ID:PARP1_HUMAN DESCRIPTION: RecName: Full=Poly [ADP-ribose] polymerase 1; Short=PARP-1; EC=2.4.2.30; AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 1; Short=ARTD1; AltName: Full=NAD(+) ADP-ribosyltransferase 1; Short=ADPRT 1; AltName: Full=Poly[ADP-ribose] synthase 1; FUNCTION: Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP- ribosyl)ation of APLF and CHFR. 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. CATALYTIC ACTIVITY: NAD(+) + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor. SUBUNIT: Component of a base excision repair (BER) complex, containing at least XRCC1, PARP2, POLB and LRIG3. Homo- and heterodimer with PARP2. Interacts with PARP3, APTX and SRY. The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70. Interacts with TIAM2 (By similarity). Interacts (when poly-ADP-ribosylated) with CHD1L. Interacts with the DNA polymerase alpha catalytic subunit POLA1; this interaction functions as part of the control of replication fork progression. Interacts with EEF1A1, RNF4 and TXK. Interacts with RNF146. Interacts with ZNF423. INTERACTION: Q7Z2E3:APTX; NbExp=7; IntAct=EBI-355676, EBI-847814; P49715:CEBPA; NbExp=2; IntAct=EBI-355676, EBI-1172054; Q01094:E2F1; NbExp=2; IntAct=EBI-355676, EBI-448924; P11308:ERG; NbExp=7; IntAct=EBI-355676, EBI-79704; O95863:SNAI1; NbExp=10; IntAct=EBI-355676, EBI-1045459; Q02085:Snai1 (xeno); NbExp=3; IntAct=EBI-355676, EBI-6049807; P04637:TP53; NbExp=3; IntAct=EBI-355676, EBI-366083; Q14191:WRN; NbExp=6; IntAct=EBI-355676, EBI-368417; SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. PTM: Phosphorylated by PRKDC and TXK. Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: Poly-ADP-ribosylated by PARP2. Poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites. PTM: S-nitrosylated, leading to inhibit transcription regulation activity (By similarity). MISCELLANEOUS: The ADP-D-ribosyl group of NAD(+) is transferred to an acceptor carboxyl group on a histone or the enzyme itself, 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. SIMILARITY: Contains 1 BRCT domain. SIMILARITY: Contains 1 PARP alpha-helical domain. SIMILARITY: Contains 1 PARP catalytic domain. SIMILARITY: Contains 2 PARP-type zinc fingers. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/adprt/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P09874
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003677 DNA binding GO:0003723 RNA binding GO:0003910 DNA ligase (ATP) activity GO:0003950 NAD+ ADP-ribosyltransferase activity GO:0005515 protein binding GO:0008134 transcription factor binding GO:0008270 zinc ion binding GO:0016740 transferase activity GO:0016757 transferase activity, transferring glycosyl groups GO:0019899 enzyme binding GO:0019901 protein kinase binding GO:0030331 estrogen receptor binding GO:0042802 identical protein binding GO:0042826 histone deacetylase binding GO:0046332 SMAD binding GO:0046872 metal ion binding GO:0047485 protein N-terminus binding GO:0051287 NAD binding GO:0070412 R-SMAD binding GO:1990404 protein ADP-ribosylase activity
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000715 nucleotide-excision repair, DNA damage recognition GO:0000723 telomere maintenance GO:0000724 double-strand break repair via homologous recombination GO:0006273 lagging strand elongation GO:0006281 DNA repair GO:0006293 nucleotide-excision repair, preincision complex stabilization GO:0006294 nucleotide-excision repair, preincision complex assembly GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion GO:0006302 double-strand break repair GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0006471 protein ADP-ribosylation GO:0006915 apoptotic process GO:0006974 cellular response to DNA damage stimulus GO:0007005 mitochondrion organization GO:0007179 transforming growth factor beta receptor signaling pathway GO:0010332 response to gamma radiation GO:0010613 positive regulation