic proteins including
CC ezrin/radixin/moesin (ERM), cyclophilin A and several members of the
CC Ras superfamily (PubMed:9516428, PubMed:15252013). Host Ras ADP-
CC ribosylation blocks its activation by its guanine nucleotide exchange
CC factor, thereby interfering with Ras-mediated signal transduction
CC (PubMed:10419499). For instance, prevents Ras from interacting with and
CC activating phosphoinositol-3-kinase (PI3K), which is required to
CC stimulate the phagocytic NADPH-oxidase that generates reactive oxygen
CC species (PubMed:28494242). The ADPRT domain contributes also to
CC bacterial dissemination to the blood during pneumonia
CC (PubMed:26090668). In addition to this activity, acts via its N-
CC terminal region as a GTPase-activating protein (GAP) for host Rho
CC GTPases including RhoA, Rac1, Cdc42 and Ras (PubMed:10593930). 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:30232373). {ECO:0000269|PubMed:10419499,
CC ECO:0000269|PubMed:10593930, ECO:0000269|PubMed:15252013,
CC ECO:0000269|PubMed:26090668, ECO:0000269|PubMed:28494242,
CC ECO:0000269|PubMed:30232373, ECO:0000269|PubMed:9516428}.
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:15252013, ECO:0000269|PubMed:9516428};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26090668}.
CC Note=Secreted via type III secretion system (T3SS) and delivered into
CC the host cytoplasm. {ECO:0000305}.
CC -!- DOMAIN: The N-terminal contains a GTPase-activating protein (GAP)
CC domain (PubMed:10593930, PubMed:15252013). The ADP-ribosyltransferase
CC domain is located within the C-terminus region (PubMed:15252013).
CC {ECO:0000269|PubMed:10593930, ECO:0000269|PubMed:15252013}.
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}.
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; AE004091; AAG07228.1; -; Genomic_DNA.
DR PIR; A53735; A53735.
DR RefSeq; NP_252530.1; NC_002516.2.
DR RefSeq; WP_003113791.1; NZ_QZGE01000001.1.
DR PDB; 6Y7T; X-ray; 2.50 A; D/E=420-430.
DR PDBsum; 6Y7T; -.
DR AlphaFoldDB; G3XDA1; -.
DR SMR; G3XDA1; -.
DR STRING; 287.DR97_4025; -.
DR PaxDb; G3XDA1; -.
DR EnsemblBacteria; AAG07228; AAG07228; PA3841.
DR GeneID; 879837; -.
DR KEGG; pae:PA3841; -.
DR PATRIC; fig|208964.12.peg.4021; -.
DR PseudoCAP; PA3841; -.
DR HOGENOM; CLU_603900_0_0_6; -.
DR OMA; MQIQANT; -.
DR BioCyc; PAER208964:G1FZ6-3913-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..453
FT /note="Secreted exoenzyme S"
FT /id="PRO_0000451079"
FT DOMAIN 239..414
FT /note="TR mART core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT REGION 1..234
FT /note="GTPase-activating protein (GAP) domain"
FT /evidence="ECO:0000269|PubMed:10593930,
FT ECO:0000269|PubMed:15252013"
FT REGION 235..453
FT /note="ADP-ribosyltransferase domain"
FT /evidence="ECO:0000269|PubMed:15252013"
FT ACT_SITE 319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 343
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT ACT_SITE 381
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340"
FT MUTAGEN 137
FT /note="R->K: No loss of ability to activate the GTPase
FT activity of host RhoA."
FT /evidence="ECO:0000269|PubMed:10593930"
FT MUTAGEN 146
FT /note="R->K: Complete loss of ability to activate the
FT GTPase activity of host RhoA."
FT /evidence="ECO:0000269|PubMed:10593930"
FT HELIX 422..425
FT /evidence="ECO:0007829|PDB:6Y7T"
SQ SEQUENCE 453 AA; 48302 MW; FEB3925EEA91461F CRC64;
MHIQSLQQSP SFAVELHQAA SGRLGQIEAR QVATPSEAQQ LAQRQDAPKG EGLLARLGAA
LVRPFVAIMD WLGKLLGSHA RTGPQPSQDA QPAVMSSAVV FKQMVLQQAL PMTLKGLDKA
SELATLTPEG LAREHSRLAS GDGALRSLST ALAGIRAGSQ VEESRIQAGR LLERSIGGIA
LQQWGTTGGA ASQLVLDASP ELRREITDQL HQVMSEVALL RQAVESEVSR VSADKALADG
LVKRFGADAE KYLGRQPGGI HSDAEVMALG LYTGIHYADL NRALRQGQEL DAGQKLIDQG
MSAAFEKSGQ AEQVVKTFRG TRGGDAFNAV EEGKVGHDDG YLSTSLNPGV ARSFGQGTIS
TVFGRSGIDV SGISNYKNEK EILYNKETDM RVLLSASDEQ GVTRRVLEEA ALGEQSGHSQ
GLLDALDLAS KPERSGEVQE QDVRLRMRGL DLA
