P11103
uniprot
P11103
canonical
activity_regulation
ACTIVITY REGULATION: ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism. In absence of activation signal, PARP1 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding. Activity is highly stimulated by signals, such as DNA strand breaks. Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition. 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. A number of factors (VCP/p97) or post-translational modifications (auto-poly-ADP-ribosylation or ubiquitination) promote PARP1 removal from chromatin. {ECO:0000250|UniProtKB:P09874}.
uniprot
proteins
amino_acid_sequence
MAEASERLYRVQYAKSGRASCKKCSESIPKDSLRMAIMVQSPMFDGKVPHWYHFSCFWKVGQSIRHPDVEVDGFSELRWDDQQKVKKTAEAGGVAGKGQDGSGGKAEKTLGDFAAEYAKSNRSMCKGCLEKIEKGQMRLSKKMVDPEKPQLGMIDRWYHPTCFVKKRDELGFRPEYSASQLKGFSLLSAEDKEALKKQLPAIKNEGKRKGDEVDGTDEVAKKKSRKETDKYSKLEKALKAQNELIWNIKDELKKACSTNDLKELLIFNQQQVPSGESAILDRVADGMAFGALLPCKECSGQLVFKSDAYYCTGDVTAWTKCMVKTQNPSRKEWVTPKEFREISYLKKLKVKKQDRIFPPESSAPITVHWPLSVTSAPTAVNSSAPADKPLSNMKILTLGKLSQNKDEAKAVIEKLGGKLTGSANKASLCISIKKEVEKMNKKMEEVKEANIRVVSEDFLQDVSASTKSLQDLLSAHSLSPWGAEVKAEPGEVVAPRGKSAAPSKKSKGCFKEEGVNKSEKRMKLTLKGGAAVDPDSGLEHSAHVLEKGGKVFSATLGLVDIVKGTNSYYKLQLLEDDKESRYWIFRSWGRLGTVIGSNKLEQMPSKEEAVEQFMKLYEEKTGNAWHSKNFTKYPKKFYPLEIDYGQDEEAVKKLTVKPGTKSKLPKPVQELVGMIFDVDSMKKALVEYEIDLQKMPLGKLSRRQIQAAYSILSEVQQPVSQGSSESQILDLSNRFYTLIPHDFGMKKPPLLNNADSVQAKVEMLDNLLDIEVAYSLLRGGSDDSSKDPIDVNYEKLKTDIKVVDRDSEEAEVIRKYVKNTHATTHNAYDLEVIDIFKIEREGESQRYKPFRQLHNRRLLWHGSRTTNFAGILSQGLRIAPPEAPVTGYMFGKGIYFADMVSKSANYCHTSQGDPIGLIMLGEVALGNMYELKHASHISKLPKGKHSVKGLGKTTPDPSASITLEGVEVPLGTGIPSGVNDTALLYNEYIVYDIAQVNLKYLLKLKFNFKTSLW
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:21680843). 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 (By similarity). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (By similarity). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:32822587). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (By similarity). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (By similarity). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (PubMed:32822587). 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 (By similarity). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (By similarity). 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 (By similarity). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR and NFAT5 (By similarity). 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 (By similarity). Required for PARP9 and DTX3L recruitment to DNA damage sites (By similarity). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (By similarity). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (PubMed:34798058). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:32822587, 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:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (By similarity). 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 (By similarity). 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 (By similarity). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (By similarity). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (PubMed:12114629, PubMed:17116882, PubMed:21467298). Also acts as a negative regulator of the cGAS-STING pathway (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 (PubMed:32822587). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (By similarity). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P09874, ECO:0000269|PubMed:12114629, ECO:0000269|PubMed:17116882, ECO:0000269|PubMed:21467298, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:32822587, ECO:0000269|PubMed:34798058, ECO:0000269|PubMed:35460603}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis. 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. {ECO:0000250|UniProtKB:P09874}.; 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:0000250|UniProtKB:P09874}.
