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Information on EC 3.2.1.143 - poly(ADP-ribose) glycohydrolase
for references in articles please use BRENDA:EC3.2.1.143
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EC Tree 3 Hydrolases
3.2 Glycosylases
3.2.1 Glycosidases, i.e. enzymes that hydrolyse O- and S-glycosyl compounds
3.2.1.143 poly(ADP-ribose) glycohydrolase
IUBMB Comments
Specific to (1′′-2′) linkage of ribose-ribose bond of poly(ADP-D-ribose).
The enzyme appears in viruses and cellular organisms
- 3.2.1.143
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polyadp-ribose
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polyadp-ribosylation
- parp-1
- polymerase-1
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adp-ribosylation
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genotoxic
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parylation
- gallotannins
- analysis
- drug development
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parthanatos
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automodification
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adp-ribosylhydrolase
- pharmacology
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padpr
- olaparib
- molecular biology
- aif
- medicine
showSynonyms
poly(adp-ribose) glycohydrolase, parg1, par glycohydrolase, poly (adp-ribose) glycohydrolase, adprhl2, poly(adp-ribose)glycohydrolase, parg110, adp-ribose glycohydrolase, drparg, adp-ribosyl-acceptor hydrolase 3, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADP-ribose glycohydrolase
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ARH3
DrPARG
FOXG_05947
Genbank AB019366-derived protein GI 6518480
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Genbank U78975-derived protein GI 2062407
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glycohydrolase, poly(adenosine diphosphoribose)
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glycohydrolase, poly(adenosine diphosphoribose) (cattle clone 4/5)
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glycohydrolase, poly(adenosine diphosphoribose) (Rattus norvegicus strain BUF gene Parg)
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PAR glycohydrolase
PARG
PARG1
poly(adenosine diphosphoribose) glycohydrolase
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poly(adenosine diphosphoribose) glycosidase
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poly(ADP-ribose) glycohydrolase
poly(ADP-ribose) glycohydrolase (Arabidopsis thaliana gene At2g31860)
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poly(ADP-ribose) glycohydrolase (Arabidopsis thaliana gene At2g31870)
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poly(ADP-ribose) glycohydrolase (cattly clone 4/5)
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poly(ADP-ribose) glycohydrolase 1
poly(ADP-ribose)glycohydrolase
poly(ADP-ribosyl) glycohydrolase
PARG
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poly(ADP-ribosyl) glycohydrolase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
catalytic mechanism, modelling, overview
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
canonical enzyme catalytic mechanism, modelling, overview
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
catalytic mechanism, structure-function analysis, overview
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme catalytic mechanism, overview
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
Asp314 is located proximal to the 1''-O-linkage in substrates. Asp314 might protonate the leaving group (general acid), forming an oxocarbenium ion intermediate, and then activate the water (general base) for back-side attack. The W1 ligand of MgB can serve as the nucleophile attacking the anomeric C1'' of the ribose''
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
reaction mechanism and structure, overview
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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hydrolyses poly(ADP-D-ribose) at glycosidic (1''-2') linkage of ribose-ribose bond to produce free ADP-D-ribose
enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis
hydrolysis of O-glycosyl bonds
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CAS REGISTRY NUMBER
COMMENTARY
190209-88-2
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253766-41-5
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253766-42-6
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253767-74-7
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9068-16-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2'-O-(ADP-ribosyl)-adenosine 5'-phosphate + H2O
?
Substrates: -
Products: -
Products: -
?
2'-O-acetyl-ADP-ribose + H2O
ADP-ribose + acetate
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Substrates: rate of hydrolysis by isoform ARH3 is 250fold that observed with isoform ARH1, isoform ARH2 is inactive with this substrate
Products: -
Products: -
?
ADP-ribose dimer + H2O
2 ADP-ribose
Substrates: the N-1 adenine group interacts with the amide nitrogen of the conserved Leu752 in human PARG, while the beta-phosphate forms H-bonds with the conserved Ala750, enzyme-substrate binding structure, crystal structure analysis, overview
Products: -
Products: -
?
ADP-ribosylated 53BP1 + H2O
53BP1 + ADP-ribose
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Substrates: NUDT16 removes 53BP1 ADP-ribosylation
Products: -
Products: -
?
ADP-ribosylated CtlP + H2O
CtlP + ADP-ribose
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Substrates: NUDT16 removes CtIP ADP-ribosylation
Products: -
Products: -
?
histone-bound poly(ADP-ribose) + H2O
ADP-ribose + ADP-ribose oligomer + ?
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Substrates: C14-labelled poly(ADP-ribose) produced by PARP-1 (poly(ADP-ribose) polymerase) of labelled NAD+
Products: -
Products: -
?
PARylated full-length HsPARP1 + H2O
HsPARP1 + poly(ADP-ribose)
Substrates: -
Products: -
Products: -
?
PARylated HsPARP1 + H2O
HsPARP1 + poly(ADP-ribose)
Substrates: 32P-PARylated full-length PARP1 is the substrate
Products: -
Products: -
?
poly(ADP-ribose)n-poly(ADP-ribose) polymerase + H2O
ADP-ribose + poly(ADP-ribose) polymerase
Substrates: -
Products: -
Products: -
?
propargyl ADP-ribose dimer + H2O
propargyl ADP-ribose + ADP-ribose
Substrates: -
Products: -
Products: -
?
(ADP-D-ribose)15 + H2O
(ADP-ribose)14 + ADP-D-ribose
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Substrates: -
Products: -
Products: -
?
(ADP-D-ribose)15 + H2O
(ADP-ribose)14 + ADP-D-ribose
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Substrates: -
Products: -
Products: -
?
PARP1-XRCC1 + H2O
?
Substrates: efficient disassembly of complexes of the DNA scaffold repair protein XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase (PARG)
Products: -
Products: -
?
PARP1-XRCC1 + H2O
?
Substrates: PARG rapidly reverses the PARylation of PARP1 and efficiently disassembles the PARP1-XRCC1 complex
Products: -
Products: -
?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
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Substrates: -
Products: -
Products: -
?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: -
Products: -
Products: -
?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: binding structure of ADP-ribose to wild-type and mutant enzymes, overview
Products: -
Products: -
?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: the activity is dependent on the conserved glutamate residues
Products: -
Products: -
?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: -
Products: -
Products: -
?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: PARylated PARP1 substrate
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: PARylated PARP1 substrate
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: commercial Bt-NAD ribosylated PARP1 substrate
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: enzyme-substrate binding complex structure analysis, overview
Products: -
Products: -
?
poly(ADP-ribose) + H2O
?
Substrates: a commercial Bt-NAD ribosylated PARP1 substrate
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose + ADP-ribose oligomer
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Substrates: tritium-labelled poly(ADP-ribose) produced by PARP-1 (poly(ADP-ribose) polymerase) with tritium-labelled NAD + sonicated DNA containing histones, and bovine albumin
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose + ADP-ribose oligomer
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Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose + ADP-ribose oligomer
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Substrates: P32-labelled poly(ADP-ribose) produced by PARP-1 (poly(ADP-ribose) polymerase) of labelled NAD+
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose oligomer + ADP-ribose
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Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose oligomer + ADP-ribose
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Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose oligomer + ADP-ribose
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose oligomer + ADP-ribose
-
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose) + H2O
ADP-ribose oligomer + ADP-ribose
-
Substrates: -
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
?
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Substrates: the enzyme may regulate functionally the chain length of poly(ADP-ribose) which plays a role in DNA synthesis or in the structure of chromatin
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
?
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Substrates: the enzyme is responsible for the catabolism of poly(ADP-ribose), the enzyme is a crucial determinant of polymer metabolism which is known to be implicated in DNA repair and other cellular processes
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
?
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Substrates: regulates differentially the levels of large and small poly(ADP-ribose) in the cell
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
?
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Substrates: poly(ADP-ribose) glycohydrolase II may be involved in extranuclear de(ADP-ribosyl)n-ation, but not in membrane de-mono(ADP-ribosyl)ation
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
ADP-ribose
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Substrates: -
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
ADP-ribose
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Substrates: n greater 20, degradation proceeds in a biphasic as well as bimodal manner
Products: -
Products: -
?
poly(ADP-ribose)n + H2O
ADP-ribose
Substrates: -
Products: and lower molecular weight poly(ADP-ribose)n fragment products, no product: phosphoribosyl-AMP
Products: and lower molecular weight poly(ADP-ribose)n fragment products, no product: phosphoribosyl-AMP
?
poly(ADP-ribose)n + H2O
ADP-ribose
Substrates: -
Products: and lower molecular weight poly(ADP-ribose)n fragment products, no product: phosphoribosyl-AMP
Products: and lower molecular weight poly(ADP-ribose)n fragment products, no product: phosphoribosyl-AMP
?
additional information
?
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Substrates: several isoforms, functions in embryonic development, genotixicity, cell cycle regulation, mitotic spindle assembly, development, differentiation, and cell death
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: enzyme DrPARG possesses endoglycohydrolase activity toward poly-ADP-ribose (PAR). DrPARG acts in both exo- and endo-glycohydrolase modes
Products: -
Products: -
?
additional information
?
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Substrates: poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase promote chromatin silencing at least in part by regulating the localization and function of silencing protein SIR2 and possible other nuclear proteins
Products: -
Products: -
?
additional information
?
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Substrates: the enzyme is responsible for the cleavage of poly(ADP-D-ribose) into the single ADP-ribose unit by hydrolyzing the ribose-ribose bonds within the polymer chain
Products: -
Products: -
?
additional information
?
-
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Substrates: the enzyme cannot hydrolyze the bond between terminal ADP-ribose and glutamate residues of automodifed PARP1
Products: -
Products: -
?
additional information
?
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Substrates: shuttling of enzyme between nucleus and cytoplasm and proper control of poly(ADP-ribose) metabolism throughout cell cycle may be an important role in regulating cell cycle progression and centrosome duplication
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Products: -
?
additional information
?
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Substrates: transient decrease in nuclear enzyme activity is important for the onset of differentiation of HL-60 cells to macrophage-like cells
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additional information
?
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Substrates: poly(ADP-ribose) glycohydrolase is a critical component of single-strand break repair and accelerates this process in concert with poly(ADP-ribose) polymerase
Products: -
Products: -
?
additional information
?
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Substrates: poly(ADP-ribose) glycohydrolase is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers
Products: -
Products: -
?
additional information
?
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Substrates: poly(ADP-ribose) glycohydrolase is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers
Products: -
Products: -
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additional information
?
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Substrates: the enzyme can effectively process the added poly-/oligo(ADP-ribose) units from both GST-Smad3 and PARP-1, but fails to act as a mono(ADP-ribose) hydrolase, inability of the enzme to cleave the last ADP-ribose unit, which is coupled to the protein substrate
Products: -
Products: -
?
additional information
?
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Substrates: synthesis of derivatives of the ADP-ribose dimer and development of a PAR Binding assay, overview. Propargyl ADP-ribose dimer binds to E756N and E755N mutants of human PARG with KD values of 83 nM and 208 nM, respectively. Fluorescent propargyl ADP-ribose dimer does not bind proteins devoid of PAR binding activity such as bovine serum albumin even at high concentrations of protein. Wild-type PARG is unable to process the truncated substrates 2'-O-alpha-D-ribofuranosyladenosine and 2'-O-(5-O-phosphono-a-D-ribofuranosyl)adenosine 5'-phosphate)
Products: -
Products: -
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additional information
?
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Substrates: synthesis of derivatives of the ADP-ribose dimer and development of a PAR Binding assay, overview. Propargyl ADP-ribose dimer binds to E756N and E755N mutants of human PARG with KD values of 83 nM and 208 nM, respectively. Fluorescent propargyl ADP-ribose dimer does not bind proteins devoid of PAR binding activity such as bovine serum albumin even at high concentrations of protein. Wild-type PARG is unable to process the truncated substrates 2'-O-alpha-D-ribofuranosyladenosine and 2'-O-(5-O-phosphono-a-D-ribofuranosyl)adenosine 5'-phosphate)
Products: -
Products: -
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additional information
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Substrates: structure of poly(ADP-ribose) glycohydrolase (PARG) in complex with the poly(ADP-ribose) (PAR) substrate reveals that PARG-PAR contacts are provided almost exclusively by the macrodomain. The accessory domain (which is part of the PARG catalytic region) has only limited interaction with PAR, but it structurally supports the PARG catalytic loop and may have an important role in regulation of PARG catalytic activity. The PARG-PAR structure also reveals that PARGs preferably bind PAR at the chain termini and primarily act as exo-glycohydrolases (whereby PARG sequentially degrades terminal ADP-ribose units). While binding along the PAR chain and endo-glycohydrolytic cleavage of PAR is structurally possible, it appears to be less efficient. Due to active site constraints and the conformation of bound PAR, canonical PARGs are unlikely to efficiently bind the aforementioned putative PAR branch sites
Products: -
Products: -
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additional information
?
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Substrates: assay using the PARylated PARP1 substrates, poly(ADP-ribose)-linked N-terminal DNA-binding domain of PARP1, i.e. PAR polymerase 1, a nicked DNA. Poly(ADP-ribose) binding structures of wild-type and D314A mutant, overview
Products: -
Products: -
?
additional information
?
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Substrates: assay using the PARylated PARP1 substrates, poly(ADP-ribose)-linked N-terminal DNA-binding domain of PARP1, i.e. PAR polymerase 1, a nicked DNA. Poly(ADP-ribose) binding structures of wild-type and D314A mutant, overview
Products: -
Products: -
?
additional information
?
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Substrates: development of a high-throughput homogeneous time-resolved fluorescence (HTRF) assay method, 6His-TEV-PAR(32:1)PARP-1(2-1014) substrate, combinantion with the activity of poly(ADP-ribose) polymerase, PARP. Enzyme PARG binds to PARylated PARP-1 and cleaves off the PAR moiety, which activates PARP-1 preventing the production of a fluorescent signal. Inactive PARP-1 leads to the production of the measurable fluoresecnt signal, mechanism and evaluation, overview
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Products: -
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additional information
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-
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Substrates: development of a high-throughput homogeneous time-resolved fluorescence (HTRF) assay method, 6His-TEV-PAR(32:1)PARP-1(2-1014) substrate, combinantion with the activity of poly(ADP-ribose) polymerase, PARP. Enzyme PARG binds to PARylated PARP-1 and cleaves off the PAR moiety, which activates PARP-1 preventing the production of a fluorescent signal. Inactive PARP-1 leads to the production of the measurable fluoresecnt signal, mechanism and evaluation, overview
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additional information
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Substrates: no substrate: beta-NAD+
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additional information
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Substrates: HsNudT16 hydrolyses the diphosphate bonds in the P32-PARylated protein, thereby removing the ADP-ribose units in the form of 32P-containing iso-ADP-ribose and the terminal 32P-containing AMP. The enzyme also hydrolyses free ADP-ribose to phosphoribose and AMP
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additional information
?
-
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Substrates: enzyme is a necessary component of the poly(ADP-ribose) polymerase 1 mediated cell death pathway
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additional information
?
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Substrates: no substrate: mono-ADP-ribosylated proteins, ADP-ribose-arginine, ADP-ribose-cysteine, ADP-ribose-diphthaminde, ADP-ribose-asparagine
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additional information
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-
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Substrates: enzyme activity modulates the inflammatory response and tissue events associated with spinal cord trauma and participates in target organ damage under these conditions
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additional information
?
-
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Substrates: modification of the adenine moiety of poly(ADP-ribose) abrogates the susceptibility to digestion by the enzyme
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additional information
?
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Substrates: the enzyme functions as an endo-glycosidase to release oligo(ADP-ribose) and as an exo-glycosidase to release ADP-ribose. Long poly(ADP-ribose) polymers are efficiently hydrolyzed by a combination of endo- and exo-glycosidic activity, whereas smaller digestion products are poor substrates for the enzyme allowing release of oligo(ADP-ribose) chains that are ligands for histones and DNA repair and damage checkpoint proteins such as XRCC1 and p53
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additional information
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Substrates: quantitative, real-time assay of PAR-dependent protein-protein interactions and PAR turnover by PARG. PARG degrades the PAR posttranslational modification by a combination of exo- and endo-glycohydrolase activity, leaving a single ADP-ribose moiety attached to PARP1 that is a substrate for the mono(ADP-ribose) (MAR) hydrolases
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additional information
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Substrates: hydrolysis of glycosidic ribose-ribose bond
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ADP-ribosylated 53BP1 + H2O
53BP1 + ADP-ribose
-
Substrates: NUDT16 removes 53BP1 ADP-ribosylation
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ADP-ribosylated CtlP + H2O
CtlP + ADP-ribose
-
Substrates: NUDT16 removes CtIP ADP-ribosylation
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PARP1-XRCC1 + H2O
?
Substrates: efficient disassembly of complexes of the DNA scaffold repair protein XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase (PARG)
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PARylated full-length HsPARP1 + H2O
HsPARP1 + poly(ADP-ribose)
Substrates: -
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?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
-
Substrates: -
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?
poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: -
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poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: the activity is dependent on the conserved glutamate residues
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poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: -
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poly(ADP-D-ribose)n + H2O
poly(ADP-D-ribose)n-1 + ADP-ribose
Substrates: -
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poly(ADP-ribose) + H2O
?
Substrates: -
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poly(ADP-ribose) + H2O
?
Substrates: -
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poly(ADP-ribose) + H2O
?
Substrates: -
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poly(ADP-ribose) + H2O
?
Substrates: -
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poly(ADP-ribose) + H2O
?
Substrates: -
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poly(ADP-ribose) + H2O
?
Substrates: -
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poly(ADP-ribose)n + H2O
?
-
Substrates: the enzyme may regulate functionally the chain length of poly(ADP-ribose) which plays a role in DNA synthesis or in the structure of chromatin
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poly(ADP-ribose)n + H2O
?
-
Substrates: the enzyme is responsible for the catabolism of poly(ADP-ribose), the enzyme is a crucial determinant of polymer metabolism which is known to be implicated in DNA repair and other cellular processes
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poly(ADP-ribose)n + H2O
?
-
Substrates: regulates differentially the levels of large and small poly(ADP-ribose) in the cell
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poly(ADP-ribose)n + H2O
?
-
Substrates: poly(ADP-ribose) glycohydrolase II may be involved in extranuclear de(ADP-ribosyl)n-ation, but not in membrane de-mono(ADP-ribosyl)ation
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additional information
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-
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Substrates: several isoforms, functions in embryonic development, genotixicity, cell cycle regulation, mitotic spindle assembly, development, differentiation, and cell death
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additional information
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Substrates: poly(ADP-ribose) polymerase and poly(ADP-ribose) glycohydrolase promote chromatin silencing at least in part by regulating the localization and function of silencing protein SIR2 and possible other nuclear proteins
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additional information
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-
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Substrates: the enzyme is responsible for the cleavage of poly(ADP-D-ribose) into the single ADP-ribose unit by hydrolyzing the ribose-ribose bonds within the polymer chain
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additional information
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Substrates: shuttling of enzyme between nucleus and cytoplasm and proper control of poly(ADP-ribose) metabolism throughout cell cycle may be an important role in regulating cell cycle progression and centrosome duplication
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additional information
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Substrates: transient decrease in nuclear enzyme activity is important for the onset of differentiation of HL-60 cells to macrophage-like cells
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additional information
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Substrates: poly(ADP-ribose) glycohydrolase is a critical component of single-strand break repair and accelerates this process in concert with poly(ADP-ribose) polymerase
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additional information
?
