Poly [ADP-ribose] polymerase 1 (P09874)

Uniprot ID P09874
Protein Name Poly [ADP-ribose] polymerase 1
Gene Name PARP1
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b) 0.197
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:26344098). 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 (PubMed:7852410, PubMed:9315851, PubMed:19764761, PubMed:25043379). Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR (PubMed:17396150, PubMed:19764761). Also mediates serine ADP-ribosylation of target proteins following interaction with HPF1; HPF1 conferring serine specificity (PubMed:28190768). Probably also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:30257210). Catalyzes the poly-ADP-ribosylation of histones in a HPF1-dependent manner (PubMed:27067600). 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 (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272). 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). 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). 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 (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). .
GO - Molecular function
  • DNA binding : TAS:ProtInc
  • DNA-binding transcription activator activity, RNA polymerase II-specific : IDA:NTNU_SB
  • enzyme binding : IPI:UniProtKB
  • estrogen receptor binding : IEA:Ensembl
  • histone deacetylase binding : IEA:Ensembl
  • identical protein binding : IPI:IntAct
  • NAD binding : IEA:Ensembl
  • NAD DNA ADP-ribosyltransferase activity : IDA:UniProtKB
  • NAD+ ADP-ribosyltransferase activity : IDA:UniProtKB
  • protein ADP-ribosylase activity : IDA:UniProtKB
  • protein kinase binding : IPI:UniProtKB
  • protein N-terminus binding : IPI:UniProtKB
  • R-SMAD binding : IEA:Ensembl
  • RNA binding : HDA:UniProtKB
  • RNA polymerase II regulatory region sequence-specific DNA binding : IDA:NTNU_SB
  • transcription factor binding : IPI:BHF-UCL
  • zinc ion binding : IEA:InterPro
GO - Biological process
  • apoptotic process : IDA:UniProtKB
  • ATP generation from poly-ADP-D-ribose : IDA:UniProtKB
  • cellular response to amyloid-beta : IEA:Ensembl
  • cellular response to DNA damage stimulus : IMP:UniProtKB
  • cellular response to insulin stimulus : IDA:BHF-UCL
  • cellular response to oxidative stress : IMP:MGI
  • cellular response to UV : IMP:BHF-UCL
  • cellular response to zinc ion : IEA:Ensembl
  • DNA ADP-ribosylation : IDA:UniProtKB
  • DNA damage response, detection of DNA damage : IEA:Ensembl
  • DNA repair : TAS:UniProtKB
  • double-strand break repair : IMP:UniProtKB
  • double-strand break repair via homologous recombination : TAS:Reactome
  • global genome nucleotide-excision repair : TAS:Reactome
  • macrophage differentiation : TAS:UniProtKB
  • mitochondrial DNA metabolic process : IMP:MGI
  • mitochondrial DNA repair : IMP:MGI
  • mitochondrion organization : IMP:MGI
  • negative regulation of ATP biosynthetic process : IMP:ParkinsonsUK-UCL
  • negative regulation of telomere maintenance via telomere lengthening : ISS:BHF-UCL
  • negative regulation of transcription by RNA polymerase II : TAS:Reactome
  • nucleotide-excision repair, DNA damage recognition : TAS:Reactome
  • nucleotide-excision repair, DNA duplex unwinding : TAS:Reactome
  • nucleotide-excision repair, DNA incision : TAS:Reactome
  • nucleotide-excision repair, DNA incision, 3'-to lesion : TAS:Reactome
  • nucleotide-excision repair, DNA incision, 5'-to lesion : TAS:Reactome
  • nucleotide-excision repair, preincision complex assembly : TAS:Reactome
  • nucleotide-excision repair, preincision complex stabilization : TAS:Reactome
  • peptidyl-glutamic acid poly-ADP-ribosylation : IDA:UniProtKB
  • peptidyl-serine ADP-ribosylation : IDA:UniProtKB
  • positive regulation of cardiac muscle hypertrophy : ISS:UniProtKB
  • positive regulation of double-strand break repair via homologous recombination : IDA:UniProtKB
  • positive regulation of intracellular estrogen receptor signaling pathway : IEA:Ensembl
  • positive regulation of mitochondrial depolarization : IEA:Ensembl
  • positive regulation of myofibroblast differentiation : IEA:Ensembl
  • positive regulation of neuron death : IEA:Ensembl
  • positive regulation of protein localization to nucleus : IEA:Ensembl
  • positive regulation of single strand break repair : IGI:UniProtKB
  • positive regulation of SMAD protein signal transduction : IEA:Ensembl
  • positive regulation of transcription by RNA polymerase II : IDA:NTNU_SB
  • positive regulation of transcription regulatory region DNA binding : IEA:Ensembl
  • protein ADP-ribosylation : IDA:UniProtKB
  • protein auto-ADP-ribosylation : IDA:UniProtKB
  • protein autoprocessing : IEA:Ensembl
  • protein modification process : IMP:MGI
  • protein poly-ADP-ribosylation : IDA:UniProtKB
  • regulation of catalytic activity : IDA:BHF-UCL
  • regulation of cellular protein localization : IMP:MGI
  • regulation of DNA methylation : IEA:Ensembl
  • regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway : IEA:Ensembl
  • regulation of SMAD protein complex assembly : IEA:Ensembl
  • response to aldosterone : IEA:Ensembl
  • response to gamma radiation : IEA:Ensembl
  • signal transduction involved in regulation of gene expression : IEA:Ensembl
  • telomere maintenance : TAS:BHF-UCL
  • transcription by RNA polymerase II : TAS:ProtInc
  • transforming growth factor beta receptor signaling pathway : IEA:Ensembl
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(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.