uniprot
proteins
mass_dalton
113100
uniprot
proteins
mutagenesis
MUTAGEN 214; /note="D->N: Abolished cleavage by caspase-7 (CASP7)."; /evidence="ECO:0000269|PubMed:22464733"; MUTAGEN 387; /note="D->A: Does not affect mono-ADP-ribosylation by SIRT6."; /evidence="ECO:0000269|PubMed:21680843"; MUTAGEN 488; /note="E->A: Does not affect mono-ADP-ribosylation by SIRT6."; /evidence="ECO:0000269|PubMed:21680843"; MUTAGEN 491; /note="E->A: Does not affect mono-ADP-ribosylation by SIRT6."; /evidence="ECO:0000269|PubMed:21680843"; MUTAGEN 498; /note="K->A: Does not affect mono-ADP-ribosylation by SIRT6."; /evidence="ECO:0000269|PubMed:21680843"; MUTAGEN 520; /note="K->A: Abolished mono-ADP-ribosylation by SIRT6."; /evidence="ECO:0000269|PubMed:21680843"; MUTAGEN 523; /note="K->A: Does not affect mono-ADP-ribosylation by SIRT6."; /evidence="ECO:0000269|PubMed:21680843
uniprot
proteins
post_translational_modification
PTM: Poly-ADP-ribosylated on serine, glutamate and aspartate residues by autocatalysis. Auto-ADP-ribosylation on serine takes place following interaction with HPF1. Auto poly-ADP-ribosylation on serine residues promotes its dissociation from chromatin. Poly-ADP-ribosylated by PARP2; poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites (By similarity). Mono-ADP-ribosylated at Lys-520 by SIRT6 in response to oxidative stress, promoting recruitment to double-strand breaks (DSBs) sites (PubMed:21680843). {ECO:0000250|UniProtKB:P09874, ECO:0000269|PubMed:21680843}.; PTM: S-nitrosylated, leading to inhibit transcription regulation activity. {ECO:0000269|PubMed:16464859}.; PTM: Phosphorylated at Thr-593 by PRKDC in response to DNA damage following virus infection, promoting its translocation to the cytosol (By similarity). Phosphorylated by TXK (By similarity). {ECO:0000250|UniProtKB:P09874}.; 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. {ECO:0000269|PubMed:22464733}.; PTM: Sumoylated with SUMO1 or SUMO2 by PIAS4 following prolonged residence (trapping) to chromatin. Sumoylation promotes ubiquitination by RNF4 and removal from chromatin by VCP/p97. {ECO:0000250|UniProtKB:P09874}.; PTM: Ubiquitinated by RNF4 following sumoylation by PIAS4 in response to prolonged residence (trapping) to chromatin. Ubiquitination promotes removal from chromatin by VCP/p97. {ECO:0000250|UniProtKB:P09874}.
uniprot
proteins
protein_family
ARTD/PARP family
uniprot
proteins
pubmed
10809783
uniprot
proteins
pubmed
11948190
uniprot
proteins
pubmed
12114629
uniprot
proteins
pubmed
12727891
uniprot
proteins
pubmed
14623329
uniprot
proteins
pubmed
16464859
uniprot
proteins
pubmed
17116882
uniprot
proteins
pubmed
17320046
uniprot
proteins
pubmed
19779455
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21467298
uniprot
proteins
pubmed
21577210
uniprot
proteins
pubmed
21680843
uniprot
proteins
pubmed
22464733
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
2498841
uniprot
proteins
pubmed
25936915
uniprot
proteins
pubmed
28991266
uniprot
proteins
pubmed
32822587
uniprot
proteins
pubmed
34580230
uniprot
proteins
pubmed
34798058
uniprot
proteins
pubmed
35460603
uniprot
proteins
pubmed
7578427
uniprot
proteins
pubmed
9642267
uniprot
proteins
sequence_length
1013
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:P09874}. Nucleus {ECO:0000250|UniProtKB:P09874}. Nucleus, nucleolus {ECO:0000250|UniProtKB:P09874}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P09874}. Note=Localizes to sites of DNA damage. Recognizes (via PARP-type zinc-fingers) and binds DNA strand breaks. Also binds normal/undamaged chromatin. Auto poly-ADP-ribosylation promotes dissociation from chromatin (By similarity). Extracted from chromatin by VCP/p97 following sumoylation and ubiquitination (By similarity). Translocates from the nucleus to the cytosol following phosphorylation by PRKDC (By similarity). Recruited to replication forks following interaction with CARM1 (By similarity). {ECO:0000250|UniProtKB:P09874}.; SUBCELLULAR LOCATION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: Chromosome {ECO:0000250|UniProtKB:P09874}. Note=Following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, this cleavage form irreversibly binds to DNA breaks. {ECO:0000250|UniProtKB:P09874}.; SUBCELLULAR LOCATION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Cytoplasm {ECO:0000250|UniProtKB:P09874}. 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:0000250|UniProtKB:P09874}.
uniprot
proteins