PARP1
entrez
142
canonical
uniprot
P09874
canonical
ensembl
ENSG00000143799
resolver
ensp
ENSP00000355759
resolver
enst
ENST00000366794
resolver
genesymbol
PARP1
resolver
genesymbol_syn
ADPRT
resolver
genesymbol_syn
PPOL
resolver
hgnc
HGNC:270
resolver
uniprot
B1ANJ4
resolver
uniprot
Q8IUZ9
resolver
uniprot_entry
PARP1_HUMAN
resolver
uniprot_sec
B1ANJ4
resolver
uniprot_sec
Q8IUZ9
resolver
activity_regulation
ACTIVITY REGULATION: ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism (PubMed:22582261, PubMed:26626479, PubMed:26626480, PubMed:32241924, PubMed:32358582). In absence of activation signal, PARP1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding (PubMed:26626479, PubMed:26626480, PubMed:32241924). Activity is highly stimulated by signals, such as DNA strand breaks (PubMed:20388712, PubMed:32241924, PubMed:32358582). Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition (PubMed:22582261, PubMed:26626479, PubMed:26626480, PubMed:32241924). Poly-ADP-ribosyltransferase activity is tightly regulated and PARP1 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences (PubMed:34210965, PubMed:34625544, PubMed:35013556). A number of factors (VCP/p97) or post-translational modifications (auto-poly-ADP-ribosylation or ubiquitination) promote PARP1 removal from chromatin (PubMed:34210965, PubMed:34625544, PubMed:35013556). ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination (PubMed:29487285, PubMed:32241924, PubMed:32358582). PARPi molecules can be classified in three categories: type I compounds (EB-47, UKTT15 and BAD) that promote allosteric retention of PARP1 on DNA, type II inhibitors (talazoparib and olaparib) that mediate a non-allosteric inhibition, and type III inhibitors (rucaparib, niraparib, and veliparib) that promote allosteric release from DNA (PubMed:29487285, PubMed:32241924, PubMed:33361107). Trapping to chromatin by PARPi molecules triggers activation of the cGAS-STING pathway (PubMed:32844745). {ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:29487285, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33361107, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:35013556}.
uniprot
proteins
amino_acid_sequence
MAESSDKLYRVEYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKVGHSIRHPDVEVDGFSELRWDDQQKVKKTAEAGGVTGKGQDGIGSKAEKTLGDFAAEYAKSNRSTCKGCMEKIEKGQVRLSKKMVDPEKPQLGMIDRWYHPGCFVKNREELGFRPEYSASQLKGFSLLATEDKEALKKQLPGVKSEGKRKGDEVDGVDEVAKKKSKKEKDKDSKLEKALKAQNDLIWNIKDELKKVCSTNDLKELLIFNKQQVPSGESAILDRVADGMVFGALLPCEECSGQLVFKSDAYYCTGDVTAWTKCMVKTQTPNRKEWVTPKEFREISYLKKLKVKKQDRIFPPETSASVAATPPPSTASAPAAVNSSASADKPLSNMKILTLGKLSRNKDEVKAMIEKLGGKLTGTANKASLCISTKKEVEKMNKKMEEVKEANIRVVSEDFLQDVSASTKSLQELFLAHILSPWGAEVKAEPVEVVAPRGKSGAALSKKSKGQVKEEGINKSEKRMKLTLKGGAAVDPDSGLEHSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKENRYWIFRSWGRVGTVIGSNKLEQMPSKEDAIEHFMKLYEEKTGNAWHSKNFTKYPKKFYPLEIDYGQDEEAVKKLTVNPGTKSKLPKPVQDLIKMIFDVESMKKAMVEYEIDLQKMPLGKLSKRQIQAAYSILSEVQQAVSQGSSDSQILDLSNRFYTLIPHDFGMKKPPLLNNADSVQAKVEMLDNLLDIEVAYSLLRGGSDDSSKDPIDVNYEKLKTDIKVVDRDSEEAEIIRKYVKNTHATTHNAYDLEVIDIFKIEREGECQRYKPFKQLHNRRLLWHGSRTTNFAGILSQGLRIAPPEAPVTGYMFGKGIYFADMVSKSANYCHTSQGDPIGLILLGEVALGNMYELKHASHISKLPKGKHSVKGLGKTTPDPSANISLDGVDVPLGTGISSGVNDTSLLYNEYIVYDIAQVNLKYLLKLKFNFKTSLW
uniprot
proteins
ec_number
2.4.2.-
uniprot
proteins
ec_number
2.4.2.30
uniprot
proteins
function
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, PubMed:41062835). 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). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:41062835, ECO:0000269|PubMed:41261216, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}.