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Substrates: poly(ADP-ribose) glycohydrolase is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers
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additional information
?
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Substrates: poly(ADP-ribose) glycohydrolase is the only enzyme known to catalyse hydrolysis of the O-glycosidic linkages of ADP-ribose polymers
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additional information
?
-
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Substrates: enzyme is a necessary component of the poly(ADP-ribose) polymerase 1 mediated cell death pathway
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?
additional information
?
-
-
Substrates: enzyme activity modulates the inflammatory response and tissue events associated with spinal cord trauma and participates in target organ damage under these conditions
Products: -
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?
additional information
?
-
Substrates: the enzyme functions as an endo-glycosidase to release oligo(ADP-ribose) and as an exo-glycosidase to release ADP-ribose. Long poly(ADP-ribose) polymers are efficiently hydrolyzed by a combination of endo- and exo-glycosidic activity, whereas smaller digestion products are poor substrates for the enzyme allowing release of oligo(ADP-ribose) chains that are ligands for histones and DNA repair and damage checkpoint proteins such as XRCC1 and p53
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
KCl
Mg2+
NaCl
Mg2+
required for activity, two MG2+ with catalytic function, mechanism, overview. Asp314 is essential for the formation of the binuclear metal center
Mg2+
required for catalysis, binuclear Mg2+ site, structure overview. The distal ribose of poly(ADP-ribose), enabling the hydroxyl groups of the distal ribose to coordinate the two Mg2+ ions. MgA is coordinated with Asp314, Asp316, Thr317, three hydroxyl groups of the distal ribose and water 269. Meanwhile, MgB is coordinated with the 2'-hydroxyl group of the distal ribose, Thr76, Asp77, Asp78, Asp316, and two water molecules (water 269 and water 85). The sequence alignment and structural comparison reveals that the Mg2+ coordinating acidic residues Asp77, Asp78, Asp314, and Asp316 are fully conserved in homologous ARH enzymes. Both Mg2+ ions are involved in the positioning of water 351 in the catalytic center through hydrogen-bonding interaction. the binding pocket of ARH3 is divided into two subunits by the binuclear Mg2+ sites
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3Z)-5-bromo-1-(2,6-dichlorobenzyl)-3-[4-oxo-3-[2-(1H-tetrazol-5-yl)ethyl]-2-thioxo-1,3-thiazolidin-5-ylidene]-1,3-dihydro-2H-indol-2-one
-
specific detergent-insensitive inhibition
(3Z)-5-chloro-1-(2,6-dichlorobenzyl)-3-[4-oxo-3-[2-(1H-tetrazol-5-yl)ethyl]-2-thioxo-1,3-thiazolidin-5-ylidene]-1,3-dihydro-2H-indol-2-one
-
specific detergent-insensitive inhibition
1,2,3,4,6-pentakis-O-galloyl-beta-D-glucoside
-
about 25% inhibition at 10 microM in vitro
1,3,6-tris-O-galloyl-beta-D-glucoside
-
about 25% inhibition at 10 microM in vitro
1,3-diethyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-2-sulfanylideneoctahydro-6H-purin-6-one
-
1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-3,4,5,7-tetrahydro-1H-purine-2,6-dione
-
1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-6-sulfanylidene-1,3,4,5,6,7-hexahydro-2H-purin-2-one
inhibitor kills cancer cells through selective PARG inhibition and causes replication fork defects
1,3-dimethyl-8-[[2-(pyrrolidin-1-yl)ethyl]sulfanyl]-6-sulfanylidene-1,3,4,5,6,7-hexahydro-2H-purin-2-one
specifically binds to the PARG adenine-binding pocket
1,3-dimethyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-(cyclopropylmethyl)-N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-(cyclopropylmethyl)-N-(1-methylcyclopropyl)-3-[(2-methylthiazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-(cyclopropylmethyl)-N-(1-methylcyclopropyl)-3-[(3-methylisoxazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-ethyl-N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-ethyl-N-(1-methylcyclopropyl)-3-[(3-methylisoxazol-5-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-ethyl-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyc lopropyl)-2,4-dioxo-3-(3-thienylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
-
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(1H-pyrazol-4-ylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(2-pyridylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(3-pyridylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(4-pyridylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(thiadiazol-4-ylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(thiazol-2-ylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-(thiazol-5-ylmethyl)quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-phenacyl-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-phenyl-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-prop-2-ynyl-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-3-[2-oxo-2-(4-pyridyl)ethyl]quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-(oxazol-4-ylmethyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-(oxetan-3-ylmethyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-3-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(1-methyltetrazol-5-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(2-methyl-4-phenyl-thiazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(2-methylpyrazol-3-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(2-methylthiazol-4-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(2-methylthiazol-5-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(3-methyl-1H-pyrazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(3-methylimidazol-4-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(3-methylisoxazol-5-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(4-methyl-1,2,4-triazol-3-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(4-methylthiadiazol-5-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(5-methylisoxazol-3-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-methyl-N-(1-methylcyclopropyl)-3-[(5-methylisoxazol-4-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
-
1-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-N-(1-methylcyclopropyl)-2-oxo-3-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1H-benzimidazole-5-sulfonamide
-
1-[(2,4-dimethylthiazol-5-yl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,4-dimethylthiazol-5-yl)methyl]-N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,4-dimethylthiazol-5-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methylthiazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,5-dimethylpyrazol-3-yl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,5-dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,5-dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methylthiazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,5-dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(3-methylisoxazol-5-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2,5-dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2-fluorophenyl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(2-methoxyphenyl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(3-fluorophenyl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(3-methoxyphenyl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(4-fluorophenyl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
1-[(4-methoxyphenyl)methyl]-3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
12-O-tetradecanoyl-phorbol-13-acetate
reduction of nuclear enzyme activity to 30-40% of control, cytosolic activity remains unchanged. Reduction is suppressed by protein kinase C inhibitor H7. Enzyme expression is reduced in presence of 12-O-tetradecanoyl-phorbol-13-acetate
2-N3-adenosine diphosphate (hydroxymethyl)pyrrolidinediol
-
50% inhibition at 0.290 mM, native protein and 50% inhibition at 0.148 mM, recombinant catalytic fragment
3,5-dichloro-2-hydroxy-N-(4-(naphthalen-2-yloxy)-3-(trifluoromethyl)phenyl)benzamide
-
-
3,5-dichloro-2-hydroxy-N-m-tolylbenzamide
-
between 10% and 30% inhibition at 0.5 mM
3,5-dichloro-2-hydroxy-N-o-tolylbenzamide
-
between 10% and 30% inhibition at 0.5 mM
3,5-dichloro-2-hydroxy-N-p-tolylbenzamide
-
between 10% and 30% inhibition at 0.5 mM
3,5-dichloro-N-(2-chlorophenyl)-2-hydroxybenzamide
-
between 10% and 30% inhibition at 0.5 mM
3,5-dichloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxy-N-methylbenzamide
-
-
3,5-dichloro-N-[3-chloro-4-(naphthalen-2-yloxy)cyclohexa-1,5-dien-1-yl]-2-hydroxybenzamide
-
3-(1H-imidazol-4-ylmethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-(3-furylmethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxoquinazoline-6-sulfonamide
-
3-(cyanomethyl)-1-(cyclopropylmethyl)-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-(cyanomethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxoquinazoline-6-sulfonamide
-
3-(cyanomethyl)-1-[(2,5-dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-(cyanomethyl)-N-(1-methylcyclopropyl)-2,4-dioxo-1-prop-2-ynyl-quinazoline-6-sulfonamide
-
3-(cyclohexylmethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-(cyclopropylmethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-(isothiazol-5-ylmethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-(isoxazol-5-ylmethyl)-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-benzyl-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-bromo-5-chloro-N-[5-chloro-2-[(1-chloronaphthalen-2-yl)oxy]phenyl]-2-hydroxybenzamide
-
-
3-bromo-N-[2-[2-bromo-6-methyl-3-(propan-2-yl)phenoxy]-5-chlorophenyl]-5-chloro-2-hydroxybenzamide
-
-
3-ethyl-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-galloyl-D-glucose
-
about 50% inhibition at 1 microM, 65% inhibition at 10 microM, about 85% at 100 microM in vitro, no inhibitory effect in HeLa cell death at 10 microM, induced by methylating agent 1-methyl-3-nitro-1-nitrosoguanidine (100 microM), because cell-permeability is probably hindered
3-methyl-N-(1-methylcyclopropyl)-1-[(2-methylpyrazol-3-yl)-methyl]-2,4-dioxo-quinazoline-6-sulfonamide
-
3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1-(2-pyridylmethyl)quinazoline-6-sulfonamide
-
3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1-(3-pyridylmethyl)quinazoline-6-sulfonamide
-
3-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1-(4-pyridylmethyl)quinazoline-6-sulfonamide
-
3-[(1-ethylpyrazol-4-yl)methyl]-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-[(2,4-dimethylthiazol-5-yl)methyl]-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-[(2-aminothiazol-5-yl)methyl]-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-[(3,5-dimethylisoxazol-4-yl)methyl]-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
3-[(5Z)-5-[1-(2-chlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
specific detergent-insensitive inhibition
3-[(5Z)-5-[5-bromo-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
specific detergent-insensitive inhibition
3-[(5Z)-5-[5-bromo-1-(2-chloro-6-fluorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
specific detergent-insensitive inhibition
3-[(5Z)-5-[5-chloro-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
3-[[1-(cyanomethyl)pyrazol-4-yl]methyl]-1-methyl-N-(1-methylcyclopropyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
8-chlorophenylthioadenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
-
50% inhibition at 0.12 mM, recombinant catalytic fragment
8-n-octyl-amino-adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A
8-N3-adenosine diphosphate (hydroxymethyl)pyrrolidinediol
-
50% inhibition at 390 nM, native protein and 50% inhibition at 0.0014 mM, recombinant catalytic fragment
adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
ADP-HPD, binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A
adenosine 5'-diphosphate-(hydroxymethyl)-pyrrolidinediol
ADP-HPD, an analogue of ADP-ribose
adenosine diphosphate (hydroxymethyl)pyrrolidine
-
50% inhibition at 0.019 mM, native protein and 50% inhibition at 0.063 mM, recombinant catalytic fragment
adenosine diphosphate (hydroxymethyl)pyrrolidine-monoalcohol
-
50% inhibition at 330nM, native protein and 50% inhibition at 440 nM, recombinant catalytic fragment
COH34
EC50 value 8.2 microM in HCT-116R-PDD cells, 8.3 microM in HCT-116 cells
Congo red
-
detergent-sensitive inhibition with complete loss of inhibition in the presence of detergent
ethacridine lactate
PARG inhibitor, synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induces a synergistic increase in reactive oxygen species that is functionally important to explain the observed cell death, synergistic cytotoxicity of ibrutinib and ethacridine. The ibrutinib-ethacridine combination is preferentially cytotoxic to a subset of primary AML cells compared to normal hematopoietic cells
GPI 16552
-
pharmacological inhibitor, treatment of wild-type mice shows a protective effect in dinitrobenzene sulfonic acid-induced colitis
GPI 18214
-
pharmacological inhibitor, treatment of wild-type mice shows a protective effect in dinitrobenzene sulfonic acid-induced colitis
-
guanosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
-
50% inhibition above 1 mM, native protein and 50% inhibition at 0.970 mM,+ recombinant catalytic fragment
methyl 2-O-galloyl-beta-D-glucoside
-
about 25% inhibition at 1 microM, 65% inhibition at 10 microM, about 85% inhibition at 100 microM in vitro
methyl 3-O-galloyl-beta-D-glucoside
-
about 25% inhibition at 1 microM, 65% inhibition at 10 microM, about 85% inhibition at 100 microM in vitro
N'1,N'4-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
N'1,N'4-bis[(E)-(3,4-dihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
slight inhibition
N'1-[(E)-(2,3,4-trihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
-
N'1-[(E)-(2,3,4-trihydroxyphenyl)methylidene]-N'4-[(Z)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
-
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
-
N'1-[(E)-(2,4,6-trihydroxyphenyl)methylidene]-N'3-[(Z)-(2,4,6-trihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
-
N'1-[(E)-(2,4,6-trihydroxyphenyl)methylidene]-N'4-[(Z)-(2,4,6-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
-
N'1-[(E)-(2,4-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,4-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
-
N'1-[(E)-(3,4,5-trihydroxyphenyl)methylidene]-N'3-[(Z)-(3,4,5-trihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
-
N'1-[(E)-(3,4,5-trihydroxyphenyl)methylidene]-N'4-[(Z)-(3,4,5-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
-
N'1-[(E)-(3,4-dihydroxyphenyl)methylidene]-N'3-[(Z)-(3,4-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
-
-
N'1-[(E)-(4,6-dihydroxycyclohexa-1,3-dien-1-yl)methylidene]-N'4-[(E)-(2,4-dihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
slight inhibition
N'1-[(E)-(5,6-dihydroxycyclohexa-1,3-dien-1-yl)methylidene]-N'4-[(E)-(2,3-dihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
-
slight inhibition
N-(1-cyanocyclopropyl)-1,3-dimethyl-2,4-dioxo-quinazoline-6-sulfonamide
-
N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)methyl]-1-(oxetan-3-ylmethyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
N-(1-methylcyclopropyl)-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-1-prop-2-ynyl-quinazoline-6-sulfonamide
-
N-(1-methylcyclopropyl)-3-[(2-methylthiazol-5-yl)methyl]-2,4-dioxo-1-prop-2-ynyl-quinazoline-6-sulfonamide
-
N-(1-methylcyclopropyl)-3-[(3-methylisoxazol-5-yl)methyl]-1-(oxetan-3-ylmethyl)-2,4-dioxo-quinazoline-6-sulfonamide
-
N-(1-methylcyclopropyl)-3-[(3-methylisoxazol-5-yl)methyl]-2,4-dioxo-1-prop-2-ynyl-quinazoline-6-sulfonamide
-
N-bis-(3-phenyl-propyl)9-oxo-fluorene-2,7-diamide
-
i.e. GPI 16552, pharmacological inhibitor. Enzyme inhibition results in significant reduction of spinal cord inflammation and tissue injury, neutrophil infiltration, cytokine production, and apoptosis upon spinal cord injury. Additionally, inhibition significantly ameliorates the recovery of limb function
N-cyclopropyl-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
-
N-ethyl-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
-
N-[4-[(3-bromonaphthalen-2-yl)oxy]-3-chlorophenyl]-3,5-dichloro-2-hydroxybenzamide
-
-
N6-benzyladenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
-
50% inhibition above 1 mM, recombinant catalytic fragment
N6-hexyladenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
-
50% inhibition at 0.51 mM, recombinant catalytic fragment
nobotanin B
-
inhibition of enzyme activity. In presence of inhibitor, reduction of cell death after exposure to hydrogen peroxide, N-methyl-D-aspartate, or N-methyl-N-nitro-N-nitrosoguanidine
nuclear matrix proteins
-
due to non-covalent interactions of the protein with free ADP-ribose polymers
-
PDD0017273
a dose of 40 microM PDD0017273 effectively inhibites PARG expression, and increases the sensitivity of AN3CA endometrial carcinoma cells to cisplatin
-
phosphorodiamidate morpholino oligonucleotide
-
antisense phosphorodiamidate morpholino oligonucleotide blocks exon 1 of the full length nuclear PARG 111 kDa isoform, slowing down the rate of nuclear poly(ADP-ribose) degradation, attenuating poly(ADP-ribose) polymerase-1 mediated cell death, reducing PARG expression as shown by immunostaining, upon incubation with 50 microM alcylating agent N-methyl-N'-nitro-N'-nitrosoguanidine to induce cell death blocking of nuclear PARG reduced cell condensation and cell death, no inhibitory influence on cytosol PARG
-
poly(etheno ADP-ribose)
-
inhibits hydrolysis of ribose-ribose bonds by the enzyme, highly resistant to digestion by the enzyme
Poly(G)
-
inhibitory effect is eliminated when 250 mM KCl is present in the reaction mixture
