ID PARP1_MOUSE Reviewed; 1013 AA. AC P11103; Q9JLX4; Q9QVQ3; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 228. DE RecName: Full=Poly [ADP-ribose] polymerase 1; DE Short=PARP-1; DE EC=2.4.2.30 {ECO:0000250|UniProtKB:P09874}; DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 1; DE Short=ARTD1; DE AltName: Full=DNA ADP-ribosyltransferase PARP1 {ECO:0000305}; DE EC=2.4.2.- {ECO:0000250|UniProtKB:P09874}; DE AltName: Full=NAD(+) ADP-ribosyltransferase 1; DE Short=ADPRT 1; DE AltName: Full=Poly[ADP-ribose] synthase 1; DE Short=msPARP; DE AltName: Full=Protein poly-ADP-ribosyltransferase PARP1 {ECO:0000305}; DE EC=2.4.2.- {ECO:0000269|PubMed:32822587}; DE Contains: DE RecName: Full=Poly [ADP-ribose] polymerase 1, processed C-terminus {ECO:0000250|UniProtKB:P09874}; DE AltName: Full=Poly [ADP-ribose] polymerase 1, 89-kDa form {ECO:0000250|UniProtKB:P09874}; DE Contains: DE RecName: Full=Poly [ADP-ribose] polymerase 1, processed N-terminus {ECO:0000250|UniProtKB:P09874}; DE AltName: Full=Poly [ADP-ribose] polymerase 1, 24-kDa form {ECO:0000250|UniProtKB:P09874}; GN Name=Parp1; Synonyms=Adprp, Adprt, Adprt1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC STRAIN=BXSB; RX PubMed=2498841; DOI=10.1093/nar/17.9.3387; RA Huppi K., Bhatia K., Siwarski D., Klinman D., Cherney B., Smulson M.; RT "Sequence and organization of the mouse poly (ADP-ribose) polymerase RT gene."; RL Nucleic Acids Res. 17:3387-3401(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC STRAIN=C57BL/6 X 129/Sv; TISSUE=Fibroblast; RX PubMed=10809783; DOI=10.1074/jbc.275.20.15504; RA Sallmann F.R., Vodenicharov M.D., Wang Z.-Q., Poirier G.G.; RT "Characterization of sPARP-1. An alternative product of PARP-1 gene with RT poly(ADP-ribose) polymerase activity independent of DNA strand breaks."; RL J. Biol. Chem. 275:15504-15511(2000). RN [3] RP PROTEIN SEQUENCE OF 109-119 AND 865-875, SUBUNIT, AND TISSUE SPECIFICITY. RC STRAIN=C57BL/6J; TISSUE=Spleen; RX PubMed=9642267; DOI=10.1074/jbc.273.27.17025; RA Borggrefe T., Wabl M., Akhmedov A.T., Jessberger R.; RT "A B-cell-specific DNA recombination complex."; RL J. Biol. Chem. 273:17025-17035(1998). RN [4] RP DISRUPTION PHENOTYPE. RX PubMed=7578427; DOI=10.1016/0300-9084(96)88158-2; RA Auer B., Flick K., Wang Z.Q., Haidacher D., Jaeger S., Berghammer H., RA Kofler B., Schweiger M., Wagner E.F.; RT "On the biological role of the nuclear polymerizing NAD+: protein(ADP- RT ribosyl) transferase (ADPRT): ADPRT from Dictyostelium discoideum and RT inactivation of the ADPRT gene in the mouse."; RL Biochimie 77:444-449(1995). RN [5] RP INTERACTION WITH PARP2; XRCC1; POLB AND LRIG3, AND DEVELOPMENTAL STAGE. RX PubMed=11948190; DOI=10.1074/jbc.m202390200; RA Schreiber V., Ame J.-C., Dolle P., Schultz I., Rinaldi B., Fraulob V., RA Menissier-de Murcia J., de Murcia G.M.; RT "Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base RT excision DNA repair in association with PARP-1 and XRCC1."; RL J. Biol. Chem. 277:23028-23036(2002). RN [6] RP FUNCTION. RX PubMed=12114629; DOI=10.1126/science.1072221; RA Yu S.W., Wang H., Poitras M.F., Coombs C., Bowers W.J., Federoff H.J., RA Poirier G.G., Dawson T.M., Dawson V.L.; RT "Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by RT apoptosis-inducing factor."; RL Science 297:259-263(2002). RN [7] RP INTERACTION WITH ZNF423. RX PubMed=14623329; DOI=10.1016/j.bbrc.2003.10.053; RA Ku M.-C., Stewart S., Hata A.; RT "Poly(ADP-ribose) polymerase 1 interacts with OAZ and regulates BMP-target RT genes."; RL Biochem. Biophys. Res. Commun. 311:702-707(2003). RN [8] RP DISRUPTION PHENOTYPE. RX PubMed=12727891; DOI=10.1093/emboj/cdg206; RA Menissier de Murcia J., Ricoul M., Tartier L., Niedergang C., Huber A., RA Dantzer F., Schreiber V., Ame J.C., Dierich A., LeMeur M., Sabatier L., RA Chambon P., de Murcia G.; RT "Functional interaction between PARP-1 and PARP-2 in chromosome stability RT and embryonic development in mouse."; RL EMBO J. 22:2255-2263(2003). RN [9] RP S-NITROSYLATION. RX PubMed=16464859; DOI=10.1074/jbc.m511049200; RA Yu Z., Kuncewicz T., Dubinsky W.P., Kone B.C.; RT "Nitric oxide-dependent negative feedback of PARP-1 trans-activation of the RT inducible nitric-oxide synthase gene."; RL J. Biol. Chem. 281:9101-9109(2006). RN [10] RP FUNCTION. RX PubMed=17116882; DOI=10.1073/pnas.0606526103; RA Andrabi S.A., Kim N.S., Yu S.W., Wang H., Koh D.W., Sasaki M., Klaus J.A., RA Otsuka T., Zhang Z., Koehler R.C., Hurn P.D., Poirier G.G., Dawson V.L., RA Dawson T.M.; RT "Poly(ADP-ribose) (PAR) polymer is a death signal."; RL Proc. Natl. Acad. Sci. U.S.A. 103:18308-18313(2006). RN [11] RP INTERACTION WITH TIAM2. RX PubMed=17320046; DOI=10.1016/j.bbrc.2007.02.028; RA Takefuji M., Mori K., Morita Y., Arimura N., Nishimura T., Nakayama M., RA Hoshino M., Iwamatsu A., Murohara T., Kaibuchi K., Amano M.; RT "Rho-kinase modulates the function of STEF, a Rac GEF, through its RT phosphorylation."; RL Biochem. Biophys. Res. Commun. 355:788-794(2007). RN [12] RP INTERACTION WITH RNF4. RX PubMed=19779455; DOI=10.1038/emboj.2009.279; RA Martin N., Schwamborn K., Schreiber V., Werner A., Guillier C., Zhang X.D., RA Bischof O., Seeler J.S., Dejean A.; RT "PARP-1 transcriptional activity is regulated by sumoylation upon heat RT shock."; RL EMBO J. 28:3534-3548(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Liver, Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [14] RP INTERACTION WITH SNAI1. RX PubMed=21577210; DOI=10.1038/onc.2011.153; RA Rodriguez M.I., Gonzalez-Flores A., Dantzer F., Collard J., RA de Herreros A.G., Oliver F.J.; RT "Poly(ADP-ribose)-dependent regulation of Snail1 protein stability."; RL Oncogene 30:4365-4372(2011). RN [15] RP FUNCTION, ADP-RIBOSYLATION AT LYS-520, AND MUTAGENESIS OF ASP-387; GLU-488; RP GLU-491; LYS-498; LYS-520 AND LYS-523. RX PubMed=21680843; DOI=10.1126/science.1202723; RA Mao Z., Hine C., Tian X., Van Meter M., Au M., Vaidya A., Seluanov A., RA Gorbunova V.; RT "SIRT6 promotes DNA repair under stress by activating PARP1."; RL Science 332:1443-1446(2011). RN [16] RP FUNCTION. RX PubMed=21467298; DOI=10.1126/scisignal.2000902; RA Wang Y., Kim N.S., Haince J.F., Kang H.C., David K.K., Andrabi S.A., RA Poirier G.G., Dawson V.L., Dawson T.M.; RT "Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical RT for PAR polymerase-1-dependent cell death (parthanatos)."; RL Sci. Signal. 