uniprot
proteins
mass_dalton
113084
uniprot
proteins
mutagenesis
MUTAGEN 18; /note="R->A: Abolished DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 25; /note="S->A: Does not affect translocation into the cytosol."; /evidence="ECO:0000269|PubMed:35460603"; MUTAGEN 34; /note="R->A: Abolished DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 34; /note="R->E: Abolished binding to DNA strand breaks."; /evidence="ECO:0000269|PubMed:22683995"; MUTAGEN 40; /note="Q->A: Does not affect DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 41; /note="S->A: No effect."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 42; /note="P->G: No effect."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 43; /note="M->A: No effect."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 43; /note="M->D: Strongly decreased homodimerization."; /evidence="ECO:0000269|PubMed:22683995"; MUTAGEN 44..48; /note="FDGKV->ADGKA: Abolished DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 44; /note="F->A: Abolished DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 44; /note="F->D: Strongly decreased homodimerization."; /evidence="ECO:0000269|PubMed:22683995"; MUTAGEN 45; /note="D->A: Does not affect DNA-binding. Decreased poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:21233213, ECO:0000269|PubMed:22582261"; MUTAGEN 119..120; /note="Missing: Abolished prolonged residence (trapping) to chromatin."; /evidence="ECO:0000269|PubMed:35013556"; MUTAGEN 122; /note="R->A: Strongly decreased DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 138; /note="R->E: Abolished binding to DNA strand breaks."; /evidence="ECO:0000269|PubMed:22683995"; MUTAGEN 151..154; /note="LGMI->AGMA: Abolished DNA-binding."; /evidence="ECO:0000269|PubMed:21233213"; MUTAGEN 214; /note="D->N: Abolished cleavage by caspase-7 (CASP7)."; /evidence="ECO:0000269|PubMed:22464733"; MUTAGEN 241; /note="Q->L: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 246; /note="W->A: Decreased poly-ADP-ribosyltransferase activity upon binding to damaged DNA."; /evidence="ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479"; MUTAGEN 298; /note="C->A: Decreased stability leading to impaired oly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:18055453"; MUTAGEN 314; /note="D->A: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 315; /note="V->A: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 316; /note="T->A: Strongly reduced poly-ADP-ribosyltransferase and ability to regulate chromatin compaction."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 317; /note="A->G: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 318; /note="W->A,R,E: Strongly reduced poly-ADP-ribosyltransferase activity. Able to bind damaged DNA, however, defects in the interdomain communication prevent unfolding of the PARP alpha-helical domain, blocking catalytic activation."; /evidence="ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:32241924"; MUTAGEN 318; /note="W->F: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 319; /note="T->A: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 320; /note="K->A: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 325; /note="T->A: Does not affect translocation into the cytosol."; /evidence="ECO:0000269|PubMed:35460603"; MUTAGEN 348..350; /note="LKV->DKD: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 357; /note="F->Y: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 358..359; /note="PP->GG: Does not affect auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:20388712"; MUTAGEN 394; /note="K->Q: Strongly decreased ability of the BRCT domain to bind intact DNA; when associated with Q-418."; /evidence="ECO:0000269|PubMed:34919819"; MUTAGEN 405..409; /note="KDEVK->QDEVQ: Strongly decreased ability of the BRCT domain to bind intact DNA."; /evidence="ECO:0000269|PubMed:34919819"; MUTAGEN 418..425; /note="KLTGTANK->QLTGTANQ: Strongly decreased ability of the BRCT domain to bind intact DNA."; /evidence="ECO:0000269|PubMed:34919819"; MUTAGEN 418; /note="K->Q: Strongly decreased ability of the BRCT domain to bind intact DNA; when associated with Q-394."; /evidence="ECO:0000269|PubMed:34919819"; MUTAGEN 441..442; /note="KK->QQ: Strongly decreased ability of the BRCT domain to bind intact DNA."; /evidence="ECO:0000269|PubMed:34919819"; MUTAGEN 490..493; /note="VEVV->GEVQ: Strongly reduced interaction with TIMELESS."; /evidence="ECO:0000269|PubMed:26344098"; MUTAGEN 499; /note="S->A: Abolishes automodification on serine following interaction with HPF1, leading to delay dissociation from chromatin; when associated with A-507 and A-519."; /evidence="ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34625544"; MUTAGEN 507; /note="S->A: Abolishes automodification on serine