ID PARP2_HUMAN Reviewed; 583 AA. AC Q9UGN5; Q8TEU4; Q9NUV2; Q9UMR4; Q9Y6C8; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 26-SEP-2001, sequence version 2. DT 27-MAR-2024, entry version 210. DE RecName: Full=Poly [ADP-ribose] polymerase 2 {ECO:0000305}; DE Short=PARP-2 {ECO:0000303|PubMed:26704974}; DE Short=hPARP-2 {ECO:0000303|PubMed:26704974}; DE EC=2.4.2.30 {ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32939087}; DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 2 {ECO:0000303|PubMed:30321391}; DE Short=ARTD2 {ECO:0000303|PubMed:30321391}; DE AltName: Full=DNA ADP-ribosyltransferase PARP2 {ECO:0000305}; DE EC=2.4.2.- {ECO:0000269|PubMed:27471034}; DE AltName: Full=NAD(+) ADP-ribosyltransferase 2; DE Short=ADPRT-2; DE AltName: Full=Poly[ADP-ribose] synthase 2 {ECO:0000303|PubMed:10338144}; DE Short=pADPRT-2 {ECO:0000303|PubMed:10338144}; DE AltName: Full=Protein poly-ADP-ribosyltransferase PARP2 {ECO:0000305}; DE EC=2.4.2.- {ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:32939087}; GN Name=PARP2 {ECO:0000303|PubMed:20092359, ECO:0000312|HGNC:HGNC:272}; GN Synonyms=ADPRT2, ADPRTL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=10364231; DOI=10.1074/jbc.274.25.17860; RA Ame J.-C., Rolli V., Schreiber V., Niedergang C., Apiou F., Decker P., RA Muller S., Hoeger T., Menissier-de Murcia J., de Murcia G.M.; RT "PARP-2, a novel mammalian DNA damage-dependent poly(ADP-ribose) RT polymerase."; RL J. Biol. Chem. 274:17860-17868(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-583 (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=10329013; DOI=10.1006/geno.1999.5799; RA Johansson M.; RT "A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of RT two novel poly(ADP-ribose) polymerase homologues."; RL Genomics 57:442-445(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-583 (ISOFORM 1). RC TISSUE=Fibroblast; RX PubMed=10338144; DOI=10.1016/s0014-5793(99)00448-2; RA Berghammer H., Ebner M., Marksteiner R., Auer B.; RT "pADPRT-2: a novel mammalian polymerizing(ADP-ribosyl)transferase gene RT related to truncated pADPRT homologues in plants and Caenorhabditis RT elegans."; RL FEBS Lett. 449:259-263(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-161; SER-168; GLY-235; RP VAL-285 AND GLN-296. RG NIEHS SNPs program; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP INTERACTION WITH PARP1; XRCC1; POLB AND LRIG3. 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 [7] RP NOMENCLATURE. RX PubMed=20106667; DOI=10.1016/j.tibs.2009.12.003; RA Hottiger M.O., Hassa P.O., Luscher B., Schuler H., Koch-Nolte F.; RT "Toward a unified nomenclature for mammalian ADP-ribosyltransferases."; RL Trends Biochem. Sci. 35:208-219(2010). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND SER-232, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [10] RP INTERACTION WITH HPF1. RX PubMed=27067600; DOI=10.1016/j.molcel.2016.03.008; RA Gibbs-Seymour I., Fontana P., Rack J.G., Ahel I.; RT "HPF1/C4orf27 is a PARP-1-interacting protein that regulates PARP-1 ADP- RT ribosylation activity."; RL Mol. Cell 62:432-442(2016). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH HPF1. RX PubMed=28190768; DOI=10.1016/j.molcel.2017.01.003; RA Bonfiglio J.J., Fontana P., Zhang Q., Colby T., Gibbs-Seymour I., RA Atanassov I., Bartlett E., Zaja R., Ahel I., Matic I.; RT "Serine ADP-ribosylation depends on HPF1."; RL Mol. Cell 0:0-0(2017). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25043379; DOI=10.1038/ncomms5426; RA Vyas S., Matic I., Uchima L., Rood J., Zaja R., Hay R.T., Ahel I., RA Chang P.; RT "Family-wide analysis of poly(ADP-ribose) polymerase activity."; RL Nat. Commun. 5:4426-4426(2014). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=27471034; DOI=10.1093/nar/gkw675; RA Talhaoui I., Lebedeva N.A., Zarkovic G., Saint-Pierre C., Kutuzov M.M., RA Sukhanova M.V., Matkarimov B.T., Gasparutto D., Saparbaev M.K., RA Lavrik O.I., Ishchenko A.A.; RT "Poly(ADP-ribose) polymerases covalently modify strand break termini in DNA RT fragments in vitro."; RL Nucleic Acids Res. 44:9279-9295(2016). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVE SITE, AND RP MUTAGENESIS OF GLU-558. RX PubMed=30104678; DOI=10.1038/s41467-018-05588-5; RA Chen Q., Kassab M.A., Dantzer F., Yu X.; RT "PARP2 mediates branched poly ADP-ribosylation in response to DNA damage."; RL Nat. Commun. 