PARP1
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of glutamate and aspartate 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. Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR. Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity. Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1. Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner. Involved in the base excision repair (BER) pathway by catalyzing the poly-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. 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. 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. Required for PARP9 and DTX3L recruitment to DNA damage sites. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage; EC 2.4.2.30; Nuclear envelope; Nuclear receptor co-regulator; Nucleolus; Transferase
Cellular Component: chromatin; cytoplasm; cytosol; mitochondrion; nuclear body; nuclear envelope; nuclear replication fork; nucleolus; nucleoplasm; nucleus; protein-containing complex; protein-DNA complex; site of DNA damage; site of double-strand break; transcription regulator complex
Molecular Function: chromatin binding; damaged DNA binding; DNA binding; enzyme binding; histone deacetylase binding; identical protein binding; NAD binding; NAD DNA ADP-ribosyltransferase activity; NAD+ ADP-ribosyltransferase activity; NAD+- protein-aspartate ADP-ribosyltransferase activity; NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity; NAD+-histone H2BS6 serine ADP-ribosyltransferase activity; NAD+-histone H3S10 serine ADP-ribosyltransferase activity; NAD+-protein ADP-ribosyltransferase activity; NAD+-protein-glutamate ADP-ribosyltransferase activity; NAD+-protein-histidine ADP-ribosyltransferase activity; NAD+-protein-serine ADP-ribosyltransferase activity; NAD+-protein-tyrosine ADP-ribosyltransferase activity; nuclear estrogen receptor binding; nucleosome binding; nucleotidyltransferase activity; pentosyltransferase activity; protein binding; protein homodimerization activity; protein kinase binding; R-SMAD binding; RNA polymerase II-specific DNA-binding transcription factor binding; ubiquitin protein ligase binding; zinc ion binding
Biological Process: apoptotic process; ATP generation from poly-ADP-D-ribose; base-excision repair; behavioral response to cocaine; carbohydrate biosynthetic process; cellular response to amyloid-beta; cellular response to insulin stimulus; cellular response to nerve growth factor stimulus; cellular response to oxidative stress; cellular response to superoxide; cellular response to transforming growth factor beta stimulus; cellular response to UV; cellular response to zinc ion; decidualization; DNA ADP-ribosylation; DNA damage response; DNA metabolic process; DNA repair; double-strand break repair; innate immune response; mitochondrial DNA metabolic process; mitochondrial DNA repair; mitochondrion organization; negative regulation of adipose tissue development; negative regulation of ATP biosynthetic process; negative regulation of DNA-templated transcription; negative regulation of innate immune response; negative regulation of interleukin-17 production; negative regulation of telomere maintenance via telomere lengthening; negative regulation of transcription by RNA polymerase II; negative regulation of transcription elongation by RNA polymerase II; positive regulation of cardiac muscle hypertrophy; positive regulation of DNA-templated transcription, elongation; positive regulation of double-strand break repair via homologous recombination; positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of intracellular estrogen receptor signaling pathway; positive regulation of mitochondrial depolarization; positive regulation of myofibroblast differentiation; positive regulation of necroptotic process; positive regulation of protein localization to nucleus; positive regulation of single strand break repair; positive regulation of SMAD protein signal transduction; positive regulation of transcription by RNA polymerase II; positive regulation of transcription regulatory region DNA binding; protein auto-ADP-ribosylation; protein autoprocessing; protein localization to chromatin; protein modification process; protein poly-ADP-ribosylation; regulation of base-excision repair; regulation of catalytic activity; regulation of circadian sleep/wake cycle, non-REM sleep; regulation of DNA methylation; regulation of growth rate; regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; regulation of protein localization; regulation of single strand break repair; replication fork reversal; response to aldosterone; response to gamma radiation; signal transduction involved in regulation of gene expression; telomere maintenance; transforming growth factor beta receptor signaling pathway; voluntary musculoskeletal movement
