Search Results
Overview
| Uniprot ID | P09874 |
|---|---|
| Protein Name | Poly [ADP-ribose] polymerase 1 |
| Gene Name | PARP1 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 105 | GQDGIGSKAEKTLGD |
| 108 | GIGSKAEKTLGDFAA |
| 119 | DFAAEYAKSNRSTCK |
| 209 | VKSEGKRKGDEVDGV |
| 222 | GVDEVAKKKSKKEKD |
| 346 | FREISYLKKLKVKKQ |
| 400 | MKILTLGKLSRNKDE |
| 434 | SLCISTKKEVEKMNK |
| 498 | EVVAPRGKSGAALSK |
| 505 | KSGAALSKKSKGQVK |
| 506 | SGAALSKKSKGQVKE |
| 512 | KKSKGQVKEEGINKS |
| 518 | VKEEGINKSEKRMKL |
| 521 | EGINKSEKRMKLTLK |
| 528 | KRMKLTLKGGAAVDP |
| 564 | LGLVDIVKGTNSYYK |
| 621 | FMKLYEEKTGNAWHS |
| 629 | TGNAWHSKNFTKYPK |
| 633 | WHSKNFTKYPKKFYP |
| 637 | NFTKYPKKFYPLEID |
| 654 | QDEEAVKKLTVNPGT |
| 662 | LTVNPGTKSKLPKPV |
| 943 | SHISKLPKGKHSVKG |
| 97 | EAGGVTGKGQDGIGS |
Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine 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:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). 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 (H2BS6ADPr and H3S10ADPr), 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, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). 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-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). 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). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). 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). Plays a role in sister chromatid cohesion by mediating ADP-ribosylation of RSMC during S phase which promotes the interaction between RSMC and CDCA5/sororin, leading to enhanced interaction of CDCA5/sororin with the cohesin complex and promotion of sister chromatid cohesion (PubMed:41261216)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Biological Process | GO:0034599 | cellular response to oxidative stress |
| Cellular Component | GO:0000785 | chromatin |
| Cellular Component | GO:0000781 | chromosome, telomeric region |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0001650 | fibrillar center |
| Cellular Component | GO:0016020 | membrane |
| Cellular Component | GO:0005739 | mitochondrion |
| Cellular Component | GO:0016604 | nuclear body |
| Cellular Component | GO:0005635 | nuclear envelope |
| Cellular Component | GO:0043596 | nuclear replication fork |
| Cellular Component | GO:0005730 | nucleolus |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0032991 | protein-containing complex |
| Cellular Component | GO:0032993 | protein-DNA complex |
| Cellular Component | GO:0090734 | site of DNA damage |
| Cellular Component | GO:0035861 | site of double-strand break |
| Cellular Component | GO:0005667 | transcription regulator complex |
| Molecular Function | GO:0003682 | chromatin binding |
| Molecular Function | GO:0003684 | damaged DNA binding |
| Molecular Function | GO:0003677 | DNA binding |
| Molecular Function | GO:0008047 | enzyme activator activity |
| Molecular Function | GO:0019899 | enzyme binding |
| Molecular Function | GO:0042826 | histone deacetylase binding |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0051287 | NAD binding |
| Molecular Function | GO:0140294 | NAD DNA ADP-ribosyltransferase activity |
| Molecular Function | GO:0003950 | NAD+ poly-ADP-ribosyltransferase activity |
| Molecular Function | GO:0140822 | NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity |
| Molecular Function | GO:0140816 | NAD+-histone H2BS6 serine ADP-ribosyltransferase activity |
| Molecular Function | GO:0140817 | NAD+-histone H3S10 serine ADP-ribosyltransferase activity |
| Molecular Function | GO:1990404 | NAD+-protein mono-ADP-ribosyltransferase activity |
| Molecular Function | GO:0140806 | NAD+-protein-aspartate ADP-ribosyltransferase activity |
| Molecular Function | GO:0140807 | NAD+-protein-glutamate ADP-ribosyltransferase activity |
| Molecular Function | GO:0140815 | NAD+-protein-histidine ADP-ribosyltransferase activity |
| Molecular Function | GO:0140805 | NAD+-protein-serine ADP-ribosyltransferase activity |
| Molecular Function | GO:0140808 | NAD+-protein-tyrosine ADP-ribosyltransferase activity |
| Molecular Function | GO:0044378 | non-sequence-specific DNA binding, bending |
| Molecular Function | GO:0030331 | nuclear estrogen receptor binding |
| Molecular Function | GO:0031491 | nucleosome binding |
| Molecular Function | GO:0016779 | nucleotidyltransferase activity |
| Molecular Function | GO:0042803 | protein homodimerization activity |
| Molecular Function | GO:0019901 | protein kinase binding |
| Molecular Function | GO:0070412 | R-SMAD binding |
| Molecular Function | GO:0003723 | RNA binding |
| Molecular Function | GO:0061629 | RNA polymerase II-specific DNA-binding transcription factor binding |