following interaction with HPF1, leading to delay dissociation from chromatin; when associated with A-499 and A-519."; /evidence="ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34625544"; MUTAGEN 519; /note="S->A: Abolishes automodification on serine following interaction with HPF1, leading to delay dissociation from chromatin; when associated with A-499 and A-507."; /evidence="ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34625544"; MUTAGEN 567; /note="N->A: Decreased poly-ADP-ribosyltransferase activity upon binding to damaged DNA."; /evidence="ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479"; MUTAGEN 589; /note="W->A: Decreased poly-ADP-ribosyltransferase activity upon binding to damaged DNA. Abolished ability to mediate DNA intrastrand transfer (named 'monkey-bar mechanism')."; /evidence="ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479"; MUTAGEN 591; /note="R->A: Decreased poly-ADP-ribosyltransferase activity upon binding to damaged DNA."; /evidence="ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479"; MUTAGEN 594; /note="T->A: Abolished phosphorylation by PRKDC, inhibiting translocation into the cytosol."; /evidence="ECO:0000269|PubMed:35460603"; MUTAGEN 633; /note="K->A: Decreased poly-ADP-ribosyltransferase activity upon binding to damaged DNA."; /evidence="ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626479"; MUTAGEN 698..701; /note="LGKL->AGKA: Increased auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:22582261"; MUTAGEN 713; /note="L->A: Increased auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:22582261"; MUTAGEN 713; /note="L->F: Leads to constitutive activity in absence of DNA damage due to unfolding of the PARP alpha-helical domain, relieving autoinhibition."; /evidence="ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:26626480"; MUTAGEN 763..770; /note="EMLDNLLD->AMLANLLA: Able to bind BAD inhibitor in absence of DNA."; /evidence="ECO:0000269|PubMed:29487285"; MUTAGEN 765; /note="L->A: Increased auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:22582261"; MUTAGEN 766..770; /note="DNLLD->ANLLA: Able to bind EB-47 or BAD inhibitors in absence of DNA. Released from DNA strand break independently of EB-47 or BAD inhibitors."; /evidence="ECO:0000269|PubMed:29487285, ECO:0000269|PubMed:32241924"; MUTAGEN 768; /note="L->A: Increased auto-poly-ADP-ribosylation."; /evidence="ECO:0000269|PubMed:22582261"; MUTAGEN 774; /note="A->S,L: Increased DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 797; /note="L->P: 1.5% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 826; /note="H->A: Strongly reduced serine ADP-ribosylation, caused by abolished interaction with HPF1."; /evidence="ECO:0000269|PubMed:32028527"; MUTAGEN 826; /note="H->E: Decreased polymerase activity, leading to the production of short poly-ADP-ribose chains."; /evidence="ECO:0000269|PubMed:34795260"; MUTAGEN 850..851; /note="Missing: Abolished interaction with TIMELESS."; /evidence="ECO:0000269|PubMed:26344098"; MUTAGEN 862; /note="H->A: Poly-ADP-ribosyltransferase activity is impaired while mono-ADP-ribosyltransferase activity is not affected; produces a mixture of short and mono ADP-ribose chains."; /evidence="ECO:0000269|PubMed:7852410"; MUTAGEN 865; /note="R->A: Increased affinity for DNA damage sites."; /evidence="ECO:0000269|PubMed:34795260"; MUTAGEN 868; /note="N->S: 4% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 870; /note="A->S,L: Increased DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 871; /note="G->L: Increased DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 871; /note="G->S: Does not affect DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 882; /note="P->G: Does not affect DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 883..887; /note="EAPVT->ASSVA: Does not affect DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 883; /note="E->Q: Does not affect ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:7852410"; MUTAGEN 885; /note="P->G,S: Does not affect DNA-independent poly-ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26626480"; MUTAGEN 890; /note="M->V: <0.5% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 893; /note="K->I: Abolishes enzymatic activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 897; /note="F->S: 10% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 899; /note="D->N: 0.6% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 908; /note="C->R: <0.5% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 923; /note="E->Q: Does not affect ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:7852410"; MUTAGEN 926; /note="L->F: 1.5% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 931; /note="E->Q: Does not affect ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:7852410"; MUTAGEN 986; /note="Y->H: 14% of wild-type activity and increased branching 15-fold."