Page last updated: 2024-10-24

protein auto-ADP-ribosylation

Definition

Target type: biologicalprocess

The ADP-ribosylation by a protein of one or more of its own amino acid residues, or residues on an identical protein. [GOC:BHF, GOC:rl]

Auto-ADP-ribosylation is a post-translational modification where an ADP-ribose moiety is transferred from NAD+ to a target protein. This process is catalyzed by a family of enzymes called ADP-ribosyltransferases (ARTs). The ADP-ribose moiety can be attached to various amino acid residues, including arginine, glutamate, and lysine. This modification can alter the activity, localization, and stability of the target protein.

Auto-ADP-ribosylation is a complex process that involves multiple steps. First, the ART enzyme binds to NAD+ and the target protein. The ART enzyme then catalyzes the transfer of the ADP-ribose moiety from NAD+ to the target protein. This transfer reaction can occur either on the same protein (auto-ADP-ribosylation) or on a different protein (inter-ADP-ribosylation).

Auto-ADP-ribosylation is a widespread modification that plays a role in a variety of cellular processes. For example, auto-ADP-ribosylation is involved in DNA repair, signal transduction, and cell death.

One important example of auto-ADP-ribosylation is the modification of PARP1 (poly(ADP-ribose) polymerase 1). PARP1 is a DNA repair enzyme that is activated by DNA damage. When PARP1 is activated, it undergoes auto-ADP-ribosylation, which leads to the formation of long chains of ADP-ribose attached to the PARP1 protein. These chains act as a signal to recruit other DNA repair proteins to the site of damage.

Auto-ADP-ribosylation is a dynamic process that is regulated by various factors, including the activity of ARTs, the availability of NAD+, and the presence of specific protein domains on the target protein. Disruptions in this process can lead to various diseases, including cancer, neurodegenerative diseases, and autoimmune disorders.

In addition to its role in various cellular processes, auto-ADP-ribosylation has also been implicated in the pathogenesis of infectious diseases. For example, the bacterial toxin cholera toxin utilizes ADP-ribosylation to cause severe diarrhea.

The study of auto-ADP-ribosylation is a rapidly expanding field with significant implications for understanding various biological processes and developing novel therapeutic strategies.'
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Proteins (12)

ProteinDefinitionTaxonomy
Poly [ADP-ribose] polymerase 1 A poly [ADP-ribose] polymerase 1 that is encoded in the genome of cow. [OMA:P18493, PRO:DNx]Bos taurus (cattle)
Protein mono-ADP-ribosyltransferase PARP3A protein mono-ADP-ribosyltransferase PARP3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y6F1]Homo sapiens (human)
Poly [ADP-ribose] polymerase 2A poly [ADP-ribose] polymerase 2 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
Protein mono-ADP-ribosyltransferase PARP11A protein mono-ADP-ribosyltransferase PARP11 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NR21]Homo sapiens (human)
Poly [ADP-ribose] polymerase tankyrase-2A poly [ADP-ribose] polymerase tankyrase-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H2K2]Homo sapiens (human)
Protein mono-ADP-ribosyltransferase PARP12A protein mono-ADP-ribosyltransferase PARP12 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H0J9]Homo sapiens (human)
Protein mono-ADP-ribosyltransferase PARP16A protein mono-ADP-ribosyltransferase PARP16 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N5Y8]Homo sapiens (human)
Protein mono-ADP-ribosyltransferase PARP8A protein mono-ADP-ribosyltransferase PARP8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8N3A8]Homo sapiens (human)
Protein mono-ADP-ribosyltransferase PARP10A protein mono-ADP-ribosyltransferase PARP10 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q53GL7]Homo sapiens (human)
Protein mono-ADP-ribosyltransferase PARP6A protein mono-ADP-ribosyltransferase PARP6 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q2NL67]Homo sapiens (human)
Poly [ADP-ribose] polymerase 1A poly [ADP-ribose] polymerase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P09874]Homo sapiens (human)
Poly [ADP-ribose] polymerase tankyrase-1A poly [ADP-ribose] polymerase tankyrase-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95271]Homo sapiens (human)

Compounds (78)

CompoundDefinitionClassesRoles
niacinamidenicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.pyridine alkaloid;
pyridinecarboxamide;
vitamin B3
anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
1,5-dihydroxyisoquinoline1,5-dihydroxyisoquinoline: structure in first source

isoquinoline-1,5-diol : An isoquinolinol that is isoquinoline in which the hydrogens at positions 1 and 5 are replaced by hydroxy groups.
isoquinolinolEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
3-aminobenzamidebenzamides;
substituted aniline
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
4'-bromoflavone4'-bromoflavone: structure in first source
4-amino-1,8-naphthalimide4-amino-1,8-naphthalimide: inhibits ADP-ribosylation; sometimes abreviated as 4-AN;benzoisoquinoline;
dicarboximide
phenanthridonephenanthridone : A member of the class of phenanthridines that is phenanthridine with an oxo substituent at position 6. A poly(ADP-ribose) polymerase (PARP) inhibitor, it has been shown to exhibit immunosuppressive activity.