RBPI-3
a rhodanine-containing mammalian PARG inhibitor, enzyme-inhibitor structure analysis, overview. RBPI-3 binds predominantly via a pi-pi stacking interaction with Tyr296 and the conserved Phe398. To accommodate the binding of RBPI-3, Phe398 moves into the adenosine binding pocket. The RBPI-3 carboxyl moiety occupies a region corresponding to the ADP-ribose alpha-phosphate group and H-bonds to main chain atoms of Lys365 and Gln254. The RBPI-3 di-chlorobenzyl moiety extends into the solvent and is disordered
Rose bengal
inhibitor occupies the active site of PARG. Two sets of sandwiched amino acids (Asn869-Tyr792 and Phe902-Tyr795) in the active site enable tight binding to the active site pocket
siRNA
-
small interfering RNA, down regulation of PARG to 50% 24 h after siRNA transfection, maximum of 84% inhibition after 72 compared to negative control with ineffective scrambled siRNA, siRNA produced in vitro from cDNA with 21-nucleotide sequence target in human coding region of the enzyme
-
Tannic acid
continous decrease in activity of nuclear enzyme activity, reduction in enzyme expression
tannin
-
0.01 mg/ml, 89% inhibition, competitive with respect to poly(ADP-ribose)
-
3-[(5Z)-5-[5-chloro-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
specific detergent-insensitive inhibition
3-[(5Z)-5-[5-chloro-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
-
adenosine diphosphate (hydroxymethyl) pyrrolidinediol
-
39% inhibition at 0.025 mM
adenosine diphosphate (hydroxymethyl) pyrrolidinediol
ADP-HPD, tight binding inhibitor, binding structure, overview
adenosine diphosphate (hydroxymethyl)pyrrolidinediol
-
partial noncompetitive inhibition
adenosine diphosphate (hydroxymethyl)pyrrolidinediol
-
i.e. APD-HPD, 50% inhibition at 0.0031 mM, native protein and 50% inhibition at 0.0042 mM, recombinant catalytic fragment
ADP-HPD
-
about 40% inhibition at 1 microM, about 70% inhibition at 10 microM, about 85% inhibition at 100 microM in vitro
ADP-ribose
-
inhibits poly(ADP-ribose) glycohydrolase II more strongly than poly(ADP-ribose) glycohydrolase I
ADP-ribose
binding structure with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A
cAMP
-
inhibits poly(ADP-ribose) glycohydrolase II more strongly than poly(ADP-ribose) glycohydrolase I
gallotannin
-
25% inhibition at 10 micorM in vitro, reduced cell death in HeLa cells at 3 and 6 h exposure
-
gallotannin
-
inhibition of enzyme activity. In presence of inhibitor, reduction of cell death after exposure to hydrogen peroxide, N-methyl-D-aspartate, or N-methyl-N-nitro-N-nitrosoguanidine
-
histone
-
due to noncovalent interactions of the protein with free ADP-ribose polymers
N-tert-butyl-9,10-dioxo-9,10-dihydroanthracene-2-sulfonamide
PDD00013907, inhibition of enzyme PARG with the small molecule leads to poly(ADP-ribose) (PAR) chain persistence in intact cells, overview. It shows cellular activity and cytotoxicity in HeLa cells
Poly(A)
-
inhibitory effect is eliminated when 250 mM KCl is present in the reaction mixture, inhibition is markedly diminished after hybridization with polyT
poly(I)
-
inhibitory effect is eliminated when 250 mM KCl is present in the reaction mixture, inhibition is markedly diminished after hybridization with polyC
additional information
-
gallotannin is a complex mixture of hydrolysable tannins, gallic acid and various galloyl glucose derivatives with up to 12 galloyl residues, from oak gall, that inhibits PARG; no inhibitory effect of 100 microM gallic acid, of 10 microM methyl gallate, of 10 microM 2,3-digalloyl-D-glucose, of 10 microM 2,3-digalloyl-O-methyl-D-glucose, of 10 microM 2,3-hexahydroxydiphenoyl-D-glucose, of 10 microM 2,3-di(3-galloyl,4,5-dihydroxy-benzoyl)-D-glucose, of 10 microM epigallocatechin gallate, and of 10 and 100 microM 3-galloyl-1,2-O-isopropylidene-alpha-D-glucose in vitro, the latter can act in vivo as cell-permeable precursor of 3-D-galloyl-D-glucose preventing poly(ADP-ribose) degradation, reduced cell death in HeLa cells at 3 and 6 h exposure (10 or 100 microM), cell death induction by methylating agent 1-methyl-3-nitro-1-nitrosoguanidine (100 microM), increased intracellular NAD content without 1-methyl-3-nitro-1-nitrosoguanidine, no effect in the presence of this agent
-
additional information
-
inhibition of PARG in HeLa cells treated with 50 microM cell death inducing alkylating agent N-methyl-N'-nitro-N'-nitrosoguanidine leads (MNNG) increases poly(ADP-ribose) levels beyond control, untreated and MNNG-treated PARG-silenced cells show a tendency to larger amounts of long (more than 20 ADP-ribose units) polymers, and a slight increase in short and medium long polymers, however PARG-silencing has no effect on cell death, no effect on translocation of apoptosis-inducing factor (AIF) into nucleus
-
additional information
-
not inhibited by benzamide, 3,5-dichloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)benzamide, 3,5-dichloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-methoxybenzamide, 2,4-dichloro-6-((3-chloro-4-(naphthalen-2-yloxy)phenylimino)methyl)phenol, 2,4-dichloro-6-((3-chloro-4-(naphthalen-2-yloxy)phenylamino)methyl)phenol, 3,5-dichloro-2-hydroxybenzamide, 3,5-dichloro-N-(3-chloro-4-hydroxyphenyl)-2-hydroxybenzamide, and 3,5-dichloro-2-hydroxy-N-benzamide
-
additional information
-
small molecule inhibitor screening, detection of rhodamine-based enzyme inhibitors (RBPIs), 3-[(5Z)-5-[1-(2-fluorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid and (3Z)-1-(2-fluorobenzyl)-3-[4-oxo-3-[2-(1H-tetrazol-5-yl)ethyl]-2-thioxo-1,3-thiazolidin-5-ylidene]-1,3-dihydro-2H-indol-2-one are inactive, RBPIs do not inhibit beta-lactamase, ADP-ribosylhydrolase 3, or poly(ADP-ribose) polymerase 1. No inhibiiton by DMO
-
additional information
structure-activity relationship analysis of the enzyme inhibitors by isothermal titration calorimetry and surface plasmon resonance, molecular modelling, overview
-
additional information
-
structure-activity relationship analysis of the enzyme inhibitors by isothermal titration calorimetry and surface plasmon resonance, molecular modelling, overview
-
additional information
first-in-class chemical probes against poly(ADP-ribose) glycohydrolase (PARG) inhibit DNA repair with differential pharmacology to poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. No inhibition of PARG by 1-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-N-methyl-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide and 1-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-N-methyl-N-(1-methylcyclopropyl)-2-oxo-3-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1H-benzimidazole-5-sulfonamide. Cytotoxicity measurements of inhibitors with different cell lines
-
additional information
development of a high-throughput homogeneous time-resolved fluorescence (HTRF) assay method allows high-throughput screening for the identification and advancement of multiple validated series of tool compounds for PARG inhibition
-
additional information
-
development of a high-throughput homogeneous time-resolved fluorescence (HTRF) assay method allows high-throughput screening for the identification and advancement of multiple validated series of tool compounds for PARG inhibition
-
additional information
specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase. Single treatment therapy with PARG inhibitors can be used for treatment of certain homologous recombination-deficient tumours and provide insight into the relationship between poly(ADP-ribose) polymerase (PARP), PARG and the processes of DNA repair
-
additional information
discovery and optimization of orally bioavailable quinazolinedione sulfonamides as cell-active small molecule inhibitors of DNA-damage repair enzyme poly(ADP-ribose) glycohydrolase (PARG), structure-based virtual screening and library design, overview. Physicochemical properties of 8a and 12b. Structure-activity relationships, cytotoxicity in HeLa cells, selectivity, and EC50 values, overview
-
additional information
-
discovery and optimization of orally bioavailable quinazolinedione sulfonamides as cell-active small molecule inhibitors of DNA-damage repair enzyme poly(ADP-ribose) glycohydrolase (PARG), structure-based virtual screening and library design, overview. Physicochemical properties of 8a and 12b. Structure-activity relationships, cytotoxicity in HeLa cells, selectivity, and EC50 values, overview
-
additional information
ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a Bruton's tyrosine kinase (BTK)-independent mechanism, synergistic cytotoxicity of ibrutinib and ethacridine. The ibrutinib-ethacridine combination is preferentially cytotoxic to a subset of primary AML cells compared to normal hematopoietic cells. The inhibitory effect of ibrutinib against BTK, as knockdown of BTK does not sensitize TEX and OCI-AML2 cells to ethacridine treatment
-
additional information
the N-terminal regulatory fragment can activate in trans the inactive enzyme fragment depleted with this segment. This suggests that, whereas the enzyme activity can be inhibited by disrupting the docking of this segment to its enzyme binding groove (via posttranslational modification or protein-proteins interactions), the enzyme can be reversibly activated once the disruptive factor is removed
-
additional information
-
the N-terminal regulatory fragment can activate in trans the inactive enzyme fragment depleted with this segment. This suggests that, whereas the enzyme activity can be inhibited by disrupting the docking of this segment to its enzyme binding groove (via posttranslational modification or protein-proteins interactions), the enzyme can be reversibly activated once the disruptive factor is removed
-
additional information
-
design and synthesis of phenolic hydrazide hydrazones as potent poly(ADP-ribose) glycohydrolase inhibitors, molecular docking analyses, overview
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
the N-terminal regulatory fragment can activate in trans the inactive enzyme fragment depleted with this segment. This suggests that, whereas the enzyme activity can be inhibited by disrupting the docking of this segment to its enzyme binding groove (via posttranslational modification or protein-proteins interactions), the enzyme can be reversibly activated once the disruptive factor is removed
-
additional information
-
the N-terminal regulatory fragment can activate in trans the inactive enzyme fragment depleted with this segment. This suggests that, whereas the enzyme activity can be inhibited by disrupting the docking of this segment to its enzyme binding groove (via posttranslational modification or protein-proteins interactions), the enzyme can be reversibly activated once the disruptive factor is removed
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Combined Targeting of PARG and Wee1 Causes Decreased Cell Survival and DNA Damage in an S-Phase-Dependent Manner.
Adenomatous Polyps
Aberration of poly(adenosine diphosphate-ribose) metabolism in human colon adenomatous polyps and cancers.
Ataxia
Bi-allelic ADPRHL2 Mutations Cause Neurodegeneration with Developmental Delay, Ataxia, and Axonal Neuropathy.
Ataxia
Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.
Ataxia
Episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome) caused by a novel mutation in ADPRHL2 (AHR3).
Ataxia
[Pediatric stress-induced epileptic ataxia syndrome caused by ADPRHL2 gene variation].
Breast Neoplasms
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.
Breast Neoplasms
Silencing of Apoptosis-Inducing factor and poly(ADP-ribose) glycohydrolase reveals novel roles in breast cancer cell death after chemotherapy.
Breast Neoplasms
Variations in the mRNA expression of poly(ADP-ribose) polymerases, poly(ADP-ribose) glycohydrolase and ADP-ribosylhydrolase 3 in breast tumors and impact on clinical outcome.
Carcinogenesis
Poly (ADP-ribose) glycohydrolase silencing-mediated maintenance of H2A and downregulation of H2AK9me protect human bronchial epithelial cells from benzo(a)pyrene-induced carcinogenesis.
Carcinogenesis
Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis.
Carcinogenesis
Poly(ADP-ribose) glycohydrolase silencing-mediated H2B expression inhibits benzo(a)pyrene-induced carcinogenesis.
Carcinogenesis
Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure.
Carcinoma
Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1.
Carcinoma
Tannic acid, an inhibitor of poly(ADP-ribose) glycohydrolase, sensitizes ovarian carcinoma cells to cisplatin.
Carcinoma, Renal Cell
Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1.
Chagas Disease
Host cell poly(ADP-ribose) glycohydrolase is crucial for Trypanosoma cruzi infection cycle.
Colonic Neoplasms
Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NF?-B Pathway.
Colorectal Neoplasms
Combined Targeting of PARG and Wee1 Causes Decreased Cell Survival and DNA Damage in an S-Phase-Dependent Manner.
Glioma
Expression and activity of poly(ADP-ribose) glycohydrolase in cultured astrocytes, neurons, and C6 glioma cells.
Herpes Simplex
Herpes simplex virus 1 infection activates poly(ADP-ribose) polymerase and triggers the degradation of poly(ADP-ribose) glycohydrolase.
Hypersensitivity
Hypersensitivity to DNA double-strand breaks associated with PARG deficiency is suppressed by exo-1 and polq-1 mutations in Caenorhabditis elegans.
Infections
Herpes simplex virus 1 infection activates poly(ADP-ribose) polymerase and triggers the degradation of poly(ADP-ribose) glycohydrolase.
Infections
Host cell poly(ADP-ribose) glycohydrolase is crucial for Trypanosoma cruzi infection cycle.
Inflammatory Bowel Diseases
Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice.
Leukemia
Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.
Leukemia, Myeloid, Acute
Erlotinib synergizes with the poly(ADP-ribose) glycohydrolase inhibitor ethacridine in acute myeloid leukemia cells.
Leukemia, T-Cell
Inhibitory effect of tannic acid on human immunodeficiency virus promoter activity induced by 12-O-tetra decanoylphorbol-13-acetate in Jurkat T-cells.
Lung Neoplasms
Dysfunction of Poly (ADP-Ribose) Glycohydrolase Induces a Synthetic Lethal Effect in Dual Specificity Phosphatase 22-Deficient Lung Cancer Cells.
Lung Neoplasms
Regulation of Wnt Singaling Pathway by Poly (ADP-Ribose) Glycohydrolase (PARG) Silencing Suppresses Lung Cancer in Mice Induced by Benzo(a)pyrene Inhalation Exposure.
Lung Neoplasms
Silencing of poly(ADP-ribose) glycohydrolase sensitizes lung cancer cells to radiation through the abrogation of DNA damage checkpoint.
Lymphoma, Mantle-Cell
Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle-cell lymphomas.
Melanoma
Poly(ADP-ribose) glycohydrolase inhibitor as chemosensitiser of malignant melanoma for temozolomide.
Neoplasm Metastasis
Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis.
Neoplasms
A macrocircular ellagitannin, oenothein B, suppresses mouse mammary tumor gene expression via inhibition of poly(ADP-ribose) glycohydrolase.
Neoplasms
Aberration of poly(adenosine diphosphate-ribose) metabolism in human colon adenomatous polyps and cancers.
Neoplasms
Decreasing P-selectin and ICAM-1 via activating Akt: a possible mechanism by which PARG inhibits adhesion of mouse colorectal carcinoma CT26 cells to platelets.
Neoplasms
Enhanced DNA accessibility and increased DNA damage induced by the absence of poly(ADP-ribose) hydrolysis.
Neoplasms
Identification of Mitochondrial-Related Prognostic Biomarkers Associated With Primary Bile Acid Biosynthesis and Tumor Microenvironment of Hepatocellular Carcinoma.
Neoplasms
Inhibition of poly(ADP-ribose) glycohydrolase (PARG) specifically kills BRCA2-deficient tumor cells.
Neoplasms
Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase.
Neoplasms
Poly(ADP-ribose) glycohydrolase inhibition sequesters NAD+ to potentiate the metabolic lethality of alkylating chemotherapy in IDH mutant tumor cells.
Neoplasms
Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1.
Neoplasms
Promoter methylation of PARG1, a novel candidate tumor suppressor gene in mantle-cell lymphomas.
Neoplasms
Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality.
Neoplasms
Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death.
Neoplasms
Silencing Poly (ADP-Ribose) Glycohydrolase (PARG) Expression Inhibits Growth of Human Colon Cancer Cells In Vitro via PI3K/Akt/NF?-B Pathway.
Neoplasms
Variations in the mRNA expression of poly(ADP-ribose) polymerases, poly(ADP-ribose) glycohydrolase and ADP-ribosylhydrolase 3 in breast tumors and impact on clinical outcome.
Neurodegenerative Diseases
Bi-allelic ADPRHL2 Mutations Cause Neurodegeneration with Developmental Delay, Ataxia, and Axonal Neuropathy.
Osteosarcoma
Hydrogen peroxide-induced poly(ADP-ribosyl)ation regulates osteogenic differentiation-associated cell death.
Ovarian Neoplasms
DNA Replication Vulnerabilities Render Ovarian Cancer Cells Sensitive to Poly(ADP-Ribose) Glycohydrolase Inhibitors.
Placenta, Retained
Poly(ADP-ribose) glycohydrolase in bovine retained and not retained placenta.
poly(adp-ribose) glycohydrolase deficiency
Poly(ADP-ribose) Glycohydrolase deficiency sensitizes mouse ES cells to DNA damaging agents.
Prostatic Neoplasms
Androgen Receptor and Poly(ADP-ribose) Glycohydrolase Inhibition Increases Efficiency of Androgen Ablation in Prostate Cancer Cells.
Retinitis
Parthanatos-associated proteins are stimulated intraocularly during development of experimental murine cytomegalovirus retinitis in mice with retrovirus-induced immunosuppression.
Seizures
Bi-allelic ADPRHL2 Mutations Cause Neurodegeneration with Developmental Delay, Ataxia, and Axonal Neuropathy.
Seizures
Episodic psychosis, ataxia, motor neuropathy with pyramidal signs (PAMP syndrome) caused by a novel mutation in ADPRHL2 (AHR3).
