Information on EC 2.4.2.30 - NAD+ ADP-ribosyltransferase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, dsDNA viruses, no RNA stage, Archaea

EC NUMBER
COMMENTARY
2.4.2.30
-
RECOMMENDED NAME
GeneOntology No.
NAD+ ADP-ribosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
NAD+ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
-
-
-
NAD+ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
E219 and Gln217 of the ARTT-motif, i.e. ADP-ribosylating turn-turn motif, are essential for activity
-
NAD+ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains; the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains
O95271, P09874, Q2NL67, Q460N5, Q8N5Y8, Q9NR21, Q9UGN5, Q9UKK3, Q9Y6F1
NAD+ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
the pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains
-
NAD+ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
mechanism and physiological function, overview
-
NAD+ + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
L428 is essential for activity
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
pentosyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NAD+:poly(ADP-D-ribosyl)-acceptor ADP-D-ribosyl-transferase
The ADP-D-ribosyl group of NAD+ is transferred to an acceptor carboxy group on a histone or the enzyme itself, and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20--30 units.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
(adenosine diphosphoribose)transferase, nicotinamide adenine dinucleotide-protein
-
-
-
-
193-kDa vault protein
-
-
-
-
adenosine diphosphate ribosyltransferase
-
-
-
-
ADP-ribosylating thermozyme
-
-
ADP-ribosylating thermozyme
Sulfolobus solfataricus MT-4
-
-
-
ADP-ribosyltransferase
-
-
-
-
ADP-ribosyltransferase
Pseudomonas aeruginosa 388, Pseudomonas aeruginosa PA103
-
-
-
ADP-ribosyltransferase (polymerizing)
-
-
-
-
ADP-ribosyltransferase C3cer
-
-
ADP-ribosyltransferase C3cer
Bacillus cereus 2339
-
-
-
ADP-ribosyltransferase-1
-
-
ADPRT
Pseudomonas aeruginosa 388
-
-
-
ADPRT
-
-
-
-
asparagine-specific ADP-ribosyltransferase
-
-
B aggressive lymphoma protein 2
Q460N5
-
C3 exoenzyme
-
-
-
-
ecto-ADP-ribosyltransferase 2.2
-
-
ecto-ADP-ribosyltransferase ART2.2
-
-
exoenzyme C3
-
-
-
-
exoenzyme C3
-
-
exoenzyme S
-
-
-
-
exoenzyme S
Pseudomonas aeruginosa 388, Pseudomonas aeruginosa ExoS, Pseudomonas aeruginosa PA103
-
-
-
exoenzyme T
-
-
ExoS
-
bifunctional type-III cytotoxin with an N-terminal RhoGAP domain and and C-terminal ADP-ribosylation domain
ExoS
-
bifunctional type-III cytotoxin. Residues 96233 comprise the Rho GTPase-activating protein domain, while residues 234453 comprise the 14-3-3-dependent ADP-ribosyltransferase domain
ExoS
Pseudomonas aeruginosa 388
-
-
-
ExoS
Pseudomonas aeruginosa ExoS
-
; bifunctional type-III cytotoxin with an N-terminal RhoGAP domain and and C-terminal ADP-ribosylation domain
-
ExoS
Pseudomonas aeruginosa ExoT
-
bifunctional type-III cytotoxin with an N-terminal RhoGAP domain and and C-terminal ADP-ribosylation domain
-
ExoT
-
bifunctional type-III cytotoxin with an N-terminal RhoGAP domain and and C-terminal ADP-ribosylation domain
ExoT
-
enzyme is comprised of an N-terminal domain with GTPase activating protein activity towards Rho family GTPases and a C-terminal ADP ribosyl-transferase (ADPRT) domain with minimal activity towards a synthetic substrate in vitro
ExoT
Pseudomonas aeruginosa ExoS, Pseudomonas aeruginosa ExoT
-
bifunctional type-III cytotoxin with an N-terminal RhoGAP domain and and C-terminal ADP-ribosylation domain
-
mono-ADP-ribosyltransferase
Q49TP5
-
msPARP
-
-
-
-
NAD(+) ADP-ribosyltransferase
-
-
-
-
NAD+:ADP-ribosyltransferase (polymerizing)
-
-
-
-
NAD-dependent ADP-ribosyltransferase
-
-
NAD-protein ADP-ribosyltransferase
-
-
-
-
pADPRT
-
-
-
-
PARP
P09874, Q2NL67, Q460N5, Q8N5Y8, Q9NR21, Q9UGN5, Q9UKK3, Q9Y6F1
-
PARP
-
-
-
-
PARP-1
-
-
PARP-1
-
-
PARP-1
Mus musculus 129/Sv x C57BL/6, Mus musculus Sv129
-
-
-
PARP-related/IalphaI-related H5/proline-rich
-
-
-
-
PARPss
Sulfolobus solfataricus MT-4
-
-
-
PH5P
-
-
-
-
poly (ADP-ribose) polymerase
-
-
poly (ADP-ribose) polymerase-1
-
-
poly(ADP-ribose) polymerase
-
-
-
-
poly(ADP-ribose) polymerase
-
-
poly(ADP-ribose) polymerase-1
-
-
poly(ADP-ribose) polymerase-1
-
-
poly(ADP-ribose) polymerase-1
-
-
poly(ADP-ribose) polymerase-1
-
-
poly(ADP-ribose) polymerase-1
Mus musculus 129/Sv x C57BL/6, Mus musculus Sv129
-
-
-
poly(ADP-ribose) polymerase-like enzyme
-
-
poly(ADP-ribose) synthase
-
-
-
-
poly(ADP-ribose) transferase
-
-
-
-
poly(ADP-ribosyl)transferase
-
-
-
-
poly[ADP-ribose] synthetase
-
-
-
-
TANK1
O95271
-
TANK1
-
-
-
-
TANK2
-
-
-
-
tankyrase I
O95271
-
Tankyrase-like protein
-
-
-
-
Tankyrase-related protein
-
-
-
-
TbSIR2RP1
-
-
TNKS-1
O95271
-
TRF1-interacting ankyrin-related ADP-ribose polymerase
O95271
-
TRF1-interacting ankyrin-related ADP-ribose polymerase
-
-
-
-
TTS-ExoS
Pseudomonas aeruginosa 388
-
-
-
type III-secreted toxin
-
-
VPARP
-
-
-
-
vsdc
Q49TP5
gene name
mono-ADP-ribosyltransferase
-
-
additional information
O95271, P09874, Q2NL67, Q460N5, Q8N5Y8, Q9NR21, Q9UGN5, Q9UKK3, Q9Y6F1
the enzyme belongs to the family of PARP-like poly(ADP-ribosyl)transferases, pARTs
additional information
-
the enzyme belongs to the family of PARP-like poly(ADP-ribosyl)transferases, pARTs
CAS REGISTRY NUMBER
COMMENTARY
58319-92-9
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
-
Q49TP5
SwissProt
Manually annotated by BRENDA team
strain 2339
-
-
Manually annotated by BRENDA team
Bacillus cereus 2339
strain 2339
-
-
Manually annotated by BRENDA team
calf
-
-
Manually annotated by BRENDA team
Cryptothecodinium cohnii
-
-
-
Manually annotated by BRENDA team
Enterobacteria phage T4 ModA
ModA
Uniprot
Manually annotated by BRENDA team
Enterobacteria phage T4 ModB
ModB
Uniprot
Manually annotated by BRENDA team
healthy people and Parkinson patients
-
-
Manually annotated by BRENDA team
PARP-1
SwissProt
Manually annotated by BRENDA team
PARP-11
SwissProt
Manually annotated by BRENDA team
PARP-14
SwissProt
Manually annotated by BRENDA team
PARP-16
SwissProt
Manually annotated by BRENDA team
PARP-2
SwissProt
Manually annotated by BRENDA team
PARP-3
SwissProt
Manually annotated by BRENDA team
PARP-4
SwissProt
Manually annotated by BRENDA team
PARP-6
SwissProt
Manually annotated by BRENDA team
TNKS1
SwissProt
Manually annotated by BRENDA team
gene parp-1
-
-
Manually annotated by BRENDA team
isozymes PARP-1 and PARP-2
-
-
Manually annotated by BRENDA team
strain 129/Sv x C57BL/6, female mice
-
-
Manually annotated by BRENDA team
Sv129 mice
-
-
Manually annotated by BRENDA team
Mus musculus 129/Sv x C57BL/6
strain 129/Sv x C57BL/6, female mice
-
-
Manually annotated by BRENDA team
Mus musculus Sv129
Sv129 mice
-
-
Manually annotated by BRENDA team
Exo53 form of exoenzyme S; ExoS form of exoenzyme S
-
-
Manually annotated by BRENDA team
strain PA103
-
-
Manually annotated by BRENDA team
strains PAK and PA14
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa 388
388
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa 388
strain 388
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa ExoS
ExoS
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa ExoT
ExoT
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
i.e. DSM5833
-
-
Manually annotated by BRENDA team
Sulfolobus solfataricus MT-4
-
SwissProt
Manually annotated by BRENDA team
Sulfolobus solfataricus MT-4
i.e. DSM5833
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
P35875
disruption of PARP1 enzymatic activity causes nucleolar disintegration and aberrant localization of nucleolar-specific proteins. PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels
metabolism
-
the lowest PARP activity, as well as the lowest quantum yield of PSII linear electron transport (FPSII) and photochemical quenching (qP), is found in outdoor during winter plants. In outdoor spring plants the recovery of photochemical activity associated to a poly(ADP-ribose)polymerase activity increase of about 50%, as compared to greenhouse plants, is observed
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
NAD+ + (ADP-D-ribosyl)n-(EF-2)
nicotinamide + (ADP-D-ribosyl)n+1-(EF-2)
show the reaction diagram
-
in native conformation, CRM66 shows limited ability to modify EF-2 covalently. Upon activation with urea and dithiothreitol CRM66 loses ADP-ribosylation activity entirely, yet it retains the ability to bind NAD+. Replacement of Tyr-426 with histidine in CRM66 completely restores cytotoxicity and ADP-ribosyltransferase activity
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
O95271, P09874, Q2NL67, Q460N5, Q8N5Y8, Q9NR21, Q9UGN5, Q9UKK3, Q9Y6F1
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of topoisomerase I
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
auto-poly(ADP-ribosyl)ation
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of high mobility group proteins, poly(ADP-ribosyl)ation of DNA ligase, poly(ADP-ribosyl)ation of endonuclease, poly(ADP-ribosyl)ation of topoisomerase II, poly(ADP-ribosyl)ation of terminal deoxynucleotidyltransferase
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of 21000-24000 Da platelet membrane proteins
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of histone H1
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of histone H1
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of histone H1
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of histone
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of histone
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
Cryptothecodinium cohnii
-
poly(ADP-ribosyl)ation of histone
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
catalyzes poly(ADP-ribosyl)ation of the synthetase itself, automodification
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation of ADP-ribosyltransferase
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ADPRT domain of ExoT is active in vivo and contributes to the pathogenesis of Pseudomonas aeruginosa infections
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
exoenzyme S is an ADP-ribosyltransferase produced and directly translocated into eukaryotic cells by the opportunistic pathogen Pseudomonas aeruginosa. Factors expressed by growing epithelial cells are required for the bacterial contact-dependent translocation of ExoS. As normal epithelial cells differentiate into polarized confluent monolayers, expression of these factors is altered, and cells in turn become more resistant to the effects of ExoS
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoS can modify multiple GTPases of the Ras superfamily in vivo. ExoS modulates the activity of several of GTP-binding proteins, such as Ras, Rap1, Rap2, Ral, Rac1, RhoA and Cdc42. It is suggested that ExoS is the major ADP-ribosyltransferase protein modulating small GTPase function encoded by Pseudomonas aeruginosa
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoT modifies and inactivates host cell proteins involved in maintaining the actin cytoskeleton in vivo by two independent mechanisms. ADP-ribosylation activity of ExoT induces an irreversible disruption of actin microfilaments of infected Hela cells
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
intracellular expression of the amino terminus of ExoS in eukaryotic cells stimulates actin reorganization without cytotoxicity, which involves small-molecular-weight GTPases of the Rho subfamily
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
intracellular Ras is modified by bacterially translocated ExoS, inhibition of target cell proliferation correlates with the efficiency of Ras modification
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoS has polysubstrate specificity and can ADP-ribosylate numerous host proteins, e.g. monomeric GTPase or vimentin. ExoS also undergoes auto-ADP-ribosylation. Ras has multiple alternative sites for ADP-ribosylation
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoS is a type III cytotoxin which modulates two eukaryotic signalling pathways. The N-terminus (residues 1-234) is a GTPase activating protein for RhoGTPases, while the C-terminus (residues 232-453) encodes an ADP-ribosyltransferase
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoT ADP-ribosylates a restricted subset of host proteins including the Crk proteins
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation, i.e. PARylation, plays diverse roles in many molecular and cellular processes, including DNA damage detection and repair, chromatin modification, transcription, cell death pathways, insulator function, and mitotic apparatus function, connections between nuclear NAD+ metabolism and nuclear signaling through PARP-1, physiologic functions, detailed overview, synthesis and degradation of PAR on an acceptor protein, pathway overview, the enzyme is involved in regulation of the steady-state levels of PAR
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
the enzyme is a DNA repair enzyme
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
linking a long negatively charged polymer to a protein, PARP catalyzes the polymerization of ADP-ribose units from donor NAD+ molecules on target proteins, resulting in the attachment of PAR, each residue in PAR contains an adenine moiety capable of base stacking and hydrogen bonding, as well as two phosphate groups that carry negative charges, substrate structure, overview
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
linking a long negatively charged polymer to a protein, PARP-1 catalyzes the polymerization of ADP-ribose units from donor NAD+ molecules on target proteins, resulting in the attachment of PAR, each residue in PAR contains an adenine moiety capable of base stacking and hydrogen bonding, as well as two phosphate groups that carry negative charges, substrate structure, overview
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
agmatine as ADPribose acceptor is used
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
Pseudomonas aeruginosa ExoS
-
ExoS has polysubstrate specificity and can ADP-ribosylate numerous host proteins, e.g. monomeric GTPase or vimentin. ExoS also undergoes auto-ADP-ribosylation. Ras has multiple alternative sites for ADP-ribosylation, ExoT ADP-ribosylates a restricted subset of host proteins including the Crk proteins
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
Pseudomonas aeruginosa ExoT
-
ExoS has polysubstrate specificity and can ADP-ribosylate numerous host proteins, e.g. monomeric GTPase or vimentin. ExoS also undergoes auto-ADP-ribosylation. Ras has multiple alternative sites for ADP-ribosylation, ExoT ADP-ribosylates a restricted subset of host proteins including the Crk proteins
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
B3EWG9, -
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
-, the emzyme protects homologous DNA against thermal denaturation by lowering the amount of melted DNA and increasing melting temperature. The archaeal protein induces structural changes of the nucleic acid by modifying the dichroic spectra towards a shape typical of condensing DNA
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
Sulfolobus solfataricus MT-4
B3EWG9
-, the emzyme protects homologous DNA against thermal denaturation by lowering the amount of melted DNA and increasing melting temperature. The archaeal protein induces structural changes of the nucleic acid by modifying the dichroic spectra towards a shape typical of condensing DNA
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-actin
nicotinamide + (ADP-D-ribosyl)n+1-actin
show the reaction diagram
Q49TP5
VahC is shown to ADP-ribosylate Arg-177 of actin. VahC activity causes depolymerization of actin filaments, which induces caspase-mediated apoptosis in HeLa Tet-Off cells
-
-
?