of cardiac muscle hypertrophy GO:0010990 regulation of SMAD protein complex assembly GO:0016540 protein autoprocessing GO:0018312 peptidyl-serine ADP-ribosylation GO:0023019 signal transduction involved in regulation of gene expression GO:0030225 macrophage differentiation GO:0032042 mitochondrial DNA metabolic process GO:0032869 cellular response to insulin stimulus GO:0033148 positive regulation of intracellular estrogen receptor signaling pathway GO:0033683 nucleotide-excision repair, DNA incision GO:0034599 cellular response to oxidative stress GO:0034644 cellular response to UV GO:0036211 protein modification process GO:0042769 DNA damage response, detection of DNA damage GO:0043504 mitochondrial DNA repair GO:0044030 regulation of DNA methylation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0050790 regulation of catalytic activity GO:0051103 DNA ligation involved in DNA repair GO:0051901 positive regulation of mitochondrial depolarization GO:0060391 positive regulation of SMAD protein import into nucleus GO:0070212 protein poly-ADP-ribosylation GO:0070911 global genome nucleotide-excision repair GO:0071294 cellular response to zinc ion GO:0071560 cellular response to transforming growth factor beta stimulus GO:1900182 positive regulation of protein localization to nucleus GO:1901216 positive regulation of neuron death GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway GO:1903518 positive regulation of single strand break repair GO:1903827 regulation of cellular protein localization GO:1904044 response to aldosterone GO:1904357 negative regulation of telomere maintenance via telomere lengthening GO:1904646 cellular response to beta-amyloid GO:1904762 positive regulation of myofibroblast differentiation GO:1990966 ATP generation from poly-ADP-D-ribose GO:2000679 positive regulation of transcription regulatory region DNA binding GO:2001170 negative regulation of ATP biosynthetic process
AK225654 - Homo sapiens mRNA for Poly [ADP-ribose] polymerase 1 variant, clone: STM01125. HV708932 - JP 2012506450-A/30: Methods for treating eye disorders. J03473 - Human poly(ADP-ribose) synthetase mRNA, complete cds. JD297989 - Sequence 279013 from Patent EP1572962. JD315593 - Sequence 296617 from Patent EP1572962. BC037545 - Homo sapiens poly (ADP-ribose) polymerase 1, mRNA (cDNA clone MGC:40266 IMAGE:5193735), complete cds. M18112 - Human poly(ADP-ribose) polymerase mRNA, complete cds. M32721 - Human poly(ADP-ribose) polymerase mRNA, complete cds. JD516437 - Sequence 497461 from Patent EP1572962. JD499214 - Sequence 480238 from Patent EP1572962. JD308509 - Sequence 289533 from Patent EP1572962. JD301908 - Sequence 282932 from Patent EP1572962. AK303340 - Homo sapiens cDNA FLJ53442 complete cds, highly similar to Poly (ADP-ribose) polymerase 1 (EC 2.4.2.30). JD548482 - Sequence 529506 from Patent EP1572962. AK125650 - Homo sapiens cDNA FLJ43662 fis, clone SYNOV4005981, highly similar to POLY [ADP-RIBOSE] POLYMERASE (EC 2.4.2.30). JD136026 - Sequence 117050 from Patent EP1572962. M17081 - Human placental poly(ADP-ribose) polymerase mRNA, partial cds. JD277127 - Sequence 258151 from Patent EP1572962. AK312339 - Homo sapiens cDNA, FLJ92658, highly similar to Homo sapiens poly (ADP-ribose) polymerase family, member 1 (PARP1), mRNA. DQ891636 - Synthetic construct clone IMAGE:100004266; FLH178858.01X; RZPDo839H11128D poly (ADP-ribose) polymerase family, member 1 (PARP1) gene, encodes complete protein. AB384394 - Synthetic construct DNA, clone: pF1KSDB0593, Homo sapiens PARP1 gene for poly [ADP-ribose] polymerase-1, complete cds, without stop codon, in Flexi system. DQ894826 - Synthetic construct Homo sapiens clone IMAGE:100009286; FLH178854.01L; RZPDo839H11127D poly (ADP-ribose) polymerase family, member 1 (PARP1) gene, encodes complete protein. JD026823 - Sequence 7847 from Patent EP1572962. JD021509 - Sequence 2533 from Patent EP1572962. JD035010 - Sequence 16034 from Patent EP1572962. DL492514 - Novel nucleic acids. DL490983 - Novel nucleic acids. CS019680 - Sequence 1 from Patent WO2005012524. DD462176 - Use of RNAi inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer. HV745827 - JP 2012102099-A/1: Use of RNAi inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer. HW411218 - JP 2014001210-A/1: Use of RNAi inhibiting PARP activity for the manufacture of a medicament for the treatment of cancer. AF401218 - Homo sapiens poly(ADP-ribose) polymerase mRNA, partial cds. BC021045 - Homo sapiens poly (ADP-ribose) polymerase 1, mRNA (cDNA clone IMAGE:2966657). BC018620 - Homo sapiens poly (ADP-ribose) polymerase 1, mRNA (cDNA clone IMAGE:5015448), partial cds. BC008660 - Homo sapiens poly (ADP-ribose) polymerase family, member 1, mRNA (cDNA clone IMAGE:3866228), with apparent retained intron. BC014206 - Homo sapiens poly (ADP-ribose) polymerase 1, mRNA (cDNA clone IMAGE:4643426), partial cds. JD227944 - Sequence 208968 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_fasPathway - FAS signaling pathway ( CD95 ) h_tnfr1Pathway - TNFR1 Signaling Pathway h_HivnefPathway - HIV-I Nef: negative effector of Fas and TNF h_caspasePathway - Caspase Cascade in Apoptosis h_aifPathway - Opposing roles of AIF in Apoptosis and Cell Survival h_d4gdiPathway - D4-GDI Signaling Pathway h_chemicalPathway - Apoptotic Signaling in Response to DNA Damage
Reactome (by CSHL, EBI, and GO)
Protein P09874 (Reactome details) participates in the following event(s):
R-HSA-2187330 PARP1 binds SMAD2/3:SMAD4 heterotrimer R-HSA-4551604 PIAS4 SUMOylates PARP1 with SUMO1 R-HSA-4551768 PIAS4 SUMOylates PARP1 with SUMO2,3 R-HSA-2187325 PARP1 ADP-ribosylates SMAD3 and SMAD4 R-HSA-5649873 PARP1,PARP2 dimers and FEN1 bind POLB and displace APEX1 from damaged AP site R-HSA-5687484 PARP1 or PARP2, FEN1 and POLQ are recruited to MMEJ site R-HSA-5696664 PARP1 or PARP2 binds DDB2 at GG-NER site R-HSA-5651828 PARG dePARylates PARP1,PARP2 R-HSA-5651739 PAR-PARP1,PAR-PARP2 dissociate from FEN1 and POLB R-HSA-5687653 PARP1,PARP2 dimers bound to MMEJ sites autoPARylate R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-5649883 POLB-mediated DNA strand displacement synthesis R-HSA-5651723 PARP1,PARP2 dimers bound to FEN1 and POLB autoPARylate R-HSA-5687640 POLQ extends annealed 3'-ssDNA overhangs in MMEJ R-HSA-5696655 PARP1 or PARP2 PARylates DDB2 and autoPARylates R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-6790454 SUMOylation of XPC R-HSA-5690996 ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-6790487 RNF111 ubiquitinates SUMOylated XPC R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-5696670 CHD1L is recruited to GG-NER site R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity R-HSA-3108214 SUMOylation of DNA damage response and repair proteins R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-110362 POLB-Dependent Long Patch Base Excision Repair R-HSA-5685939 HDR through MMEJ (alt-NHEJ) R-HSA-5696394 DNA Damage Recognition in GG-NER R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-212436 Generic Transcription Pathway R-HSA-2990846 SUMOylation R-HSA-5696400 Dual Incision in GG-NER R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway R-HSA-5693538 Homology Directed Repair R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-9006936 Signaling by TGF-beta family members R-HSA-73857 RNA Polymerase II Transcription R-HSA-597592 Post-translational protein modification R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-73933 Resolution of Abasic Sites (AP sites) R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-5696398 Nucleotide Excision Repair R-HSA-162582 Signal Transduction R-HSA-74160 Gene expression (Transcription) R-HSA-392499 Metabolism of proteins R-HSA-73884 Base Excision Repair R-HSA-73894 DNA Repair
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