9:3233-3233(2018). RN [15] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=29361132; DOI=10.1093/nar/gkx1318; RA Zarkovic G., Belousova E.A., Talhaoui I., Saint-Pierre C., Kutuzov M.M., RA Matkarimov B.T., Biard D., Gasparutto D., Lavrik O.I., Ishchenko A.A.; RT "Characterization of DNA ADP-ribosyltransferase activities of PARP2 and RT PARP3: new insights into DNA ADP-ribosylation."; RL Nucleic Acids Res. 46:2417-2431(2018). RN [16] RP ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-558. RX PubMed=33275888; DOI=10.1016/j.molcel.2020.10.009; RA Blessing C., Mandemaker I.K., Gonzalez-Leal C., Preisser J., Schomburg A., RA Ladurner A.G.; RT "The oncogenic helicase ALC1 regulates PARP inhibitor potency by trapping RT PARP2 at DNA breaks."; RL Mol. Cell 80:862-875(2020). RN [17] RP FUNCTION. RX PubMed=34732825; DOI=10.1038/s42003-021-02780-0; RA Kurgina T.A., Moor N.A., Kutuzov M.M., Naumenko K.N., Ukraintsev A.A., RA Lavrik O.I.; RT "Dual function of HPF1 in the modulation of PARP1 and PARP2 activities."; RL Commun. Biol. 4:1259-1259(2021). RN [18] RP FUNCTION. RX PubMed=34486521; DOI=10.7554/elife.71420; RA Bacic L., Gaullier G., Sabantsev A., Lehmann L.C., Brackmann K., RA Dimakou D., Halic M., Hewitt G., Boulton S.J., Deindl S.; RT "Structure and dynamics of the chromatin remodeler ALC1 bound to a RT PARylated nucleosome."; RL Elife 10:0-0(2021). RN [19] RP FUNCTION. RX PubMed=34874266; DOI=10.7554/elife.71502; RA Mohapatra J., Tashiro K., Beckner R.L., Sierra J., Kilgore J.A., RA Williams N.S., Liszczak G.; RT "Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin RT remodeling."; RL Elife 10:0-0(2021). RN [20] RP FUNCTION. RX PubMed=34795260; DOI=10.1038/s41467-021-27043-8; RA Langelier M.F., Billur R., Sverzhinsky A., Black B.E., Pascal J.M.; RT "HPF1 dynamically controls the PARP1/2 balance between initiating and RT elongating ADP-ribose modifications."; RL Nat. Commun. 12:6675-6675(2021). RN [21] RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-153 AND RP HIS-428. RX PubMed=35349716; DOI=10.1093/nar/gkac188; RA Lin X., Jiang W., Rudolph J., Lee B.J., Luger K., Zha S.; RT "PARP inhibitors trap PARP2 and alter the mode of recruitment of PARP2 at RT DNA damage sites."; RL Nucleic Acids Res. 50:3958-3973(2022). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 235-579 IN COMPLEX WITH PARP RP INHIBITORS, AND SUBUNIT. RX PubMed=20092359; DOI=10.1021/bi902079y; RA Karlberg T., Hammarstrom M., Schutz P., Svensson L., Schuler H.; RT "Crystal structure of the catalytic domain of human PARP2 in complex with RT PARP inhibitor ABT-888."; RL Biochemistry 49:1056-1058(2010). RN [23] {ECO:0007744|PDB:5DSY} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 348-583. RX PubMed=26626480; DOI=10.1016/j.molcel.2015.10.013; RA Dawicki-McKenna J.M., Langelier M.F., DeNizio J.E., Riccio A.A., Cao C.D., RA Karch K.R., McCauley M., Steffen J.D., Black B.E., Pascal J.M.; RT "PARP-1 activation requires local unfolding of an autoinhibitory domain."; RL Mol. Cell 60:755-768(2015). RN [24] {ECO:0007744|PDB:5D5K} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-91, SUBCELLULAR LOCATION, RP NUCLEAR LOCALIZATION SIGNAL, DOMAIN, ACTIVE SITE, AND MUTAGENESIS OF RP 21-LYS-ARG-22; 37-LYS-LYS-38; ASN-129; TYR-201 AND GLU-558. RX PubMed=26704974; DOI=10.1093/nar/gkv1376; RA Riccio A.A., Cingolani G., Pascal J.M.; RT "PARP-2 domain requirements for DNA damage-dependent activation and RT localization to sites of DNA damage."; RL Nucleic Acids Res. 44:1691-1702(2016). RN [25] {ECO:0007744|PDB:6F1K, ECO:0007744|PDB:6F5B, ECO:0007744|PDB:6F5F} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 90-218, FUNCTION, CATALYTIC RP ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF ASN-127; RP ASN-128; LYS-130; TYR-132; TRP-151; ARG-153; GLN-159; LYS-183 AND TYR-201. RX PubMed=30321391; DOI=10.1093/nar/gky927; RA Obaji E., Haikarainen T., Lehtioe L.; RT "Structural basis for DNA break recognition by ARTD2/PARP2."; RL Nucleic Acids Res. 46:12154-12165(2018). RN [26] {ECO:0007744|PDB:6TX3} RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF 323-583 IN COMPLEX WITH NAD RP ANALOG AND HPF1, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, INTERACTION RP WITH HPF1, AND MUTAGENESIS OF HIS-394 AND 582-LEU-TRP-583. RX PubMed=32028527; DOI=10.1038/s41586-020-2013-6; RA Suskiewicz M.J., Zobel F., Ogden T.E.H., Fontana P., Ariza A., Yang J.C., RA Zhu K., Bracken L., Hawthorne W.J., Ahel D., Neuhaus