NAD+ + (ADP-D-ribosyl)n-apolipoprotein
nicotinamide + (ADP-D-ribosyl)n+1-apolipoprotein
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-Crk-I
nicotinamide + (ADP-D-ribosyl)n+1-Crk-I
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-Crk-II
nicotinamide + (ADP-D-ribosyl)n+1-Crk-II
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-His6HRas
nicotinamide + (ADP-D-ribosyl)n+1-His6HRas
show the reaction diagram
-
the enzyme preferentially ADP-ribosylates membrane-associated His6HRas relative to its cytosolic His6HRasDELTACAAX with a C-terminal deletion
-
-
?
NAD+ + (ADP-D-ribosyl)n-immunoglobulin A
nicotinamide + (ADP-D-ribosyl)n+1-immunoglobulin A
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-immunoglobulin G
nicotinamide + (ADP-D-ribosyl)n+1-immunoglobulin G
show the reaction diagram
-
preferentially IgG3
-
-
?
NAD+ + (ADP-D-ribosyl)n-p21ras
nicotinamide + (ADP-D-ribosyl)n+1-p21ras
show the reaction diagram
-
-, ADP-ribosylation of p21ras does not alter interactions with guanidine nucleotides. Possible function of the enzyme in pathogenesis
-
-
?
NAD+ + (ADP-D-ribosyl)n-Rab2
nicotinamide + (ADP-D-ribosyl)n+1-Rab2
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-Rab3
nicotinamide + (ADP-D-ribosyl)n+1-Rab3
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-rab4
nicotinamide + (ADP-D-ribosyl)n+1-rab4
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-rab4
nicotinamide + (ADP-D-ribosyl)n+1-rab4
show the reaction diagram
-
ADP-ribosylation affects Rab4 function in membrane recycling
-
-
?
NAD+ + (ADP-D-ribosyl)n-Rab5
nicotinamide + (ADP-D-ribosyl)n+1-Rab5
show the reaction diagram
-
-, ADP-ribosylation of Rab5 by ExoS affects endocytosis. Interaction of Rab5 with endosome antigen 1 is markedly diminished after Rab5 ADP-ribosylation by ExoS
-
-
?
NAD+ + (ADP-D-ribosyl)n-RalA
nicotinamide + (ADP-D-ribosyl)n+1-RalA
show the reaction diagram
-
-, ADP-ribosylation of RalA by ExoS interferes with RalA activation and binding to its downstream effector in J774A.1 macrophages and suggests the potential of ExoS ADPRT activity to interfere with filiopodium formation through the inactivation of RalA and downstream effects mediated through the exocyst complex
-
-
?
NAD+ + (ADP-D-ribosyl)n-Rap1A
nicotinamide + (ADP-D-ribosyl)n+1-Rap1A
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-Ras
nicotinamide + (ADP-D-ribosyl)n+1-Ras
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-Ras
nicotinamide + (ADP-D-ribosyl)n+1-Ras
show the reaction diagram
-
ADP-ribosylation of Ras at Arg41 disrupts Ras-Cdc25 interactions, which inhibits the rate-limiting step in Ras signal transduction, the activation of Ras by its guanine nucleotide exchange factor
-
-
?
NAD+ + (ADP-D-ribosyl)n-Ras protein
nicotinamide + (ADP-D-ribosyl)n+1-Ras protein
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-soybean trypsin inhibitor
nicotinamide + (ADP-D-ribosyl)n+1-soybean trypsin inhibitor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-soybean-trypsin-inhibitor
nicotinamide + (ADP-D-ribosyl)n+1-soybean-trypsin-inhibitor
show the reaction diagram
-
-
-
-
?
NAD+ + cyclophilin A
nicotinamide + (ADP-D-ribosyl)-cyclophilin A
show the reaction diagram
-
cytosolic protein of several human epithelial cells, modification at Arg55 and Arg69 of cyclophilin A, ADP-ribosylation of CpA efficiently inhibits CpA binding to calcineurin/PP2B phosphatase, overview, a non-G-protein substrate with peptidyl-prolyl isomerase activity, from several human epithelial cells, modification at Arg55 and Arg69, but not at Arg148, of cyclophilin A, i.e. CpA, ADP-ribosylation of CpA efficiently inhibits CpA binding to calcineurin/PP2B phosphatase, activity with CpA mutants, overview
-
-
?
NAD+ + cyclophilin A
nicotinamide + (ADP-D-ribosyl)-cyclophilin A
show the reaction diagram
Pseudomonas aeruginosa 388
-
cytosolic protein of several human epithelial cells, modification at Arg55 and Arg69 of cyclophilin A, ADP-ribosylation of CpA efficiently inhibits CpA binding to calcineurin/PP2B phosphatase, overview, a non-G-protein substrate with peptidyl-prolyl isomerase activity, from several human epithelial cells, modification at Arg55 and Arg69, but not at Arg148, of cyclophilin A, i.e. CpA, ADP-ribosylation of CpA efficiently inhibits CpA binding to calcineurin/PP2B phosphatase, activity with CpA mutants, overview
-
-
?
NAD+ + GTPase RhoA
nicotinamide + (ADP-D-ribosyl)-GTPase RhoA
show the reaction diagram
-
the exoenzyme modifies the low-molecular-mass GTPases RhoA, B, and C specifically at Asn41
-
-
?
NAD+ + GTPase RhoB
nicotinamide + (ADP-D-ribosyl)-GTPase RhoB
show the reaction diagram
-
the exoenzyme modifies the low-molecular-mass GTPases RhoA, B, and C specifically at Asn41
-
-
?
NAD+ + GTPase RhoC
nicotinamide + (ADP-D-ribosyl)-GTPase RhoC
show the reaction diagram
-
the exoenzyme modifies the low-molecular-mass GTPases RhoA, B, and C specifically at Asn41
-
-
?
NAD+ + H2O
nicotinamide + ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + histone H1
nicotinamide + (ADP-D-ribosyl)-histone H1
show the reaction diagram
-
-
-
-
?
NAD+ + histone H2A
nicotinamide + (ADP-D-ribosyl)-histone H2A
show the reaction diagram
-
the enzyme catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B. Histone modification by TbSIR2RP1 is involved in DNA repair, the enzyme catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B
-
-
?
NAD+ + histone H2B
nicotinamide + (ADP-D-ribosyl)-histone H2B
show the reaction diagram
-
-
-
-
?
NAD+ + histone H2B
nicotinamide + (ADP-D-ribosyl)-histone H2B
show the reaction diagram
-
the enzyme catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B. Histone modification by TbSIR2RP1 is involved in DNA repair, the enzyme catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B
-
-
?
NAD+ + lymphocyte function-associated antigen LFA-1
nicotinamide + ?
show the reaction diagram
-
-
-
-
?
NAD+ + moesin
nicotinamide + (ADP-D-ribosyl)-moesin
show the reaction diagram
-
ADP-ribosylated-moesin is a poor target for phosphorylation by protein kinase C and Rho kinase, which shows that ADP-ribosylation directly inhibits ERM phosphorylation, modification of Arg553, Arg560 and Arg563, activity with wild-type and mutant moesins, overview
-
-
?
NAD+ + non-muscle actin from human platelets
nicotinamide + (ADP-D-ribosyl)-non-muscle actin from human platelets
show the reaction diagram
-
-
-
-
?
NAD+ + p53
nicotinamide + (ADP-D-ribosyl)-p53
show the reaction diagram
-
-, PARP-1 interacts with and poly(ADP-ribosyl)ates p53, which participates in DNA recombination
-
-
?
NAD+ + poly(ADP-ribose) polymerase-1
nicotinamide + (ADP-ribosyl)-poly(ADP-ribose) polymerase-1
show the reaction diagram
-
the 40 kDa CD fragment of avian PARP-1 efficiently catalyzes a covalent auto-poly-(ADP-ribosyl)ation reaction via an intermolecular mechanism that is completely independent of DNA
-
-
?
NAD+ + Rab5 protein
nicotinamide + (ADP-D-ribosyl)-Rab5 protein + H+
show the reaction diagram
-
Rab5 mediates entry of the EGFR into early endosomes
-
-
?
NAD+ + Rab9 protein
nicotinamide + (ADP-D-ribosyl)-Rab9 protein + H+
show the reaction diagram
-
-
-
-
?
NAD+ + rabbit muscle actin
nicotinamide + (ADP-D-ribosyl)-rabbit muscle actin
show the reaction diagram
-
-
-
-
?
NAD+ + Ras
nicotinamide + (ADP-D-ribosyl)-Ras
show the reaction diagram
-
interaction requires residue Leu428
-
-
?
NAD+ + Ras GTPase
nicotinamide + (ADP-D-ribosyl)-Ras GTPase
show the reaction diagram
-
-
-
-
?
NAD+ + Ras2p
nicotinamide + (ADP-D-ribosyl)-Ras2p + H+
show the reaction diagram
-
Ras2p is a yeast protein, activity absolutely requires the yeast protein Bmh1p
-
-
?
NAD+ + RhoA
nicotinamide (ADP-D-ribosyl)-RhoA
show the reaction diagram
Bacillus cereus, Bacillus cereus 2339
-
-
-
-
?
NAD+ + RhoB
nicotinamide (ADP-D-ribosyl)-RhoB
show the reaction diagram
Bacillus cereus, Bacillus cereus 2339
-
-
-
-
?
NAD+ + RhoC
nicotinamide (ADP-D-ribosyl)-RhoC
show the reaction diagram
Bacillus cereus, Bacillus cereus 2339
-
weak activity
-
-
?
NAD+ + RNA polymerase
nicotinamide + (ADP-D-ribosyl)-RNA polymerase
show the reaction diagram
P12726
-, three ADP-ribosyltransferases, Alt, ModA, and ModB participate in the regulation of the T4 replication cycle by ADP-ribosylating a defined set of host proteins. ADP-ribosylation of RNA polymerase and of other host proteins allows initial phage-directed mRNA synthesis reactions to escape from host control
-
-
?
NAD+ + soybean trypsin inhibitor
nicotinamide + (ADP-D-ribosyl)-soybean trypsin inhibitor
show the reaction diagram
-
the exoenzyme modifies the substrate at an arginine residue
-
-
?
NAD+ + topoisomerase I
nicotinamide + (ADP-D-ribosyl)-topoisomerase I
show the reaction diagram
-
-, PARP-1 interacts with and poly(ADP-ribosyl)ates topoisomerase I, which participates in DNA recombination, I-SceI-meganuclease-mediated cleavage terminates the interaction, overview
-
-
?
NAD+ + vimentin
nicotinamide + (ADP-D-ribosyl)-vimentin
show the reaction diagram
-
-
-
-
?
NAD+ + wild-type exoenzyme C3
nicotinamide + (ADP-D-ribosyl)-wild-type exoenzyme C3
show the reaction diagram
-
activity of the recombinant mutant Q217E exoenzyme C3, modification at Arg86
-
-
?
integrin alpha7 + NAD+
(ADP-D-ribosyl)-integrin alpha7 + nicotinamide
show the reaction diagram
-
the extracellular domain of integrin alpha7 is ADP-ribosylated by an arginine-specific ecto-ADP-ribosyltransferase after adding exogenous NAD+ to intact C2C12 muscle cells, integrin alpha7 N-terminal ADP-ribosylation inhibits the binding of integrin alpha7beta1 to laminin activation status of integrin alpha7beta1 in intact myotubes, overview, the extracellular domain of integrin alpha7 is ADP-ribosylated by an arginine-specific ecto-ADP-ribosyltransferase after adding exogenous NAD+ to intact C2C12 muscle cells, integrin alpha7 ADP-ribosylation inhibits the binding of integrin alpha7beta1 to laminin, binding site, overview
-
-
?
additional information
?
-
-
ADP-ribosylation seems to be involved in regulation of differentiation, the enzyme may be centrally involved in tumorigenic cell transformation, the enzyme appears to be a central controller of cell processes: higher activities shift the cell towards proliferation, low activities shift the cell towards differentiation, role of the enzyme in DNA repair
-
-
-
additional information
?
-
-
cuts produced in vivo on DNA during DNA repair activate the enzyme, which then synthesiszes poly(ADP-ribose) on histone H1, in particular, and contributes to the opening of the 25 nm chromatin fiber, resulting in the increased accessibility of DNA to excision repair enzymes
-
-
-
additional information
?
-
-
the enzyme modifies eukaryotic 21000-24000 Da GTP-binding proteins
-
-
-
additional information
?
-
-
role of the enzyme in DNA repair, the unmodified polymerase molecules bind tightly to DNA strand breaks: auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes
-
-
-
additional information
?