4:ra20-ra20(2011). RN [17] RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-214. RX PubMed=22464733; DOI=10.1016/j.molcel.2012.02.016; RA Erener S., Petrilli V., Kassner I., Minotti R., Castillo R., Santoro R., RA Hassa P.O., Tschopp J., Hottiger M.O.; RT "Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression RT of a subset of NF-kappaB target genes."; RL Mol. Cell 46:200-211(2012). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [19] RP INTERACTION WITH KHDC3L, AND SUBCELLULAR LOCATION. RX PubMed=25936915; DOI=10.1016/j.stem.2015.03.017; RA Zhao B., Zhang W.D., Duan Y.L., Lu Y.Q., Cun Y.X., Li C.H., Guo K., RA Nie W.H., Li L., Zhang R., Zheng P.; RT "Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards RT Genomic Stability."; RL Cell Stem Cell 16:684-698(2015). RN [20] RP INTERACTION WITH MACROH2A1. RX PubMed=28991266; DOI=10.1038/nsmb.3481; RA Posavec Marjanovic M., Hurtado-Bages S., Lassi M., Valero V., RA Malinverni R., Delage H., Navarro M., Corujo D., Guberovic I., Douet J., RA Gama-Perez P., Garcia-Roves P.M., Ahel I., Ladurner A.G., Yanes O., RA Bouvet P., Suelves M., Teperino R., Pospisilik J.A., Buschbeck M.; RT "MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ RT consumption."; RL Nat. Struct. Mol. Biol. 24:902-910(2017). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH NMNAT1. RX PubMed=32822587; DOI=10.1016/j.molcel.2020.08.002; RA Huang D., Camacho C.V., Setlem R., Ryu K.W., Parameswaran B., Gupta R.K., RA Kraus W.L.; RT "Functional interplay between histone H2B ADP-ribosylation and RT phosphorylation controls adipogenesis."; RL Mol. Cell 79:934-949(2020). RN [22] RP DISRUPTION PHENOTYPE. RX PubMed=34580230; DOI=10.1073/pnas.2109252118; RA Kelleher A.M., Setlem R., Dantzer F., DeMayo F.J., Lydon J.P., Kraus W.L.; RT "Deficiency of PARP-1 and PARP-2 in the mouse uterus results in RT decidualization failure and pregnancy loss."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [23] RP FUNCTION. RX PubMed=34798058; DOI=10.1016/j.molcel.2021.10.026; RA Zada D., Sela Y., Matosevich N., Monsonego A., Lerer-Goldshtein T., Nir Y., RA Appelbaum L.; RT "Parp1 promotes sleep, which enhances DNA repair in neurons."; RL Mol. Cell 81:4979-4993(2021). RN [24] RP FUNCTION. RX PubMed=35460603; DOI=10.1016/j.molcel.2022.03.034; RA Wang F., Zhao M., Chang B., Zhou Y., Wu X., Ma M., Liu S., Cao Y., RA Zheng M., Dang Y., Xu J., Chen L., Liu T., Tang F., Ren Y., Xu Z., Mao Z., RA Huang K., Luo M., Li J., Liu H., Ge B.; RT "Cytoplasmic PARP1 links the genome instability to the inhibition of RT antiviral immunity through PARylating cGAS."; RL Mol. Cell 0:0-0(2022). CC -!- FUNCTION: Poly-ADP-ribosyltransferase that mediates poly-ADP- CC ribosylation of proteins and plays a key role in DNA repair CC (PubMed:21680843). Mediates glutamate, aspartate, serine, histidine or CC tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of CC NAD(+) is transferred to the acceptor carboxyl group of target residues CC and further ADP-ribosyl groups are transferred to the 2'-position of CC the terminal adenosine moiety, building up a polymer with an average CC chain length of 20-30 units (By similarity). Serine ADP-ribosylation of CC proteins constitutes the primary form of ADP-ribosylation of proteins CC in response to DNA damage (By similarity). Specificity for the CC different amino acids is conferred by interacting factors, such as HPF1 CC and NMNAT1 (PubMed:32822587). Following interaction with HPF1, CC catalyzes serine ADP-ribosylation of target proteins; HPF1 confers CC serine specificity by completing the PARP1 active site (By similarity). CC Also catalyzes tyrosine ADP-ribosylation of target proteins following CC interaction with HPF1 (By similarity). Following interaction with CC NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target CC proteins; NMNAT1 confers glutamate and aspartate specificity CC (PubMed:32822587). PARP1 initiates the repair of DNA breaks: recognizes CC and binds DNA breaks within chromatin and recruits HPF1, licensing CC serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr CC and H3S10ADPr), thereby promoting decompaction of chromatin and the CC recruitment of repair factors leading to the reparation of DNA strand CC breaks (By similarity). HPF1 initiates serine ADP-ribosylation but CC restricts the polymerase activity of PARP1 in order to limit the length CC of poly-ADP-ribose chains (By similarity). In addition to base excision CC repair (BER) pathway, also involved in double-strand breaks (DSBs) CC repair: together with TIMELESS, accumulates at DNA damage sites and CC promotes homologous recombination repair by mediating poly-ADP- CC ribosylation (By similarity). Mediates the poly-ADP-ribosylation of a CC number of proteins, including itself, APLF, CHFR and NFAT5 (By CC similarity). In addition to proteins, also able to ADP-ribosylate DNA: CC catalyzes ADP-ribosylation of DNA strand break termini containing CC terminal phosphates and a 2'-OH group in single- and double-stranded CC DNA, respectively (By similarity). Required for PARP9 and DTX3L CC recruitment to DNA damage sites (By similarity). PARP1-dependent PARP9- CC DTX3L-mediated ubiquitination promotes the rapid and specific CC recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage CC sites (By similarity). PARP1-mediated