Spinal Cord Injuries
Poly(ADP-Ribose) Glycohydrolase Activity Mediates Post-Traumatic Inflammatory Reaction after Experimental Spinal Cord Trauma.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00058
(ADP-ribose)n
-
average chain length n = 27, poly(ADP-ribose) glycohydrolase I
0.0011
(ADP-ribose)n
-
average chain length n = 21, poly(ADP-ribose) glycohydrolase I
0.002
(ADP-ribose)n
-
average chain length n = 15, poly(ADP-ribose) glycohydrolase I
0.0031
(ADP-ribose)n
-
average chain length n = 27, poly(ADP-ribose) glycohydrolase II
0.004
(ADP-ribose)n
-
average chain length n = 21, poly(ADP-ribose) glycohydrolase II
0.0045
(ADP-ribose)n
-
average chain length n = 6.7, poly(ADP-ribose) glycohydrolase I
0.0048
(ADP-ribose)n
-
average chain length n = 15, poly(ADP-ribose) glycohydrolase II
0.0066
(ADP-ribose)n
-
average chain length n = 6.7, poly(ADP-ribose) glycohydrolase II
0.00296
Poly(ADP-ribose)
pH 7.5, 37°C, recombinant wild-type enzyme
0.009
Poly(ADP-ribose)
purified recombinant catalytic enzyme domain, in 50 mM KPO4 (pH 7.2), at 37°C
0.00934
Poly(ADP-ribose)
pH 7.5, 37°C, recombinant mutant T267R
0.01114
Poly(ADP-ribose)
pH 7.5, 37°C, recombinant mutant T267K
additional information
additional information
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
additional information
additional information
Michaelis-Menten kinetics
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
266.4
Poly(ADP-ribose)
pH 7.5, 37°C, recombinant wild-type enzyme
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
90000
Poly(ADP-ribose)
pH 7.5, 37°C, recombinant wild-type enzyme
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0045
(3Z)-5-bromo-1-(2,6-dichlorobenzyl)-3-[4-oxo-3-[2-(1H-tetrazol-5-yl)ethyl]-2-thioxo-1,3-thiazolidin-5-ylidene]-1,3-dihydro-2H-indol-2-one
Homo sapiens
-
pH not specified in the publication, 37°C
0.0123
(3Z)-5-chloro-1-(2,6-dichlorobenzyl)-3-[4-oxo-3-[2-(1H-tetrazol-5-yl)ethyl]-2-thioxo-1,3-thiazolidin-5-ylidene]-1,3-dihydro-2H-indol-2-one
Homo sapiens
-
pH not specified in the publication, 37°C
0.1
1,3-dimethyl-2,6-bis(sulfanylidene)octahydro-8H-purin-8-one
Homo sapiens
37°C, pH not specified in the publication
1
1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-2-sulfanylideneoctahydro-6H-purin-6-one
Homo sapiens
37°C, pH not specified in the publication
0.0257
1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-3,4,5,7-tetrahydro-1H-purine-2,6-dione
Homo sapiens
37°C, pH not specified in the publication
0.0004
1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-6-sulfanylidene-1,3,4,5,6,7-hexahydro-2H-purin-2-one
Homo sapiens
37°C, pH not specified in the publication
0.9
1,3-dimethyl-8-[[2-(pyrrolidin-1-yl)ethyl]sulfanyl]-6-sulfanylidene-1,3,4,5,6,7-hexahydro-2H-purin-2-one
Homo sapiens
37°C, pH not specified in the publication
0.000026
1-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
Homo sapiens
pH 7.4, 22°C
0.00004
1-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-N-(1-methylcyclopropyl)-2-oxo-3-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1H-benzimidazole-5-sulfonamide
Homo sapiens
pH 7.4, 22°C
0.072
2-(3-chloro-4-(naphthalen-2-yloxy)phenylcarbamoyl)benzoic acid
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.025
3,5-dichloro-2-hydroxy-N-(3-methyl-4-(naphthalen-2-yloxy)phenyl)benzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.021
3,5-dichloro-2-hydroxy-N-(4-(naphthalen-2-yloxy)-3-(trifluoromethyl)phenyl)benzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.042
3,5-dichloro-2-hydroxy-N-(4-(naphthalen-2-yloxy)phenyl)benzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.14
3,5-dichloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxy-N-methylbenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.012
3,5-dichloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.026
3,5-dichloro-N-(3-chloro-4-(p-tolyloxy)phenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.061
3,5-dichloro-N-(3-chloro-4-phenoxyphenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.261
3,5-dichloro-N-(3-chlorophenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.027
3,5-dichloro-N-(3-fluoro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.5
3,5-dichloro-N-(4-chlorophenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.012
3,5-dichloro-N-[3-chloro-4-(naphthalen-2-yloxy)phenyl]-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.022
3-bromo-5-chloro-N-[5-chloro-2-[(1-chloronaphthalen-2-yl)oxy]phenyl]-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.026
3-bromo-N-[2-[2-bromo-6-methyl-3-(propan-2-yl)phenoxy]-5-chlorophenyl]-5-chloro-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.061
3-chloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.0465
3-[(5Z)-5-[1-(2-chlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Homo sapiens
-
pH not specified in the publication, 37°C
0.0029
3-[(5Z)-5-[5-bromo-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Homo sapiens
-
pH not specified in the publication, 37°C
0.003
3-[(5Z)-5-[5-bromo-1-(2-chloro-6-fluorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Homo sapiens
-
pH not specified in the publication, 37°C
0.0058
3-[(5Z)-5-[5-chloro-1-(2,6-dichlorobenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid
Homo sapiens
-
pH not specified in the publication, 37°C
0.117
5-chloro-N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.0163
8-n-octyl-amino-adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
Homo sapiens
with wild-type enzyme, pH 7.0, 25°C
0.00012
adenosine 5'-diphosphate-(hydroxymethyl)-pyrrolidinediol
Mus musculus
pH and temperature not specified in the publication
0.0001
adenosine diphosphate (hydroxymethyl) pyrrolidinediol
Rattus norvegicus
-
pH 7.5, 37°C
0.00012
ADP-(hydroxymethyl)pyrrolidinediol
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.0031
N'',N'''-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]carbonohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0028
N'',N'''-bis[(E)-(3,4,5-trihydroxyphenyl)methylidene]carbonohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0016
N'1,N'3-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]propanedihydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0154
N'1,N'3-bis[(E)-(3,4,5-trihydroxyphenyl)methylidene]propanedihydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0098
N'1,N'4-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]butanedihydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0082
N'1,N'4-bis[(E)-(3,4,5-trihydroxyphenyl)methylidene]butanedihydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0139
N'1,N'5-bis[(E)-(2,3,4-trihydroxyphenyl)methylidene]pentanedihydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0274
N'1,N'5-bis[(E)-(3,4,5-trihydroxyphenyl)methylidene]pentanedihydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0031
N'1-[(E)-(2,3,4-trihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.001
N'1-[(E)-(2,3,4-trihydroxyphenyl)methylidene]-N'4-[(Z)-(2,3,4-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0148
N'1-[(E)-(2,3-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,3-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0188
N'1-[(E)-(2,4,6-trihydroxyphenyl)methylidene]-N'3-[(Z)-(2,4,6-trihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0099
N'1-[(E)-(2,4,6-trihydroxyphenyl)methylidene]-N'4-[(Z)-(2,4,6-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0401
N'1-[(E)-(2,4-dihydroxyphenyl)methylidene]-N'3-[(Z)-(2,4-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0032
N'1-[(E)-(3,4,5-trihydroxyphenyl)methylidene]-N'3-[(Z)-(3,4,5-trihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0021
N'1-[(E)-(3,4,5-trihydroxyphenyl)methylidene]-N'4-[(Z)-(3,4,5-trihydroxyphenyl)methylidene]benzene-1,4-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.0192
N'1-[(E)-(3,4-dihydroxyphenyl)methylidene]-N'3-[(Z)-(3,4-dihydroxyphenyl)methylidene]benzene-1,3-dicarbohydrazide
Rattus norvegicus
-
pH 7.5, 37°C
0.5
N-(3-chloro-4-(naphthalen-2-yloxy)phenyl)-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.06
N-tert-butyl-9,10-dioxo-9,10-dihydroanthracene-2-sulfonamide
Homo sapiens
pH 7.4, 22°C
0.08
N-[4-[(3-bromonaphthalen-2-yl)oxy]-3-chlorophenyl]-3,5-dichloro-2-hydroxybenzamide
Homo sapiens
-
in 150 mM potassium phosphate buffer, pH 7.5, 150 mM KCl, 0.3 mg/ml bovine serum albumin, and 30 mM 2-mercaptoethanol, at 37°C
0.0000026
PDD00017273
Homo sapiens
pH and temperature not specified in the publication
0.0011
adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
Homo sapiens
with mutant enzyme K616A/Q617A/K618A/E688A/K689A/K690A, pH 7.0, 25°C
0.0031
adenosine 5'-diphosphate (hydroxymethyl)pyrrolidinediol
Homo sapiens
with wild-type enzyme, pH 7.0, 25°C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00102
-
full length enzyme PARG111, pH and temperature not specified in the publication
additional information
protocol for detection of PARG activity in solution and on dot blot
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
7.5
-
activity is less in Tris-HCl buffer than in sodium phosphate buffer or N-2-hydroxyethylpiperazine-N-ethanesulfonic acid-NaOH buffer
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8
6 - 8.5
-
pH 6.0: about 50% of maximal activity, pH 8.5: about 35% of maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 50
-
30°C: about 25% of maximal activity, 55°C: about 50% of maximal activity, no activity at 60°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isoforms PME-3, expression throughout the life cycle
SwissProt
brenda
isoforms PME-4, expression throughout the life cycle
SwissProt
brenda
-
UniProt
brenda
identification of enzyme-interacting proteins by mass spectometric analysis of enzyme pulled down proteins
-
-
brenda
recombinant protein with GFP- or Myc-tag, subcellular distribution of enzmye changes dramatically during cell cycle
-
-
brenda
splicing variants hPARG60 and hPARG55. HPARG55 is expressed through alternative translation initiation from hPARG60 transcripts
-
-
brenda
two splice variants of enzyme mRNA leading to isoforms of 102 kDa, hPARG102, and of 99 kDA, hPARG99, in addition to full-length protein hPARG111
UniProt
brenda
hypomorphic mouse model in which exons 2 and 3 of PARG gene have been deleted
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
the enzyme is expressed in a life stage-dependant manner
brenda
-
differentiating rat germinal cell, presence of both enzyme isoforms of 60 kDa and 110 kDa
brenda
-
primary culture, highest ratio of nuclear to cytoplasmic enzyme activity
brenda
variant of the cell line HCT-116, exhibits resistance to the PARG inhibitor PDD00017273. HCT-116R-PDD cells contain PARG mutation Glu352Gln and PARP1 mutation Lys134Asn
brenda
predominant expression in nerve cells of head and tail
brenda
predominant expression in nerve cells of head and tail
brenda
predominant expression in nerve cells of head and tail
brenda
additional information
-
primary culture of astrocytes, neurons, and C6 glioma cells, no overall differences in enzyme activity between these cell types
brenda
-
primary culture, lowest ratio of nuclear to cytoplasmic enzyme activity
brenda
additional information
PARG1 is induced primarily in mitotically active cells
brenda
additional information
-
PARG1 is induced primarily in mitotically active cells
-
brenda
additional information
tomato seedlings of non-resistant Money-maker cultivar plants are inoculated with wild-type and DELTAparg mutant
brenda
additional information
-
tomato seedlings of non-resistant Money-maker cultivar plants are inoculated with wild-type and DELTAparg mutant
-
brenda
additional information
-
tomato seedlings of non-resistant Money-maker cultivar plants are inoculated with wild-type and DELTAparg mutant
-
brenda
additional information
-
tomato seedlings of non-resistant Money-maker cultivar plants are inoculated with wild-type and DELTAparg mutant
-
brenda
additional information
-
tomato seedlings of non-resistant Money-maker cultivar plants are inoculated with wild-type and DELTAparg mutant
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
GFP-fusion protein of enzyme, and its 74 kDA and 85 kDa apoptotic fragments
brenda
additional information
-
GFP-fusion protein of enzyme, and its 74 kDA and 85 kDa apoptotic fragments
brenda
isoforms hPARG102, hPARG99, which account for most of enzyme activity in the absence and presence of genotoxic stress
brenda
-
relocalization of 110 kDa isoform in response to DNA damage
brenda
-
and mitochondrion, predominant localization of isoform hPARG60
brenda
-
in response to DNA damage induced by gamma-irradiation, the cytoplasmic 103 kDa enzyme isoform translocates into the nucleus and nuclear green fluorescent protein-hPAREG110 enzyme relocalizes to the cytoplasm
brenda
-
isoform hPARG55, strictly targeted to mitochondria. Isoform hPARG may be capable of shuttling between nucleus and mitochondria
brenda
-
PARG59 expression constructs with amino acids encoded by exon 4 at the N-terminus are targeted to the mitochondrial matrix
brenda
-
in response to DNA damage induced by gamma-irradiation translocation of 103 kDA isoform
brenda
-
induction of redistribution of enzyme and its 74 kDA and 85 kDa apoptotic fragments from cytoplasm to nucleus by leptomycin B
brenda
isoform hPARG111, due to nuclear targeting signal in exon 1
brenda
reduction of nuclear enzyme activity to 30-40% of control by treatment with 12-O-tetradecanoyl-phorbol-13-acetate, cytosolic activity remains unchanged. Reduction is suppressed by protein kinase C inhibitor H7
brenda
-
isoform hPARG may be capable of shuttling between nucleus and mitochondria
brenda
-
in response to DNA damage induced by gamma-irradiation, the cytoplasmic 103 kDa enzyme isoform translocates into the nucleus and nuclear green fluorescent protein-hPAREG110 enzyme relocalizes to the cytoplasm
brenda
-
of primary spermatocyte, mainly presence and activity of 110 kDa isoform
brenda
the enzyme is localized in the nucleus independently of the presence of DNA damage or cell cycle stage
brenda
additional information
contains a putative bipartite nuclear location signal
-
brenda
additional information
-
contains a putative bipartite nuclear location signal
-
brenda
additional information
-
dynamic distribution between cytoplasm and nucleoplasm and high mobility of major enzyme isoforms
-
brenda
additional information
-
dynamic distribution between cytoplasm and nucleoplasm and high mobility of major enzyme isoforms
-
brenda
additional information
-
enzyme is resident in fragile-x mental retardation protein-associated messenger ribonucleoparticle complexes, which are part of the translation machinery
-
brenda
additional information
-
the major enzyme isoforms exhibit a dynamic distribution between nucleoplasm and cytoplasm and a high mobility
-
brenda
additional information
-
in round spermatids, high level of 60 kDa isoform in post-nuclear fraction
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
canonical poly(ADP-ribose) glycohydrolase is a highly conserved protein found in organisms ranging from protozoa to humans, phylogenetic analysis. The full-length enzyme from Tetrahymena thermophila is highly similar to the minimal catalytic region of thhe human enzyme, but it lacks the obvious RS/MTS motif
evolution
conservation of key residues involved in the catalytic process
evolution
conservation of overall fold amongst mammalian enzyme glycohydrolase domains, additional flexible regions in the catalytic site, overview
evolution
function and domain architecture of human ADP-ribosylation removing enzymes, overview. The key poly(ADP-ribose) (PAR) processing enzyme, PARG, emerged only recently
evolution
full-length ARH3 (ARH3FL) adopts a compact all-alpha-helical fold with a central deep ADPR-binding cleft, a signature of the ARH3 superfamily
malfunction
-
osmotic (mannitol treatment) or oxidative (methyl viologen treatment) stress reduces germination rates of the mutant parg1-3 seeds compared with wild type seeds. The parg1-3 plants show reduced tolerance to drought (withholding water), osmotic, and oxidative stress, as well as increased levels of cell damage under osmotic and oxidative stress and reduced survival under drought stress when compared with the wild type plants. Stomata of the parg1-3 plants fail to close under drought stress conditions
malfunction
benzo(a)pyrene induces the cell cycle in enzyme-suppressed shPARG cells, phenotype, overview
malfunction
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poly(ADP-ribose) glycohydrolase loss-of-function causes increased Hrp38 poly(ADP-ribosyl)ation and also results in the rough-eye phenotype with disrupted ommatidial lattice and and bristles and reduced number of photoreceptor cells. Hrp38 is essential for fly eye development. Parg mutant eye clones have decreased expression level of DE-cadherin with orientation defects, which is reminiscent of DE-cadherin mutant eye phenotype. The Parg mutant eye accumulates a large amount of poly(ADP-ribose)
malfunction
-
RNAi knockdown of PARG or pretreatment with 2-((R)-2-methylpyrrolidin-2-yl)-1H-benzimidazole-4-carboxamide (ABT-888), meaning an increase in poly(ADP-ribose) level, lead to increased HeLa cell death in N-methyl-N'-nitro-N-nitrosoguanidine-treated HeLa cells. The effect can be reduced by PARP-1 inhibitors. Combination of poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase inhibition in chemotherapy does not produce increased HeLa cell death
malfunction
-
knockout mutants of isozyme PARG110 show resistance to photoreceptor degeneration, the mutant retina is morphologically and functionally undistinguishable from wild-type. Absence of PARG110 disrupts the poly-ADP-ribose polymerase activation
malfunction
-
silencing of endogenous enzyme expression causes inhibition of TGFbeta-mediated transcription. This can be relieved after simultaneous depletion of poly(ADP-ribose) polymerase 1
malfunction
lack of poly(ADPribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process
malfunction
enzyme deficiency leads to cell death whilst enzyme depletion causes sensitisation to certain DNA damaging agents
malfunction
-
genetic disruption of the enzyme leads to increased level of cell death by accumulation of poly(ADP-ribose)
malfunction
a deficiency in PARG glycohydrolase activity prolongs DNA damage foci, containing PAR, and similarly delays DNA repair, causing hypersensitivity to DNA damaging agents and selective killing of repair-deficient tumors such as BRCA mutated breast cancers-deficient cancer cells in a manner similar to PARP inhibition
malfunction
poly(ADP-ribosyl) glycohydrolase (PARG) depletion affects cell proliferation and DNA synthesis, leading to replication-coupled H2AX phosphorylation. PARG depletion or inhibition per se slows down individual replication forks similarly to mild chemotherapeutic treatment. Electron microscopic analysis of replication intermediates reveals marked accumulation of reversed forks and single-stranded DNA (ssDNA) gaps in unperturbed PARG-defective cells. PARG-defective cells display both ataxia-telangiectasia-mutated (ATM) and ataxia-Rad3-related (ATR) activation, as well as chromatin recruitment of standard double-strand-break-repair factors, such as 53BP1 and RAD51, but no physical evidence for chromosomal breakage. PARG-deficient cell phenotype, detailed overview. PARG depletion results in slow replication fork progression even in the absence of genotoxic treatments. PARG downregulation and inhibition lead to similar phenotypic consequences
malfunction
the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
malfunction
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
malfunction
poly(ADP-ribose) glycohydrolase (PARG) silencing suppresses benzo(a)pyrene induced cell transformation. Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant and known carcinogen, which can induce malignant transformation in cells. PARG silencing dramatically reduces DNA damages, chromosome abnormalities, and micronuclei formations in the PARG-deficient human bronchial epithelial cells compared to the control 16HBE cells. PARG silencing down-regulates cell colony formation induced by BaP, reduces BaP-induced genomic instability, and protects cells from BaP-induced DNA damage
malfunction