-
-
mechanistic basis for the physiological function of PARP-1 in the dynamics of the local modulation of chromatin structure. PARP-1 activation upon binding to base-unpaired regions and stem-loops structures in DNA leads to a local PAR modification of histones and non-histone proteins at genomic sites where such DNA structures are formed. Subsequent PARP-1 automodification results in its dissociation from DNA leading to an enzymatic self-inactivation thus ensuring a transient character of chromatin ADP-ribosylation. In combination with the PAR-glycohydrolase degradation of ADP-ribose polymers on acceptor proteins, PARP-1 interaction with DNA secondary structures provides a mechanism for local and transient chromatin modification by PAR during physiological nuclear processes
-
-
-
additional information
?
-
-
raft association focuses ART2.2 on specific targets that constitutively or inducibly assoiate with lipid rafts
-
-
-
additional information
?
-
-
ART1 is an arginine-specific transferase
-
-
-
additional information
?
-
-
narE possesses ADP-ribosylating and NAD-glycohydrolase activities
-
-
-
additional information
?
-
-
exoenzyme S and 14-3-3 interact in a direct fashion, interaction involves the conserved amphiphatic groove of 14-3-3
-
-
-
additional information
?
-
-
exoenzyme S is an important adhesin
-
-
-
additional information
?
-
-
ExoS is a virulence factor of the pathogen
-
-
-
additional information
?
-
-
PARP-1 inhibits the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein, TonEBP/OREBP. Inhibition of TonEBP/OREBP transcriptional activity by PARP-1 does not require PARP-1 catalytic activity, functional interaction anaylsis, overview
-
-
-
additional information
?
-
-
PARP-1 is involved in modulation of NO-derived injury and response to genotoxic damage
-
-
-
additional information
?
-
-
PARP-1 plays an essential role in the control of cell repair and tissue remodeling after hyperoxia-induced lung injury, overview
-
-
-
additional information
?
-
-
PARP-1 plays fundamental roles in the recruitment and modulation of enzymatic and regulatory factors involved in transcription, DNA replication, repair and recombination, the enzyme antagonizes topoisomerase I-dependent recombination stimulation by P53
-
-
-
additional information
?
-
-
PARP-1 responds to DNA damage by transferring 50 to 200 molecules of ADP-ribose to various nuclear proteins, including transcription factors, histones and PARP-1 itself, interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition, ATM and PARP-1 are two of the most important players in the cell's response to DNA damage, PARP-1 is needed for optimal activation of ATM, overview
-
-
-
additional information
?
-
-
Pseudomonas aeruginosa inhibits mammalian cytokinesis in a type III secretion system and exotoxin T-dependent manner, the ADP-ribosyl transferase domain inhibits late steps of cytokinesis by blocking syntaxin-2 localization to the midbody, an event essential for completion of cytokinesis, e.g. in Madin-Darby canine kidney cells, mechanism, overview
-
-
-
additional information
?
-
-
role for PARP-1 in DNA double-strand break repair, the enzyme is not required for homologous recombination itself, it regulates the process through its involvement in the repair of DNA single-strand breaks, PARP-1 binds to DNA breaks to facilitate DNA repair, but the role of PARP-1 in DNA repair appears to not be critical since PARP-1 knockout mice are viable, fertile and do not develop early onset tumors, DNA binding and auto-modification of PARP-1 attracts the DNA repair proteins
-
-
-
additional information
?
-
-
the bacterial enzyme shows the ability to mediate cell death in the host and is a toxin, residues 426-428 are required for this activity
-
-
-
additional information
?
-
-
the enzyme is involved in endothelial cell dysfunction
-
-
-
additional information
?
-
-
the enzyme is involved in pathogenesis of Parkinson's disease, analysis of polymorphisms, overview
-
-
-
additional information
?
-
-
transcriptional regulation mechanism, overview
-
-
-
additional information
?
-
-
exoenzyme S is a bifunctional type III secretion, TTS, effector protein, with GTPase-activating and ADP-ribosyltransferase activities
-
-
-
additional information
?
-
-
ExoS is a bifunctional toxin with an N-terminal Rho GTPase activating protein, GAP, domain, and a C-terminal ADP-ribosyltransferase domain which transfers ADP-ribose from NAD onto substrates such as the Ras GTPases and vimentin
-
-
-
additional information
?
-
-
ExoT is a bifunctional type III secretion system effector protein that contains an N-terminal GTPase-activating protein domain and a C-terminal ADP-ribosyl transferase domain
-
-
-
additional information
?
-
-
PARP-1 protein has an N-terminal DNA binding domain containing two large zinc fingers that bind to both DNA single-strand breaks and DNA double-strand breaks, DNA binding by PARP-1 triggers its activity and it adds poly(ADP-ribose) polymers to itself and to surrounding histones, overview
-
-
-
additional information
?
-
-
the enzyme also shows NAD+-hydrolase activity
-
-
-
additional information
?
-
-
the enzyme shows DNA-binding activity, and is physically associated with the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein, TonEBP/OREBP
-
-
-
additional information
?
-
-
ExoS is a toxin playing a pivotal role during Pseudomonas aeruginosa infections, it is a virulence factor causing growth inhibition in Saccharomyces cerevisiae. Exoenzyme S ADP-ribosylates identical targets in both human and yeast
-
-
-
additional information
?
-
-
ExoS is a type III cytotoxin, that ADP-ribosylates Rab GTPases to inhibit host cell vesicle trafficking pathways by modulating HeLa host cell endocytosis, wild-type ExoS uncouples Rab5-early endosome antigen 1 interaction and inhibits fluid phase uptake, as well as Pseudomonas aeruginosa internalization, RhoGAP, but not ADPr, the ADPr domain is dispensable for anti-internalization function, but is required for inhibition of EGF-activated EGFR degradation in HeLa cells, mechanism, overview, ExoS is a bi-functional type III cytotoxin that possesses Rho GTPase activating protein and ADP-ribosyltransferase activities, no activity with Rab4 protein, overview
-
-
-
additional information
?
-
Pseudomonas aeruginosa 388
-
exoenzyme S is a bifunctional type III secretion, TTS, effector protein, with GTPase-activating and ADP-ribosyltransferase activities
-
-
-
additional information
?
-
Mus musculus 129/Sv x C57BL/6
-
the enzyme is involved in endothelial cell dysfunction
-
-
-
additional information
?
-
Mus musculus Sv129
-
PARP-1 plays an essential role in the control of cell repair and tissue remodeling after hyperoxia-induced lung injury, overview
-
-
-
additional information
?
-
-
ExoS is a type III cytotoxin, that ADP-ribosylates Rab GTPases to inhibit host cell vesicle trafficking pathways by modulating HeLa host cell endocytosis, wild-type ExoS uncouples Rab5-early endosome antigen 1 interaction and inhibits fluid phase uptake, as well as Pseudomonas aeruginosa internalization, RhoGAP, but not ADPr, the ADPr domain is dispensable for anti-internalization function, but is required for inhibition of EGF-activated EGFR degradation in HeLa cells, mechanism, overview, ExoS is a bi-functional type III cytotoxin that possesses Rho GTPase activating protein and ADP-ribosyltransferase activities, no activity with Rab4 protein, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
O95271, P09874, Q2NL67, Q460N5, Q8N5Y8, Q9NR21, Q9UGN5, Q9UKK3, Q9Y6F1
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ADPRT domain of ExoT is active in vivo and contributes to the pathogenesis of Pseudomonas aeruginosa infections
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
exoenzyme S is an ADP-ribosyltransferase produced and directly translocated into eukaryotic cells by the opportunistic pathogen Pseudomonas aeruginosa. Factors expressed by growing epithelial cells are required for the bacterial contact-dependent translocation of ExoS. As normal epithelial cells differentiate into polarized confluent monolayers, expression of these factors is altered, and cells in turn become more resistant to the effects of ExoS
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoS can modify multiple GTPases of the Ras superfamily in vivo. ExoS modulates the activity of several of GTP-binding proteins, such as Ras, Rap1, Rap2, Ral, Rac1, RhoA and Cdc42. It is suggested that ExoS is the major ADP-ribosyltransferase protein modulating small GTPase function encoded by Pseudomonas aeruginosa
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
ExoT modifies and inactivates host cell proteins involved in maintaining the actin cytoskeleton in vivo by two independent mechanisms. ADP-ribosylation activity of ExoT induces an irreversible disruption of actin microfilaments of infected Hela cells
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
intracellular expression of the amino terminus of ExoS in eukaryotic cells stimulates actin reorganization without cytotoxicity, which involves small-molecular-weight GTPases of the Rho subfamily
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
intracellular Ras is modified by bacterially translocated ExoS, inhibition of target cell proliferation correlates with the efficiency of Ras modification
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
poly(ADP-ribosyl)ation, i.e. PARylation, plays diverse roles in many molecular and cellular processes, including DNA damage detection and repair, chromatin modification, transcription, cell death pathways, insulator function, and mitotic apparatus function, connections between nuclear NAD+ metabolism and nuclear signaling through PARP-1, physiologic functions, detailed overview, synthesis and degradation of PAR on an acceptor protein, pathway overview, the enzyme is involved in regulation of the steady-state levels of PAR
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor
show the reaction diagram
-
the enzyme is a DNA repair enzyme
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
the emzyme protects homologous DNA against thermal denaturation by lowering the amount of melted DNA and increasing melting temperature. The archaeal protein induces structural changes of the nucleic acid by modifying the dichroic spectra towards a shape typical of condensing DNA
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
Sulfolobus solfataricus MT-4
B3EWG9
the emzyme protects homologous DNA against thermal denaturation by lowering the amount of melted DNA and increasing melting temperature. The archaeal protein induces structural changes of the nucleic acid by modifying the dichroic spectra towards a shape typical of condensing DNA
-
-
?
NAD+ + (ADP-D-ribosyl)n-acceptor
nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H+
show the reaction diagram
-
-
-
-
?
NAD+ + (ADP-D-ribosyl)n-p21ras
nicotinamide + (ADP-D-ribosyl)n+1-p21ras
show the reaction diagram
-
ADP-ribosylation of p21ras does not alter interactions with guanidine nucleotides. Possible function of the enzyme in pathogenesis
-
-
?
NAD+ + (ADP-D-ribosyl)n-rab4
nicotinamide + (ADP-D-ribosyl)n+1-rab4
show the reaction diagram
-
ADP-ribosylation affects Rab4 function in membrane recycling
-
-
?
NAD+ + (ADP-D-ribosyl)n-Rab5
nicotinamide + (ADP-D-ribosyl)n+1-Rab5
show the reaction diagram
-
ADP-ribosylation of Rab5 by ExoS affects endocytosis. Interaction of Rab5 with endosome antigen 1 is markedly diminished after Rab5 ADP-ribosylation by ExoS
-
-
?
NAD+ + (ADP-D-ribosyl)n-RalA
nicotinamide + (ADP-D-ribosyl)n+1-RalA
show the reaction diagram
-
ADP-ribosylation of RalA by ExoS interferes with RalA activation and binding to its downstream effector in J774A.1 macrophages and suggests the potential of ExoS ADPRT activity to interfere with filiopodium formation through the inactivation of RalA and downstream effects mediated through the exocyst complex
-
-
?
NAD+ + (ADP-D-ribosyl)n-Ras
nicotinamide + (ADP-D-ribosyl)n+1-Ras
show the reaction diagram
-
ADP-ribosylation of Ras at Arg41 disrupts Ras-Cdc25 interactions, which inhibits the rate-limiting step in Ras signal transduction, the activation of Ras by its guanine nucleotide exchange factor
-
-
?
NAD+ + cyclophilin A
nicotinamide + (ADP-D-ribosyl)-cyclophilin A
show the reaction diagram
Pseudomonas aeruginosa, Pseudomonas aeruginosa 388
-
cytosolic protein of several human epithelial cells, modification at Arg55 and Arg69 of cyclophilin A, ADP-ribosylation of CpA efficiently inhibits CpA binding to calcineurin/PP2B phosphatase, overview
-
-
?
NAD+ + histone H2A
nicotinamide + (ADP-D-ribosyl)-histone H2A
show the reaction diagram
-
the enzyme catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B. Histone modification by TbSIR2RP1 is involved in DNA repair
-
-
?
NAD+ + histone H2B
nicotinamide + (ADP-D-ribosyl)-histone H2B
show the reaction diagram
-
the enzyme catalyses both ADP-ribosylation and deacetylation of histones, particulary H2A and H2B. Histone modification by TbSIR2RP1 is involved in DNA repair
-
-
?
NAD+ + moesin
nicotinamide + (ADP-D-ribosyl)-moesin
show the reaction diagram
-
ADP-ribosylated-moesin is a poor target for phosphorylation by protein kinase C and Rho kinase, which shows that ADP-ribosylation directly inhibits ERM phosphorylation
-
-
?
NAD+ + p53
nicotinamide + (ADP-D-ribosyl)-p53
show the reaction diagram
-
-
-
-
?
NAD+ + Rab5 protein
nicotinamide + (ADP-D-ribosyl)-Rab5 protein + H+
show the reaction diagram
-
Rab5 mediates entry of the EGFR into early endosomes
-
-
?
NAD+ + Rab9 protein
nicotinamide + (ADP-D-ribosyl)-Rab9 protein + H+
show the reaction diagram
-
-
-
-
?
NAD+ + Ras
nicotinamide + (ADP-D-ribosyl)-Ras
show the reaction diagram
-
interaction requires residue Leu428
-
-
?
NAD+ + Ras GTPase
nicotinamide + (ADP-D-ribosyl)-Ras GTPase
show the reaction diagram
-
-
-
-
?
NAD+ + RNA polymerase
nicotinamide + (ADP-D-ribosyl)-RNA polymerase
show the reaction diagram
P12726
three ADP-ribosyltransferases, Alt, ModA, and ModB participate in the regulation of the T4 replication cycle by ADP-ribosylating a defined set of host proteins. ADP-ribosylation of RNA polymerase and of other host proteins allows initial phage-directed mRNA synthesis reactions to escape from host control
-
-
?
NAD+ + topoisomerase I
nicotinamide + (ADP-D-ribosyl)-topoisomerase I
show the reaction diagram
-
-
-
-
?
