General Information:

Id: 2,336
Diseases: Pseudomonas aeruginosa diseases
pathogen-host system
Pseudomonas aeruginosa/mammalia
review
Reference: Hauser AR(2009) The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat. Rev. Microbiol. 7: 654-665 [PMID: 19680249]

Interaction Information:

Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 20362

gene/protein

exoS

interacts (colocalizes) with

gene/protein

RAB5

Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 20363

gene/protein

exoS

interacts (colocalizes) with

gene/protein

RAB6

Drugbank entries Show/Hide entries for RAB6
Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 20364

gene/protein

exoS

interacts (colocalizes) with

gene/protein

RAB9

Comment ExoS is a GTPase activating protein. Residues 96-233 of ExoS form a GAP domain that targets RhoA, Rac1, and Cdc42, small GTPases that maintain the organization of the actin cytoskeleton. These regulatory GTPases normally switch between an active GTP-bound form and an inactive GDP-bound form, but the ExoS GAP domain biases the switch towards the ADP-bound inactive form, leading to disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20367

gene/protein

exoS

decreases_activity of

gene/protein

RHOA

Drugbank entries Show/Hide entries for RHOA
Comment ExoS is a GTPase activating protein. Residues 96-233 of ExoS form a GAP domain that targets RhoA, Rac1, and Cdc42, small GTPases that maintain the organization of the actin cytoskeleton. These regulatory GTPases normally switch between an active GTP-bound form and an inactive GDP-bound form, but the ExoS GAP domain biases the switch towards the ADP-bound inactive form, leading to disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20368

gene/protein

exoS

decreases_activity of

gene/protein

RAC1

Drugbank entries Show/Hide entries for RAC1
Comment ExoS is a GTPase activating protein. Residues 96-233 of ExoS form a GAP domain that targets RhoA, Rac1, and Cdc42, small GTPases that maintain the organization of the actin cytoskeleton. These regulatory GTPases normally switch between an active GTP-bound form and an inactive GDP-bound form, but the ExoS GAP domain biases the switch towards the ADP-bound inactive form, leading to disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20369

gene/protein

exoS

decreases_activity of

gene/protein

CDC42

Drugbank entries Show/Hide entries for CDC42
Comment ExoS is a GTPase activating protein. Residues 96-233 of ExoS form a GAP domain that targets RhoA, Rac1, and Cdc42, small GTPases that maintain the organization of the actin cytoskeleton. These regulatory GTPases normally switch between an active GTP-bound form and an inactive GDP-bound form, but the ExoS GAP domain biases the switch towards the ADP-bound inactive form, leading to disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20370

gene/protein

exoS

decreases_activity of

Comment ExoS catalyzes the transfer of ADP-ribose to many different host proteins. Substrates of special interest are Ras and the ezrin, radixin and moesin (ERM) family of proteins.
Formal Description
Interaction-ID: 20373

gene/protein

exoS

affects_activity of

gene/protein

HRAS

Drugbank entries Show/Hide entries for HRAS
Comment ExoS catalyzes the transfer of ADP-ribose to many different host proteins. Substrates of special interest are Ras and the ezrin, radixin and moesin (ERM) family of proteins. ADP-ribosylation of ERM proteins prevents their phosphorylation, resulting in inactivation.
Formal Description
Interaction-ID: 20374

gene/protein

exoS

decreases_activity of

gene/protein

EZR

Comment ExoS catalyzes the transfer of ADP-ribose to many different host proteins. Substrates of special interest are Ras and the ezrin, radixin and moesin (ERM) family of proteins. ADP-ribosylation of ERM proteins prevents their phosphorylation, resulting in inactivation.
Formal Description
Interaction-ID: 20375

gene/protein

exoS

decreases_activity of

gene/protein

RDX

Drugbank entries Show/Hide entries for RDX
Comment ExoS catalyzes the transfer of ADP-ribose to many different host proteins. Substrates of special interest are Ras and the ezrin, radixin and moesin (ERM) family of proteins. ADP-ribosylation of ERM proteins prevents their phosphorylation, resulting in inactivation.
Formal Description
Interaction-ID: 20376

gene/protein

exoS

decreases_activity of

gene/protein

MSN

Comment Similar to ExoS, ExoT residues 78-235 contain GAP activity towards Rac, Rho, and Cdc42. This activity appears to be very similar to that of the N-terminus of ExoS and causes reversible disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20379

gene/protein

exoT

decreases_activity of

gene/protein

RAC1

Drugbank entries Show/Hide entries for RAC1
Comment Similar to ExoS, ExoT residues 78-235 contain GAP activity towards Rac, Rho, and Cdc42. This activity appears to be very similar to that of the N-terminus of ExoS and causes reversible disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20380

gene/protein

exoT

decreases_activity of

gene/protein

RHOA

Drugbank entries Show/Hide entries for RHOA
Comment Similar to ExoS, ExoT residues 78-235 contain GAP activity towards Rac, Rho, and Cdc42. This activity appears to be very similar to that of the N-terminus of ExoS and causes reversible disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20381