| Molecular Function | GO:1990165 | single-strand break-containing DNA binding |
| Molecular Function | GO:0140537 | transcription regulator activator activity |
| Molecular Function | GO:0031625 | ubiquitin protein ligase binding |
| Molecular Function | GO:0008270 | zinc ion binding |
| Biological Process | GO:0006915 | apoptotic process |
| Biological Process | GO:1990966 | ATP generation from poly-ADP-D-ribose |
| Biological Process | GO:0016051 | carbohydrate biosynthetic process |
| Biological Process | GO:1904646 | cellular response to amyloid-beta |
| Biological Process | GO:0032869 | cellular response to insulin stimulus |
| Biological Process | GO:1990090 | cellular response to nerve growth factor stimulus |
| Biological Process | GO:0034644 | cellular response to UV |
| Biological Process | GO:0071294 | cellular response to zinc ion |
| Biological Process | GO:0046697 | decidualization |
| Biological Process | GO:0030592 | DNA ADP-ribosylation |
| Biological Process | GO:0006974 | DNA damage response |
| Biological Process | GO:0006281 | DNA repair |
| Biological Process | GO:0006302 | double-strand break repair |
| Biological Process | GO:0071169 | establishment of protein localization to chromatin |
| Biological Process | GO:0045087 | innate immune response |
| Biological Process | GO:0030225 | macrophage differentiation |
| Biological Process | GO:0032042 | mitochondrial DNA metabolic process |
| Biological Process | GO:0043504 | mitochondrial DNA repair |
| Biological Process | GO:0007005 | mitochondrion organization |
| Biological Process | GO:1904178 | negative regulation of adipose tissue development |
| Biological Process | GO:2001170 | negative regulation of ATP biosynthetic process |
| Biological Process | GO:0160049 | negative regulation of cGAS/STING signaling pathway |
| Biological Process | GO:0045892 | negative regulation of DNA-templated transcription |
| Biological Process | GO:0045824 | negative regulation of innate immune response |
| Biological Process | GO:1904357 | negative regulation of telomere maintenance via telomere lengthening |
| Biological Process | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| Biological Process | GO:0034244 | negative regulation of transcription elongation by RNA polymerase II |
| Biological Process | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction |
| Biological Process | GO:0010613 | positive regulation of cardiac muscle hypertrophy |
| Biological Process | GO:0032786 | positive regulation of DNA-templated transcription, elongation |
| Biological Process | GO:1905168 | positive regulation of double-strand break repair via homologous recombination |
| Biological Process | GO:0033148 | positive regulation of intracellular estrogen receptor signaling pathway |
| Biological Process | GO:0051901 | positive regulation of mitochondrial depolarization |
| Biological Process | GO:1904762 | positive regulation of myofibroblast differentiation |
| Biological Process | GO:0060545 | positive regulation of necroptotic process |
| Biological Process | GO:1900182 | positive regulation of protein localization to nucleus |
| Biological Process | GO:0060391 | positive regulation of SMAD protein signal transduction |
| Biological Process | GO:0045944 | positive regulation of transcription by RNA polymerase II |
| Biological Process | GO:0070213 | protein auto-ADP-ribosylation |
| Biological Process | GO:0016540 | protein autoprocessing |
| Biological Process | GO:0071168 | protein localization to chromatin |
| Biological Process | GO:0036211 | protein modification process |
| Biological Process | GO:0070212 | protein poly-ADP-ribosylation |
| Biological Process | GO:1905051 | regulation of base-excision repair |
| Biological Process | GO:0045188 | regulation of circadian sleep/wake cycle, non-REM sleep |
| Biological Process | GO:1903376 | regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway |
| Biological Process | GO:0032880 | regulation of protein localization |
| Biological Process | GO:0071932 | replication fork reversal |
| Biological Process | GO:1904044 | response to aldosterone |
| Biological Process | GO:0045471 | response to ethanol |
| Biological Process | GO:0010332 | response to gamma radiation |
| Biological Process | GO:0023019 | signal transduction involved in regulation of gene expression |
| Biological Process | GO:0000012 | single strand break repair |
| Biological Process | GO:0000723 | telomere maintenance |
| Biological Process | GO:0006366 | transcription by RNA polymerase II |
| Biological Process | GO:0007179 | transforming growth factor beta receptor signaling pathway |
Reference
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