DNA repair in neurons plays a CC role in sleep: senses DNA damage in neurons and promotes sleep, CC facilitating efficient DNA repair (PubMed:34798058). In addition to DNA CC repair, also involved in other processes, such as transcription CC regulation, programmed cell death, membrane repair, adipogenesis and CC innate immunity (PubMed:32822587, PubMed:35460603). Acts as a repressor CC of transcription: binds to nucleosomes and modulates chromatin CC structure in a manner similar to histone H1, thereby altering RNA CC polymerase II (PubMed:22464733). Acts both as a positive and negative CC regulator of transcription elongation, depending on the context (By CC similarity). Acts as a positive regulator of transcription elongation CC by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding CC activity of NELFE and relieving transcription pausing (By similarity). CC Acts as a negative regulator of transcription elongation in response to CC DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the CC phase separation activity of CCNT1 and subsequent activation of CDK9 CC (By similarity). Involved in replication fork progression following CC interaction with CARM1: mediates poly-ADP-ribosylation at replication CC forks, slowing fork progression (By similarity). Poly-ADP-ribose chains CC generated by PARP1 also play a role in poly-ADP-ribose-dependent cell CC death, a process named parthanatos (PubMed:12114629, PubMed:17116882, CC PubMed:21467298). Also acts as a negative regulator of the cGAS-STING CC pathway (PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CC CGAS: PARP1 translocates into the cytosol following phosphorylation by CC PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS CC (PubMed:35460603). Acts as a negative regulator of adipogenesis: CC catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) CC following interaction with NMNAT1, inhibiting phosphorylation of H2B at CC 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic CC genes (PubMed:32822587). Involved in the synthesis of ATP in the CC nucleus, together with NMNAT1, PARG and NUDT5 (By similarity). Nuclear CC ATP generation is required for extensive chromatin remodeling events CC that are energy-consuming (By similarity). CC {ECO:0000250|UniProtKB:P09874, ECO:0000269|PubMed:12114629, CC ECO:0000269|PubMed:17116882, ECO:0000269|PubMed:21467298, CC ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, CC ECO:0000269|PubMed:32822587, ECO:0000269|PubMed:34798058, CC ECO:0000269|PubMed:35460603}. CC -!- FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: CC Promotes AIFM1-mediated apoptosis. This form, which translocates into CC the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 CC (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and CC serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis. CC {ECO:0000250|UniProtKB:P09874}. CC -!- FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This CC cleavage form irreversibly binds to DNA breaks and interferes with DNA CC repair, promoting DNA damage-induced apoptosis. CC {ECO:0000250|UniProtKB:P09874}. CC -!- CATALYTIC ACTIVITY: CC Reaction=NAD(+) + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D- CC ribosyl)n+1-acceptor + H(+).; EC=2.4.2.30; CC Evidence={ECO:0000250|UniProtKB:P09874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + NAD(+) = H(+) + nicotinamide + O-(ADP-D- CC ribosyl)-L-seryl-[protein]; Xref=Rhea:RHEA:58232, Rhea:RHEA- CC COMP:9863, Rhea:RHEA-COMP:15091, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29999, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:142556; Evidence={ECO:0000250|UniProtKB:P09874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58233; CC Evidence={ECO:0000250|UniProtKB:P09874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L- CC aspartyl-[protein] + nicotinamide; Xref=Rhea:RHEA:54424, Rhea:RHEA- CC COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:17154, CC ChEBI:CHEBI:29961, ChEBI:CHEBI:57540, ChEBI:CHEBI:138102; CC Evidence={ECO:0000269|PubMed:32822587}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54425; CC Evidence={ECO:0000269|PubMed:32822587}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L- CC glutamyl-[protein] + nicotinamide; Xref=Rhea:RHEA:58224, Rhea:RHEA- CC COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:17154, CC ChEBI:CHEBI:29973, ChEBI:CHEBI:57540, ChEBI:CHEBI:142540; CC Evidence={ECO:0000269|PubMed:32822587}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58225; CC Evidence={ECO:0000269|PubMed:32822587}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + NAD(+) = H(+) + nicotinamide + O-(ADP-D- CC ribosyl)-L-tyrosyl-[protein]; Xref=Rhea:RHEA:58236, Rhea:RHEA- CC COMP:10136, Rhea:RHEA-COMP:15092, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:46858, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:142557; Evidence={ECO:0000250|UniProtKB:P09874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58237; CC Evidence={ECO:0000250|UniProtKB:P09874}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-histidyl-[protein] + NAD(+) = H(+) + N(tele)-(ADP-D- CC ribosyl)-L-histidyl-[protein] + nicotinamide; Xref=Rhea:RHEA:72071, CC Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:18085, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29979, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:191398; Evidence={ECO:0000250|UniProtKB:P09874}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72072; CC Evidence={ECO:0000250|UniProtKB:P09874}; CC -!