NAD+ + vimentin
nicotinamide + (ADP-D-ribosyl)-vimentin
show the reaction diagram
-
-
-
-
?
integrin alpha7 + NAD+
(ADP-D-ribosyl)-integrin alpha7 + nicotinamide
show the reaction diagram
-
the extracellular domain of integrin alpha7 is ADP-ribosylated by an arginine-specific ecto-ADP-ribosyltransferase after adding exogenous NAD+ to intact C2C12 muscle cells, integrin alpha7 N-terminal ADP-ribosylation inhibits the binding of integrin alpha7beta1 to laminin activation status of integrin alpha7beta1 in intact myotubes, overview
-
-
?
additional information
?
-
-
ADP-ribosylation seems to be involved in regulation of differentiation, the enzyme may be centrally involved in tumorigenic cell transformation, the enzyme appears to be a central controller of cell processes: higher activities shift the cell towards proliferation, low activities shift the cell towards differentiation, role of the enzyme in DNA repair
-
-
-
additional information
?
-
-
cuts produced in vivo on DNA during DNA repair activate the enzyme, which then synthesiszes poly(ADP-ribose) on histone H1, in particular, and contributes to the opening of the 25 nm chromatin fiber, resulting in the increased accessibility of DNA to excision repair enzymes
-
-
-
additional information
?
-
-
the enzyme modifies eukaryotic 21000-24000 Da GTP-binding proteins
-
-
-
additional information
?
-
-
role of the enzyme in DNA repair, the unmodified polymerase molecules bind tightly to DNA strand breaks: auto-poly(ADP-ribosyl)ation of the protein then effects its release and allows access to lesions for DNA repair enzymes
-
-
-
additional information
?
-
-
mechanistic basis for the physiological function of PARP-1 in the dynamics of the local modulation of chromatin structure. PARP-1 activation upon binding to base-unpaired regions and stem-loops structures in DNA leads to a local PAR modification of histones and non-histone proteins at genomic sites where such DNA structures are formed. Subsequent PARP-1 automodification results in its dissociation from DNA leading to an enzymatic self-inactivation thus ensuring a transient character of chromatin ADP-ribosylation. In combination with the PAR-glycohydrolase degradation of ADP-ribose polymers on acceptor proteins, PARP-1 interaction with DNA secondary structures provides a mechanism for local and transient chromatin modification by PAR during physiological nuclear processes
-
-
-
additional information
?
-
-
raft association focuses ART2.2 on specific targets that constitutively or inducibly assoiate with lipid rafts
-
-
-
additional information
?
-
-
exoenzyme S and 14-3-3 interact in a direct fashion, interaction involves the conserved amphiphatic groove of 14-3-3
-
-
-
additional information
?
-
-
exoenzyme S is an important adhesin
-
-
-
additional information
?
-
-
ExoS is a virulence factor of the pathogen
-
-
-
additional information
?
-
-
PARP-1 inhibits the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein, TonEBP/OREBP. Inhibition of TonEBP/OREBP transcriptional activity by PARP-1 does not require PARP-1 catalytic activity, functional interaction anaylsis, overview
-
-
-
additional information
?
-
-
PARP-1 is involved in modulation of NO-derived injury and response to genotoxic damage
-
-
-
additional information
?
-
-
PARP-1 plays an essential role in the control of cell repair and tissue remodeling after hyperoxia-induced lung injury, overview
-
-
-
additional information
?
-
-
PARP-1 plays fundamental roles in the recruitment and modulation of enzymatic and regulatory factors involved in transcription, DNA replication, repair and recombination, the enzyme antagonizes topoisomerase I-dependent recombination stimulation by P53
-
-
-
additional information
?
-
-
PARP-1 responds to DNA damage by transferring 50 to 200 molecules of ADP-ribose to various nuclear proteins, including transcription factors, histones and PARP-1 itself, interaction between ATM and PARP-1 in response to DNA damage and sensitization of ATM deficient cells through PARP inhibition, ATM and PARP-1 are two of the most important players in the cell's response to DNA damage, PARP-1 is needed for optimal activation of ATM, overview
-
-
-
additional information
?
-
-
Pseudomonas aeruginosa inhibits mammalian cytokinesis in a type III secretion system and exotoxin T-dependent manner, the ADP-ribosyl transferase domain inhibits late steps of cytokinesis by blocking syntaxin-2 localization to the midbody, an event essential for completion of cytokinesis, e.g. in Madin-Darby canine kidney cells, mechanism, overview
-
-
-
additional information
?
-
-
role for PARP-1 in DNA double-strand break repair, the enzyme is not required for homologous recombination itself, it regulates the process through its involvement in the repair of DNA single-strand breaks, PARP-1 binds to DNA breaks to facilitate DNA repair, but the role of PARP-1 in DNA repair appears to not be critical since PARP-1 knockout mice are viable, fertile and do not develop early onset tumors, DNA binding and auto-modification of PARP-1 attracts the DNA repair proteins
-
-
-
additional information
?
-
-
the bacterial enzyme shows the ability to mediate cell death in the host and is a toxin, residues 426-428 are required for this activity
-
-
-
additional information
?
-
-
the enzyme is involved in endothelial cell dysfunction
-
-
-
additional information
?
-
-
the enzyme is involved in pathogenesis of Parkinson's disease, analysis of polymorphisms, overview
-
-
-
additional information
?
-
-
transcriptional regulation mechanism, overview
-
-
-
additional information
?
-
-
ExoS is a toxin playing a pivotal role during Pseudomonas aeruginosa infections, it is a virulence factor causing growth inhibition in Saccharomyces cerevisiae. Exoenzyme S ADP-ribosylates identical targets in both human and yeast
-
-
-
additional information
?
-
-
ExoS is a type III cytotoxin, that ADP-ribosylates Rab GTPases to inhibit host cell vesicle trafficking pathways by modulating HeLa host cell endocytosis, wild-type ExoS uncouples Rab5-early endosome antigen 1 interaction and inhibits fluid phase uptake, as well as Pseudomonas aeruginosa internalization, RhoGAP, but not ADPr, the ADPr domain is dispensable for anti-internalization function, but is required for inhibition of EGF-activated EGFR degradation in HeLa cells, mechanism, overview
-
-
-
additional information
?
-
Mus musculus 129/Sv x C57BL/6
-
the enzyme is involved in endothelial cell dysfunction
-
-
-
additional information
?
-
Mus musculus Sv129
-
PARP-1 plays an essential role in the control of cell repair and tissue remodeling after hyperoxia-induced lung injury, overview
-
-
-
additional information
?
-
-
ExoS is a type III cytotoxin, that ADP-ribosylates Rab GTPases to inhibit host cell vesicle trafficking pathways by modulating HeLa host cell endocytosis, wild-type ExoS uncouples Rab5-early endosome antigen 1 interaction and inhibits fluid phase uptake, as well as Pseudomonas aeruginosa internalization, RhoGAP, but not ADPr, the ADPr domain is dispensable for anti-internalization function, but is required for inhibition of EGF-activated EGFR degradation in HeLa cells, mechanism, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
additional information
-
Bmh1p, a yeast homologue of the human FAS, acts as an ExoS cofactor, overview
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ba2+
-
enhances activity
Fe2+
-
enzyme binds iron through a Fe-S center, which is crucial for the catalytic activity
Mg2+
-
enhances both the automodification and poly(ADP-ribosyl)ation of histone H1
Mg2+
-
divalent cation required, Mg2+ preferred to Mn2+, optimal concentration 5 mM
Mg2+
-
activates
Mg2+
-
required
Mg2+
-
-
Mg2+
-
0.1 mM, 4.1fold activation
Mn2+
-
divalent cation required, Mg2+ preferred to Mn2+
Mn2+
-
required for activity, cannot be substituted by Mg2+
Sr2+
-
enhances activity
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0469-0796
-
restores yeast growth after treatment with ExoS
1(2H)-phthalazinone
-
IC50: 0.012 mM
1,2-benzopyrone
-
IC50: 2.8 mM
1,3-benzodiazine
-
IC50: 2.0 mM
1,3-dihydroxynaphthalene
-
IC50: 1.3 mM
1,4-benzoquinone
-
IC50: 0.4 mM
1,4-naphthalenedione
-
IC50: 0.25 mM
1,5-dihydroxyisoquinoline
-
IC50: 0.00039 mM
1,8-naphthalimide
-
IC50: 0.0014 mM
1-hydroxy-2-methyl-4-aminonaphthalene
-
IC50: 1.3 mM
1-hydroxyisoquinoline
-
IC50: 0.007 mM
1-Indanone
-
IC50: 0.81 mM
1-methylnicotinamide chloride
-
IC50: 3.8 mM
1-methylnicotinamide chloride
-
IC50: 1.7 mM
2,3-benzodiazine
-
IC50: 0.15 mM
2,3-dichloro-1,4-naphthoquinone
-
IC50: 0.26 mM
2,3-dihydro-1,4-phthalazinedione
-
IC50: 0.03 mM
2,3-dihydro-5-hydroxy-1,4-phthalazinedione
-
0.001 mM, 95% inhibition of the 116000 Da enzyme
-
2,4(1H,3H)-quinazolinedione
-
IC50: 0.0081 mM
2,6-difluorobenzamide
-
IC50: 0.18 mM
2-(4-[4-[(2,4-dimethoxyphenyl)amino]quinazolin-2-yl]piperazin-1-yl)ethanol
Q49TP5
-
-
2-acetamidobenzamide
-
IC50: 1.0 mM
2-amino-3-chloro-1,4-naphthoquinone
-
IC50: 0.82 mM
2-Aminobenzamide
-
IC50: 0.65 mM
2-Aminobenzamide
-
IC50: 0.1 mM
2-bromobenzamide
-
IC50: 2.9 mM
2-chlorobenzamide
-
IC50: 1.0 mM
2-fluorobenzamide
-
IC50: 0.12 mM
2-Hydroxy-1,4-naphthoquinone
-
IC50: 0.33 mM
2-hydroxybenzamide
-
IC50: 0.82 mM
2-mercapto-4(3H)-quinazolinone
-
IC50: 0.044 mM
2-Methoxybenzamide
-
IC50: 0.2 mM
2-methyl-1,4-benzopyrone
-
IC50: 0.045 mM
2-methyl-1,4-naphthoquinone
-
IC50: 0.42 mM
2-methyl-3-phytyl-1,4-naphthoquinone
-
IC50: 0.52 mM
2-methyl-4(3H)-quinazolinone
-
IC50: 0.056 mM
2-methylbenzamide
-
IC50: 1.5 mM
2-methylchromone
-
IC50: 0.045 mM
2-nitro-6(5H)-phenanthridione
-
IC50: 0.00035 mM
2-phenylchromone
-
IC50: 0.022 mM
2-trichloromethyl-4(3H)-quinazolinone
-
IC50: 2.2 mM
2H-benz[c]isoquinolin-1-one
-
IC50: 0.0003 mM
2H-benz[de]isoquinoline-1,3-dione
-
IC50: 0.0014 mM
3,4-dihydro-1(2H)-naphthalenone
-
IC50: 0.31 mM
3,5-dibromosalicylamide
-
IC50: 0.56 mM
3,5-dimethoxybenzamide
-
IC50: 1.2 mM
3,5-dinitrobenzamide
-
IC50: 2.5 mM
3-(N,N-dimethylamino)benzamide
-
IC50: 0.12 mM
3-Acetamidobenzamide
-
IC50: 0.012 mM
3-acetamidosalicylamide
-
IC50: 2.0 mM
3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole
-
i.e. Trp-P-1, 94% inhibition at 5 mM, IC50: 0.22 mM
3-amino-1-methyl-5H-pyrido[4,3-b]indole
-
i.e. Trp-P-2, 34% activation at 1 mM, 7% inhibition at 5 mM, IC50: 2.2 mM
3-Aminobenzamide
-
1 mM, 99% inhibition
3-Aminobenzamide
-
1 mM, 98% inhibition
3-Aminobenzamide
-
IC50: 0.33 mM
3-Aminobenzamide
-
IC50: 0.0054
3-Aminobenzamide
-
-
3-Aminobenzamide
-
-
3-Aminobenzamide
-
10 mM, 47% inhibition; 10 mM, 47% inhibition
3-aminobenzoic acid
-
1 mM, 12% inhibition
3-Aminophthalhydrazide
-
0.1 mM, 98% inhibition of the 116000 Da enzyme
3-Aminophthalhydrazide
-
IC50: 0.023 mM
3-amminobenzamide
-
1 mM, remaining activity: 3.9%
-
3-bromobenzamide
-
IC50: 0.055 mM
3-Chlorobenzamide
-
IC50: 0.22 mM
3-Fluorobenzamide
-
IC50: 0.2 mM
3-Guanidinobenzamide
-
0.1 mM, 71% inhibition of the 116000 Da enzyme
3-Hydroxybenzamide
-
0.1 mM, 89% inhibition of the 116000 Da enzyme
3-Hydroxybenzamide
-
IC50: 0.0091 mM
3-isobutyl-1-methylxanthine
-
IC50: 3.1 mM
3-Methoxybenzamide
-
1 mM, 98% inhibition
3-Methoxybenzamide
-
0.01 mM, 85% inhibition of the 116000 Da enzyme, 84% inhibition of the 90000 Da enzyme; 1 mM, 96% inhibition of the 116000 Da enzyme, 95% inhibition of the 90000 Da enzyme
3-Methoxybenzamide
-
IC50: 0.017 mM
3-Methoxybenzamide
-
IC50: 0.0034 mM
3-Methylbenzamide
-
IC50: 0.19 mM
3-nitrobenzamide
-
IC50: 0.16 mM
3-nitrophthalhydrazide
-
IC50: 0.072 mM
3-nitrosalicylamide
-
IC50: 1.6 mM
4,8-dihydroxy-2-quinolinecarboxylic acid
-
IC50: 0.19 mM
4-amino-1,8-naphthalimide
-
IC50: 0.00018 mM
4-Aminobenzamide
-
IC50: 1.8 mM
4-Aminobenzamide
-
IC50: 0.4 mM
4-aminophthalhydrazide
-
IC50: 0.29 mM
4-bromobenzamide
-
IC50: 2.2 mM
4-chlorobenzamide
-
IC50: 0.3 mM
4-chromanone
-
IC50: 0.72 mM
4-fluorobenzamide
-
IC50: 0.2 mM
4-hydroxy-2-methylquinoline
-
IC50: 0.074 mM
4-hydroxy-2-quinolinecarboxylic acid
-
IC50: 0.67 mM
4-hydroxybenzamide
-
IC50: 0.28 mM
4-Hydroxycoumarin
-
IC50: 0.57 mM
4-hydroxypyridine
-
IC50: 2.3 mM
4-hydroxyquinazoline
-
IC50: 0.0095 mM
4-hydroxyquinoline
-
IC50: 0.08 mM
4-methoxybenzamide
-
IC50: 1.1 mM
4-methylbenzamide
-
IC50: 1.8 mM
4-nitrophthalhydrazide
-
IC50: 0.51 mM
4296-1011
-
restores yeast growth after treatment with ExoS