mutation of PARG1 results in increased DNA damage level and enhanced cell death in plants after bleomycin treatment. Inhibition or silencing of PARPs improves abiotic stress tolerance, enhancing resistance to drought, high light, heat and oxidative stresses, and perturbs innate immune responses to microbe-associated molecular patterns such as flg22 and elf18, resulting in a compromised basal defense response. Phenotypic comparison of the loss-of-function mutants of all PARP and PARG genes in Arabidopsis thaliana, overview. Loss-of-PARG1 leads to the transcriptional up-regulation of DNA repair genes and increase of cellular DNA damage level. The parg1 mutants show only yellow instead of green seedlings with reduced fresh weight compared to wild-type. The parg1-4 mutant root is more sensitive to bleomycin than that of wild-type Col-0
malfunction
PARG inhibition increases endogenous DNA damage, stalls replication forks and increases homologous recombination, and the lack of homologous recombination (HR) proteins at PARG inhibitor-induced stalled replication forks induces cell death. siRNA screen for increased DNA damage with PARG depletion. Model whereby inhibition or depletion of PARG leads to fork stalling and fork aberrations, resulting in signalling and recruitment of HRR proteins for repair. Therefore in the absence of these homologous recombination repair (HRR) proteins, PARG depleted or inhibited cells cannot survive
malfunction
demodification of PARylated PARP1 is more efficient with the DELTA17, F36A, F61S, and F36A/F61S mutations but is ablated by the H24W mutation
malfunction
mutants that possess a wider active site show better accommodation of protein-conjugated ADP-ribose, rational mutant design, overview
malfunction
-
overexpression of a catalytically inactive NUDT16 mutant is unable to rescue decreased CtIP protein and impaired CtIP recruitment to double-strand breaks (DSBs). CtIP mutants 324A/S326A/S327A and S313A/K314A/E319A/E320A show greatly diminished presence of PAR chains suggesting that these residues are ADP-ribosylation sites of CtIP
malfunction
-
mutation of PARG1 results in increased DNA damage level and enhanced cell death in plants after bleomycin treatment. Inhibition or silencing of PARPs improves abiotic stress tolerance, enhancing resistance to drought, high light, heat and oxidative stresses, and perturbs innate immune responses to microbe-associated molecular patterns such as flg22 and elf18, resulting in a compromised basal defense response. Phenotypic comparison of the loss-of-function mutants of all PARP and PARG genes in Arabidopsis thaliana, overview. Loss-of-PARG1 leads to the transcriptional up-regulation of DNA repair genes and increase of cellular DNA damage level. The parg1 mutants show only yellow instead of green seedlings with reduced fresh weight compared to wild-type. The parg1-4 mutant root is more sensitive to bleomycin than that of wild-type Col-0
-
malfunction
-
the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
-
malfunction
-
the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
-
malfunction
-
the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
-
malfunction
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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metabolism
-
isozyme PARG110 and poly-ADP-ribose polymerase-1 act in a positive feedback loop, which is especially active under pathologic conditions
metabolism
-
poly(ADP-ribose) glycohydrolase partly controls the turnover of dynamic protein ADP-ribosylation mediated by poly(ADP-ribose) polymerase 1, PARP-1. Poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains from target proteins of PARP-1. Endogenous PARP-1 and the enzyme have opposing roles on TGFbeta-induced gene expression, overview
metabolism
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molecular mechanism(s) connecting poly(ADP-ribosyl)ation with DNA methylation, giving a possible explanation as to how DNA methylation modulates by poly(ADP-ribosyl)ation as the posttranslational modification. DNA methyltransferases also interact with poly(ADP-D-ribose)
metabolism
poly(ADP-ribosyl)ation is a reversible post-translational modification of proteins, characterized by the addition of poly(ADP-ribose) (PAR) to proteins by poly(ADP-ribose) polymerase (PARP), and removal of PAR by poly(ADP-ribose) glycohydrolase (PARG). Three PARPs and two PARGs have been found in Arabidopsis thaliana. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions
metabolism
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poly(ADP-ribosyl)ation is a reversible post-translational modification of proteins, characterized by the addition of poly(ADP-ribose) (PAR) to proteins by poly(ADP-ribose) polymerase (PARP), and removal of PAR by poly(ADP-ribose) glycohydrolase (PARG). Three PARPs and two PARGs have been found in Arabidopsis thaliana. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions
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physiological function
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generation of A549 lung adenocarcinoma cell lines with stably suppressed PARG and poly(ADP-ribose) polymerase PARP-1 expression, i.e. shPARG and shPARP1 cell lines, respectively. shPARG cells accumulate large amounts of poly-(ADP-ribosyl)ated proteins and exhibit reduced PARP activation. Hydrogen peroxide-induced cell death is regulated by PARG in a dual fashion. Whereas the shPARG cell line is resistant to the necrotic effect of high concentrations of hydrogen peroxide, these cells exhibit stronger apoptotic response. Both shPARP1 and especially shPARG cells display a delayed repair of DNA breaks and exhibit reduced clonogenic survival following hydrogen peroxide treatment. Translocation of apoptosis-inducing factor cannot be observed, but cells can be saved by methyl pyruvate and alpha-ketoglutarate
physiological function
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stable knock-down of poly(ADP-ribose) polymerase PARP-1 and PARG. The majority of genes affected by the knockdown of one factor are similarly affected by the knockdown of the other factor. The most robustly regulated common genes are enriched for stress-response and metabolic functions. PARP-1 and PARG localize to the promoters of positively and negatively regulated target genes. The levels of chromatin-bound PARG at a given promoter generally correlate with the levels of PARP-1 across the subset of promoters tested. For about half of the genes tested, the binding of PARP-1 at the promoter is dependent on the binding of PARG. PARP-1 and PARG enzymatic activities are required for some, but not all, target genes
physiological function
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homozygous T-DNA knockout line parg1 seedlings exhibit exaggerated seedling growth inhibition and pigment accumulation in response to elf18 and are hypersensitive to the DNA-damaging agent mitomycin C. Both parg1 and parg2 knockout plants show accelerated onset of disease symptoms when infected with Botrytis cinerea. Cellular levels of ADP-ribose polymer increase after infection with avirulent Pseudomonas syringae pv tomato DC3000 avrRpt2+, and pathogen-dependent changes in the poly(ADP-ribosyl)ation of discrete proteins are also observed
physiological function
-
coordinate regulation of PARP-1 and -2 and PARG is required for cellular responses to genotoxic stress
physiological function
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poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death. Transient receptor potential 2 is the primary Ca2+ channel for cell death signaling under poly(ADP-ribose)glycohydrolase control
physiological function
-
at higher levels of DNA damage, the coordinate activities of PARPs-1/2 and PARG can rapidly deplete the pool of cellular NAD(H), facilitating the release of mitochondrial proteins through signaling pathways that promote cell death
physiological function
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Arabidopsis poly(ADP-ribose) glycohydrolase 1 is required for drought, osmotic and oxidative stress responses
physiological function
poly(ADP-ribosyl)ation is a crucial regulator of cell fate in response to genotoxic stress, poly(ADP-ribose) degradation is carried out mainly by poly(ADP-ribose) glycohydrolase, role of poly(ADP-ribose) glycohydrolase in the regulation of cell fate in response to benzo(a)pyrene, overview
physiological function
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the enzyme activity regulates cellular poly(ADP-ribose) level. Since the enzyme cannot cleave the terminal ADP-ribose unit at the protein bound to glutamate residues, the residual activities of MacroD2 and TARG1 may contribute to the accumulation of poly(ADP-D-ribose)in the Parg knockout animals
physiological function
poly(ADP-ribose) glycohydrolase catalyzes the removal of poly(ADP-ribose) chains from posttranslationally modified proteins by hydrolysis of alpha(122-22) O-glycosidic linkages, functioning as an endo-glycosidase to release oligo(ADP-ribose) and as an exo-glycosidase to release ADP-ribose
physiological function
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causal involvement of wild-type isozyme PARG110 in the process of photoreceptor degeneration. Contrasting its anticipated role as a functional antagonist, absence of PARG110 correlated with low PARP activity, suggesting that PARG110 and PARP1 act in a positive feedback loop, which is especially active under pathologic conditions
physiological function
the reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) glycohydrolase, which specifically targets the unique PAR (1''-2') ribose-ribose bonds
physiological function
protein poly(ADP-ribosyl)ation regulates a number of important cellular processes. Poly(ADP-ribose) glycohydrolase is the primary enzyme responsible for hydrolyzing the poly(ADP-ribose) polymer in vivo
physiological function
poly(ADP-ribose) glycohydrolase (PARG) represents the main poly(ADP-D-ribose) hydrolyzing activity in the cell to ADP-ribose units. The enzyme is crucial for Trypanosoma cruzi infection cycle in the human host cell. Both, Trypanosoma cruzi and the human host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi
physiological function
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by regulating the hydrolytic arm of poly(ADP-ribosyl)ation, the enzyme participates in a number of biological processes, including the repair of DNA damage, chromatin dynamics, transcriptional regulation, and cell death. Role of silencing of the enzyme in DNA methylation pattern changed by benzo(a)pyrene, a carcinogen cytotoxic which can trigger extensive cellular responses
physiological function
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the enzyme is responsible for the degradation of poly(ADP-ribose) (PAR) polymers
physiological function
poly(ADP-ribosyl)ation is a common post-translational modification that mediates a wide variety of cellular processes including DNA damage repair, chromatin regulation, transcription, and apoptosis, involving interactions of PAR with poly(ADP-ribose) glycohydrolase (PARG) and other binding proteins
physiological function
the poly(ADP-ribose) glycohydrolase (PARG) endo-glycohydrolase activity may become significant in vivo at high PAR/PARG ratios (for example, in the case of an extreme cellular insult), thus releasing free PAR fragments to mediate apoptotic signaling
physiological function
the PAR posttranslational modification by itself is a high affinity ligand for XRCC1, requiring a minimum chain length of 7 ADP-ribose units in the oligo(ADP-ribose) ligand for a stable interaction with XRCC1. This discrete binding interface enables the poly(ADP-ribose) (PAR) glycohydrolase (PARG) to completely disassemble the PARP1-XRCC1 complex without assistance from a mono(ADP-ribose) glycohydrolase. XRCC1 and other PAR-binding proteins mediate many of the downstream responses to PARP1 activation in the face of DNA damage. PARG rapidly reverses the PARylation of PARP1 and efficiently disassembles the PARP1-XRCC1 complex, thereby uncoupling the DNA repair scaffolding activities of XRCC1 from PARP1, which is targeted for proteasomal degradation after recruiting XRCC1 to sites of DNA damage. Ability of PARG to regulate the PARP1-XRCC1 interaction by converting PARylated PARP1 into MARylated PARP1, which retains a terminal ADP-ribose modification but does not bind to XRCC1
physiological function
a single poly(ADP-ribosyl) glycohydrolase (PARG) mediates PAR degradation. PARG prevents the accumulation of unusual replication structures during unperturbed S phase. Role of PARG in the replication of human chromosomes. PAR degradation is essential to promote resumption of replication at endogenous and e-exogenous lesions, preventing idle recruitment of repair factors to remodeled replication forks
physiological function
degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
physiological function
enzyme ARH3 is a multifunctional enzyme that also hydrolyzes poly(ADP-ribose) (PAR). ARH3 can specifically hydrolyze PAR, mono-ADP-ribose post-translational modifications (MARPTMs), and O-acetyl-ADP-ribose. For all these substrates, ARH3 preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADPR. In mammals, two enzymes, ADP-ribosyl-acceptor hydrolase 3 (ARH3 or ADPRHL2) and PAR glycohydrolase (PARG), function in tandem to reverse PARylation. These hydrolytic enzymes commonly cleave the alpha(1''-2') O-glycosidic linkages in PAR chains. ARH3 appears to catalyze primarily exocytic cleavage of PAR, generating free ADPR. It is reported that ARH3 protects cells from oxidative stress-induced parthanatos by lowering the cytoplasmic PAR level. ARH3 is a distinctive, multitasking enzyme that controls two biologically important NAD+-dependent cellular signaling pathways
physiological function
enzyme ARH3 is a multifunctional enzyme that also hydrolyzes poly(ADP-ribose) (ADPR). Enzyme ARH3 plays a role in DNA damage repair. The recruitment of ARH3 to DNA lesions is mediated by ADPR recognition. The catalytic mechanism of protein ADP-ribose hydrolases can be classified into two different groups, namely metal-dependent and metal-independent catalysis. ARHs, such as ARH3, belong to metal-dependent catalysis, utilizing two Mg2+ ions and acidic residues to complete the catalytic reaction, which might be highly conserved. In contrast, the catalytic mechanism is not conserved in the macrodomain ADP-ribose hydrolases, For example, Glu756 and a water molecule act together to catalyze the reaction in PARG, whereas the key catalytic factor in MacroD2 is an activated water. The charge characteristic of the binding pocket in ARH3 is remarkably distinguished from that in PARG. The binding pocket of PARG, accommodating the ADPR dimer, is mostly composed of the basic region
physiological function
poly(ADPribose) glycohydrolase (PARG) is the primary enzyme that catalyzes the degradation of poly (ADP-ribose) (PAR), it plays an important role in regulating DNA damage repair and maintaining genomic stability
physiological function
PARG1 has poly(ADP-ribose) (PAR)-degrading activity and regulates poly(ADP-ribose) level in vivo. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions. PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 antagonistically modulates the DNA repair process by preventing the over-induction of DNA repair genes. PARG1 plays a critical role in this process. Roles of PARP1 and PARP2 in DNA damage signaling. Induction of PARG1 gene is ATM- and ATR-dependent and PARG1 represses the transcriptional upregulation of ATM, ATR and SOG1. ATM and ATR are two critical kinases which transduce double and single strand break signals to DNA repair machinery, respectively. They phosphorylate the transcription factor SOG1, which then induces the expression of DNA repair genes
physiological function
the enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). Critical to this repair process is the orderly degradation of PAR chains. The roles of PARG and poly(ADP-ribose) polymerase (PARP) are closely intertwined
physiological function
poly(ADP-ribosyl)ation (PARylation) is a transient posttranslational modification that generates a signaling mechanism with diverse roles within molecular and cellular processes. PAR chains remaining from DNA repair are broken down by the enzyme poly(ADP-ribose) glycohydrolase (PARG). PARG catalyzes the hydrolysis of endo- and exoglycosidic bonds within the poly(ADP-ribose) (PAR) polymers
physiological function
poly(ADP-ribosylation) of proteins follows DNA damage. Like addition of poly(ADP-ribose) (PAR) by poly(ADP-ribose) polymerase (PARP), removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for con-tinued replication at perturbed forks. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleaveglycosidic bonds, rapidly reversing the action of PARP enzymes. The functions of PARP and PARG may not be completely identical
physiological function
active breakpoint cluster region-related (Abr) protein interacts with poly(ADP-ribose) glycohydrolase (PARG) and Rho GTPases. Abr modulates osteoclastogenesis by enhancing lamellipodia formation via its interaction with PARG
physiological function
inhibition of PARG induces poly(ADP-ribose)accumulation and gammaH2AX foci in nuclei, sensitizes cells to radiation-induced DNA damage, suppresses replication fork progression and impedes cancer cell survival. In PARP inhibitor-resistant A172 glioblastoma cells
physiological function
dual specificity phosphatase 22 (DUSP22) is a synthetic lethal gene related to PARG dysfunction. In the absence of DNA damage, dual depletion of PARG and DUSP22 in HeLa and lung cancer A-549 cells reduces survival compared with single-knockdown counterparts, increases the apoptotic sub-G1 fraction and upregulates PUMA, and inhibits the PI3K/AKT/mTOR pathway in A-549 cells
physiological function
PARG-1 is the main PAR glycohydrolase in the germ line, its loading during meiotic prophase I requires HTP-3. PARG-1 influences processing of recombination intermediates and augments the formation of meiotic double-strand breaks. PARG-1 and HIM-5 modulate crossover numbers and PARG-1 shapes the recombination landscape without requiring its catalytic activity
physiological function
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NUDT16 regulates CtIP PARylation to dictate homologous recombination repair. CtIP initiates DNA end resection and mediates homologous recombination (HR) repair. The hydrolase activity of NUDT16 plays a major role in controlling CtIP protein levels. ADP-ribosylation of CtIP is required for its interaction with NUDT16, its localization at double-strand breaks (DSBs), and for homologous recombinantion (HR) repair. NUDT16 can also be ADP-ribosylated. NUDT16 can remove the PAR chains from CtIP. Posttranslational modification of CtIP by ADP-ribosylation is targeted by a PAR-binding E3 ubiquitin ligase, RNF146, leading to CtIP ubiquitination and degradation. NUDT16 cleaves the ADP-ribosylation of 53BP1, which inhibits 53BP1 ubiquitination and degradation, and stabilizes 53BP1 protein
physiological function
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PARG1 has poly(ADP-ribose) (PAR)-degrading activity and regulates poly(ADP-ribose) level in vivo. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions. PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 antagonistically modulates the DNA repair process by preventing the over-induction of DNA repair genes. PARG1 plays a critical role in this process. Roles of PARP1 and PARP2 in DNA damage signaling. Induction of PARG1 gene is ATM- and ATR-dependent and PARG1 represses the transcriptional upregulation of ATM, ATR and SOG1. ATM and ATR are two critical kinases which transduce double and single strand break signals to DNA repair machinery, respectively. They phosphorylate the transcription factor SOG1, which then induces the expression of DNA repair genes
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physiological function
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degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
-
degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
-
degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
-
degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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additional information
enzyme structure-function relationship, computational analysis based on the crystal structure, PDB ID 3SIG, modelling of active site structure and SN2 mechanism catalytic mechanism, overview. The oxocarbenium expected by Dea Slade is a possible transition state but not an intermediate.