- ACTIVITY REGULATION: ADP-ribosyltransferase activity is regulated via CC an allosteric activation mechanism. In absence of activation signal, CC PARP1 is autoinhibited by the PARP alpha-helical domain (also named HD CC region), which prevents effective NAD(+)-binding. Activity is highly CC stimulated by signals, such as DNA strand breaks. Binding to damaged CC DNA unfolds the PARP alpha-helical domain, relieving autoinhibition. CC Poly-ADP-ribosyltransferase activity is tightly regulated and PARP1 is CC removed from damaged chromatin following initial poly-ADP-ribosylation CC of chromatin to avoid prolonged residence (trapping) that has cytotoxic CC consequences. A number of factors (VCP/p97) or post-translational CC modifications (auto-poly-ADP-ribosylation or ubiquitination) promote CC PARP1 removal from chromatin. {ECO:0000250|UniProtKB:P09874}. CC -!- SUBUNIT: Homodimer; PARP-type zinc-fingers from separate PARP1 CC molecules form a dimer module that specifically recognizes DNA strand CC breaks (By similarity). Heterodimer; heterodimerizes with PARP2 CC (PubMed:11948190). Interacts (via the PARP catalytic domain) with HPF1 CC (By similarity). Interacts with NMNAT1 (PubMed:32822587). Interacts CC with nucleosomes; with a preference for nucleosomes containing H2A.X CC (By similarity). Interacts with APTX (By similarity). Component of a CC base excision repair (BER) complex, containing at least XRCC1, PARP1, CC PARP2, POLB and LRIG3 (PubMed:11948190). Interacts with SRY (By CC similarity). The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70 CC (PubMed:9642267). Interacts with TIAM2 (PubMed:17320046). Interacts CC with PARP3; leading to activate PARP1 in absence of DNA (By CC similarity). Interacts (when poly-ADP-ribosylated) with CHD1L (via CC macro domain) (By similarity). Interacts with the DNA polymerase alpha CC catalytic subunit POLA1; this interaction functions as part of the CC control of replication fork progression (By similarity). Interacts with CC EEF1A1 and TXK (By similarity). Interacts with RNF4 (PubMed:19779455). CC Interacts with RNF146 (By similarity). Interacts with ZNF423 CC (PubMed:14623329). Interacts with APLF (By similarity). Interacts with CC SNAI1 (via zinc fingers); the interaction requires SNAI1 to be poly- CC ADP-ribosylated and non-phosphorylated (active) by GSK3B CC (PubMed:21577210). Interacts (when poly-ADP-ribosylated) with PARP9 (By CC similarity). Interacts with NR4A3; activates PARP1 by improving CC acetylation of PARP1 and suppressing the interaction between PARP1 and CC SIRT1 (By similarity). Interacts (via catalytic domain) with PUM3; the CC interaction inhibits the poly-ADP-ribosylation activity of PARP1 and CC the degradation of PARP1 by CASP3 following genotoxic stress. Interacts CC with ZNF365. Interacts with RRP1B. Interacts with TIMELESS; the CC interaction is direct. Interacts with CGAS; leading to impede the CC formation of the PARP1-TIMELESS complex. Interacts with KHDC3L, the CC interaction is increased following the formation of DNA double-strand CC breaks (PubMed:25936915). Interacts (when auto-poly-ADP-ribosylated) CC with XRCC1; leading to inhibit PARP1 ADP-ribosyltransferase activity CC (By similarity). Interacts with SPINDOC; promoting PARP1 ADP- CC ribosyltransferase activity (By similarity). Interacts with BANF1; CC leading to inhibit PARP1 ADP-ribosyltransferase activity in response to CC oxidative DNA damage (By similarity). Interacts (when sumoylated and CC ubiquitinated) with VCP/p97; leading to its extraction from chromatin CC (By similarity). Interacts with YARS1; promoting PARP1 ADP- CC ribosyltransferase activity (By similarity). Interacts with PACMP CC micropeptide; Interacts with PACMP micropeptide; interaction (By CC similarity). Interacts (when poly-ADP-ribosylated) with isoform 1 of CC MACROH2A1; MACROH2A1 specifically binds to poly-ADP-ribose chains and CC inhibits PARP1 activity, limiting the consumption of nuclear NAD(+) CC (PubMed:28991266). Interacts with CARM1; promoting recruitment to CC replication forks (By similarity). Interacts with RECQL (By CC similarity). Interacts with ZNF32; the interaction reshapes ZNF432 CC interacting proteins (By similarity). {ECO:0000250|UniProtKB:P09874, CC ECO:0000250|UniProtKB:P27008, ECO:0000269|PubMed:11948190, CC ECO:0000269|PubMed:14623329, ECO:0000269|PubMed:17320046, CC ECO:0000269|PubMed:19779455, ECO:0000269|PubMed:21577210, CC ECO:0000269|PubMed:25936915, ECO:0000269|PubMed:28991266, CC ECO:0000269|PubMed:32822587, ECO:0000269|PubMed:9642267}. CC -!- SUBUNIT: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: CC Interacts (when auto-poly-ADP-ribosylated) with AIFM1. CC {ECO:0000250|UniProtKB:P09874}. CC -!- INTERACTION: CC P11103; Q9WTL8: Bmal1; NbExp=7; IntAct=EBI-642213, EBI-644534; CC P11103; P70677: Casp3; NbExp=3; IntAct=EBI-642213, EBI-1790419; CC P11103; P97864: Casp7; NbExp=3; IntAct=EBI-642213, EBI-5307197; CC P11103; P70288: Hdac2; NbExp=3; IntAct=EBI-642213, EBI-302251; CC P11103; P20263: Pou5f1; NbExp=2; IntAct=EBI-642213, EBI-1606219; CC P11103; Q3TKT4: Smarca4; NbExp=2; IntAct=EBI-642213, EBI-1210244; CC P11103; P03087; Xeno; NbExp=2; IntAct=EBI-642213, EBI-1555770; CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:P09874}. CC Nucleus {ECO:0000250|UniProtKB:P09874}. Nucleus, nucleolus CC {ECO:0000250|UniProtKB:P09874}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P09874}. Note=Localizes to sites of DNA damage. CC Recognizes (via PARP-type zinc-fingers) and binds DNA strand breaks. CC Also binds normal/undamaged chromatin. Auto poly-ADP-ribosylation CC promotes dissociation from chromatin (By similarity). Extracted from CC chromatin by VCP/p97 following sumoylation and ubiquitination (By CC similarity). Translocates from the nucleus to the cytosol following CC phosphorylation by PRKDC (By similarity). Recruited to replication CC forks following interaction with CARM1 (By similarity). CC {ECO:0000250|UniProtKB:P09874}. CC -!- SUBCELLULAR LOCATION: [Poly [ADP-ribose] polymerase 1, processed N- CC terminus]: Chromosome {ECO:0000250|UniProtKB:P09874}. Note=Following CC cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to CC apoptosis, this cleavage form irreversibly binds to DNA breaks. CC {ECO:0000250|UniProtKB:P09874}. CC -!