PARP1
This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes.
Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:25043379, PubMed:33186521, PubMed:32028527, PubMed:26344098).
Mediates glutamate, aspartate, serine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD+ is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:7852410, PubMed:9315851, PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836).
Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521).
Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:19764761, PubMed:25043379).
Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:33186521, PubMed:32028527).
Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:30257210, PubMed:29954836).
PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600).
In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214).
Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR (PubMed:17396150, PubMed:19764761).
In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034).
Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272).
PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272).
Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150 (PubMed:19344625).
Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and EEF1A1 (PubMed:17177976).
Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257).
Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257).
Biological Process
Apoptotic process Source: UniProtKB
ATP generation from poly-ADP-D-ribose Source: UniProtKB
Base-excision repair, gap-filling Source: Reactome
Cellular response to amyloid-beta Source: Ensembl
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to insulin stimulus Source: BHF-UCL
Cellular response to oxidative stress Source: MGI
Cellular response to UV Source: BHF-UCL
Cellular response to zinc ion Source: Ensembl
DNA ADP-ribosylation Source: UniProtKB
DNA damage response, detection of DNA damage Source: Ensembl
DNA repair Source: UniProtKB
Double-strand break repair Source: UniProtKB
Double-strand break repair via homologous recombination Source: Reactome
Global genome nucleotide-excision repair Source: Reactome
Macrophage differentiation Source: UniProtKB
Mitochondrial DNA metabolic process Source: MGI
Mitochondrial DNA repair Source: MGI
Mitochondrion organization Source: MGI
Negative regulation of ATP biosynthetic process Source: ParkinsonsUK-UCL
Negative regulation of telomere maintenance via telomere lengthening Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: Reactome
Nucleotide-excision repair, DNA damage recognition Source: Reactome
Nucleotide-excision repair, DNA duplex unwinding Source: Reactome
Nucleotide-excision repair, DNA incision Source: Reactome
Nucleotide-excision repair, DNA incision, 3'-to lesion Source: Reactome
Nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
Nucleotide-excision repair, preincision complex assembly Source: Reactome
Nucleotide-excision repair, preincision complex stabilization Source: Reactome
Peptidyl-glutamic acid poly-ADP-ribosylation Source: UniProtKB
Peptidyl-serine ADP-ribosylation Source: UniProtKB
Positive regulation of cardiac muscle hypertrophy Source: UniProtKB
Positive regulation of double-strand break repair via homologous recombination Source: UniProtKB
Positive regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
Positive regulation of mitochondrial depolarization Source: Ensembl
Positive regulation of myofibroblast differentiation Source: Ensembl
Positive regulation of neuron death Source: Ensembl
Positive regulation of protein localization to nucleus Source: Ensembl
Positive regulation of single strand break repair Source: UniProtKB
Positive regulation of SMAD protein signal transduction Source: Ensembl
Positive regulation of transcription by RNA polymerase II Source: NTNU_SB
Positive regulation of transcription regulatory region DNA binding Source: Ensembl
Protein ADP-ribosylation Source: UniProtKB
Protein auto-ADP-ribosylation Source: UniProtKB
Protein autoprocessing Source: Ensembl
Protein modification process Source: MGI
Protein poly-ADP-ribosylation Source: UniProtKB
Regulation of catalytic activity Source: BHF-UCL
Regulation of cellular protein localization Source: MGI
Regulation of DNA methylation Source: Ensembl
Regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway Source: Ensembl
Regulation of SMAD protein complex assembly Source: Ensembl
Response to aldosterone Source: Ensembl
Response to gamma radiation Source: Ensembl
Signal transduction involved in regulation of gene expression Source: Ensembl
Telomere maintenance Source: BHF-UCL
Transcription by RNA polymerase II Source: ProtInc
Transforming growth factor beta receptor signaling pathway Source: Ensembl
PTM
Poly-ADP-ribosylated on glutamate and aspartate residues by autocatalysis (PubMed:19764761). Poly-ADP-ribosylated by PARP2; poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites (PubMed:19661379). ADP-ribosylated on serine by autocatalysis; serine ADP-ribosylation takes place following interaction with HPF1 (PubMed:28190768). Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP1-HPF1 complex from chromatin (By similarity).
Phosphorylated by PRKDC (PubMed:10467406). Phosphorylated by TXK (PubMed:17177976).
S-nitrosylated, leading to inhibit transcription regulation activity.
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Datasheet