additional information
structure analysis and comparisons, overview. The poorly structured A-domain does not contribute to PARG activity in vitro. The rPARG385 catalytic domain adopts a beanshaped structure with a deep central cleft containing the conserved PARG-signature motif (GGG-X6-8-QEE)10 and Tyr791 that contributes strongly to PARG catalytic efficiency and inhibitor binding. The active site cleft lies on one edge of the beta-sheet and an extended N-terminal segment containing the MTS wraps around the other edge of the beta-sheet, contributing to the PARG catalytic domain
additional information
E748 and E749 are the key catalytic residues in the signature loop, N733 directly recognizes the 3'-OH on the proximal ribose, catalytic domain structure in apo- and liganded-states, overview. The N-terminal flexible peptide preceding the enzyme's catalytic domain may regulate the enzymatic activity, catalytic and regulatory mechanisms, overview. A binding site outside of the catalytic cleft for iso-ADP-ribose, which is probably the smallest enzyme subtrate containing the alpha(1->2) ribose-ribose glycosidic bond, may explain the processivity of the enzyme activity
additional information
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E748 and E749 are the key catalytic residues in the signature loop, N733 directly recognizes the 3'-OH on the proximal ribose, catalytic domain structure in apo- and liganded-states, overview. The N-terminal flexible peptide preceding the enzyme's catalytic domain may regulate the enzymatic activity, catalytic and regulatory mechanisms, overview. A binding site outside of the catalytic cleft for iso-ADP-ribose, which is probably the smallest enzyme subtrate containing the alpha(1->2) ribose-ribose glycosidic bond, may explain the processivity of the enzyme activity
additional information
structure-based mechanism for the reported endo- and exo-glycohydrolase activities in human enzyme, overview
additional information
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structure-based mechanism for the reported endo- and exo-glycohydrolase activities in human enzyme, overview
additional information
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the Glu752 residue plays an important role in the enzyme's catalytic activity by functioning as a general acid or base to protonate the 2'-OH of the ribose of the leaving group, and subsequently activating a water molecule for nucleophilic attack
additional information
quantitative, real-time assay of PAR-dependent protein-protein interactions and PAR turnover by PARG is an excellent tool for high-throughput screening to identify pharmacological modulators of PAR metabolism that
additional information
proposed catalytic role of residue Asp314. Asp314 is located proximal to the 1''-O-linkage in substrates. Asp314 might protonate the leaving group (general acid), forming an oxocarbenium ion intermediate, and then activate the water (general base) for back-side attack. The W1 ligand of MgB can serve as the nucleophile attacking the anomeric C1'' of the ribose''. This is consistent with the observed O18 incorporation during hydrolysis of O-acetyl-ADP-ribose, reaction mechanism, overview. Asp314 is essential for the formation of the binuclear metal center. A conformational switch of ARH3 enables specific substrate recognition. ARH3 specifically exposes the scissile 1''-O-linkage in substrates for cleavage
additional information
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proposed catalytic role of residue Asp314. Asp314 is located proximal to the 1''-O-linkage in substrates. Asp314 might protonate the leaving group (general acid), forming an oxocarbenium ion intermediate, and then activate the water (general base) for back-side attack. The W1 ligand of MgB can serve as the nucleophile attacking the anomeric C1'' of the ribose''. This is consistent with the observed O18 incorporation during hydrolysis of O-acetyl-ADP-ribose, reaction mechanism, overview. Asp314 is essential for the formation of the binuclear metal center. A conformational switch of ARH3 enables specific substrate recognition. ARH3 specifically exposes the scissile 1''-O-linkage in substrates for cleavage
additional information
analysis of the catalytic site structure of ARH3, overview
additional information
CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
additional information
identification of the active site for binding and processing free and protein-conjugated ADP-ribose into phosphoribose forms, structure analysis and modelling, overview. Structural determinants of ADP-ribose recognition by HsNudT16 are buried in the core of the enzyme. The 2'-OH terminus of dimeric ADPr binds towards the edge of the Nudix fold of HsNudT16
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
-
CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
-
CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
additional information
-
CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
-
Show AA Sequence and Transmembrane Helices (6654 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
138000
x * 91256, calculated for His-tagged protein, x * 138000, SDS-PAGE of His-tagged protein, enzyme behaves abnormally in SDS-PAGE
39000
59000
91256
x * 91256, calculated for His-tagged protein, x * 138000, SDS-PAGE of His-tagged protein, enzyme behaves abnormally in SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
x * 91256, calculated for His-tagged protein, x * 138000, SDS-PAGE of His-tagged protein, enzyme behaves abnormally in SDS-PAGE
additional information
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enzyme N-terminal sequence is important for moduling enzyme nucleocytoplasmic trafficking properties
additional information
two splice variants of enzyme mRNA leading to isoforms of 102 kDa, hPARG102, and of 99 kDA, hPARG99, in addition to full-length protein hPARG111
additional information
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two splice variants of enzyme mRNA leading to isoforms of 102 kDa, hPARG102, and of 99 kDA, hPARG99, in addition to full-length protein hPARG111
additional information
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identification of enzyme-interacting proteins by mass spectrometric analysis of enzyme pulled down proteins
additional information
the catalytic domain of poly(ADP-ribose) glycohydrolase interacts with the automodification domain of poly(ADP-ribose) polymerase. Poly(ADP-ribose) glycohydrolase also interacts with DNA repair factor XRCC1
additional information
human as well as other vertebrate PARGs are composed of three domains: two of these domains, namely macrodomain and the PARG accessory domain, make up the minimal PARG catalytic region, while the third domain, which shows significantly less sequence conservation, is the putative PARG regulatory region. The latter regulatory domain is absent in PARGs of the majority of eukaryotes, and it is not important for PAR hydrolysis in vitro
additional information
determination and analysis of the quarternary structures of wild-type and mutant enzymes, overview
additional information
structure analysis and comparisons, overview. The enzyme comprises an N-terminal regulatory and targeting domain (A-domain; residues 1-456), a central mitochondrial targeting sequence (MTS, residues 457-472), and a C-terminal catalytic domain (residues 473-972). The rPARG385 catalytic domain adopts a beanshaped structure with a deep central cleft containing the conserved PARG-signature motif (GGG-X6-8-QEE)10 and Tyr791 that contributes strongly to PARG catalytic efficiency and inhibitor binding. The structure consists of a alpha-beta-alpha fold with a nine-stranded, mixed beta-sheet flanked by several layers of alpha-helices
additional information
the enzyme structure consists of a macrodomain sandwiched between a large N-terminal accessory domain and a smaller carboxy-terminal extension, structure overview
additional information
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the enzyme structure consists of a macrodomain sandwiched between a large N-terminal accessory domain and a smaller carboxy-terminal extension, structure overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acylation
PARG is O-GlcNAcylated at Ser26. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen
proteolytic modification
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PARG59 expression constructs with amino acids encoded by exon 4 at the N-terminus are targeted to the mitochondria. Deletion and missense mutants allow identification of a canonical N-terminal mitochondrial targeting sequence consisting of the first 16 amino acids encoded by PARG exon 4. Sub-mitochondrial localization experiments indicate that this mitochondrial PARG isoform is targeted to the mitochondrial matrix
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallization of ADP-ribose bound wild-type enzyme and mutant enzymes T267K and T267R, X-ray diffraction structure determination and analysis at 1.97 A resolution, monoclinic crystals with space group P21
purified ARH3-ADPR substrate complex, sitting drop vapour diffusion method, ARH3 and ADPR are mixed in the molar ratio of 1:3, mixing of equal volumes of 11 mg/ml protein complex in 10 mM Tris-HCl, pH 8.0, and 100 mM NaCl with reservoir solution consisting of 0.1 M MES, pH 6.0, and 20% w/v PEG MME 2000, addition of 0.2 M non-detergent sulfobetaine NDSB-201, 20°C, X-ray diffraction structure determination and analysis at 1.58 A resolution, molecular replacement using the structure of apo-ARH3 (PDB ID 2FOZ) as the search model, modeling
purified enzyme in complex with ADP-ribose dimer, X-ray diffraction structure determination and analysis at 1.9 A resolution
purified recombinant full-length ARH3 wild-type enzyme and D314E mutant in complex with ADP-ribose and Mg2+, hanging drop vapor diffusion method, 10 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM DTT, and 5% glycerol, is mixed with reservoir solution containing 22% PEG 4000, 0.1 M sodium acetate, pH 4.5, and 0.1 M MgSO4, at 22°C, crystals are briefly equilibrated in a harvesting solution containing 26% PEG 4000, 0.1 M sodium acetate, pH 4.5, 0.1 M MgSO4, and 5 mM ADP-ribose, transferred to a cryoprotectant solution (26% PEG 4000, 0.1 M sodium acetate, pH 4.5, 0.1 M MgSO4, 5 mM ADPR, and 15% glycerol), and then flash-cooled in liquid nitrogen for data collection, X-ray diffraction structure determination and analysis at 1.6-1.7 A resolution, molecular replacement using the apo-ARH3DELTAN16 structure as a search model
purified recombinant mutant K616A/Q617A/K618A/E688A/K689A/K690A, also in selenomethionine-labeld form, in complex with inhibitors, sitting drop vapour diffusion, mixing protein in SEC buffer at 7.5 mg/mL with a precipitant consisting of 28% PEG 3350, 0.2 M magnesium chloride, 0.1 M PCTP (0.04 M sodium propionate, 0.02 M sodium cacodylate, 0.04 M Bis-Tris propane), pH 7.5, in a 1:1 ratio to give a 0.004 ml drop, 20°C, X-ray diffraction structure determination and analysis at 1.75-1.83 A resolution, molecular replacement
purified recombinant wild-type and mutant HsNudT16 proteins in complex with monomeric and dimeric ADP-ribose, hanging drop vapor diffusion, 20°C, for wild-type enzyme crystals, mixing of 0.001 ml of 26 mg/ml protein in solution containing 2 mM ADPr with 0.001 ml of 0.1 M Tris-HCl, pH 8.5, 0.2 M, sodium acetate trihydrate, and 25% PEG 4000, at 20°C, for enzyme mutants crystals, mixing of 0.001 ml of 15 mg/ml protein in solution containing 2 mM ADPr with crystallization solution containing 0.1 M CHES, pH 9.5, and 20% PEG 8000, 20°C, X-ray diffraction structure determination and analysis at 2.10-3.14 A resolution
structure in complex with inhibitors 1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-6-sulfanylidene-1,3,4,5,6,7-hexahydro-2H-purin-2-one and 1,3-dimethyl-8-[[2-(morpholin-4-yl)ethyl]sulfanyl]-3,4,5,7-tetrahydro-1H-purine-2,6-dione
enzyme catalytic domain free or in complexes with ADP-ribose and inhibitor ADP-HPD, as well as four enzyme catalytic residues mutants, X-ray diffraction structure determination and analysis
purified truncated native and selenomethionine-labeled enzymes comprising residues 385-972 and lacking the A-domain, free or in complex with adenosine diphosphate (hydroxymethyl) pyrrolidinediol, hanging drop vapour diffusion method, mixing of 15 mg/ml protein in 25 mM HEPES, pH 7.5, 150 mM NaCl, 5% glycerol and 2 mM DTT, with an equal volume of well solution containing 16-20% w/v PEG 2000 monomethylether, 0.1 M Tris-HCl, pH 7.5, 0.1 M NaCl, and 0.2 M potassium thiocyanate, 22°C, X-ray diffraction structure determination and analysis at 1.95 A resolution
purified recombinant His-tagged enzyme in complex with ADP-ribose or inhibitor RBPI-3, and as selenomethionine-labeled enzyme, sitting drop vapour diffusion method, 15 mg/ml protein is mixed with a 1:1 molar ratio with ADP-ribose, and with an equal volume of a solution containing 0.15 M potassium thiocyanate, 0.1 M Tris, pH 8.5, and 15% PEG 6000, or with 0.2 M potassium bromide, 0.1 M Tris, pH 7.5, and 15% PEG 4000, X-ray diffraction structure determination and analysis at 1.95 A resolution
in complexes with ADP-ribose and inhibitor adenosine 5'-diphosphate (hydroxymethyl) pyrrolidinediol
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E273N
E756N
T267K
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
T267R
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267K
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
T267R
-
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
-
D314A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
D314E
site-directed mutagenesis, poly(ADP-ribose) binding structures of wild-type and D314A mutant, overview
D77N
E41Q
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
F36A
site-directed mutagenesis, the mutant shows reduced activity for free ADP-ribose, similar processing ability against protein-conjugated mono(ADP-ribose), and improved catalytic efficiency for protein-conjugated poly(ADP-ribose), all compared to the wild-type enzyme
F61S
site-directed mutagenesis, the mutant shows reduced activity for free ADP-ribose, similar processing ability against protein-conjugated mono(ADP-ribose), and improved catalytic efficiency for protein-conjugated poly(ADP-ribose), all compared to the wild-type enzyme
H182A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
K616A/Q617A/K618A/E688A/K689A/K690A
site-directed mutagenesis, six surface entropy reduction mutations
L11D/L13D/L14D
-
the mutant results in no detectable activity (less than 0.1% activity)
S148A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
S26A
O-GlcNAc-deficient mutant, promotes hepatocellular carcinoma in mouse xenograft models
T317A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
Y149A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
D77N/D78N
no enzymic activity, binding of ADP-ribose is similar to wild-type
E748N
site-directed mutagenesis, the mutant is inactive, activity is disrupted due to significant conformational changes
E748Q
site-directed mutagenesis, the mutant activity is highly reduced compared to the wild-type enzyme
E749N
site-directed mutagenesis, the mutant is inactive, activity is disrupted due to significant conformational changes
E749Q
site-directed mutagenesis, the mutant activity is highly reduced compared to the wild-type enzyme
F868A
site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme
G737A/G738A
site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme
G866A
site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme
E114A
-
the mutant shows about 2% activity compared to the wild type enzyme
S298K
-
the mutant shows about 2% activity compared to the wild type enzyme
V226W
-
the mutant shows about 5% activity compared to the wild type enzyme
additional information
D77N
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
additional information
enzyme knock-down by RNAi results in increased radiation sensitivity of worms
additional information
enzyme knock-down by RNAi results in increased radiation sensitivity of worms
additional information
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enzyme knock-down by RNAi results in increased radiation sensitivity of worms
additional information
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
-
additional information
-
decrease or loss of enzyme expression by partial gene deletion or RNA results in mislocalization and hypermodification of silencing protein SIR2
additional information
construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
-
additional information
-
construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
-
additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
-
additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
-
additional information
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quantification of single-strand break repair rates in A-549 cells depleted of poly(ADP-ribose) glycohydrolase, poly(ADP-ribose) polymerase 1 and poly(ADP-ribose) polymerase 2, both separately and in combination. Poly(ADP-ribose) glycohydrolase is a critical component of single-strand break repair and accelerates this process in concert with poly(ADP-ribose) polymerase
additional information
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transient transfection of HeLa cells with PARG expression constructs with amino acids encoded by exon 4 at the N-terminus. Proteins are targeted to the mitochondria. Deletion and missense mutants allow identification of a canonical N-terminal mitochondrial targeting sequence consisting of the first 16 amino acids encoded by PARG exon 4. Sub-mitochondrial localization experiments indicate that this mitochondrial PARG isoform is targeted to the mitochondrial matrix
additional information
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deletion of the regulatory segment/MTS from full-length human PARG111 results in a complete loss of activity
additional information
lentiviral gene silencing is used to generate 16HBE cell lines with stably suppressed enzyme, and determination of parameters of cell death and cell cycle following benz[a]pyrene exposure, overview
additional information
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lentiviral gene silencing is used to generate 16HBE cell lines with stably suppressed enzyme, and determination of parameters of cell death and cell cycle following benz[a]pyrene exposure, overview
additional information
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constitutive expression shRNA directed against the catalytic domain of all enzyme isoforms in the 16HBE cell line
additional information
enzyme knockout by expression of ARH3 siRNA in U2OS cells
additional information
poly(ADP-ribose) glycohydrolase (PARG) silencing and generation of PARG-deficient human bronchial epithelial cells. Silencing of PARG significantly reduces the volume and weight of tumors in Balb/c nude mice injected with benzo(a)pyrene (BaP)-induced transformed human bronchial epithelial cells. PARG-silenced shPARG cells show less chromosomal damage than wild-type 16HBE cells. PARG silencing inhibits BaP-induced micronuclei formation. PARG silencing protects cells against BaP-induced cytotoxicity and cytogenetic damage, and inhibits BaP-induced cell transformation by reducing genomic instability in cells. PARG-deficient phenotype, overview
additional information
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poly(ADP-ribose) glycohydrolase (PARG) silencing and generation of PARG-deficient human bronchial epithelial cells. Silencing of PARG significantly reduces the volume and weight of tumors in Balb/c nude mice injected with benzo(a)pyrene (BaP)-induced transformed human bronchial epithelial cells. PARG-silenced shPARG cells show less chromosomal damage than wild-type 16HBE cells. PARG silencing inhibits BaP-induced micronuclei formation. PARG silencing protects cells against BaP-induced cytotoxicity and cytogenetic damage, and inhibits BaP-induced cell transformation by reducing genomic instability in cells. PARG-deficient phenotype, overview
additional information
siRNA screen for synthetic lethality with PARG depletion, lethal with depletion of BRCA2. Reduction of expression of PARG protein by 80-90% without significant change in poly(ADP-ribose) polymerase PARP1 protein levels. Disruption of BRCA1, BRCA2, PALB2, RAD51D, BRIP1, BARD1, MRE11, NBN, RAD50, TP53, and FAM175A can be considered synthetically lethal with PARG depletion
additional information
rational design of NudT16 mutants with improved processing of poly(ADP-ribosyl)ated proteins via structural analyses of NudT16-ADP-ribose complex, overview. Several HsNudT16 mutants (DELTA17, F36A, and F61S) have reduced activity for free ADP-ribose, similar processing ability against protein-conjugated mono(ADP-ribose), but improved catalytic efficiency for protein-conjugated poly(ADP-ribose)
additional information
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the loss of NUDT16 reduces CtIP protein levels on chromatin in NUDT16 KO cells, and further decreases the accumulation of CtIP protein on chromatin in response to IR, compared with wild-type MDA-MB-231 cells. NUDT16 loss impairs CtIP recruitment to DSBs following DNA damage
additional information
-
enzyme knockout mutation is lethal. Silencing by RNA interference results in 10% of enzyme protein that are sufficient to ensure normal proliferation through several subculturing rounds and cells that are able to repair DNA damage induced by sublethal doses of H2O2. Silenced cells are more resistant than wild-type to oxidant-induced apoptosis while exhibiting delayed poly(ADP-ribose) degradation and transient accumulation of ADP-ribose polymers
additional information
-
deletion of enzyme gene by gene targeting in embryonic stem cells and mice, severe compromisation of automodification of poly(ADP-ribose) polymerase 1. Enzyme deficient mice are viable and fertile, but hypersensitive to alkylating agents and ionizing radiation, and susceptible to streptozotocin-induced diabetes and endotoxic shock
additional information
-
mice lacking the functional 110 kDa isoform of enzyme are resistant to colon injury by dinitrobenzene sulfonic acid. Mucosa of mutant mice colon tissue shows reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Overproduction of proinflammatory factors tumor necrosis factor alpha and interleukin 1beta and activation of cell death signaling pathway are inhibited in these mice
additional information
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hypomorphic mouse model in which exons 2 and 3 of PARG gene have been deleted. Mutants exhibits nuclear localization of the enzyme which contains a catalytic domain but lacks the N-terminal region. Following DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine, activity of both poly(ADP-ribose) glycohydrolase and poly(ADP-ribose) polymerase in mutant cell increases. Increase in poly(ADP-ribose) glycohydrolase activity leads to decrease in poly(ADP-ribose) polymerase-1 automodification resulting in increased activity. Mutant cells also show reduced formation of XCRR1 foci, delayed H2AX phosphorylation, decreased DNA break intermediates during repair, and increased cell death
additional information
-
disruption of poly(ADP-ribose) glycohydrolase gene results in significant reduction of spinal cord inflammation and tissue injury, neutrophil infiltration, cytokine production, and apoptosis upon spinal cord injury
additional information
-
the catalytic activity of poly(ADP-ribose) glucohydrolase strongly depends on the two Glu residues in the GGG-X6-8-QEE motif (E114 and E115)
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
poly(ADP-ribose) protects the enzyme from thermal inactivation
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, 20% loss of activity after 1 month, addition of 0.1 mg/ml bovine serum albumin or 0.1 M NaCl to the diluted enzyme solution stabilizes the enzyme activity
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
fast and reproducible purification protocol for recombinant enzyme fused to GST and expressed in Escherichia coli. GST-PARG-fusion proteins from the crude extract are affinity purified by glutathione 4B sepharose chromatography and freed from their GST-fusion by overnight enzymatic cleavage using the preScission protease
recombinant C-terminally His-tagged hPARG from Escherichia coli BL21(DE3) Gold by nickel affinity chromatography and gel filtration
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain CodonPlus RIPL by nickel affinity chromatography, tag cleavage through TEV protease and dialysis
recombinant His-tagged wild-type and selenomethionine-labeled enzymes from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged wild-type enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage through rhinovirus 3C (HRV 3C) protease, anion exchange chromatography, gel filtration, and ultrafiltration, recombinant GST-tagged mutant enzymes by glutathione affinity chromatography
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His6-tagged truncated enzyme, native and selenomethionine-labeled, from Escherichia coli strain BL21 by nickel affinity and heparin affinity chromatography, and gel filtration
recombinant human PARG catalytic domain (residues 448-976) from Escherichia coli strain Rosetta (DE3) by nickel affinity chromatography, heparin chromatography, and gel filtration, recombinant His-tagged full-length wild-type and mutant D314E enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage through PreScission protease, and gel filtration, followed by ultrafiltration
recombinant N-terminally, TEV protease-cleavable His6-tagged wild-type and mutant enzymes, and selenomethionine-labeled enzyme from Escherichia coli strains BL21 (DE3) GOLD and B834 (DE3) by nickel affinity chromatography and gel filtration
Talon immobilized metal affinity resin column chromatography and glutathione-Sepharose column chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning from genomic DNA, DNA and amino acid sequence determination and analysis, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3), quantitative RT-PCR expression analysis
expressed in Escherichia coli
expression in Escherichia coli
expression of His-tagged wild-type and mutant enzymes and selenomethionine-labeled enzyme in Escherichia coli strain BL21 (DE3) GOLD
fusion to enhanced green fluorescent protein and expression in Drosophila melanogaster
-
gene ADPRHL2, recombinant expression of His-tagged human PARG catalytic domain (residues 448-976) from Escherichia coli strain Rosetta (DE3), recombinant expression of His-tagged full-length wild-type and mutant D314E enzymes in Escherichia coli strain BL21(DE3)
gene ADPRHL2, sequence comparisons, recombinant expression of N-terminally His-tagged wild-type enzyme and GST-tagged mutant enzymes in Escherichia coli strain BL21(DE3)
gene NUDT16, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain CodonPlus RIPL
gene NUDT16, recombinant expression of wild-type and mutant enzyme NudT16 in MCF10A cells and MDA-MB-231 cells
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gene PARG, recombinant expression of wild-type enzyme and catalytically inactive mutant E752N, both comprising residues 385-972, in Escherichia coli strain Tuner (DE3) cells, coexpression of GroESL chaperone
gene PARG, single gene, recombinant expression of C-terminally His-tagged hPARG in Escherichia coli BL21(DE3) Gold
gene PARG1, recombinant expression of GST-tagged wild-type and mutant enzymes
phylogenetic analysis, expression of wild-type and selenomethionin-labeled enzymes in Escherichia coli strain Rosetta (DE3)
recombinant expression of His6-tagged truncated enzyme comprising residues 385-972 in Escherichia coli strain BL21 co-expressing GroESL chaperone
the catalytic domain is expressed in Escherichia coli Rosetta2 (DE3) cells as a fusion protein with a glutathione S-transferase tag at the N-terminus and a hexahistidine tag at the C-terminus
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is 80fold induced by exposure to Al3+ for 10 days, decreases thereafter. Exposure to Al3+ leads to altered histology of zebrafish brain tissue, resulting in demyelination and neurodegeneration with poly(ADPribosyl)ation hyperactivation
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in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 is induced primarily in mitotically active cells
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
in the radio-resistant bacterium Deinococcus radiodurans, the PARG homologue, DrPARG, expression is upregulated after radiation damage
-
-
PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 is induced primarily in mitotically active cells
PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 is induced primarily in mitotically active cells
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-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
drug development
medicine
molecular biology
specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase
pharmacology
analysis
-
non-radioactive and quantitative assay system for PARG activity based on dot-blot assay using anti-poly(ADP-ribose) and nitrocellulose membrane. The maximum velocity Vmax and the Michaelis constant Km of PARG reaction according to this method are 4.46 microM and 128.33 micromol/min/mg, respectively
analysis
protocol for detection of PARG activity in solution and on dot blot
drug development
the protozoan enzyme represents a good model for human PARG and is therefore likely to prove useful in guiding structure-based discovery of new classes of PARG inhibitors
drug development
the enzyme is a target for development of specific inhibitors
drug development
-
inhibitors of the enzyme are potent anticancer drug candidates
drug development
DNA damage repair enzymes, including the enzyme poly(ADP-ribose) glycohydrolase (PARG), are promising targets in the development of therapeutic agents for a wide range of cancers and potentially other diseases
drug development
single treatment therapy with PARG inhibitors can be used for treatment of certain homologous recombination-deficient tumours
medicine
-
treatment of wild-type mice with pharmacological inhibitors GPI 16552 or GPI 18214 shows a protective effect in dinitrobenzene sulfonic acid-induced colitis. Mice lacking the functional 110 kDa isoform of enzyme are resistant to colon injury by dinitrobenzene sulfonic acid. Mucosa of mutant mice colon tissue shows reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Overproduction of proinflammatory factors tumor necrosis factor alpha and interleukin 1beta and activation of cell death signaling pathway are inhibited in these mice
medicine
DNA repair factor XRCC1 is involved in regulating a poly(ADP-ribose)-mediated apoptotic cell death
medicine
-
enzyme activity modulates the inflammatory response and tissue events associated with spinal cord trauma and participates in target organ damage under these conditions
medicine
-
since combination of poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase inhibition in chemotherapy does not produce increased HeLa cell death, strategies that target poly(ADP-ribose) metabolism for the improved treatment of cancer may be required to target poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase individually in order to optimize cancer cell death
medicine
-
the enzyme is a potential target for neuroprotective treatments for retinal degeneration
medicine
the enzyme is a promising therapeutic target for the treatment of Chagas' disease
medicine
in hepatocellular carcinoma cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 and attenuates its autoubiquitination
medicine
dual specificity phosphatase 22 deficiency exerts a synthetic lethal effect when combined with PARG dysfunction. The growth of tumors derived from DUSP22/PARG double knockdown A-549 cells is slower compared with those derived from control siRNA-transfected cells
medicine
COV-2 Mac1 and human PARG macrodomains share critical adenosyl and ribose residues. Active site residues with the greatest shared functional conservation are CoV-2 Mac1 (F156, D22, N40, F132) and PARG (F902, E727, N740, F875)
medicine
enhancing tumor cell levels of NAD+ by the addition of dihydronicotinamide riboside strongly increases the cytotoxicity of temozolomide + PARG inhibition cotreatment. Dihydronicotinamide riboside administration rapidly increases NAD+ levels in both temozolomide-sensitive and -resistant GBM cells and enhances the accumulation of poly(ADP-ribose) following treatment with temozolomide. The combination strongly suppresses the cell growth of GBM cells depleted of MSH6 or cells expressing repair protein O6-methylguanine-DNA methyltransferase
medicine
HCT-116R-PDD cell line exhibits resistance to the PARG inhibitor PDD00017273. HCT-116R-PDD cells contain PARG mutation Glu352Gln and PARP1 mutation Lys134Asn. The levels of PARG protein are comparable between HCT-116R-PDD cell line and HCT-116 cells. The PARP1 protein levels in HCT-116R-PDD are significantly lower than those in HCT116. The levels of intracellular poly(ADP-ribosyl)ation are elevated in HCT-116R-PDD and cells do not exhibit cross-resistance to PARG inhibitor COH34
medicine
PARG overexpression is a promising immunohistochemical marker to predict the occurrence and prognosis of endometrial carcinoma. Expression of PARG in endometrial tissues, endometrial hyperplasia without atypia, atypical endometrial hyperplasia, and endometrial carcinoma increases gradually. Compared with low PARG expression in PTEN-positive endometrial cancer, patients with high PARG expression in PTEN-negative endometrial carcinoma have more advanced clinical stages and shorter overall survival time. PARG inhibition produces antitumor effects and increases the sensitivity of endometrial carcinoma cells with PTEN deficiency to cisplatin
pharmacology
the enzyme is a promising therapeutic target for the treatment of Chagas' disease
pharmacology
PARG is a potential interventional target to improve the efficacy of cancer chemotherapy
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lin, W.; Ame, J.C.; Aboul-Ela, N.; Jacobson, E.L.; Jacobson, M.K.