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 988; /note="E->A,D,Q,K: Poly-ADP-ribosyltransferase activity is inhibited while mono-ADP-ribosyltransferase activity is not affected; only monomers are added. Disrupts interaction with CHD1L and ability to recruit PARP2 to DNA damage sites."; /evidence="ECO:0000269|PubMed:29220653, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851"; MUTAGEN 993; /note="D->G: Abolished interaction with TIMELESS."; /evidence="ECO:0000269|PubMed:26344098"; MUTAGEN 1003; /note="L->P: 1.5% of wild-type activity."; /evidence="ECO:0000269|PubMed:9315851"; MUTAGEN 1013..1014; /note="LW->EE: Strongly reduced serine ADP-ribosylation, caused by abolished interaction with HPF1."; /evidence="ECO:0000269|PubMed:32028527
uniprot
proteins
post_translational_modification
PTM: Poly-ADP-ribosylated on serine, glutamate and aspartate residues by autocatalysis (PubMed:19764761, PubMed:20388712, PubMed:22582261). Auto-ADP-ribosylation on serine takes place following interaction with HPF1 (PubMed:28190768, PubMed:34625544). Auto poly-ADP-ribosylation on serine residues promotes its dissociation from chromatin (PubMed:15607977, PubMed:30675909, PubMed:32358582, PubMed:34210965, PubMed:34625544). Poly-ADP-ribosylated by PARP2; poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites (PubMed:19661379). Mono-ADP-ribosylated at Lys-521 by SIRT6 in response to oxidative stress, promoting recruitment to double-strand breaks (DSBs) sites (PubMed:21680843, PubMed:22753495, PubMed:27568560). {ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:22753495, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:30675909, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34625544}.; PTM: Phosphorylated at Thr-594 by PRKDC in response to DNA damage following virus infection, promoting its translocation to the cytosol (PubMed:10467406, PubMed:35460603). Phosphorylated by TXK (PubMed:17177976). {ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:35460603}.; PTM: S-nitrosylated, leading to inhibit transcription regulation activity. {ECO:0000250|UniProtKB:P11103}.; PTM: Proteolytically cleaved by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis to generate the Poly [ADP-ribose] polymerase 1, processed N-terminus and Poly [ADP-ribose] polymerase 1, processed C-terminus forms (PubMed:10497198, PubMed:16374543, PubMed:22451931, PubMed:22464733, PubMed:33168626, PubMed:35104452, PubMed:7596430). CASP3-mediated cleavage is promoted by the TP53/p53-induced long non-coding RNA SPARCLE, which binds PARP1 in response to genotoxic stress (PubMed:35104452). {ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:16374543, ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:33168626, ECO:0000269|PubMed:35104452, ECO:0000269|PubMed:7596430}.; PTM: Sumoylated with SUMO1 or SUMO2 by PIAS4 following prolonged residence (trapping) to chromatin (PubMed:35013556). Sumoylation promotes ubiquitination by RNF4 and removal from chromatin by VCP/p97 (PubMed:35013556). {ECO:0000269|PubMed:35013556}.; PTM: Ubiquitinated by RNF4 following sumoylation by PIAS4 in response to prolonged residence (trapping) to chromatin (PubMed:35013556). Ubiquitination promotes removal from chromatin by VCP/p97 (PubMed:35013556). {ECO:0000269|PubMed:35013556}.
uniprot
proteins
protein_family
ARTD/PARP family
uniprot
proteins
pubmed
10467406
uniprot
proteins
pubmed
10497198
uniprot
proteins
pubmed
15044383
uniprot
proteins
pubmed
1505517
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15607977
uniprot
proteins
pubmed
16374543
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16904257
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17177976
uniprot
proteins
pubmed
17396150
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
18055453
uniprot
proteins
pubmed
18172500
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19344625
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19661379
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19710015
uniprot
proteins
pubmed
19764761
uniprot
proteins
pubmed
19779455
uniprot
proteins
pubmed
20064938
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20106667
uniprot
proteins
pubmed
20388712
uniprot
proteins
pubmed
2108670
uniprot
proteins
pubmed
2109322
uniprot
proteins
pubmed
2121735
uniprot
proteins
pubmed
21233213
uniprot
proteins
pubmed
2123876
uniprot
proteins
pubmed
2125269
uniprot
proteins
pubmed
21266351
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21577210
uniprot
proteins
pubmed
21680843
uniprot
proteins
pubmed
21799911
uniprot
proteins
pubmed
22002106
uniprot
proteins
pubmed
22300411
uniprot
proteins
pubmed