- SUBCELLULAR LOCATION: [Poly [ADP-ribose] polymerase 1, processed C- CC terminus]: Cytoplasm {ECO:0000250|UniProtKB:P09874}. Note=Following CC cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to CC apoptosis, translocates into the cytoplasm, where the auto-poly-ADP- CC ribosylated form serves as a poly-ADP-ribose carrier to induce AIFM1- CC mediated apoptosis. {ECO:0000250|UniProtKB:P09874}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; Synonyms=Long; CC IsoId=P11103-1; Sequence=Displayed; CC Name=2; Synonyms=Short {ECO:0000303|PubMed:10809783}, sPARP-1 CC {ECO:0000303|PubMed:10809783}; CC IsoId=P11103-2; Sequence=VSP_018970; CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9642267). Expression is CC correlated with proliferation, with higher levels occurring during CC early fetal development and organogenesis and in the highly CC proliferative cell compartments of adult (PubMed:9642267). Expressed in CC B-cells that have been induced to switch to various Ig isotypes CC (PubMed:9642267). {ECO:0000269|PubMed:9642267}. CC -!- DEVELOPMENTAL STAGE: At stage 12.5 dpc, expressed at high level in the CC developing liver and kidneys (PubMed:11948190). Expressed at higher CC level in the genital ridge and the spinal ganglia (PubMed:11948190). At CC 18.5 dpc, preferentially expressed in the thymus and in regions of the CC nervous system (PubMed:11948190). Within the developing trunk, CC preferential expression persisted in the liver and became restricted to CC the cortical region of the kidney, spleen, adrenal gland, and to CC stomach and intestinal epithelia (PubMed:11948190). From 14.5 dpc to CC 18.5 dpc, as well as in the adult, expressed at the highest level in CC thymus (PubMed:11948190). Expression is particularly high in the CC subcapsular zone of the thymus where immature lymphocytes proliferate CC (PubMed:11948190). Expressed at high level in the seminiferous tubules CC of the developing testis (PubMed:11948190). CC {ECO:0000269|PubMed:11948190}. CC -!- DOMAIN: The two PARP-type zinc-fingers (also named Zn1 and Zn2) CC specifically recognize DNA strand breaks: PARP-type zinc-finger 1 binds CC PARP-type zinc-finger 2 from a separate PARP1 molecule to form a CC dimeric module that specifically recognizes DNA strand breaks. CC {ECO:0000250|UniProtKB:P09874}. CC -!- DOMAIN: The PADR1-type (also named Zn3) zinc-finger mediates an CC interdomain contact and is required for the ability of PARP1 to CC regulate chromatin structure. {ECO:0000250|UniProtKB:P09874}. CC -!- DOMAIN: The BRCT domain is able to bind intact DNA without activating CC the poly-ADP-ribosyltransferase activity. The BRCT domain mediates DNA CC intrastrand transfer (named 'monkey-bar mechanism') that allows rapid CC movements of PARP1 through the nucleus. {ECO:0000250|UniProtKB:P09874}. CC -!- DOMAIN: The WGR domain bridges two nucleosomes, with the broken DNA CC aligned in a position suitable for ligation. The bridging induces CC structural changes in PARP1 that signal the recognition of a DNA break CC to the catalytic domain of PARP1, promoting HPF1 recruitment and CC subsequent activation of PARP1, licensing serine ADP-ribosylation of CC target proteins. {ECO:0000250|UniProtKB:Q9UGN5}. CC -!- DOMAIN: The PARP alpha-helical domain (also named HD region) prevents CC effective NAD(+)-binding in absence of activation signal. Binding to CC damaged DNA unfolds the PARP alpha-helical domain, relieving CC autoinhibition. {ECO:0000250|UniProtKB:P09874}. CC -!- PTM: Poly-ADP-ribosylated on serine, glutamate and aspartate residues CC by autocatalysis. Auto-ADP-ribosylation on serine takes place following CC interaction with HPF1. Auto poly-ADP-ribosylation on serine residues CC promotes its dissociation from chromatin. Poly-ADP-ribosylated by CC PARP2; poly-ADP-ribosylation mediates the recruitment of CHD1L to DNA CC damage sites (By similarity). Mono-ADP-ribosylated at Lys-520 by SIRT6 CC in response to oxidative stress, promoting recruitment to double-strand CC breaks (DSBs) sites (PubMed:21680843). {ECO:0000250|UniProtKB:P09874, CC ECO:0000269|PubMed:21680843}. CC -!- PTM: S-nitrosylated, leading to inhibit transcription regulation CC activity. {ECO:0000269|PubMed:16464859}. CC -!- PTM: Phosphorylated at Thr-593 by PRKDC in response to DNA damage CC following virus infection, promoting its translocation to the cytosol CC (By similarity). Phosphorylated by TXK (By similarity). CC {ECO:0000250|UniProtKB:P09874}. CC -!- PTM: Proteolytically cleaved by caspase-3 (CASP3) and caspase-7 (CASP7) CC in response to apoptosis to generate the Poly [ADP-ribose] polymerase CC 1, processed N-terminus and Poly [ADP-ribose] polymerase 1, processed CC C-terminus forms. {ECO:0000269|PubMed:22464733}. CC -!- PTM: Sumoylated with SUMO1 or SUMO2 by PIAS4 following prolonged CC residence (trapping) to chromatin. Sumoylation promotes ubiquitination CC by RNF4 and removal from chromatin by VCP/p97. CC {ECO:0000250|UniProtKB:P09874}. CC -!- PTM: Ubiquitinated by RNF4 following sumoylation by PIAS4 in response CC to prolonged residence (trapping) to chromatin. Ubiquitination promotes CC removal from chromatin by VCP/p97. {ECO:0000250|UniProtKB:P09874}. CC -!- DISRUPTION PHENOTYPE: Mice show a complete lack of nuclear poly-ADP- CC ribosylation (PubMed:7578427). Mice are however viable and fertile CC (PubMed:7578427). Moreover, repair of UV and MNNG induced DNA damage CC are not affected (PubMed:7578427). However, about 30% of the mutant CC mice developed pathological skin aberrations on a mixed 129/Sv x CC C57B1/6 genetic background (PubMed:7578427). Mice lacking both Parp1 CC and Parp2 are not viable and die at the onset of gastrulation CC (PubMed:12727891). Female mice lacking both Parp1 and Parp2 in the CC uterus display infertility; defects are caused by decidualization CC failure and pregnancy loss (PubMed:34580230). CC {ECO:0000269|PubMed:12727891, ECO:0000269|PubMed:34580230, CC ECO:0000269|PubMed:7578427}. CC -!