5-acetamidosalicylamide
-
IC50: 0.045 mM
5-aminosalicylamide
-
IC50: 0.1 mM
5-bromodeoxyuridine
-
IC50: 0.015 mM
5-Bromouracil
-
IC50: 0.16 mM
5-Bromouridine
-
IC50: 0.21 mM
5-chlorosalicylamide
-
IC50: 0.19 mM
5-Chlorouracil
-
IC50: 0.27 mM
5-hydroxy-1,4-naphthoquinone
-
IC50: 0.25 mM
5-Hydroxy-2-methyl-1,4-naphthoquinone
-
IC50: 0.7 mM
5-Iodouracil
-
IC50: 0.071 mM
5-iodouridine
-
IC50: 0.043 mM
5-Methylnicotinamide
-
IC50: 0.35 mM
5-Methylnicotinamide
Cryptothecodinium cohnii
-
0.15 mM, 31% inhibition
5-Methylnicotinamide
-
IC50: 0.07
5-methyluracil
-
IC50: 0.29 mM
5-Nitrouracil
-
IC50: 0.43 mM
6(5H)-phenanthridinone
-
IC50: 0.0003 mM
6-aminocoumarin
-
IC50: 0.85 mM
6-Aminonicotinamide
-
IC50: 1.1 mM
8-acetamidocarsalam
-
IC50: 1.4 mM
8-Methylnicotinamide
-
IC50: 7.8 mM
acetophenone
-
IC50: 2.3 mM
ADP-D-ribose
-
5 mM, remaining activity: 7.3%
all-trans-retinal
-
IC50: 0.45 mM
Alpha-NAD+
-
0.5 mM, 40% inhibition of the 116000 Da enzyme, 44% inhibition of the 90000 Da enzyme
alpha-picolinamide
-
IC50: 0.25 mM
AMP
-
1 mM, remaining activity: 3.6%
arachidonic acid
-
-
Benzamide
-
IC50: 0.22 mM
Benzamide
Cryptothecodinium cohnii
-
0.15 mM, 48% inhibition
Benzamide
-
IC50: 0.0033 mM
benzoyleneurea
-
IC50: 0.0081 mM
Caffeine
-
1 mM, 23% inhibition
Caffeine
-
1 mM, 86% inhibition of the 116000 Da enzyme, 57% inhibition of the 90000 Da enzyme
Caffeine
-
IC50: 1.4 mM
carbonylsalicylamide
-
IC50: 0.46 mM
carsalam
-
5 mM, 88% inhibition in presence of Mg2+, 68% inhibition in absence of Mg2+
Chlorthenoxazin
-
IC50: 0.0085 mM
chromone-2-carboxylic acid
-
IC50: 0.56 mM
cyclohexanecarboxamide
-
IC50: 0.62 mM
diosmin
-
restores yeast growth after treatment with ExoS
E216-5303
-
restores yeast growth after treatment with ExoS
EDTA
-
5 mM, 41% inhibition in presence of Mg2+, 2% inhibition in absence of Mg2+
everninic acid
-
restores yeast growth after treatment with ExoS
exosin
-
a small molecule inhibitor, that modulates ExoS ADP-ribosyltransferase activity in vitro, suggesting the inhibition is direct. Exosin and two of its analogues display a significant protective effect against Pseudomonas infection in vivo, competitive against NAD+
flavokawain B
-
restores yeast growth after treatment with ExoS
flavone
-
IC50: 0.022 mM
gamma-linolenic acid
-
IC50: 0.12 mM
GTP(gammaS)
-
in presence of Mg2+
hypoxanthine
-
IC50: 1.7 mM
Isonicotinamide
-
IC50: 0.99 mM
Isonicotinate hydrazide
-
IC50: 4.8 MM
isoquiniolinedol
-
0.5 mM, remaining activity: 2.4%
-
Isoquinoline
-
5 mM, 47% inhibition in presence of Mg2+, 34% inhibition in absence of Mg2+
KCl
-
100 mM, 85% inhibition of the 90000 Da enzyme
KCl
-
0.05 mM, remaining activity: 6.8%
linoleic acid
-
IC50: 0.048 mM
linolenic acid
-
IC50: 0.11 mM
m-acetamidoacetophenone
-
IC50: 0.93 mM
m-aminoacetophenone
-
IC50: 1.9 mM
m-hydroxyacetophenone
-
IC50: 0.6 mM
m-phthalamide
-
IC50: 0.05 mM
N-(2-chloroethyl)1,8-naphthalamide
-
IC50: above 1.8 mM
N-(6-oxo-5,6-dihydrophenanthrolin-2-yl)-(N,N-dimethylamino)acetamide
-
0.1 mM, remaining activity: 36.2%
-
N-(acridin-9-yl)-4-nitrobenzamide
Q49TP5
-
-
N-hydroxynaphthalimide sodium salt
-
IC50: 0.45 mM
N-[2-oxo-4-(phenylamino)-3,8a-dihydro-2H-chromen-3-yl]acetamide
Q49TP5
-
-
Nicotinamide
-
1 mM, 93% inhibition
Nicotinamide
-
1 mM, 91% inhibition
Nicotinamide
-
1 mM, 96% inhibition of the 116000 Da enzyme, 95% inhibition of the 90000 Da enzyme
Nicotinamide
-
IC50: 0.21 mM
Nicotinamide
Cryptothecodinium cohnii
-
0.15 mM, 25% inhibition
Nicotinamide
-
IC50: 0.031 mM
Nicotinamide
-
0.05 mM, remaining activity: 27.3%
Nicotinamide
-
10 mM, 14% inhibition; 10 mM, 14% inhibition
norharman
-
IC50: 4.7 mM
novobiocin
-
IC50: 2.2 mM, 5 mM, 90% inhibition in presence of Mg2+, 59% inhibition in absence of Mg2+
oleic acid
-
IC50: 0.082 mM
palmitoleic acid
-
IC50: 0.095 mM
PCMB
-
complete
phenontridione
-
5 mM, remaining activity: 35.1%
-
phthalamide
-
IC50: 1.0 mM
Phthalazine
-
5 mM, 91% inhibition in presence of Mg2+, 79% inhibition in absence of Mg2+
PJ34
-
potent PARP inhibitor
Pyrazinamide
-
IC50: 0.13 mM
Quinazoline
-
5 mM, 63% inhibition in presence of Mg2+, 50% inhibition in absence of Mg2+
reserpine
-
IC50: 0.79 mM
Theobromine
-
1 mM, 76% inhibition
Theobromine
-
IC50: 0.11 mM
theophylline
-
1 mM, 72% inhibition
theophylline
-
1 mM, 68% inhibition of the 116000 Da enzyme, 39% inhibition of the 90000 Da enzyme
theophylline
Cryptothecodinium cohnii
-
0.15 mM, 62% inhibition
theophylline
-
IC50: 0.0046
thiobenzamide
-
IC50: 0.62 mM
Thionicotinamide
-
IC50: 1.8 mM
thymidine
-
1 mM, 70% inhibition
thymidine
-
1 mM, 94% inhibition of the 116000 Da enzyme, 88% inhibition of the 90000 Da enzyme
thymidine
-
IC50: 0.18 mM
thymidine
Cryptothecodinium cohnii
-
0.15 mM, 39% inhibition
thymidine
-
IC50: 0.043
trans-decahydro-1-naphthalenone
-
IC50: 4.3 mM
V8 protease
Q49TP5
-
-
vitamin K1
-
IC50: 0.0019 mM
vitamin K3
-
IC50: 0.42 mM
xanthurenic acid
-
5 mM, 88% inhibition in presence of Mg2+, 65% inhibition in absence of Mg2+
Zinc acetate
-
0.1 mM, remaining activity: 0.5%
Zn2+
-
ZnCl2, IC50: 0.077 mM
Zn2+
-
0.5 mM, 47% inhibition; 0.5 mM, 50% inhibition
menadione sodium bisulfite
-
IC50: 0.72 mM
additional information
-
PARP inhibitors promote ATM activation through induction of double strand breaks
-
additional information
-
comparison of the effects of heterocyclic amines acting as potent carcinogens on PARP-1 and the arginine-specific mono-ADP-ribosyltransferase A, MART-A, EC 2.4.2.31, overview
-
additional information
-
identification of small molecule inhibitors of Pseudomonas aeruginosa exoenzyme S using a yeast phenotypic screening, overview
-
additional information
-
phenanthroline has no or a slightly activating effect
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
3-amino-1-methyl-5H-pyrido[4,3-b]indole
-
i.e. Trp-P-2, 34% activation at 1 mM, 7% inhibition at 5 mM, IC50: 2.2 mM
ATP
-
5-10 mM, 20-30% stimulation
Bmh1p
-
a yeast homologue of the human FAS, acts as an activating ExoS cofactor, overview
-
DNA
-
absolute requirement
DNA
-
absolute requirement
DNA
Cryptothecodinium cohnii
-
required
DNA
-
the enzyme is completely dependent on the presence of DNA containing single or double stranded breaks. Activation results in a decondensation of chromatin superstructure in vitro, which is caused mainly by hyper(ADP-ribosyl)ation of histone H1
DNA
-
enzyme has an N-terminal binding domain
DNA
-
slightly increases activity
FAS
-
exoenzyme S absolutely requires a soluble eukaryotic protein, named FAS (Factor Activating exoenzyme E), in order to ADP-ribosylate all substrates. In the presence of FAS, exoenzyme S ADP-ribosylates several proteins in lysates of Pseudomonas aeruginosa. Purification and characterization of FAS
-
GDP
-
increases activity in absence of Mg2+
GTP
-
increases activity in absence of Mg2+
GTP(gammaS)
-
increases activity in absence of Mg2+
harmaline hydrochloride
-
activates more strongly in absence of Mg2+ than in presence of Mg2+
oligodeoxyribonucleotides
-
slightly enhance enzyme activity with the maximal increase of 50% as compared to the control
Phenanthroline
-
0.1 mM, 1.1fold activation
Phthalic acid
-
activates more strongly in absence of Mg2+ than in presence of Mg2+
protein 14-3-3
-
dependent on
-
protein 14-3-3
-
required, interaction analysis, interaction equires residues L426, D427, and L428, overview, binding study of mutant enzymes, overview
-
Mg2+
-
5 mM, 6.3fold activation
additional information
-
in native conformation, CRM66 shows limited ability to modify EF-2 covalently. Upon activation with urea and dithiothreitol CRM66 loses ADP-ribosylation activity entirely, yet it retains the ability to bind NAD+. Replacement of Tyr-426 with histidine in CRM66 completely restores cytotoxicity and ADP-ribosyltransferase activity
-
additional information
-
PARP-1 is activated in response to DNA damage and participates in DNA repair, genomic integrity and cell death
-
additional information
-
stable expression of the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein, TonEBP/OREBP, clone KIAA0827/amino acids 1-547, in HEK-293 cells increases the expression of the enzyme
-
additional information
-
DNA binding by PARP-1 triggers its activity and it adds poly(ADP-ribose) polymers to itself and to surrounding histones, overview
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.011
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant N86A, 25C, pH not specified in the publication
-
0.02
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant E213A, 25C, pH not specified in the publication
-
0.023
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant E215A, 25C, pH not specified in the publication
-
0.024
-
(ADP-D-ribosyl)n-actin
Q49TP5
wild-type, 25C, pH not specified in the publication
-
0.033
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant S178A, 25C, pH not specified in the publication
-
0.035
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant Y82A, 25C, pH not specified in the publication
-
0.037
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant Y77A, 25C, pH not specified in the publication
-
0.03
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
recombinant full-length enzyme
-
0.037
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
recombinant DELTAN222
-
0.049
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
DELTAN222
-
0.23
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
DELTAN222/E381S
-
0.387
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
DELTAN222/E381D
-
0.004
-
NAD+
Q49TP5
mutant N86A, 25C, pH not specified in the publication
0.005
-
NAD+
Q49TP5
mutant E213A, 25C, pH not specified in the publication
0.006
-
NAD+
Q49TP5
wild-type, 25C, pH not specified in the publication
0.008
-
NAD+
Q49TP5
mutant Y77A, 25C, pH not specified in the publication
0.009
-
NAD+
-
pH 6.0, 30C, in absence of exosin
0.012
-
NAD+
Q49TP5
mutant Y82A, 25C, pH not specified in the publication
0.014
-
NAD+
Q49TP5
mutant E215A, 25C, pH not specified in the publication
0.0171
-
NAD+
-
pH 7.3, 37C, cosubstrate RhoC
0.018
-
NAD+
Q49TP5
mutant S178A, 25C, pH not specified in the publication
0.02
-
NAD+
-
90000 Da protein
0.02
-
NAD+
-
hydrolysis of NAD+, wild-type enzyme
0.0208
-
NAD+
-
pH 7.3, 37C, cosubstrate RhoA
0.0267
-
NAD+
-
-
0.03
-
NAD+
-
pH 6.0, 30C, in presence of exosin
0.0564
-
NAD+
-
pH 7.3, 37C, cosubstrate RhoB
0.077
-
NAD+
-
116000 Da protein
0.22
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme F349A, cosubstrate: non-muscle actin from human platelets
0.58
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme N255A, cosubstrate: non-muscle actin from human platelets
0.69
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme F349A, cosubstrate: rabbit muscle actin
0.77
-
NAD+
-
ADP-ribosyltransferase activity, wild-type enzyme, cosubstrate: non-muscle actin from human platelets
0.92
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme Y246A, cosubstrate: non-muscle actin from human platelets
0.93
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme Y246A, cosubstrate: rabbit muscle actin
1.28
-
NAD+
-
ADP-ribosyltransferase activity, wild-type enzyme, cosubstrate: rabbit muscle actin
4.48
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme N255A, cosubstrate: rabbit muscle actin
8.67
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme Y251A, cosubstrate: non-muscle actin from human platelets
0.429
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
DELTAN222/E381A
-
additional information
-
additional information
-
kinetics for NAD+ utilization are not Michaelis-Menten type
-
additional information
-
additional information
-
-
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.05
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant E215A, co-substrate: NAD+, 25C, pH not specified in the publication
-
0.11
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant E213A, co-substrate: NAD+, 25C, pH not specified in the publication
-
0.65
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant Y82A, co-substrate: NAD+, 25C, pH not specified in the publication
-
1.3
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant Y77A, co-substrate: NAD+, 25C, pH not specified in the publication
-
1.38
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant S178A, co-substrate: NAD+, 25C, pH not specified in the publication