phenanthridone: coal tar derivative; structure given in first source
lactam;
phenanthridines
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
immunosuppressive agent;
mutagen
5-aminoisoquinolinone5-aminoisoquinolinone: structure in first sourceisoquinolines
benzamidebenzamide : An aromatic amide that consists of benzene bearing a single carboxamido substituent. The parent of the class of benzamides.benzamides
pj-34PJ34 : A member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties.phenanthridines;
secondary carboxamide;
tertiary amino compound
angiogenesis inhibitor;
anti-inflammatory agent;
antiatherosclerotic agent;
antineoplastic agent;
apoptosis inducer;
cardioprotective agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
neuroprotective agent
carbostyrilquinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.

Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.
monohydroxyquinoline;
quinolone
bacterial xenobiotic metabolite
3-aminobenzoic acid3-aminobenzoic acid : An aminobenzoic acid carrying an amino group at position 3.

3-aminobenzoic acid: RN given refers to parent cpd
aminobenzoic acid
1-hydroxyphthalazine1-hydroxyphthalazine: RN given refers to cpd with unspecified locants; do not confuse with cpd phthalazinol RN: 56611-65-5phthalazines
chlorthenoxazinchlorthenoxazin: RN given refers to parent cpd; structurebenzoxazine
isocarbostyrilisoquinolinone : An isoquinoline containing one or more oxo groups.isoquinolines
flavoneflavone : The simplest member of the class of flavones that consists of 4H-chromen-4-one bearing a phenyl substituent at position 2.

flavone: RN given refers to unlabeled cpd; structure given in first source
flavonesmetabolite;
nematicide
2,4(1h,3h)-quinazolinedione2,4(1H,3H)-quinazolinedione: structure given in first source
4-hydroxybenzamide
naphthalimidesNaphthalimides: Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS.
4-methylquinolin-2(1H)-one4-methylquinolin-2(1H)-one : A quinolone that is quinolin-2(1H)-one substituted by a methyl group at position 4.quinolone
4-fluorobenzamide4-fluorobenzamide: structure in first source
5-iodo-6-amino-1,2-benzopyrone
alantolactonealantolactone : A sesquiterpene lactone that is 3a,5,6,7,8,8a,9,9a-octahydronaphtho[2,3-b]furan-2-one bearing two methyl substituents at positions 5 and 8a as well as a methylidene substituent at position 3.

alantolactone: allergenic sesquiterpene lactone; crystalline mixture of alantolactones from group of sesquiterpenes; structure
naphthofuran;
olefinic compound;
sesquiterpene lactone
antineoplastic agent;
apoptosis inducer;
plant metabolite
4-aminobenzamidebenzamides
4-Methoxybenzamidebenzamides
4'-methoxyflavone4'-methoxyflavone: from seeds of Psoralea corylifolia (Fabaceae); structure in first sourceether;
flavonoids
3-methoxybenzamide
lestaurtinibindolocarbazole
3',4'-dihydroxyflavone3',4'-dihydroxyflavone: inhibitors of arachidonic acid peroxidation
3-methoxyflavone3-methoxyflavone: from Aspergillus niger; structure in first source
2'-methoxyflavoneether;
flavonoids
6-methoxyflavone6-methoxyflavone: suppresses NFAT-mediated T cell activation; structure in first sourceether;
flavonoids
3,4-dihydro-5-methyl-1(2h)-isoquinolinone3,4-dihydro-5-methyl-1(2H)-isoquinolinone: structure given in first sourceisoquinolines
1-oxo-1,2,3,4-tetrahydroisoquinoline1-oxo-1,2,3,4-tetrahydroisoquinoline: structure given in first source
4'-chloroflavone4'-chloroflavone: structure given in first source
cyclo(alanylalanyl)
sorafenib(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
phenylureas;
pyridinecarboxamide
angiogenesis inhibitor;
anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
ferroptosis inducer;
tyrosine kinase inhibitor
4'-hydroxyflavone4'-hydroxyflavone: structure in first source
6-chloroflavone6-chloroflavone: structure in first source
e-z cinnamic acidcinnamic acid : A monocarboxylic acid that consists of acrylic acid bearing a phenyl substituent at the 3-position. It is found in Cinnamomum cassia.