- SIMILARITY: Belongs to the ARTD/PARP family. {ECO:0000255|PROSITE- CC ProRule:PRU01351, ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X14206; CAA32421.1; -; mRNA. DR EMBL; AF126717; AAF61293.1; -; mRNA. DR PIR; S04200; S04200. DR AlphaFoldDB; P11103; -. DR SMR; P11103; -. DR CORUM; P11103; -. DR DIP; DIP-39371N; -. DR IntAct; P11103; 21. DR MINT; P11103; -. DR STRING; 10090.ENSMUSP00000027777; -. DR BindingDB; P11103; -. DR ChEMBL; CHEMBL3740; -. DR MoonProt; P11103; -. DR GlyGen; P11103; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P11103; -. DR PhosphoSitePlus; P11103; -. DR SwissPalm; P11103; -. DR EPD; P11103; -. DR MaxQB; P11103; -. DR PaxDb; 10090-ENSMUSP00000027777; -. DR PeptideAtlas; P11103; -. DR ProteomicsDB; 288064; -. [P11103-1] DR ProteomicsDB; 288065; -. [P11103-2] DR Pumba; P11103; -. DR AGR; MGI:1340806; -. DR MGI; MGI:1340806; Parp1. DR eggNOG; KOG1037; Eukaryota. DR InParanoid; P11103; -. DR PhylomeDB; P11103; -. DR Reactome; R-MMU-110362; POLB-Dependent Long Patch Base Excision Repair. DR Reactome; R-MMU-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-MMU-5685939; HDR through MMEJ (alt-NHEJ). DR Reactome; R-MMU-5696394; DNA Damage Recognition in GG-NER. DR Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER. DR Reactome; R-MMU-5696400; Dual Incision in GG-NER. DR ChiTaRS; Parp1; mouse. DR PRO; PR:P11103; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P11103; Protein. DR GO; GO:0000785; C:chromatin; IDA:UniProt. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISO:MGI. DR GO; GO:0016604; C:nuclear body; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; ISO:MGI. DR GO; GO:0043596; C:nuclear replication fork; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0032993; C:protein-DNA complex; ISO:MGI. DR GO; GO:0090734; C:site of DNA damage; IDA:UniProt. DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; ISO:MGI. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0051287; F:NAD binding; ISO:MGI. DR GO; GO:0140294; F:NAD DNA ADP-ribosyltransferase activity; ISO:MGI. DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:MGI. DR GO; GO:0140806; F:NAD+- protein-aspartate ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0140822; F:NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity; IDA:UniProt. DR GO; GO:0140816; F:NAD+-histone H2BS6 serine ADP-ribosyltransferase activity; ISO:MGI. DR GO; GO:0140817; F:NAD+-histone H3S10 serine ADP-ribosyltransferase activity; ISO:MGI. DR GO; GO:1990404; F:NAD+-protein ADP-ribosyltransferase activity; IDA:MGI. DR GO; GO:0140807; F:NAD+-protein-glutamate ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0140815; F:NAD+-protein-histidine ADP-ribosyltransferase activity; ISS:UniProtKB. DR GO; GO:0140805; F:NAD+-protein-serine ADP-ribosyltransferase activity; ISS:UniProtKB. DR GO; GO:0140808; F:NAD+-protein-tyrosine ADP-ribosyltransferase activity; ISS:UniProtKB. DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI. DR GO; GO:0031491; F:nucleosome binding; ISS:UniProtKB. DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0070412; F:R-SMAD binding; ISO:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0140537; F:transcription regulator activator activity; ISO:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; ISO:MGI. DR GO; GO:1990966; P:ATP generation from poly-ADP-D-ribose; ISS:UniProtKB. DR GO; GO:0006284; P:base-excision repair; IMP:MGI. DR GO; GO:0048148; P:behavioral response to cocaine; IMP:MGI. DR GO; GO:0016051; P:carbohydrate biosynthetic process; ISO:MGI. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI. DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISO:MGI. DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:MGI. DR GO; GO:0071451; P:cellular response to superoxide; IDA:MGI. DR GO; GO:0034644; P:cellular response to UV; ISO:MGI. DR GO; GO:0046697; P:decidualization; IMP:UniProtKB. DR GO; GO:0030592; P:DNA ADP-ribosylation; ISS:UniProtKB. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. DR GO; GO:0006259; P:DNA metabolic process; IMP:MGI. DR GO; GO:0006281; P:DNA repair; IDA:UniProt. DR GO; GO:0006302; P:double-strand break repair; IGI:MGI. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0032042; P:mitochondrial DNA metabolic process; ISO:MGI. DR GO; GO:0043504; P:mitochondrial DNA repair; ISO:MGI. DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI. DR GO; GO:1904178; P:negative regulation of adipose tissue development; IDA:UniProt. DR GO; GO:2001170; P:negative regulation of ATP biosynthetic process; ISO:MGI. DR GO; GO:0160049; P:negative regulation of cGAS/STING signaling pathway; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProt. DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:MGI. DR GO; GO:1904357; P:negative regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0034244; P:negative regulation of transcription elongation by RNA polymerase II; ISO:MGI. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB. DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; ISO:MGI. DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; ISS:UniProtKB. DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; ISO:MGI. DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; ISO:MGI. DR GO; GO:1904762; P:positive regulation of myofibroblast differentiation; ISO:MGI. DR GO; GO:0060545; P:positive regulation of necroptotic process; IDA:UniProtKB. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI. DR GO; GO:1903518; P:positive regulation of single strand break repair; IGI:UniProtKB. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0070213; P:protein auto-ADP-ribosylation; ISS:UniProtKB. DR GO; GO:0016540; P:protein autoprocessing; ISO:MGI. DR GO; GO:0071168; P:protein localization to chromatin; ISO:MGI. DR GO; GO:0036211; P:protein modification process; ISO:MGI. DR GO; GO:1905051; P:regulation of base-excision repair; ISO:MGI. DR GO; GO:0045188; P:regulation of circadian sleep/wake cycle, non-REM sleep; IMP:UniProtKB. DR GO; GO:0044030; P:regulation of DNA methylation; ISO:MGI. DR GO; GO:0040009; P:regulation of growth rate; IMP:MGI. DR GO; GO:1903376; P:regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; ISO:MGI. DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI. DR GO; GO:1903516; P:regulation of single strand break repair; IMP:MGI. DR GO; GO:0071932; P:replication fork reversal; ISS:UniProtKB. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; ISO:MGI. DR GO; GO:0000723; P:telomere maintenance; IMP:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI. DR GO; GO:0050882; P:voluntary musculoskeletal movement; IGI:UniProtKB. DR CDD; cd17747; BRCT_PARP1; 1. DR CDD; cd01437; parp_like; 1. DR CDD; cd08001; WGR_PARP1_like; 1. DR Gene3D; 1.10.20.130; -; 1. DR Gene3D; 2.20.25.630; -; 1. DR Gene3D; 3.90.228.10; -; 1. DR Gene3D; 3.40.50.10190; BRCT domain; 1. DR Gene3D; 1.20.142.10; Poly(ADP-ribose) polymerase, regulatory domain; 1. DR Gene3D; 3.30.1740.10; Zinc finger, PARP-type; 2. DR InterPro; IPR001357; BRCT_dom. DR InterPro; IPR036420; BRCT_dom_sf. DR InterPro; IPR038650; PADR1_C_dom_sf. DR InterPro; IPR008288; PARP. DR InterPro; IPR049296; PARP1-like_PADR1_N. DR InterPro; IPR012982; PARP1-like_PADR1_Zn_ribbon. DR InterPro; IPR012317; Poly(ADP-ribose)pol_cat_dom. DR InterPro; IPR004102; Poly(ADP-ribose)pol_reg_dom. DR InterPro; IPR036616; Poly(ADP-ribose)pol_reg_dom_sf. DR InterPro; IPR036930; WGR_dom_sf. DR InterPro; IPR008893; WGR_domain. DR InterPro; IPR001510; Znf_PARP. DR InterPro; IPR036957; Znf_PARP_sf. DR PANTHER; PTHR10459; DNA LIGASE; 1. DR PANTHER; PTHR10459:SF112; POLY [ADP-RIBOSE] POLYMERASE 1; 1. DR Pfam; PF00533; BRCT; 1. DR Pfam; PF21728; PADR1_N; 1. DR Pfam; PF08063; PADR1_Zn_ribbon; 1. DR Pfam; PF00644; PARP; 1. DR Pfam; PF02877; PARP_reg; 1. DR Pfam; PF05406; WGR; 1. DR Pfam; PF00645; zf-PARP; 2. DR PIRSF; PIRSF000489; NAD_ADPRT; 1. DR SMART; SM00292; BRCT; 1. DR SMART; SM01335; PADR1; 1. DR SMART; SM00773; WGR; 1. DR SMART; SM01336; zf-PARP; 2. DR SUPFAM; SSF56399; ADP-ribosylation; 1. DR SUPFAM; SSF52113; BRCT domain; 1. DR SUPFAM; SSF47587; Domain of poly(ADP-ribose) polymerase; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 2. DR SUPFAM; SSF142921; WGR domain-like; 1. DR PROSITE; PS50172; BRCT; 1. DR PROSITE; PS52007; PADR1; 1. DR PROSITE; PS51060; PARP_ALPHA_HD; 1. DR PROSITE; PS51059; PARP_CATALYTIC; 1. DR PROSITE; PS51977; WGR; 1. DR PROSITE; PS00347; ZF_PARP_1; 2. DR PROSITE; PS50064; ZF_PARP_2; 2. PE 1: Evidence at protein level; KW Acetylation; ADP-ribosylation; Allosteric enzyme; Alternative initiation; KW Apoptosis; Chromosome; Cytoplasm; Direct protein sequencing; DNA damage; KW DNA repair; DNA-binding; Glycosyltransferase; Immunity; Innate immunity; KW Isopeptide bond; Metal-binding; NAD; Nucleotidyltransferase; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; S-nitrosylation; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CHAIN 2..1013 FT /note="Poly [ADP-ribose] polymerase 1" FT /id="PRO_0000023259" FT CHAIN 2..214 FT /note="Poly [ADP-ribose] polymerase 1, processed N- FT terminus" FT /evidence="ECO:0000250|UniProtKB:P09874" FT /id="PRO_0000456363" FT CHAIN 215..1013 FT /note="Poly [ADP-ribose] polymerase 1, processed C- FT terminus" FT /evidence="ECO:0000250|UniProtKB:P09874" FT /id="PRO_0000456364" FT DOMAIN 225..359 FT /note="PADR1 zinc-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01351" FT DOMAIN 385..476 FT /note="BRCT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033" FT DOMAIN 541..637 FT /note="WGR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01321" FT DOMAIN 661..778 FT /note="PARP alpha-helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00398" FT DOMAIN 787..1013 FT /note="PARP catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00397" FT ZN_FING 9..93 FT /note="PARP-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT ZN_FING 113..203 FT /note="PARP-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT REGION 200..226 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 290..332 FT /note="Zinc ribbon" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01351" FT REGION 373..523 FT /note="Automodification domain" FT /evidence="ECO:0000250|UniProtKB:P09874" FT REGION 489..508 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 207..209 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOTIF 221..226 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:P09874" FT ACT_SITE 987 FT /note="For poly [ADP-ribose] polymerase activity" FT /evidence="ECO:0000250|UniProtKB:P09874" FT BINDING 21 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 24 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 53 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 56 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 125 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 128 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 159 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 162 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00264" FT BINDING 295 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01351" FT BINDING 298 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01351" FT BINDING 311 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01351" FT BINDING 321 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01351" FT BINDING 861..863 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q9UGN5" FT BINDING 870 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q9UGN5" FT BINDING 