-
9.35
-
(ADP-D-ribosyl)n-actin
Q49TP5
mutant N86A, co-substrate: NAD+, 25C, pH not specified in the publication
-
22
-
(ADP-D-ribosyl)n-actin
Q49TP5
wild-type, co-substrate: NAD+, 25C, pH not specified in the publication
-
0.0031
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
recombinant DELTAN222
-
0.008
-
(ADP-D-ribosyl)n-soybean-trypsin-inhibitor
-
recombinant full-length enzyme
-
0.000067
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme F349A, cosubstrate: non-muscle actin from human platelets
0.00012
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme F349A, cosubstrate: rabbit muscle actin
0.00015
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme Y246A, cosubstrate: rabbit muscle actin
0.0002
-
NAD+
-
hydrolysis of NAD+, mutant enzyme Q187A/189A
0.0005
-
NAD+
-
hydrolysis of NAD+, mutant enzyme E189I
0.00133
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme Y246A, cosubstrate: non-muscle actin from human platelets; ADP-ribosyltransferase activity, mutant enzyme Y251A, cosubstrate: non-muscle actin from human platelets
0.00183
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme N255A, cosubstrate: non-muscle actin from human platelets
0.002
-
NAD+
-
hydrolysis of NAD+, mutant enzyme E189A; hydrolysis of NAD+, mutant enzyme E189S
0.0062
-
NAD+
-
ADP-ribosyltransferase activity, wild-type enzyme, cosubstrate: non-muscle actin from human platelets
0.01
-
NAD+
-
ADP-ribosyltransferase activity, wild-type enzyme, cosubstrate: rabbit muscle actin
0.014
-
NAD+
-
ADP-ribosyltransferase activity, mutant enzyme N255A, cosubstrate: rabbit muscle actin
0.05
-
NAD+
Q49TP5
mutant E215A, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
0.11
-
NAD+
Q49TP5
mutant E213A, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
0.65
-
NAD+
Q49TP5
mutant Y82A, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
1.3
-
NAD+
Q49TP5
mutant Y77A, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
1.38
-
NAD+
Q49TP5
mutant S178, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
9.35
-
NAD+
Q49TP5
mutant N86A, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
12
-
NAD+
-
hydrolysis of NAD+, wild-type enzyme
22
-
NAD+
Q49TP5
wild-type, co-substrate: (ADP-D-ribosyl)n-actin, 25C, pH not specified in the publication
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0075
-
2-(4-[4-[(2,4-dimethoxyphenyl)amino]quinazolin-2-yl]piperazin-1-yl)ethanol
Q49TP5
25C, pH not specified in the publication
-
0.033
-
exosin
-
pH 6.0, 30C
0.0041
-
N-(acridin-9-yl)-4-nitrobenzamide, N-[2-oxo-4-(phenylamino)-3,8a-dihydro-2H-chromen-3-yl]acetamide
Q49TP5
25C, pH not specified in the publication
-
0.001
-
suramin
Q49TP5
25C, pH not specified in the publication
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.012
-
1(2H)-phthalazinone
-
IC50: 0.012 mM
2.8
-
1,2-benzopyrone
-
IC50: 2.8 mM
2
-
1,3-benzodiazine
-
IC50: 2.0 mM
1.3
-
1,3-dihydroxynaphthalene
-
IC50: 1.3 mM
0.4
-
1,4-benzoquinone
-
IC50: 0.4 mM
0.25
-
1,4-naphthalenedione
-
IC50: 0.25 mM
0.00039
-
1,5-dihydroxyisoquinoline
-
IC50: 0.00039 mM
0.0014
-
1,8-naphthalimide
-
IC50: 0.0014 mM
1.3
-
1-hydroxy-2-methyl-4-aminonaphthalene
-
IC50: 1.3 mM
0.007
-
1-hydroxyisoquinoline
-
IC50: 0.007 mM
0.81
-
1-Indanone
-
IC50: 0.81 mM
1.7
-
1-methylnicotinamide chloride
-
IC50: 1.7 mM
3.8
-
1-methylnicotinamide chloride
-
IC50: 3.8 mM
0.15
-
2,3-benzodiazine
-
IC50: 0.15 mM
0.26
-
2,3-dichloro-1,4-naphthoquinone
-
IC50: 0.26 mM
0.03
-
2,3-dihydro-1,4-phthalazinedione
-
IC50: 0.03 mM
0.0081
-
2,4(1H,3H)-quinazolinedione
-
IC50: 0.0081 mM
0.18
-
2,6-difluorobenzamide
-
IC50: 0.18 mM
1
-
2-acetamidobenzamide
-
IC50: 1.0 mM
0.82
-
2-amino-3-chloro-1,4-naphthoquinone
-
IC50: 0.82 mM
0.1
-
2-Aminobenzamide
-
IC50: 0.1 mM
0.65
-
2-Aminobenzamide
-
IC50: 0.65 mM
2.9
-
2-bromobenzamide
-
IC50: 2.9 mM
1
-
2-chlorobenzamide
-
IC50: 1.0 mM
0.12
-
2-fluorobenzamide
-
IC50: 0.12 mM
0.33
-
2-Hydroxy-1,4-naphthoquinone
-
IC50: 0.33 mM
0.82
-
2-hydroxybenzamide
-
IC50: 0.82 mM
0.044
-
2-mercapto-4(3H)-quinazolinone
-
IC50: 0.044 mM
0.2
-
2-Methoxybenzamide
-
IC50: 0.2 mM
0.045
-
2-methyl-1,4-benzopyrone
-
IC50: 0.045 mM
0.42
-
2-methyl-1,4-naphthoquinone
-
IC50: 0.42 mM
0.52
-
2-methyl-3-phytyl-1,4-naphthoquinone
-
IC50: 0.52 mM
0.056
-
2-methyl-4(3H)-quinazolinone
-
IC50: 0.056 mM
1.5
-
2-methylbenzamide
-
IC50: 1.5 mM
0.045
-
2-methylchromone
-
IC50: 0.045 mM
0.00035
-
2-nitro-6(5H)-phenanthridione
-
IC50: 0.00035 mM
0.022
-
2-phenylchromone
-
IC50: 0.022 mM
2.2
-
2-trichloromethyl-4(3H)-quinazolinone
-
IC50: 2.2 mM
0.0003
-
2H-benz[c]isoquinolin-1-one
-
IC50: 0.0003 mM
0.0014
-
2H-benz[de]isoquinoline-1,3-dione
-
IC50: 0.0014 mM
0.31
-
3,4-dihydro-1(2H)-naphthalenone
-
IC50: 0.31 mM
0.56
-
3,5-dibromosalicylamide
-
IC50: 0.56 mM
1.2
-
3,5-dimethoxybenzamide
-
IC50: 1.2 mM
2.5
-
3,5-dinitrobenzamide
-
IC50: 2.5 mM
0.12
-
3-(N,N-dimethylamino)benzamide
-
IC50: 0.12 mM
0.012
-
3-Acetamidobenzamide
-
IC50: 0.012 mM
2
-
3-acetamidosalicylamide
-
IC50: 2.0 mM
0.22
-
3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole
-
i.e. Trp-P-1, 94% inhibition at 5 mM, IC50: 0.22 mM
2.2
-
3-amino-1-methyl-5H-pyrido[4,3-b]indole
-
i.e. Trp-P-2, 34% activation at 1 mM, 7% inhibition at 5 mM, IC50: 2.2 mM
0.0054
-
3-Aminobenzamide
-
IC50: 0.0054
0.33
-
3-Aminobenzamide
-
IC50: 0.33 mM
0.023
-
3-Aminophthalhydrazide
-
IC50: 0.023 mM
0.055
-
3-bromobenzamide
-
IC50: 0.055 mM
0.22
-
3-Chlorobenzamide
-
IC50: 0.22 mM
0.2
-
3-Fluorobenzamide
-
IC50: 0.2 mM
0.0091
-
3-Hydroxybenzamide
-
IC50: 0.0091 mM
3.1
-
3-isobutyl-1-methylxanthine
-
IC50: 3.1 mM
0.0034
-
3-Methoxybenzamide
-
IC50: 0.0034 mM
0.017
-
3-Methoxybenzamide
-
IC50: 0.017 mM
0.19
-
3-Methylbenzamide
-
IC50: 0.19 mM
0.16
-
3-nitrobenzamide
-
IC50: 0.16 mM
0.072
-
3-nitrophthalhydrazide
-
IC50: 0.072 mM
1.6
-
3-nitrosalicylamide
-
IC50: 1.6 mM
0.19
-
4,8-dihydroxy-2-quinolinecarboxylic acid
-
IC50: 0.19 mM
0.00018
-
4-amino-1,8-naphthalimide
-
IC50: 0.00018 mM
0.4
-
4-Aminobenzamide
-
IC50: 0.4 mM
1.8
-
4-Aminobenzamide
-
IC50: 1.8 mM
0.29
-
4-aminophthalhydrazide
-
IC50: 0.29 mM
2.2
-
4-bromobenzamide
-
IC50: 2.2 mM
0.3
-
4-chlorobenzamide
-
IC50: 0.3 mM
0.72
-
4-chromanone
-
IC50: 0.72 mM
0.2
-
4-fluorobenzamide
-
IC50: 0.2 mM
0.074
-
4-hydroxy-2-methylquinoline
-
IC50: 0.074 mM
0.67
-
4-hydroxy-2-quinolinecarboxylic acid
-
IC50: 0.67 mM
0.28
-
4-hydroxybenzamide
-
IC50: 0.28 mM
0.57
-
4-Hydroxycoumarin
-
IC50: 0.57 mM
2.3
-
4-hydroxypyridine
-
IC50: 2.3 mM
0.0095
-
4-hydroxyquinazoline
-
IC50: 0.0095 mM
0.08
-
4-hydroxyquinoline
-
IC50: 0.08 mM
1.1
-
4-methoxybenzamide
-
IC50: 1.1 mM
1.8
-
4-methylbenzamide
-
IC50: 1.8 mM
0.51
-
4-nitrophthalhydrazide
-
IC50: 0.51 mM
0.006
-
4296-1011
-
pH 6.0, 30C
0.045
-
5-acetamidosalicylamide
-
IC50: 0.045 mM
0.1
-
5-aminosalicylamide
-
IC50: 0.1 mM
0.015
-
5-bromodeoxyuridine
-
IC50: 0.015 mM
0.16
-
5-Bromouracil
-
IC50: 0.16 mM
0.21
-
5-Bromouridine
-
IC50: 0.21 mM
0.19
-
5-chlorosalicylamide
-
IC50: 0.19 mM
0.27
-
5-Chlorouracil
-
IC50: 0.27 mM
0.25
-
5-hydroxy-1,4-naphthoquinone
-
IC50: 0.25 mM
0.7
-
5-Hydroxy-2-methyl-1,4-naphthoquinone
-
IC50: 0.7 mM
0.071
-
5-Iodouracil
-
IC50: 0.071 mM
0.043
-
5-iodouridine
-
IC50: 0.043 mM
0.07
-
5-Methylnicotinamide
-
IC50: 0.07 mM
0.35
-
5-Methylnicotinamide
-
IC50: 0.35 mM
0.29
-
5-methyluracil
-
IC50: 0.29 mM
0.43
-
5-Nitrouracil
-
IC50: 0.43 mM
0.0003
-
6(5H)-phenanthridinone
-
IC50: 0.0003 mM
0.85
-
6-aminocoumarin
-
IC50: 0.85 mM
1.1
-
6-Aminonicotinamide
-
IC50: 1.1 mM
1.4
-
8-acetamidocarsalam
-
IC50: 1.4 mM
7.8
-
8-Methylnicotinamide
-
IC50: 7.8 mM
2.3
-
acetophenone
-
IC50: 2.3 mM
0.45
-
all-trans-retinal
-
IC50: 0.45 mM
0.25
-
alpha-picolinamide
-
IC50: 0.25 mM
0.0033
-
Benzamide
-
IC50: 0.0033 mM
0.22
-
Benzamide
-
IC50: 0.22 mM
0.0081
-
benzoyleneurea
-
IC50: 0.0081 mM
1.4
-
Caffeine
-
IC50: 1.4 mM
0.46
-
carbonylsalicylamide
-
IC50: 0.46 mM
0.0085
-
Chlorthenoxazin
-
IC50: 0.0085 mM
0.56
-
chromone-2-carboxylic acid
-
IC50: 0.56 mM
0.62
-
cyclohexanecarboxamide
-
IC50: 0.62 mM
0.003
-
diosmin
-
pH 6.0, 30C
0.023
-
E216-5303
-
pH 6.0, 30C
0.021
-
everninic acid
-
pH 6.0, 30C
0.022
-
flavone
-
IC50: 0.022 mM
0.12
-
gamma-linolenic acid
-
IC50: 0.12 mM
1.7
-
hypoxanthine
-
IC50: 1.7 mM
0.99
-
Isonicotinamide
-
IC50: 0.99 mM
4.8
-
Isonicotinate hydrazide
-
IC50: 4.8 mM
0.048
-
linoleic acid
-
IC50: 0.048 mM
0.11
-
linolenic acid
-
IC50: 0.11 mM
0.93
-
m-acetamidoacetophenone
-
IC50: 0.93 mM
1.9
-
m-aminoacetophenone
-
IC50: 1.9 mM
0.6
-
m-hydroxyacetophenone
-
IC50: 0.6 mM
0.05
-
m-phthalamide
-
IC50: 0.05 mM
0.72
-
menadione sodium bisulfite
-
IC50: 0.72 mM
1.8
-
N-(2-chloroethyl)1,8-naphthalamide
-
IC50: above 1.8 mM
0.0858
-
N-(acridin-9-yl)-4-nitrobenzamide
Q49TP5
25C, pH not specified in the publication
-
0.45
-
N-hydroxynaphthalimide sodium salt
-
IC50: 0.45 mM
0.086
-
N-[2-oxo-4-(phenylamino)-3,8a-dihydro-2H-chromen-3-yl]acetamide
Q49TP5
25C, pH not specified in the publication
-
0.031
-
Nicotinamide
-
IC50: 0.031 mM
0.21
-
Nicotinamide
-
IC50: 0.21 mM
4.7
-
norharman
-
IC50: 4.7 mM
2.2
-
novobiocin
-
IC50: 2.2 mM, 5 mM, 90% inhibition in presence of Mg2+, 59% inhibition in absence of Mg2+
0.082
-
oleic acid
-
IC50: 0.082 mM
0.095
-
palmitoleic acid
-
IC50: 0.095 mM
1
-
phthalamide
-
IC50: 1.0 mM
0.13
-
Pyrazinamide
-
IC50: 0.13 mM
0.79
-
reserpine
-
IC50: 0.79 mM
0.02
-
suramin
Q49TP5
25C, pH not specified in the publication
0.11
-
Theobromine
-
IC50: 0.11 mM
0.046
-
theophylline
-
IC50: 0.046 mM
0.62
-
thiobenzamide
-
IC50: 0.62 mM
1.8
-
Thionicotinamide
-
IC50: 1.8 mM
0.043
-
thymidine
-
IC50: 0.043 mM
0.18
-
thymidine
-
IC50: 0.18 mM
4.3
-
trans-decahydro-1-naphthalenone
-
IC50: 4.3 mM
0.157
-
V8 protease
Q49TP5
25C, pH not specified in the publication
-
0.0019
-
vitamin K1
-
IC50: 0.0019 mM
0.42
-
vitamin K3
-
IC50: 0.42 mM
0.077
-
Zn2+
-
ZnCl2, IC50: 0.077 mM
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0545
-
-
-
0.325
-
-
-
1.02
-
-
-
22.25
-
-
-
80
-
-
wild-type enzyme, substrate RhoA
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
-
-
assay at
7.4
-
-
assay at
7.5
-
-
assay at
7.5
-
-
assay at
7.6
-
-
assay at
8
-
-
in presence of DNA and histone H1
8
-
-
assay at
8
-
-
assay at
8.5
-
-
reaction with histone in presence of DNA, 0.1 M glycine-NaOH buffer
8.7
-
-
reaction with histone in presence of DNA, 0.1 M Tris-HCl buffer
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
9.5
-
pH 7.0: about 75% of maximal activity, pH 9.5: about 70% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5
-
-
116000 Da enzyme
10
-
-
90000 Da enzyme
25
-
-
assay at
30
37
-
assay at
30
-
-
assay at
30
-
-
assay at
37
-
-
assay at
37
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.3
-
-
isoelectric focusing. ExoS shows pI heterogeneity, that is independent of a mass change and thus represents molecular charge conformers
5.5
-
-
isoelectric focusing. ExoS shows pI heterogeneity, that is independent of a mass change and thus represents molecular charge conformers
5.7
-
-
isoelectric focusing. ExoS shows pI heterogeneity, that is independent of a mass change and thus represents molecular charge conformers
5.9
-
-
isoelectric focusing. ExoS shows pI heterogeneity, that is independent of a mass change and thus represents molecular charge conformers
7
7.2
-
; isoelectric focusing
9.3
-
-
theoretical value
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
Pseudomonas aeruginosa 388
-
-
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa 388
-
-
-
Manually annotated by BRENDA team
Mus musculus 129/Sv x C57BL/6
-
primary
-
Manually annotated by BRENDA team
Mus musculus Sv129
-
-
-
Manually annotated by BRENDA team
-
primary, from lung
Manually annotated by BRENDA team
Mus musculus Sv129
-
primary, from lung
-
Manually annotated by BRENDA team
-
PARP-1 in lung repair during recovery after hyperoxia, that is induced by 5-bromo-2-deoxyuridine, overview
Manually annotated by BRENDA team
Mus musculus Sv129
-
PARP-1 in lung repair during recovery after hyperoxia, that is induced by 5-bromo-2-deoxyuridine, overview
-
Manually annotated by BRENDA team
-
transfectants expressing either ART2.2 with its native anchor (RT2.2-GPI) or ART2.2 with a grafted transmembrane anchor
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
TbSIR2RP1 is a nuclear protein that colocalizes with telomeric sequences and minichromosomes