gene/protein

exoT

decreases_activity of

gene/protein

CDC42

Drugbank entries Show/Hide entries for CDC42
Comment Similar to ExoS, ExoT residues 78-235 contain GAP activity towards Rac, Rho, and Cdc42. This activity appears to be very similar to that of the N-terminus of ExoS and causes reversible disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 20382

gene/protein

exoT

decreases_activity of

Comment ExoT ADP-ribosylates a distinct and limited number of host proteins, in particular the CT10-regulator of kinase (Crk)-I and Crk-II, adaptor proteins.
Formal Description
Interaction-ID: 20384

gene/protein

exoT

affects_activity of

gene/protein

CRK

Comment The GAP (GTPase activating protein) and ADPRT (adenosine diphosphate ribosyl transferase activity) activities of ExoT work together to alter the actin cytoskeleton and to inhibit cell migration, adhesion, and proliferation. The net effect of these activities is to block phagocytosis and disrupt epithelial barriers to facilitate bacterial dissemination.
Formal Description
Interaction-ID: 20385

gene/protein

exoT

decreases_activity of

process

phagocytosis

Comment ExoT forms a complex with its substrate Crk and a Crk ligand, the E3 ubiquitin ligase Cbl-b, leading to polyubiquitination of ExoT by Cbl-b and subsequent proteasomal degradation.
Formal Description
Interaction-ID: 20386

gene/protein

exoT

interacts (colocalizes) with

gene/protein

CRK

Comment ExoT forms a complex with its substrate Crk and a Crk ligand, the E3 ubiquitin ligase Cbl-b, leading to polyubiquitination of ExoT by Cbl-b and subsequent proteasomal degradation.
Formal Description
Interaction-ID: 20387

gene/protein

exoT

interacts (colocalizes) with

gene/protein

CBLB

Comment ExoT forms a complex with its substrate Crk and a Crk ligand, the E3 ubiquitin ligase Cbl-b, leading to polyubiquitination of ExoT by Cbl-b and subsequent proteasomal degradation.
Formal Description
Interaction-ID: 20388

gene/protein

CBLB

increases_ubiquitination/sumoylation of

gene/protein

exoT

Comment Cbl-b functions as a host-defense molecule by facilitating the degradation of ExoT.
Formal Description
Interaction-ID: 20389

gene/protein

CBLB

decreases_activity of

process

P. aeruginosa infection

Comment ExoU has phospholipase A2 (PLA2) activity. The lipase activity of ExoU has a broad range of substrates, including phospholipids, lysophospholipids, and neutral lipids.
Formal Description
Interaction-ID: 20394

gene/protein

exoU

decreases_quantity of

drug/chemical compound

Phospholipid

by degradation
Comment ExoU has phospholipase A2 (PLA2) activity. The lipase activity of ExoU has a broad range of substrates, including phospholipids, lysophospholipids, and neutral lipids.
Formal Description
Interaction-ID: 20403

gene/protein

exoU

decreases_quantity of

drug/chemical compound

Lysophospholipid

by degradation
Comment Injection of ExoY into mammalian cells results in an elevation of intracellular cAMP concentration and differential expression of multiple genes, including many known to be regulated by cAMP.
Formal Description
Interaction-ID: 20417

gene/protein

exoY

increases_quantity of

drug/chemical compound

cAMP

in intracellular host cell compartment
Drugbank entries Show/Hide entries for cAMP
Comment ExoU requires the eukaryotic cofactor SOD1 for activation.
Formal Description
Interaction-ID: 20586

gene/protein

SOD1

increases_activity of

gene/protein

exoU

Drugbank entries Show/Hide entries for SOD1
Comment ExoT ADP-ribosylates a distinct and limited number of host proteins, in particular the CT10-regulator of kinase (Crk)-I and Crk-II, adaptor proteins.
Formal Description
Interaction-ID: 23445

gene/protein

exoT

increases_activity of

Comment ExoS is a GTPase activating protein. Residues 96-233 of ExoS form a GAP domain that targets RhoA, Rac1, and Cdc42, small GTPases that maintain the organization of the actin cytoskeleton. These regulatory GTPases normally switch between an active GTP-bound form and an inactive GDP-bound form, but the ExoS GAP domain biases the switch towards the ADP-bound inactive form, leading to disruption of the actin cytoskeleton.
Formal Description
Interaction-ID: 23446

gene/protein

exoS

increases_activity of

Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 38840

gene/protein

RAB5

is localized in

cellular component

early endosome

Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 38841

gene/protein

RAB6

is localized in

cellular component

late endosome

Drugbank entries Show/Hide entries for RAB6
Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 38843

gene/protein

RAB9

is localized in

cellular component

late endosome

Comment The membrane localization domain (MLD) (residues 51-72) of the P. aeruginosa effector ExoS is responsible for the initial transient localization to the plasma membrane of the host cell. Subsequent trafficking to the Golgi and endoplasmic reticulum in the perinuclear region of the cell occurs in association with markers for Rab5-containing early endosomes and Rab6- and Rab9-containing late endosomes.
Formal Description
Interaction-ID: 38846

gene/protein

exoS

is localized in

cellular component

host cell plasma membrane

transient localization