877 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q9UGN5" FT BINDING 903 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:Q9UGN5" FT SITE 214..215 FT /note="Cleavage; by caspase-3 and caspase-7" FT /evidence="ECO:0000269|PubMed:22464733" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 41 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 97 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 105 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 131 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 177 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 179 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 185 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 274 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 387 FT /note="PolyADP-ribosyl aspartic acid" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 407 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 413 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 435 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 437 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 444 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 445 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 448 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 456 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 484 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 488 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 491 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 499 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 503 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 506 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 512 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 513 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 518 FT /note="ADP-ribosylserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 519 FT /note="PolyADP-ribosyl glutamic acid" FT /evidence="ECO:0000255" FT MOD_RES 520 FT /note="N6-(ADP-ribosyl)lysine" FT /evidence="ECO:0000269|PubMed:21680843" FT MOD_RES 593 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 599 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 620 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 781 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT MOD_RES 785 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 192 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 203 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 203 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 249 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 467 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 486 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 486 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 511 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 527 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 747 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:P09874" FT CROSSLNK 747 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:P09874" FT VAR_SEQ 1..521 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10809783" FT /id="VSP_018970" FT MUTAGEN 214 FT /note="D->N: Abolished cleavage by caspase-7 (CASP7)." FT /evidence="ECO:0000269|PubMed:22464733" FT MUTAGEN 387 FT /note="D->A: Does not affect mono-ADP-ribosylation by FT SIRT6." FT /evidence="ECO:0000269|PubMed:21680843" FT MUTAGEN 488 FT /note="E->A: Does not affect mono-ADP-ribosylation by FT SIRT6." FT /evidence="ECO:0000269|PubMed:21680843" FT MUTAGEN 491 FT /note="E->A: Does not affect mono-ADP-ribosylation by FT SIRT6." FT /evidence="ECO:0000269|PubMed:21680843" FT MUTAGEN 498 FT /note="K->A: Does not affect mono-ADP-ribosylation by FT SIRT6." FT /evidence="ECO:0000269|PubMed:21680843" FT MUTAGEN 520 FT /note="K->A: Abolished mono-ADP-ribosylation by SIRT6." FT /evidence="ECO:0000269|PubMed:21680843" FT MUTAGEN 523 FT /note="K->A: Does not affect mono-ADP-ribosylation by FT SIRT6." FT /evidence="ECO:0000269|PubMed:21680843" FT CONFLICT 114 FT /note="A -> L (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 591 FT /note="L -> V (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 608 FT /note="E -> D (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 612 FT /note="Q -> H (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 629 FT /note="N -> D (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 679 FT /note="D -> E (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 717 FT /note="Q -> E (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 758 FT /note="Q -> L (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" FT CONFLICT 982 FT /note="A -> C (in Ref. 2; AAF61293)" FT /evidence="ECO:0000305" SQ SEQUENCE 1013 AA; 113100 MW; 5E54C3E5F60BB922 CRC64; MAEASERLYR VQYAKSGRAS CKKCSESIPK DSLRMAIMVQ SPMFDGKVPH WYHFSCFWKV GQSIRHPDVE VDGFSELRWD DQQKVKKTAE AGGVAGKGQD GSGGKAEKTL GDFAAEYAKS NRSMCKGCLE KIEKGQMRLS KKMVDPEKPQ LGMIDRWYHP TCFVKKRDEL GFRPEYSASQ LKGFSLLSAE DKEALKKQLP AIKNEGKRKG DEVDGTDEVA KKKSRKETDK YSKLEKALKA QNELIWNIKD ELKKACSTND LKELLIFNQQ QVPSGESAIL DRVADGMAFG ALLPCKECSG QLVFKSDAYY CTGDVTAWTK CMVKTQNPSR KEWVTPKEFR EISYLKKLKV KKQDRIFPPE SSAPITVHWP LSVTSAPTAV NSSAPADKPL SNMKILTLGK LSQNKDEAKA VIEKLGGKLT GSANKASLCI SIKKEVEKMN KKMEEVKEAN IRVVSEDFLQ DVSASTKSLQ DLLSAHSLSP WGAEVKAEPG EVVAPRGKSA APSKKSKGCF KEEGVNKSEK RMKLTLKGGA AVDPDSGLEH SAHVLEKGGK VFSATLGLVD IVKGTNSYYK LQLLEDDKES RYWIFRSWGR LGTVIGSNKL EQMPSKEEAV EQFMKLYEEK TGNAWHSKNF TKYPKKFYPL EIDYGQDEEA VKKLTVKPGT KSKLPKPVQE LVGMIFDVDS MKKALVEYEI DLQKMPLGKL SRRQIQAAYS ILSEVQQPVS QGSSESQILD LSNRFYTLIP HDFGMKKPPL LNNADSVQAK VEMLDNLLDI EVAYSLLRGG SDDSSKDPID VNYEKLKTDI KVVDRDSEEA EVIRKYVKNT HATTHNAYDL EVIDIFKIER EGESQRYKPF RQLHNRRLLW HGSRTTNFAG ILSQGLRIAP PEAPVTGYMF GKGIYFADMV SKSANYCHTS QGDPIGLIML GEVALGNMYE LKHASHISKL PKGKHSVKGL GKTTPDPSAS ITLEGVEVPL GTGIPSGVND TALLYNEYIV YDIAQVNLKY LLKLKFNFKT SLW //