Manually annotated by BRENDA team
-
10% of the activity
Manually annotated by BRENDA team
-
membrane localization domain
Manually annotated by BRENDA team
-
90% of the activity. Chromatin-bound
Manually annotated by BRENDA team
-
localizes in eukaryotic cells to the perinuclear region
-
Manually annotated by BRENDA team
-
despite the absence of a signal peptide, the protein is efficiently exported into periplasm
-
Manually annotated by BRENDA team
Pseudomonas aeruginosa ExoS, Pseudomonas aeruginosa ExoT
-
membrane localization domain
-
Manually annotated by BRENDA team
additional information
-
residues 5172 represent a membrane localization domain, which targets ExoS to perinuclear vesicles within mammalian cells
-
Manually annotated by BRENDA team
additional information
-
residues 52-72, membrane localization domain within the N-terminus of ExoS, is necessary and sufficient for membrane localization within eukaryotic cells, plays a role in targeting of ExoS to eukaryotic signalling factors
-
Manually annotated by BRENDA team
additional information
-
subcellular distribution, overview
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
46500
-
-
gel filtration; gel filtration
80000
-
-
-
300000
-
-
ultrafiltration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
1 * 116000, two active proteins are detected: MW 90000 Da and 116000 Da, SDS-PAGE; 1 * 90000, two active proteins are detected: MW 90000 Da and 116000 Da, SDS-PAGE
?
-
x * 25000, SDS-PAGE
?
-
exoenzyme S activity and 53000 Da and 49000 Da proteins cofractionate, SDS-PAGE
?
-
x * 54000-55000, SDS-PAGE
?
Pseudomonas aeruginosa 388
-
exoenzyme S activity and 53000 Da and 49000 Da proteins cofractionate, SDS-PAGE
-
monomer
-
1 * 116000, SDS-PAGE
monomer
-
1 * 50000, SDS-PAGE
additional information
-
PARP-1 protein has an N-terminal DNA binding domain containing two large zinc fingers that bind to both DNA single-strand breaks and DNA double-strand breaks
additional information
-
the N-terminus with amino acids 96219 encodes a Rho GTPase activating protein domain, the C-terminus with amino acids 234453 encodes a 14-3-3-dependent ADP-ribosyltransferase domain
additional information
-
structural and functional organizations of PARP-1 and PARP-2, overview
additional information
-
the bifunctional ExoT contains an N-terminal GTPase-activating protein domain, GAP domain, and a C-terminal ADP-ribosyl transferase domain, ADPRT domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
the full-length form is processed to a soluble fragment, which possesses both the GAP and ADP-ribosyltransferase activities
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
structure of the Ia complex with NADH at 1.8 A. Vapor diffusion method
-
structures of complexes between wild-type and two mutant enzymes (E189I and E189A) on the one hand and the substrate analogues beta-methylenethiazole-4-carboxamideadenine dinucleotide and NADH as well as the substrate NAD+ on the other
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
80
-
-
half-life: 204 min
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
unstable in absence of Mg2+
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-20C, 40% glycerol, stable for several months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-
Cryptothecodinium cohnii
-
partial
-
recombinant catalytic domain DELTAN22 and DELTAN222 mutants, expression in Escherichia coli
-
recombinant cytosolic His function protein, rHisExoS
-
the membrane-binding domain (amino acids 51-72) is involved in membrane binding and aggregation, which complicates the purification schemes. Purification of recombinant forms of ExoS that lack the membrane binding domain, rExoS78-453 and rExoSDELTA51-72. Both forms possess Rho GAP activity and ADP ribosyltransferase activity comparable to wild-type ExoS
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli as GST-tagged proteins
-
trancriptional regulation, overview
-
40 kDa carboxy-terminal catalytic fragment of PARP-1 comprising residues 6541014 is genetically expressed in insect cells (Spodoptera frugiperda, Sf9)
-
expression of the enzyme in HEK-293 cells using a luciferase reporter vector, PARP-1 expression analysis, overview
-
gene PARP11, chromosomal location 12p13.3, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP14, chromosomal location 3q21.1, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP16, chromosomal location 15q22.2, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP1, chromosomal location 1q41-q42, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP2, chromosomal location 14q11.2-q12, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP3, chromosomal location 3p21.1-22.2, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP4, chromosomal location 13q11, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene PARP6, chromosomal location 15q22.23, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview; gene TNKS1, chromosomal location 8p23.1, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview
O95271, P09874, Q2NL67, Q460N5, Q8N5Y8, Q9NR21, Q9UGN5, Q9UKK3, Q9Y6F1
PARP-1, DNA and amino acid sequence determination and analysis of wild-type and mutant genes
-
gene PARP, DNA and amino acid sequence determination, exon compositions, phylogenetic analysis, identification of two subgroups of the family of PARP-like poly(ADP-ribosyl)transferases, depending on the active site residues, overview
-
gene parp-1, expression in LMV cells and subclones, derived from the parental line LLC-MK2 from rhesus monkey Macaca mulatta kidney, stably expressing the estradiol-inducible transcriptional transactivation factor Gal4ERVP
-
trancriptional regulation, overview
-
expressed in Escherichia coli
-
expression in Escherichia coli as a histidine-tag fusion protein
-
catalytic domain DELTAN22 and DELTAN222 mutants, expression in Escherichia coli
-
expressed in Escherichia coli as a soluble, cytosolic His function protein, rHisExoS
-
expression of ExoS in HeLa cells leads to a loss of phosphorylation of ERM proteins, overview, expression of wild-type and mutant ExoS in enzyme-deficient strain PA103, co-expression with 14-3-3
-
expression of ExoT and the isolated GAP and ADPRT enzyme domains, respectively, in A-549 cells
-
expression of various GST-fusion protein constructs of ExoS mutants in HeLa cells
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E213A
Q49TP5
kcat highly decreased compared to wild-type, Km similar to wild-type
E215A
Q49TP5
kcat highly decreased compared to wild-type, Km (ADP-D-ribosyl)n-actin similar to wild-type, Km (NAD+) increased compared to wild-type
N86A
Q49TP5
kcat moderately decreased compared to wild-type, Km decreased compared to wild-type
S178A
Q49TP5
kcat decreased compared to wild-type, Km increased compared to wild-type
Y77A
Q49TP5
kcat decreased compared to wild-type, Km increased compared to wild-type
Y82A
Q49TP5
kcat decreased compared to wild-type, Km increased compared to wild-type
C19A
-
ADP-ribosyltransferase activity is 118% of the wild-type activity
E185Q
-
no ADP-ribosyltransferase activity
Q183E
-
no ADP-ribosyltransferase activity
R155E
-
ADP-ribosyltransferase activity is 0.2% of the wild-type activity
R59K
-
ADP-ribosyltransferase activity is 1.1% of the wild-type activity
R59K/R97K
-
no ADP-ribosyltransferase activity
R97K
-
ADP-ribosyltransferase activity is 1.9% of the wild-type activity
T178A
-
ADP-ribosyltransferase activity is 1.3% of the wild-type activity
T178A/Q183E
-
no ADP-ribosyltransferase activity
Y151V
-
ADP-ribosyltransferase activity is 1.6% of the wild-type activity
Y180T
-
no ADP-ribosyltransferase activity
C19A
Bacillus cereus 2339
-
ADP-ribosyltransferase activity is 118% of the wild-type activity
-
R155E
Bacillus cereus 2339
-
ADP-ribosyltransferase activity is 0.2% of the wild-type activity
-
R59K
Bacillus cereus 2339
-
ADP-ribosyltransferase activity is 1.1% of the wild-type activity
-
R59K/R97K
Bacillus cereus 2339
-
no ADP-ribosyltransferase activity
-
R97K
Bacillus cereus 2339
-
ADP-ribosyltransferase activity is 1.9% of the wild-type activity
-
E219Q
-
site-directed mutagenesis, inactive mutant
Q217E
-
site-directed mutagenesis, the point mutation alters the asparagine-specificity of the enzyme to an arginie-specificity, the mutant does not show ADP-ribosyltransferase activity towards RhoA, but is still capable of NAD-binding and possesses NAD+ glycohydrolase activity, the mutant exoenzyme C3 is capable of ADP-ribosylation of poly-arginine, but not poly-asparagine, and shows high activity with Arg residues of soybean trypsin inhibitor
R151A
-
site-directed mutagenesis, the mutation does not alter the enzyme activity or its potential as substrate for the C3 mutant Q217E
R61A
-
site-directed mutagenesis, the mutation does not alter the enzyme activity or its potential as substrate for the C3 mutant Q217E
R86A
-
site-directed mutagenesis, the mutation does not alter the enzyme activity but its potential as substrate for the C3 mutant Q217E, which cannot ADP-ribosylate this mutant
E301A
-
no NADase activity detected
F349A
-
the ratio of turnover-number to Km-value in the NADase reaction is 1% of the wild-type ratio. The ratio of turnover-number to Km-value in the ADP-ribosyltransferase activity is 1.9% of the wild-type ratio with rabbit muscle actin as substrate and 4% of the wild-type ratio with non-muscle actin from human platelets as substrate
F349Y
-
the ratio of turnover-number to Km-value in the NADase reaction is 110% of the wild-type ratio
N255A
-
the ratio of turnover-number to Km-value in the NADase reaction is 90% of the wild-type ratio. The ratio of turnover-number to Km-value in the ADP-ribosyltransferase activity is 20% of the wild-type ratio with rabbit muscle actin as substrate and 77% of the wild-type ratio with non-muscle actin from human platelets as substrate
R352A
-
no ADP-ribosyltransferase activity with rabbit muscle actin and non-muscle actin from human platelets; the ratio of turnover-number to Km-value in the NADase reaction is 2% of the wild-type ratio, no activity
Y246A
-
the ratio of turnover-number to Km-value in the NADase reaction is 90% of the wild-type ratio. The ratio of turnover-number to Km-value in the ADP-ribosyltransferase activity is 1.9% of the wild-type ratio with rabbit muscle actin as substrate and 19% of the wild-type ratio with non-muscle actin from human platelets as substrate
Y251A
-
the ratio of turnover-number to Km-value in the NADase reaction is 10% of the wild-type ratio
E118A
P12726
mutation reduces the toxicity of the enzyme and still allows small colonies to grow
E163A
P12726
mutation reduces toxicity of ModA to a minor extent
E165A
P12726
mutation in ModA reduces the toxicity to colony growth
E171A
P12726
mutation reduces the toxicity of the enzyme and still allows small colonies to grow
E173A
P12726
mutation largly abolishes enzyme activity
F127A
P12726
mutation in ModA reduces the toxicity to colony growth
F129A
P12726
mutation in ModA reduces the toxicity to colony growth; mutation largly abolishes enzyme activity
I176A
P12726
mutation reduces the toxicity of the enzyme and still allows small colonies to grow
L71A
P12726
mutation largly abolishes enzyme activity
N128A
P12726
mutation reduces toxicity of ModA to a minor extent
N130A
P12726
mutant enzyme with toxicity close to that of wild-type enzyme
Q116A
P12726
mutation reduces toxicity of ModA to a minor extent
Q164A
P12726
mutation reduces toxicity of ModA to a minor extent
Q172A
P12726
mutant enzyme with toxicity close to that of wild-type enzyme
R72A
P12726
mutation in ModA reduces the toxicity to colony growth
R73A
P12726
mutation largly abolishes enzyme activity
S109A
P12726
mutation in ModA reduces the toxicity to colony growth
S111A
P12726
mutant enzyme with toxicity close to that of wild-type enzyme
DELTA106-288
-
mutant enzyme has NADase activity, lack of transferase activity
DELTA24288
-
signal sequences necessary for export from the ER (at the amino terminus) and addition of a GPI-anchor (at the carboxyl terminus) are deleted. The resulting mutants retain the catalytic properties of the mature wild-type ART1. Their NADase activities relative to transferase activities are very low, and nicotinamide release is enhanced in the presence of the ADP-ribose acceptor, agmatine