Isolation and characterization of the cDNA encoding bovine poly(ADP-ribose) glycohydrolase
J. Biol. Chem.
272
11895-11901
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Bos taurus (O02776), Bos taurus
brenda
Maruta, H.; Inageda, K.; Aoki, T.; Nishina, H.; Tanuma, S.I.
Characterization of two forms of poly(ADP-ribose) glycohydrolase in guniea pig liver
Biochemistry
30
5907-5912
1991
Cavia porcellus
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Brochu, G.; Shah, G.M.; Poirier, G.G.
Purification of poly(ADP-ribose) glycohydrolase detection of its isoforms by a zymogram following one- or two-dimensional electrophoresis
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218
265-272
1994
Bos taurus
brenda
Sugimura, T.; Yamada, M.; Miwa, M.; Matsushima, T.; Hidaka, T.; Nagao, M.; Inui, N.; Takayama, S.
Properties of poly(adenosine diphosphate ribose) polymerase, poly(adenosine diphosphate ribose) glycohydrolase and poly(adenosine diphosphate ribose)
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1
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1973
Bos taurus
-
brenda
Pacheco-Rodriguez, G.; Alvarez-Gonzalez, R.
Measurement of poly(ADP-ribose) glycohydrolase activity by high resolution polyacrylamide gel electrophoresis: specific inhibition by histones and nuclear matrix proteins
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193
13-18
1999
Rattus norvegicus
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Concha, I.I.; Koide, S.S.; Burzio, L.O.
Characteristics of the inhibition of poly(ADP-ribose) glycohydrolase by homopolypurines
Biochem. Int.
16
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1988
Rattus norvegicus
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Tanuma, S.i.; Sakagami, H.; Endo, H.
Inhibitory effect of tannin on poly(ADP-rinbose) glycohydrolase
Biochem. Int.
18
701-708
1989
Homo sapiens
brenda
Miwa, M.; Sugimura, T.
Splitting of the ribose-ribose linkage of poly(adenosine diphosphate-ribose) by a calf thymus extract
J. Biol. Chem.
246
6362-6364
1971
Bos taurus
brenda
Miwa, M.; Tanaka, M.; Matsushima, T.; Sugimura, T.
Purification and properties of a glycohydrolase from calf thymus splitting ribose-ribose linkages of poly(adenosine diphosphate ribose)
J. Biol. Chem.
249
3475-3482
1974
Bos taurus
brenda
Hatakeyama, K.; Nemoto, Y.; Ueda, K.; Hayaishi, O.
Purification and characterization of poly(ADP-ribose) glycohydrolase. Different modes of action on large and small poly(ADP-ribose)
J. Biol. Chem.
261
14902-14911
1986
Bos taurus
brenda
Tanuma, S.i.; Kawashima, K.; Endo, H.
Purification and properties of an (ADP-ribose)n glycohydrolase from guinea pig liver nuclei
J. Biol. Chem.
261
965-969
1986
Cavia porcellus
brenda
Tanuma, S.i.; Endo, H.
Purification and characterization of an (ADP-ribose)n glycohydrolase from human erythrocytes
Eur. J. Biochem.
191
57-63
1990
Homo sapiens
brenda
Tavassoli, M.; Tavassoli, M.H.; Shall, S.
Isolation and purification of poly(ADP-ribose) glycohydrolase from pig thymus
Eur. J. Biochem.
135
449-455
1983
Sus scrofa
brenda
Slama, J.T.; Aboul-Ela, N.; Jacobson, M.K.
Mechanism of inhibition of poly(ADP-ribose) glycohydrolase by adenosine diphosphate (hydroxymethyl)pyrrolidinediol
J. Med. Chem.
38
4332-4336
1995
Bos taurus
brenda
Abe, H.; Tanuma, S.
Properties of poly(ADP-ribose) glycohydrolase purified from pig testis nuclei
Arch. Biochem. Biophys.
336
139-146
1996
Sus scrofa
brenda
Ohashi, S.; Kanai, M.; Hanai, S.; Uchiumi, F.; Maruta, H.; Tanuma, S.; Miwa, M.
Subcellular localization of poly(ADP-ribose) glycohydrolase in mammalian cells
Biochem. Biophys. Res. Commun.
307
915-921
2003
Homo sapiens
brenda
Patel, C.N.; Koh, D.W.; Jacobson, M.K.; Oliveira, M.A.
Identification of three critical acidic residues of poly(ADP-ribose) glycohydrolase involved in catalysis: determining the PARG catalytic domain
Biochem. J.
388
493-500
2005
Bos taurus (O02776), Bos taurus
brenda
Gagne, J.P.; Bonicalzi, M.E.; Gagne, P.; Ouellet, M.E.; Hendzel, M.J.; Poirier, G.G.
Poly(ADP-ribose) glycohydrolase is a component of the FMRP-associated messenger ribonucleoparticles
Biochem. J.
392
499-509
2005
Homo sapiens
brenda
Blenn, C.; Althaus, F.R.; Malanga, M.
Poly(ADP-ribose) glycohydrolase silencing protects against H2O2-induced cell death
Biochem. J.
396
419-429
2006
Mus musculus
brenda
Uchiumi, F.; Ikeda, D.; Tanuma, S.
Changes in the activities and gene expressions of poly(ADP-ribose) glycohydrolases during the differentiation of human promyelocytic leukemia cell line HL-60
Biochim. Biophys. Acta
1676
1-11
2004
Homo sapiens (Q86W56)
brenda
Haince, J.F.; Ouellet, M.E.; McDonald, D.; Hendzel, M.J.; Poirier, G.G.
Dynamic relocation of poly(ADP-ribose) glycohydrolase isoforms during radiation-induced DNA damage
Biochim. Biophys. Acta
1763
226-237
2006
Bos taurus, Homo sapiens
brenda
Bonicalzi, M.E.; Vodenicharov, M.; Coulombe, M.; Gagne, J.P.; Poirier, G.G.
Alteration of poly(ADP-ribose) glycohydrolase nucleocytoplasmic shuttling characteristics upon cleavage by apoptotic proteases
Biol. Cell.
95
635-644
2003
Bos taurus
brenda
Sevigny, M.B.; Silva, J.M.; Lan, W.C.; Alano, C.C.; Swanson, R.A.
Expression and activity of poly(ADP-ribose) glycohydrolase in cultured astrocytes, neurons, and C6 glioma cells
Brain Res. Mol. Brain Res.
117
213-220
2003
Mus musculus
brenda
Meyer-Ficca, M.L.; Meyer, R.G.; Coyle, D.L.; Jacobson, E.L.; Jacobson, M.K.
Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments
Exp. Cell Res.
297
521-532
2004
Homo sapiens (Q86W56), Homo sapiens
brenda
Oka, S.; Kato, J.; Moss, J.
Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase
J. Biol. Chem.
281
705-713
2006
Mus musculus (Q8CG72), Homo sapiens (Q9NX46), Homo sapiens
brenda
Koh, D.W.; Coyle, D.L.; Mehta, N.; Ramsinghani, S.; Kim, H.; Slama, J.T.; Jacobson, M.K.
SAR analysis of adenosine diphosphate (hydroxymethyl)pyrrolidinediol inhibition of poly(ADP-ribose) glycohydrolase
J. Med. Chem.
46
4322-4332
2003
Bos taurus
brenda
Di Meglio, S.; Denegri, M.; Vallefuoco, S.; Tramontano, F.; Scovassi, A.I.; Quesada, P.
Poly(ADPR) polymerase-1 and poly(ADPR) glycohydrolase level and distribution in differentiating rat germinal cells
Mol. Cell. Biochem.
248
85-91
2003
Rattus norvegicus
brenda
Cortes, U.; Tong, W.M.; Coyle, D.L.; Meyer-Ficca, M.L.; Meyer, R.G.; Petrilli, V.; Herceg, Z.; Jacobson, E.L.; Jacobson, M.K.; Wang, Z.Q.
Depletion of the 110-kilodalton isoform of poly(ADP-ribose) glycohydrolase increases sensitivity to genotoxic and endotoxic stress in mice
Mol. Cell. Biol.
24
7163-7178
2004
Mus musculus
brenda
Ying, W.; Sevigny, M.B.; Chen, Y.; Swanson, R.A.
Poly(ADP-ribose) glycohydrolase mediates oxidative and excitotoxic neuronal death
Proc. Natl. Acad. Sci. USA
98
12227-12232
2001
Mus musculus
brenda
Shirato, M.; Tozawa, S.; Maeda, D.; Watanabe, M.; Nakagama, H.; Masutani, M.
Poly(etheno ADP-ribose) blocks poly(ADP-ribose) glycohydrolase activity
Biochem. Biophys. Res. Commun.
355
451-456
2007
Rattus norvegicus
brenda
St-Laurent, J.F.; Gagnon, S.N.; Dequen, F.; Hardy, I.; Desnoyers, S.
Altered DNA damage response in Caenorhabditis elegans with impaired poly(ADP-ribose) glycohydrolases genes expression
DNA Repair
6
329-343
2007
Caenorhabditis elegans (Q867X0), Caenorhabditis elegans (Q9N5L4), Caenorhabditis elegans
brenda
Meyer, R.G.; Meyer-Ficca, M.L.; Whatcott, C.J.; Jacobson, E.L.; Jacobson, M.K.
Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity
Exp. Cell Res.
313
2920-2936
2007
Homo sapiens
brenda
Gao, H.; Coyle, D.L.; Meyer-Ficca, M.L.; Meyer, R.G.; Jacobson, E.L.; Wang, Z.Q.; Jacobson, M.K.
Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase
Exp. Cell Res.
313
984-996
2007
Mus musculus
brenda
Cuzzocrea, S.; Mazzon, E.; Genovese, T.; Crisafulli, C.; Min, W.K.; Di Paola, R.; Muia, C.; Li, J.H.; Malleo, G.; Xu, W.; Massuda, E.; Esposito, E.; Zhang, J.; Wang, Z.Q.
Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice
Free Radic. Biol. Med.
42
90-105
2007
Mus musculus
brenda
Tulin, A.; Naumova, N.M.; Menon, A.K.; Spradling, A.C.
Drosophila poly(ADP-ribose) glycohydrolase mediates chromatin structure and SIR2-dependent silencing
Genetics
172
363-371
2006
Drosophila melanogaster
brenda
Keil, C.; Groebe, T.; Oei, S.L.
MNNG-induced cell death is controlled by interactions between PARP-1, poly(ADP-ribose) glycohydrolase, and XRCC1
J. Biol. Chem.
281
34394-34405
2006
Homo sapiens (Q0MQR4)
brenda
Cuzzocrea, S.; Genovese, T.; Mazzon, E.; Crisafulli, C.; Min, W.; Di Paola, R.; Muia, C.; Li, J.H.; Esposito, E.; Bramanti, P.; Xu, W.; Massuda, E.; Zhang, J.; Wang, Z.Q.
Poly(ADP-ribose) glycohydrolase activity mediates post-traumatic inflammatory reaction after experimental spinal cord trauma
J. Pharmacol. Exp. Ther.
319
127-138
2006
Mus musculus
brenda
Fisher, A.E.; Hochegger, H.; Takeda, S.; Caldecott, K.W.
Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase
Mol. Cell. Biol.
27
5597-5605
2007
Homo sapiens
brenda
Ono, T.; Kasamatsu, A.; Oka, S.; Moss, J.
The 39-kDa poly(ADP-ribose) glycohydrolase ARH3 hydrolyzes O-acetyl-ADP-ribose, a product of the Sir2 family of acetyl-histone deacetylases
Proc. Natl. Acad. Sci. USA
103
16687-16691
2006
Homo sapiens
brenda
Formentini, L.; Arapistas, P.; Pittelli, M.; Jacomelli, M.; Pitozzi, V.; Menichetti, S.; Romani, A.; Giovannelli, L.; Moroni, F.; Chiarugi, A.
Mono-galloyl glucose derivatives are potent poly(ADP-ribose) glycohydrolase (PARG) inhibitors and partially reduce PARP-1-dependent cell death
Br. J. Pharmacol.
155
1235-1249
2008
Bos taurus
brenda
Cohausz, O.; Blenn, C.; Malanga, M.; Althaus, F.R.
The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death
Cell. Mol. Life Sci.
65
644-655
2008
Homo sapiens
brenda
Burns, D.M.; Ying, W.; Kauppinen, T.M.; Zhu, K.; Swanson, R.A.
Selective down-regulation of nuclear poly(ADP-ribose) glycohydrolase
PLoS ONE
4
e4896
2009
Mus musculus
brenda
Adams-Phillips, L.; Briggs, A.G.; Bent, A.F.
Disruption of poly(ADP-ribosyl)ation mechanisms alters responses of Arabidopsis to biotic stress
Plant Physiol.
152
267-280
2010
Arabidopsis thaliana
brenda
Okita, N.; Ashizawa, D.; Ohta, R.; Abe, H.; Tanuma, S.
Discovery of novel poly(ADP-ribose) glycohydrolase inhibitors by a quantitative assay system using dot-blot with anti-poly(ADP-ribose)
Biochem. Biophys. Res. Commun.
392
485-489
2010
Bos taurus
brenda
Whatcott, C.J.; Meyer-Ficca, M.L.; Meyer, R.G.; Jacobson, M.K.
A specific isoform of poly(ADP-ribose) glycohydrolase is targeted to the mitochondrial matrix by a N-terminal mitochondrial targeting sequence
Exp. Cell Res.
315
3477-3485
2009
Homo sapiens
brenda
Erdelyi, K.; Bai, P.; Kovacs, I.; Szabo, E.; Mocsar, G.; Kakuk, A.; Szabo, C.; Gergely, P.; Virag, L.
Dual role of poly(ADP-ribose) glycohydrolase in the regulation of cell death in oxidatively stressed A549 cells
FASEB J.
23
3553-3563
2009
Homo sapiens
brenda
Frizzell, K.M.; Gamble, M.J.; Berrocal, J.G.; Zhang, T.; Krishnakumar, R.; Cen, Y.; Sauve, A.A.; Kraus, W.L.
Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells
J. Biol. Chem.
284
33926-33938
2009
Homo sapiens
brenda
Botta, D.; Jacobson, M.K.
Identification of a regulatory segment of poly(ADP-ribose) glycohydrolase
Biochemistry
49
7674-7682
2010
Homo sapiens
brenda
Blenn, C.; Wyrsch, P.; Bader, J.; Bollhalder, M.; Althaus, F.R.
Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death
Cell. Mol. Life Sci.
68
1455-1466
2011
Mus musculus
brenda
Steffen, J.D.; Coyle, D.L.; Damodaran, K.; Beroza, P.; Jacobson, M.K.