22451931
uniprot
proteins
pubmed
22464733
uniprot
proteins
pubmed
22582261
uniprot
proteins
pubmed
22683995
uniprot
proteins
pubmed
22753495
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
22863007
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23213405
uniprot
proteins
pubmed
23230272
uniprot
proteins
pubmed
23966166
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24906880
uniprot
proteins
pubmed
25043379
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
2513174
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25533949
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
25772364
uniprot
proteins
pubmed
26344098
uniprot
proteins
pubmed
26626479
uniprot
proteins
pubmed
26626480
uniprot
proteins
pubmed
27067600
uniprot
proteins
pubmed
27256882
uniprot
proteins
pubmed
27257257
uniprot
proteins
pubmed
27471034
uniprot
proteins
pubmed
27568560
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28190768
uniprot
proteins
pubmed
2824474
uniprot
proteins
pubmed
2891139
uniprot
proteins
pubmed
29220653
uniprot
proteins
pubmed
29487285
uniprot
proteins
pubmed
29954836
uniprot
proteins
pubmed
30104678
uniprot
proteins
pubmed
30257210
uniprot
proteins
pubmed
30356214
uniprot
proteins
pubmed
30675909
uniprot
proteins
pubmed
3113420
uniprot
proteins
pubmed
3120710
uniprot
proteins
pubmed
3121332
uniprot
proteins
pubmed
31609975
uniprot
proteins
pubmed
31796734
uniprot
proteins
pubmed
31848352
uniprot
proteins
pubmed
32028527
uniprot
proteins
pubmed
32241924
uniprot
proteins
pubmed
32315358
uniprot
proteins
pubmed
32358582
uniprot
proteins
pubmed
32844745
uniprot
proteins
pubmed
33168626
uniprot
proteins
pubmed
33186521
uniprot
proteins
pubmed
33361107
uniprot
proteins
pubmed
33412112
uniprot
proteins
pubmed
33589610
uniprot
proteins
pubmed
33683197
uniprot
proteins
pubmed
34049076
uniprot
proteins
pubmed
34102106
uniprot
proteins
pubmed
34210965
uniprot
proteins
pubmed
34465625
uniprot
proteins
pubmed
34625544
uniprot
proteins
pubmed
34732825
uniprot
proteins
pubmed
34737271
uniprot
proteins
pubmed
34795260
uniprot
proteins
pubmed
34811483
uniprot
proteins
pubmed
34874266
uniprot
proteins
pubmed
34919819
uniprot
proteins
pubmed
35013556
uniprot
proteins
pubmed
35025765
uniprot
proteins
pubmed
35104452
uniprot
proteins
pubmed
35124853
uniprot
proteins
pubmed
35219381
uniprot
proteins
pubmed
35393539
uniprot
proteins
pubmed
35460603
uniprot
proteins
pubmed
37823600
uniprot
proteins
pubmed
41062835
uniprot
proteins
pubmed
41261216
uniprot
proteins
pubmed
7596430
uniprot
proteins
pubmed
7852410
uniprot
proteins
pubmed
9315851
uniprot
proteins
pubmed
9518481
uniprot
proteins
pubmed
9721847
uniprot
proteins
sequence_length
1014
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:22683995, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:30675909, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:35013556}. Nucleus {ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:35460603}. Nucleus, nucleolus {ECO:0000269|PubMed:9518481}. Cytoplasm, cytosol {ECO:0000269|PubMed:35460603}. Note=Localizes to sites of DNA damage (PubMed:22683995, PubMed:23230272, PubMed:26344098, PubMed:27568560, PubMed:30675909, PubMed:32241924, PubMed:32358582, PubMed:34625544, PubMed:34795260). Recognizes (via PARP-type zinc-fingers) and binds DNA strand breaks (PubMed:22683995). Also binds normal/undamaged chromatin (PubMed:15607977). Auto poly-ADP-ribosylation promotes dissociation from chromatin (PubMed:15607977, PubMed:30675909, PubMed:32358582, PubMed:34625544). Extracted from chromatin by VCP/p97 following sumoylation and ubiquitination (PubMed:35013556). Translocates from the nucleus to the cytosol following phosphorylation by PRKDC (PubMed:35460603). Recruited to replication forks following interaction with CARM1 (PubMed:33412112). {ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:22683995, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:30675909, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:35013556, ECO:0000269|PubMed:35460603}.; SUBCELLULAR LOCATION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: Chromosome {ECO:0000269|PubMed:33168626, ECO:0000269|PubMed:35104452, ECO:0000269|PubMed:9721847}. Note=Following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, this cleavage form irreversibly binds to DNA breaks. {ECO:0000269|PubMed:33168626, ECO:0000269|PubMed:35104452, ECO:0000269|PubMed:9721847}.; SUBCELLULAR LOCATION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Cytoplasm {ECO:0000269|PubMed:33168626}. Note=Following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, translocates into the cytoplasm, where the auto-poly-ADP-ribosylated form serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis. {ECO:0000269|PubMed:33168626}.
uniprot
proteins