E111D
-
catalytic activity close to wild-type
E120D
-
catalytic activity highly decreased
R7K
-
catalytic activity highly decreased
A425K
-
site-directed mutagenesis, phenotypic analysis
D424A
-
site-directed mutagenesis, phenotypic analysis
D424A/D427A
-
site-directed mutagenesis, reduced interaction with 14-3-3, phenotypic analysis
D424A/L426A/D427A/L428A
-
site-directed mutagenesis, the mutant shows a highly reduced expression level, phenotypic analysis
D427A
-
site-directed mutagenesis, the mutant shows a reduced expression level, phenotypic analysis
DELTAN222
-
the carboxy-terminal 222 amino acids, catalytic domain
DELTAN222
-
carboxyl-terminal 222 amino acids of exoenzyme S, catalyzes the ADP-ribosylation of soybean trypsin inhibitor at a rate sixfold greater than rHisExoS. Relative to rHisExoS, DN222 has a similar affinity for NAD, a threefold greater affinity for soybean trypsin inhibitor, and a four- to eight-fold greater turnover number for the ADP-ribosylation of soybean trypsin inhibitor. DN222 does not chromatograph as an aggregate, which shows that the amino-terminal 99 amino acids of exoenzyme S are responsible for the aggregation phenotype
DELTAN222/E381A
-
possesses 0.02% of the ADP-ribosyltransferase activity of DELTAN222. KM-value for (ADP-D-ribosyl)n-soybean-trypsin-inhibitor is 8.7fold higher than the KM-value for DELTAN222
DELTAN222/E381D
-
possesses 0.6% of the ADP-ribosyltransferase activity of DELTAN222. KM-value for (ADP-D-ribosyl)n-soybean-trypsin-inhibitor is 7.9fold higher than the KM-value for DELTAN222
DELTAN222/E381S
-
possesses 0.01% of the ADP-ribosyltransferase activity of DELTAN222. KM-value for (ADP-D-ribosyl)n-soybean-trypsin-inhibitor is 4.7fold higher than the KM-value for DELTAN222
DELTAN222/E387A
-
possesses 31% of the ADP-ribosyltransferase activity of DELTAN222
DELTAN222/E399A
-
possesses 28% of the ADP-ribosyltransferase activity of DELTAN222
DELTAN222/E414A
-
possesses 20% of the ADP-ribosyltransferase activity of DELTAN222
E379D
-
mutation inhibits expression of ADP-ribosyltransferase activity, but has little effect on the expression of NAD glycohydrolase activity
E381D
-
mutant deficient in ADP-ribosyltransferase activity, possesses pI heterogeneity that is different than that of auto-ADP-ribosylated wild-type ExoS
E381D
-
mutation inhibits expression of both ADP-ribosyltransferase activity and NAD glycohydrolase activity
E381D
-
site-directed mutagenesis, the mutation within the active site for the ADPr domain
G421A
-
site-directed mutagenesis, phenotypic analysis
L422A
-
site-directed mutagenesis, phenotypic analysis
L423A
-
site-directed mutagenesis, phenotypic analysis
L426A
-
site-directed mutagenesis, phenotypic analysis
L426A/D427A
-
site-directed mutagenesis, the mutant shows a highly reduced expression level and slightly reduced cytotoxicity, no interaction with 14-3-3, phenotypic analysis
L426A/D427A/L428A
-
site-directed mutagenesis, the mutant shows a highly reduced expression level and cytotoxicity, no interaction with 14-3-3, phenotypic analysis
Q420A
-
site-directed mutagenesis, phenotypic analysis
R146K
-
site-directed mutagenesis, the mutation within the active site for the RhoGAP domain
R146K/E379/381D
-
inactive mutant, does not inhibit Pseudomonas aeruginosa internalization into ExoS-transfected HeLa cells in contrast to the wild-type enzyme
S419I
-
site-directed mutagenesis, phenotypic analysis
E381D
Pseudomonas aeruginosa ExoS
-
mutant deficient in ADP-ribosyltransferase activity, possesses pI heterogeneity that is different than that of auto-ADP-ribosylated wild-type ExoS
-
E381D
-
site-directed mutagenesis, the mutation within the active site for the ADPr domain
-
R146K
-
site-directed mutagenesis, the mutation within the active site for the RhoGAP domain
-
R146K/E379/381D
-
inactive mutant, does not inhibit Pseudomonas aeruginosa internalization into ExoS-transfected HeLa cells in contrast to the wild-type enzyme
-
E189A
-
about 5200fold decrease in NAD+ hydrolysis activity
E189I
-
20000fold decrease in NAD+ hydrolysis activity
E189S
-
about 5200fold decrease in NAD+ hydrolysis activity
Q187A/E189A
-
50000fold decrease in NAD+ hydrolysis activity
Y251F
-
the ratio of turnover-number to Km-value in the NADase reaction is 40% of the wild-type ratio
additional information
-
phenotypes of isozyme-deficient mutant mice, overview
Y131A
P12726
mutation largly abolishes enzyme activity
additional information
-
stable expression of the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein, TonEBP/OREBP, amino acids 1-547, in HEK-293 cells increases the expression of the enzyme
additional information
-
analysis of polymorphisms of PARP-1 promoter sequence in Parkinson patients, variations in the regulatory region are probably involved in increased risk for the disease, overview
DELTA24293
-
signal sequences necessary for export from the ER (at the amino terminus) and addition of a GPI-anchor (at the carboxyl terminus) are deleted. The resulting mutants retain the catalytic properties of the mature wild-type ART1. Their NADase activities relative to transferase activities are very low, and nicotinamide release is enhanced in the presence of the ADP-ribose acceptor, agmatine
additional information
-
knockout mice show increased inflammatory response in PARP-1 -/- compared to wild-type animals, characterized by neutrophil infiltration and increased IL-6 levels in broncho-alveolar lavages, the lesions are reversible, since the extent of the hyperplastic regions is reduced after 21 days of recovery and do not result in fibrosis, phenotype, overview
additional information
-
effects of ADP-ribosylation of integrin alpha7 on the expression of the monoclonal anti-integrin antibody 9EG7 epitope in intact differentiated C2C12 cells in presence or absene of NAD+ and Mn2+, overview
additional information
-
construction of parp-1-knockout mice
additional information
-
PARP-1 knockout mice are viable, fertile and do not develop early onset tumors, cells isolated from these mice show an increased level of homologous recombination
additional information
-
phenotypes of isozyme-deficient mutant mice, overview
additional information
-
establishment of an immortalized PARP-1-/- murine endothelial cell line HYKO6 by transfection of primary cells with a plasmid containing the SV40 genome, expression of epitopes for detection by antibodies, phenotype, overview
additional information
-
PARP-1 knockout mice are much less sensitive to inflammatory stress as a result of a diminished release of pro-inflammatory mediators, including nitric oxide, parp-1 knockout mice show reduced NO-induced oxidative injury and response to genotoxic damage during carcinogenesis and inflammation
additional information
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downregulatory effect of PARP-1 on the p53-dependent regulation of recombination between SV40 minichromosomes in primate cell lines conditionally expressing exogenous PARP-1 in a wild-type p53-positive or -negative background, respectively, overview
additional information
Mus musculus 129/Sv x C57BL/6
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establishment of an immortalized PARP-1-/- murine endothelial cell line HYKO6 by transfection of primary cells with a plasmid containing the SV40 genome, expression of epitopes for detection by antibodies, phenotype, overview
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additional information
Mus musculus Sv129
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knockout mice show increased inflammatory response in PARP-1 -/- compared to wild-type animals, characterized by neutrophil infiltration and increased IL-6 levels in broncho-alveolar lavages, the lesions are reversible, since the extent of the hyperplastic regions is reduced after 21 days of recovery and do not result in fibrosis, phenotype, overview
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L428A
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site-directed mutagenesis, reduced interaction with 14-3-3, the mutant shows highly reduced cytotoxicity, phenotypic analysis
additional information
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enzyme is comprised of an N-terminal domain with GTPase activating protein activity towards Rho family GTPases and a C-terminal ADP ribosyl-transferase (ADPRT) domain with minimal activity towards a synthetic substrate in vitro. Deletion of a majority of the ADPRT domain (residues 234 to 438) or point mutations of the ADPRT catalytic site (residues 383 to 385) leads to distinct changes in host cell morphology and substantially reduces the ability of ExoT to inhibit in vitro epithelial wound healing over a 24-h period. In contrast, only subtle effects on the efficiency of ExoT-induced bacterial internalization are observed in the ADPRT mutant forms
additional information
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the recombinant deletion protein N223-53 which contains the catalytic domain of Exo53, comprising its 223 carboxyl-terminal residues catalyzes the FAS-dependent ADP-ribosylation of soybean trypsin inhibitor at 0.4% and of the Ras protein at 1.0% of the rates of catalysis by N222-49 (a protein comprising the 222 carboxyl-terminal residues of ExoS, which represent its catalytic domain). N223-53 possesesses binding affinities for NAD+ and SBTI similar to those of N222-49 but shows a lower rate for the ADP-ribosylation of SBTI; the recombinant deletion protein N223-53 which contains the catalytic domain of Exo53, comprising its 223 carboxyl-terminal residues catalyzes the FAS-dependent ADP-ribosylation of soybean trypsin inhibitor at 0.4% and of the Ras protein at 1.0% of the rates of catalysis by N222-49 (a protein comprising the 222 carboxyl-terminal residues of ExoS, which represent its catalytic domain). N223-53 possesesses binding affinities for NAD+ and SBTI similar to those of N222-49 but shows a lower velocity rate for the ADP-ribosylation of SBTI
additional information
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construction of an enzyme-deficient strain 388DELTAexoS
additional information
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construction of a truncated ExoS mutant DELTA51-72
Y426H
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in native conformation, CRM66 shows limited ability to modify EF-2 covalently. Upon activation with urea and dithiothreitol CRM66 loses ADP-ribosylation activity entirely, yet it retains the ability to bind NAD+. Replacement of Tyr-426 with histidine in CRM66 completely restores cytotoxicity and ADP-ribosyltransferase activity
additional information
Pseudomonas aeruginosa 388
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construction of an enzyme-deficient strain 388DELTAexoS
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APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
analysis
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establishment of an immortalized PARP-1-/- murine endothelial cell line HYKO6 as a tool to study PARP-1-mediated endothelial cell dysfunction
molecular biology
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establishment of an immortalized PARP-1-/- murine endothelial cell line HYKO6 as a tool to study PARP-1-mediated endothelial cell dysfunction
pharmacology
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the enzyme inhibition is a possible tool in cancer therapy both in prophylactic and therapeutic treatment, e.g. by targeting BRCA2 tumors with PARP inhibitors, overview
analysis
Mus musculus 129/Sv x C57BL/6
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establishment of an immortalized PARP-1-/- murine endothelial cell line HYKO6 as a tool to study PARP-1-mediated endothelial cell dysfunction
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molecular biology
Mus musculus 129/Sv x C57BL/6
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establishment of an immortalized PARP-1-/- murine endothelial cell line HYKO6 as a tool to study PARP-1-mediated endothelial cell dysfunction
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drug development
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the enzyme can be a target for anti-bacterial treatment