Discovery and structure-activity relationships of modified salicylanilides as cell permeable inhibitors of poly(ADP-ribose) glycohydrolase (PARG)
J. Med. Chem.
54
5403-5413
2011
Homo sapiens
brenda
Slade, D.; Dunstan, M.; Barkauskaite, E.; Weston, R.; Lafite, P.; Dixon, N.; Ahel, M.; Leys, D.; Ahel, I.
The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase
Nature
477
616-622
2011
Homo sapiens, Thermomonospora curvata
brenda
Li, G.; Nasar, V.; Yang, Y.; Li, W.; Liu, B.; Sun, L.; Li, D.; Song, F.
Arabidopsis poly(ADP-ribose) glycohydrolase 1 is required for drought, osmotic and oxidative stress responses
Plant Sci.
180
283-291
2011
Arabidopsis thaliana
brenda
Okita, N.; Ohta, R.; Ashizawa, D.; Yamada, Y.; Abe, H.; Abe, T.; Tanuma, S.
Bacterial production of recombinant human poly(ADP-ribose) glycohydrolase
Protein Expr. Purif.
75
230-235
2011
Homo sapiens (Q86W56), Homo sapiens
brenda
Hassler, M.; Jankevicius, G.; Ladurner, A.G.
PARG: A macrodomain in disguise
Structure
19
1351-1353
2011
Thermomonospora curvata
brenda
Finch, K.E.; Knezevic, C.E.; Nottbohm, A.C.; Partlow, K.C.; Hergenrother, P.J.
Selective small molecule inhibition of poly(ADP-ribose) glycohydrolase (PARG)
ACS Chem. Biol.
7
563-570
2012
Homo sapiens
brenda
Huang, H.; Hu, G.; Cai, J.; Xia, B.; Liu, J.; Li, X.; Gao, W.; Zhang, J.; Liu, Y.; Zhuang, Z.
Role of poly(ADP-ribose) glycohydrolase silencing in DNA hypomethylation induced by benzo(a)pyrene
Biochem. Biophys. Res. Commun.
452
708-714
2014
Homo sapiens
brenda
Islam, R.; Koizumi, F.; Kodera, Y.; Inoue, K.; Okawara, T.; Masutani, M.
Design and synthesis of phenolic hydrazide hydrazones as potent poly(ADP-ribose) glycohydrolase (PARG) inhibitors
Bioorg. Med. Chem. Lett.
24
3802-3806
2014
Rattus norvegicus
brenda
Sahaboglu, A.; Tanimoto, N.; Bolz, S.; Garrido, M.G.; Ueffing, M.; Seeliger, M.W.; Loewenheim, H.; Ekstroem, P.; Paquet-Durand, F.
Knockout of PARG110 confers resistance to cGMP-induced toxicity in mammalian photoreceptors
Cell Death Dis.
5
e1234
2014
Mus musculus
brenda
Huang, H.Y.; Cai, J.F.; Liu, Q.C.; Hu, G.H.; Xia, B.; Mao, J.Y.; Wu, D.S.; Liu, J.J.; Zhuang, Z.X.
Role of poly(ADP-ribose) glycohydrolase in the regulation of cell fate in response to benzo(a)pyrene
Exp. Cell Res.
318
682-690
2012
Homo sapiens (Q86W56), Homo sapiens
brenda
Ji, Y.; Jarnik, M.; Tulin, A.V.
Poly(ADP-ribose) glycohydrolase and poly(ADP-ribose)-interacting protein Hrp38 regulate pattern formation during Drosophila eye development
Gene
526
187-194
2013
Drosophila melanogaster
brenda
Feng, X.; Koh, D.W.
Inhibition of poly(ADP-ribose) polymerase-1 or poly(ADP-ribose) glycohydrolase individually, but not in combination, leads to improved chemotherapeutic efficacy in HeLa cells
Int. J. Oncol.
42
749-756
2013
Homo sapiens
brenda
Hou, Q.; Hu, X.; Sheng, X.; Liu, Y.; Liu, C.
Theoretical study on the degradation of ADP-ribose polymer catalyzed by poly(ADP-ribose) glycohydrolase
J. Mol. Graph. Model.
42
26-31
2013
Thermomonospora curvata (D1AC29)
brenda
Kim, I.K.; Kiefer, J.R.; Ho, C.M.; Stegeman, R.A.; Classen, S.; Tainer, J.A.; Ellenberger, T.
Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element
Nat. Struct. Mol. Biol.
19
653-656
2012
Rattus norvegicus (Q9QYM2)
brenda
Dunstan, M.S.; Barkauskaite, E.; Lafite, P.; Knezevic, C.E.; Brassington, A.; Ahel, M.; Hergenrother, P.J.; Leys, D.; Ahel, I.
Structure and mechanism of a canonical poly(ADP-ribose) glycohydrolase
Nat. Commun.
3
878
2012
Tetrahymena thermophila (I6L8L8), Tetrahymena thermophila
brenda
Tucker, J.A.; Bennett, N.; Brassington, C.; Durant, S.T.; Hassall, G.; Holdgate, G.; McAlister, M.; Nissink, J.W.; Truman, C.; Watson, M.
Structures of the human poly (ADP-ribose) glycohydrolase catalytic domain confirm catalytic mechanism and explain inhibition by ADP-HPD derivatives
PLoS ONE
7
e50889
2012
Homo sapiens (Q86W56), Homo sapiens
brenda
Vilchez Larrea, S.C.; Schlesinger, M.; Kevorkian, M.L.; Flawia, M.M.; Alonso, G.D.; Fernandez Villamil, S.H.
Host cell poly(ADP-ribose) glycohydrolase is crucial for Trypanosoma cruzi infection cycle
PLoS ONE
8
e67356
2013
Trypanosoma cruzi (Q0PW90), Trypanosoma cruzi
brenda
Dahl, M.; Maturi, V.; Loenn, P.; Papoutsoglou, P.; Zieba, A.; Vanlandewijck, M.; van der Heide, L.P.; Watanabe, Y.; Soederberg, O.; Hottiger, M.O.; Heldin, C.H.; Moustakas, A.
Fine-tuning of Smad protein function by poly(ADP-ribose) polymerases and poly(ADP-ribose) glycohydrolase during transforming growth factor beta signaling
PLoS ONE
9
e103651
2014
Homo sapiens
brenda
Wang, Z.; Gagne, J.P.; Poirier, G.G.; Xu, W.
Crystallographic and biochemical analysis of the mouse poly(ADP-ribose) glycohydrolase
PLoS ONE
9
e86010
2014
Mus musculus (O88622), Mus musculus
brenda
James, D.I.; Smith, K.M.; Jordan, A.M.; Fairweather, E.E.; Griffiths, L.A.; Hamilton, N.S.; Hitchin, J.R.; Hutton, C.P.; Jones, S.; Kelly, P.; McGonagle, A.E.; Small, H.; Stowell, A.I.; Tucker, J.; Waddell, I.D.; Waszkowycz, B.; Ogilvie, D.J.
First-in-class chemical probes against poly(ADP-ribose) glycohydrolase (PARG) inhibit DNA repair with differential pharmacology to Olaparib
ACS Chem. Biol.
11
3179-3190
2016
Homo sapiens (Q86W56)
brenda
Stowell, A.I.; James, D.I.; Waddell, I.D.; Bennett, N.; Truman, C.; Hardern, I.M.; Ogilvie, D.J.
A high-throughput screening-compatible homogeneous time-resolved fluorescence assay measuring the glycohydrolase activity of human poly(ADP-ribose) glycohydrolase
Anal. Biochem.
503
58-64
2016
Homo sapiens (Q86W56), Homo sapiens
brenda
Araiza-Cervantes, C.; Meza-Carmen, V.; Martinez-Cadena, G.; Roncero, M.; Reyna-Lopez, G.; Franco, B.
Biochemical and genetic analysis of a unique poly(ADP-ribosyl) glycohydrolase (PARG) of the pathogenic fungus Fusarium oxysporum f. sp. lycopersici
Antonie Van Leeuwenhoek
111
285-295
2018
Fusarium oxysporum f. sp. lycopersici (A0A0D2XPQ9), Fusarium oxysporum f. sp. lycopersici 4287 (A0A0D2XPQ9), Fusarium oxysporum f. sp. lycopersici CBS 123668 (A0A0D2XPQ9), Fusarium oxysporum f. sp. lycopersici FGSC 9935 (A0A0D2XPQ9), Fusarium oxysporum f. sp. lycopersici NRRL 34936 (A0A0D2XPQ9)
-
brenda
Gravells, P.; Grant, E.; Smith, K.M.; James, D.I.; Bryant, H.E.
Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase
DNA Repair
52
81-91
2017
Homo sapiens (Q86W56)
brenda
Lambrecht, M.J.; Brichacek, M.; Barkauskaite, E.; Ariza, A.; Ahel, I.; Hergenrother, P.J.
Synthesis of dimeric ADP-ribose and its structure with human poly(ADP-ribose) glycohydrolase
J. Am. Chem. Soc.
137
3558-3564
2015
Homo sapiens (Q86W56), Homo sapiens
brenda
Kim, I.; Stegeman, R.; Brosey, C.; Ellenberger, T.
A quantitative assay reveals ligand specificity of the DNA scaffold repair protein XRCC1 and efficient disassembly of complexes of XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase
J. Biol. Chem.
290
3775-3783
2015
Rattus norvegicus (Q9QYM2)
-
brenda
Pourfarjam, Y.; Ventura, J.; Kurinov, I.; Cho, A.; Moss, J.; Kim, I.K.
Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition
J. Biol. Chem.
293
12350-12359
2018
Homo sapiens (Q9NX46), Homo sapiens
brenda
Wang, M.; Yuan, Z.; Xie, R.; Ma, Y.; Liu, X.; Yu, X.
Structure-function analyses reveal the mechanism of the ARH3-dependent hydrolysis of ADP-ribosylation
J. Biol. Chem.
293
14470-14480
2018
Homo sapiens (Q9NX46)
brenda
Waszkowycz, B.; Smith, K.M.; McGonagle, A.E.; Jordan, A.M.; Acton, B.; Fairweather, E.E.; Griffiths, L.A.; Hamilton, N.M.; Hamilton, N.S.; Hitchin, J.R.; Hutton, C.P.; James, D.I.; Jones, C.D.; Jones, S.; Mould, D.P.; Small, H.F.; Stowell, A.I.J.; Tucker, J.A.; Waddell, I.D.; Ogilvie, D.J.
Cell-active small molecule inhibitors of the DNA-damage repair enzyme poly(ADP-ribose) glycohydrolase (PARG) discovery and optimization of orally bioavailable quinazolinedione sulfonamides
J. Med. Chem.
61
10767-10792
2018
Homo sapiens (Q86W56), Homo sapiens
brenda
Barkauskaite, E.; Jankevicius, G.; Ahel, I.
Structures and mechanisms of enzymes employed in the synthesis and degradation of PARP-dependent protein ADP-ribosylation
Mol. Cell
58
935-946
2015
Homo sapiens (Q86W56)
brenda
Chaudhuri, A.; Ahuja, A.; Herrador, R.; Lopes, M.
Poly(ADP-ribosyl) glycohydrolase prevents the accumulation of unusual replication structures during unperturbed S phase
Mol. Cell. Biol.
35
856-865
2015
Homo sapiens (Q86W56)
-
brenda
Cho, C.C.; Chien, C.Y.; Chiu, Y.C.; Lin, M.H.; Hsu, C.H.
Structural and biochemical evidence supporting poly ADP-ribosylation in the bacterium Deinococcus radiodurans
Nat. Commun.
10
1491
2019
Deinococcus radiodurans (Q9RZM4), Deinococcus radiodurans, Deinococcus radiodurans ATCC 13939 (Q9RZM4), Deinococcus radiodurans DSM 20539 (Q9RZM4), Deinococcus radiodurans JCM 16871 (Q9RZM4), Deinococcus radiodurans LMG 4051 (Q9RZM4), Deinococcus radiodurans NBRC 15346 (Q9RZM4), Deinococcus radiodurans NCIMB 9279 (Q9RZM4), Deinococcus radiodurans R1 (Q9RZM4), Deinococcus radiodurans VKM B-1422 (Q9RZM4)
brenda
Rotin, L.E.; Gronda, M.; MacLean, N.; Hurren, R.; Wang, X.; Lin, F.H.; Wrana, J.; Datti, A.; Barber, D.L.; Minden, M.D.; Slassi, M.; Schimmer, A.D.
Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism
Oncotarget
7
2765-2779
2016
Homo sapiens (Q86W56)
brenda
Li, X.; Li, X.; Zhu, Z.; Huang, P.; Zhuang, Z.; Liu, J.; Gao, W.; Liu, Y.; Huang, H.
Poly(ADP-Ribose) glycohydrolase (PARG) silencing suppresses benzo(a)pyrene induced cell transformation
PLoS ONE
11
e0151172
2016
Homo sapiens (Q86W56), Homo sapiens
brenda
Zhang, H.; Gu, Z.; Wu, Q.; Yang, L.; Liu, C.; Ma, H.; Xia, Y.; Ge, X.
Arabidopsis PARG1 is the key factor promoting cell survival among the enzymes regulating post-translational poly(ADP-ribosyl)ation
Sci. Rep.
5
15892
2015
Arabidopsis thaliana (Q9SKB3), Arabidopsis thaliana Col-0 (Q9SKB3)
brenda
Stevens, L.A.; Kato, J.; Kasamatsu, A.; Oda, H.; Lee, D.Y.; Moss, J.
The ARH and macrodomain families of alpha-ADP-ribose-acceptor hydrolases catalyze alpha-NAD+ hydrolysis
ACS Chem. Biol.
14
2576-2584
2019
Homo sapiens (Q9NX46)
brenda
Shibui, Y.; Oyama, T.; Okazawa, M.; Yoshimori, A.; Abe, H.; Uchiumi, F.; Tanuma, S.
Structural insights into the active site of poly(ADP-ribose) glycohydrolase using docking modes of 6-hydroxy-3H-xanthen-3-one derivative inhibitors
Bioorg. Med. Chem.
28
115249
2020
Homo sapiens (Q86W56)
brenda
Tsuda, K.; Kurasaka, C.; Ogino, Y.; Sato, A.
Genomic and biological aspects of resistance to selective poly(ADP-ribose) glycohydrolase inhibitor PDD00017273 in human colorectal cancer cells
Cancer Rep. (Hoboken)
6
e1709
2023
Homo sapiens (Q86W56)
brenda
Sasaki, Y.; Fujimori, H.; Hozumi, M.; Onodera, T.; Nozaki, T.; Murakami, Y.; Ashizawa, K.; Inoue, K.; Koizumi, F.; Masutani, M.
Dysfunction of poly (ADP-Ribose) glycohydrolase induces a synthetic lethal effect in dual specificity phosphatase 22-deficient lung cancer cells
Cancer Res.
79
3851-3861
2019
Homo sapiens (Q86W56)
brenda
Li, J.; Koczor, C.A.; Saville, K.M.; Hayat, F.; Beiser, A.; McClellan, S.; Migaud, M.E.; Sobol, R.W.
Overcoming temozolomide resistance in glioblastoma via enhanced NAD+ bioavailability and inhibition of poly-ADP-ribose glycohydrolase
Cancers (Basel)
14
3572
2022
Homo sapiens (Q86W56)
brenda
Bianchi, A.R.; La Pietra, A.; Guerretti, V.; De Maio, A.; Capriello, T.; Ferrandino, I.
Synthesis and degradation of poly(ADP-ribose) in zebrafish brain exposed to aluminum
Int. J. Mol. Sci.
24
8766
2023
Danio rerio
brenda
Li, J.; Liu, X.; Peng, B.; Feng, T.; Zhou, W.; Meng, L.; Zhao, S.; Zheng, X.; Wu, C.; Wu, S.; Chen, X.; Xu, X.; Sun, J.; Li, J.
O-GlcNAc has crosstalk with ADP-ribosylation via PARG
J. Biol. Chem.
299
105354
2023
Homo sapiens (Q86W56)
brenda
Sun, Y.; Shi, Y.; Liu, H.; Lv, C.; Zhang, A.
The role of poly (ADP-ribose) glycohydrolase in phosphatase and tensin homolog deficiency endometrial cancer
J. Obstet. Gynaecol. Res.
49
1244-1254
2023
Homo sapiens (Q86W56)
brenda
Ame, J.C.; Dantzer, F.
Purification of recombinant human PARG and activity assays
Methods Mol. Biol.
2609
399-418
2023
Homo sapiens (Q86W56)
brenda
Farhana, F.; Sakai, E.; Koyanagi, Y.; Yamaguchi, Y.; Alam, M.I.; Okamoto, K.; Tsukuba, T.
Abr, a Rho-regulating protein, modulates osteoclastogenesis by enhancing lamellipodia formation by interacting with poly(ADP-ribose) glycohydrolase
Mol. Biol. Rep.
50
7557-7569
2023
Mus musculus (O88622)
brenda
Houl, J.H.; Ye, Z.; Brosey, C.A.; Balapiti-Modarage, L.P.F.; Namjoshi, S.; Bacolla, A.; Laverty, D.; Walker, B.L.; Pourfarjam, Y.; Warden, L.S.; Babu Chinnam, N.; Moiani, D.; Stegeman, R.A.; Chen, M.K.; Hung, M.C.; Nagel, Z.D.; Ellenberger, T.; Kim, I.K.; Jones, D.E.; Ahmed, Z.; Tainer, J.A.
Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death
Nat. Commun.
10
5654
2019
Homo sapiens (Q86W56)
brenda
Janisiw, E.; Raices, M.; Balmir, F.; Paulin, L.F.; Baudrimont, A.; von Haeseler, A.; Yanowitz, J.L.; Jantsch, V.; Silva, N.
Poly(ADP-ribose) glycohydrolase coordinates meiotic DNA double-strand break induction and repair independent of its catalytic activity
Nat. Commun.
11
4869
2020
Caenorhabditis elegans (Q867X0)
brenda
Brosey, C.A.; Houl, J.H.; Katsonis, P.; Balapiti-Modarage, L.P.F.; Bommagani, S.; Arvai, A.; Moiani, D.; Bacolla, A.; Link, T.; Warden, L.S.; Lichtarge, O.; Jones, D.E.; Ahmed, Z.; Tainer, J.A.
Targeting SARS-CoV-2 Nsp3 macrodomain structure with insights from human poly(ADP-ribose) glycohydrolase (PARG) structures with inhibitors
Prog. Biophys. Mol. Biol.
163
171-186
2021
Homo sapiens (Q86W56)
brenda
Zhang, Z.; Samsa, W.E.; Gong, Z.
NUDT16 regulates CtIP PARylation to dictate homologous recombination repair
Nucleic Acids Res.
52
3761-3777
2024
Homo sapiens
brenda
Thirawatananond, P.; McPherson, R.L.; Malhi, J.; Nathan, S.; Lambrecht, M.J.; Brichacek, M.; Hergenrother, P.J.; Leung, A.K.L.; Gabelli, S.B.
Structural analyses of NudT16-ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins
Sci. Rep.
9
5940
2019
Homo sapiens (Q96DE0)
brenda
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