trans-cinnamic acid : The E (trans) isomer of cinnamic acid
cinnamic acidplant metabolite
7-methoxyflavone7-methoxyflavone: an aromatase inhibitorether;
flavonoids
6-methylflavone6-methylflavone: structure in first source
N-(3-methylphenyl)-4-tetrazolo[1,5-a]quinoxalinaminequinoxaline derivative
iwr-1 exoIWR-1-exo : A dicarboximide having an exo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group. It is a weak axin stabilizer, an analogue of IWR-1-endo.bridged compound;
dicarboximide
axin stabilizer
N-[4-[[[4-(4-methoxyphenyl)-4-oxanyl]methylamino]-oxomethyl]phenyl]-2-furancarboxamidearomatic amide;
furans
tandutinibaromatic ether;
N-arylpiperazine;
N-carbamoylpiperazine;
phenylureas;
piperidines;
quinazolines;
tertiary amino compound
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
ha 1100HA 1100: intracellular calcium antagonist
apigeninChamomile: Common name for several daisy-like plants (MATRICARIA; TRIPLEUROSPERMUM; ANTHEMIS; CHAMAEMELUM) native to Europe and Western Asia, now naturalized in the United States and Australia.trihydroxyflavoneantineoplastic agent;
metabolite
luteolin3'-hydroxyflavonoid;
tetrahydroxyflavone
angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
amentoflavonebiflavonoid;
hydroxyflavone;
ring assembly
angiogenesis inhibitor;
antiviral agent;
cathepsin B inhibitor;
P450 inhibitor;
plant metabolite
3',4',7-trihydroxyflavone3',4',7-trihydroxyflavone: from the Sudanese medicinal plant Albizia zygia; structure in first sourceflavones
su 11248monocarboxylic acid amide;
pyrroles
angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
immunomodulator;
neuroprotective agent;
vascular endothelial growth factor receptor antagonist
adenosine diphosphate (hydroxymethyl)pyrrolidinedioldihydroxypyrrolidine;
purine ribonucleoside 5'-diphosphate
midostaurinmidostaurin : An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.benzamides;
gamma-lactam;
indolocarbazole;
organic heterooctacyclic compound
antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
ag 14361benzimidazoles
gpi 6150
rucaparibAG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first sourceazepinoindole;
caprolactams;
organofluorine compound;
secondary amino compound
antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
3,4-dihydro-5-(4-(1-piperidinyl)butoxy)-1(2h)-isoquinolinone
latonduine alatonduine A: structure in first source
veliparibbenzimidazolesEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
N-(4-methylphenyl)-4-tetrazolo[1,5-a]quinoxalinaminequinoxaline derivative
olaparibcyclopropanes;
monofluorobenzenes;
N-acylpiperazine;
phthalazines
antineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
quizartinibbenzoimidazothiazole;
isoxazoles;
morpholines;
phenylureas
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
necroptosis inhibitor
niraparib2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide : A member of the class of indazoles that is 2H-indazole substituted by 4-(piperidin-3-yl)phenyl and aminocarbonyl groups at positions 2 and 7, respectively. It is a potent PARP1 inhibitor with IC50 of 3.2 nM.benzenes;
indazoles;
piperidines;
primary carboxamide
antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
niraparibniraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.

niraparib: structure in first source
2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamideantineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
radiosensitizing agent
cep 26401pyridazines;
ring assembly
iwr-1 endoIWR-1-endo : A dicarboximide having an endo bridged phthalimide structure, substituted at nitrogen by a 4-(quinolin-8-ylcarbamoyl)benzoyl group.benzamides;
bridged compound;
dicarboximide;
quinolines
axin stabilizer;
Wnt signalling inhibitor
nms-p118NMS-P118: a PARP-1 inhibitor; structure in first source
g007-lkG007-LK: potent and specific small-molecule tankyrase inhibitor; structure in first source
CCT251545CCT251545 : A chloropyridine that is 3-chloropyridine substituted by a 1-oxo-2,8-diazaspiro[4.5]decan-8-yl group and a 4-(1-methyl-1H-pyrazol-4-yl)phenyl group at positions 4 and 5, respectively. It is an orally bioavailable inhibitor of Wnt signaling (IC50 = 5 nM) and a potent and selective chemical probe for cyclin-dependent kinases CDK8 and CDK19.

CCT251545: a Wnt signaling inhibitor; structure in first source
azaspiro compound;
chloropyridine;
pyrazoles
antineoplastic agent;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor;
Wnt signalling inhibitor
nu 1025NU 1064: structure in first sourcephenols;
quinazolines
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
2-methyl-4(3h)-quinazolinone2-methyl-4(3H)-quinazolinone: from Bacillus cereus; structure given in first source
4-hydroxyquinazoline4-oxo-3,4-dihydroquinazoline: structure in first sourcequinazolines
1,4-Dihydrothieno[3,2-d]pyrimidin-4-oneorganic heterobicyclic compound;
organonitrogen heterocyclic compound;
organosulfur heterocyclic compound
xav939XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group.

XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source
(trifluoromethyl)benzenes;
thiopyranopyrimidine
tankyrase inhibitor
2-(4-methoxyphenyl)-1H-quinazolin-4-onequinazolines
bmn 673talazoparib: inhibits both PARP1 and PARP2; structure in first source
me0328ME0328: inhibits ARTD3; structure in first source
nvp-tnks656