D., Ahel I.; RT "HPF1 completes the PARP active site for DNA damage-induced ADP- RT ribosylation."; RL Nature 579:598-602(2020). RN [27] {ECO:0007744|PDB:6X0L, ECO:0007744|PDB:6X0M, ECO:0007744|PDB:6X0N} RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) IN COMPLEX WITH RP NUCLEOSOME AND HPF1, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, RP INTERACTION WITH HPF1, DOMAIN, ADP-RIBOSYLATION AND NUCLEOSOME CORE RP COMPLEX, AND MUTAGENESIS OF ARG-153 AND VAL-154. RX PubMed=32939087; DOI=10.1038/s41586-020-2725-7; RA Bilokapic S., Suskiewicz M.J., Ahel I., Halic M.; RT "Bridging of DNA breaks activates PARP2-HPF1 to modify chromatin."; RL Nature 585:609-613(2020). RN [28] {ECO:0007744|PDB:6USJ} RP STRUCTURE BY ELECTRON MICROSCOPY (10.50 ANGSTROMS) IN COMPLEX WITH HPF1 AND RP NUCLEOSOME CORE COMPLEX, INTERACTION WITH HPF1, SUBCELLULAR LOCATION, RP DOMAIN, AND MUTAGENESIS OF 125-GLN-PHE-126. RX PubMed=33141820; DOI=10.1371/journal.pone.0240932; RA Gaullier G., Roberts G., Muthurajan U.M., Bowerman S., Rudolph J., RA Mahadevan J., Jha A., Rae P.S., Luger K.; RT "Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances RT its interaction with HPF1."; RL PLoS ONE 15:e0240932-e0240932(2020). RN [29] {ECO:0007744|PDB:7AEO} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 90-583 IN COMPLEX WITH DNA, RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DOMAIN, INTERACTION WITH RP HPF1, AND MUTAGENESIS OF ASN-129; ARG-153; TYR-201; GLU-286 AND GLY-338. RX PubMed=34108479; DOI=10.1038/s41467-021-23800-x; RA Obaji E., Maksimainen M.M., Galera-Prat A., Lehtioe L.; RT "Activation of PARP2/ARTD2 by DNA damage induces conformational changes RT relieving enzyme autoinhibition."; RL Nat. Commun. 12:3479-3479(2021). CC -!- FUNCTION: Poly-ADP-ribosyltransferase that mediates poly-ADP- CC ribosylation of proteins and plays a key role in DNA repair CC (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, CC PubMed:32028527, PubMed:32939087, PubMed:34486521, PubMed:34874266, CC PubMed:34108479). Mediates glutamate, aspartate or serine ADP- CC ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is CC transferred to the acceptor carboxyl group of target residues and CC further ADP-ribosyl groups are transferred to the 2'-position of the CC terminal adenosine moiety, building up a polymer with an average chain CC length of 20-30 units (PubMed:25043379, PubMed:30104678, CC PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the CC primary form of ADP-ribosylation of proteins in response to DNA damage CC (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of CC target proteins in absence of HPF1 (PubMed:25043379). Following CC interaction with HPF1, catalyzes serine ADP-ribosylation of target CC proteins; HPF1 conferring serine specificity by completing the PARP2 CC active site (PubMed:28190768, PubMed:32028527, PubMed:34486521, CC PubMed:34874266, PubMed:34108479). PARP2 initiates the repair of CC double-strand DNA breaks: recognizes and binds DNA breaks within CC chromatin and recruits HPF1, licensing serine ADP-ribosylation of CC target proteins, such as histones, thereby promoting decompaction of CC chromatin and the recruitment of repair factors leading to the CC reparation of DNA strand breaks (PubMed:10364231, PubMed:32939087, CC PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts CC the polymerase activity of PARP2 in order to limit the length of poly- CC ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically CC mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). CC Branched poly-ADP-ribose chains are specifically recognized by some CC factors, such as APLF (PubMed:30104678). In addition to proteins, also CC able to ADP-ribosylate DNA: preferentially acts on 5'-terminal CC phosphates at DNA strand breaks termini in nicked duplex CC (PubMed:27471034, PubMed:29361132). {ECO:0000269|PubMed:10364231, CC ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:27471034, CC ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29361132, CC ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, CC ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, CC ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:34486521, CC ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34795260, CC ECO:0000269|PubMed:34874266}. 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:0000269|PubMed:25043379, ECO:0000269|PubMed:30104678, CC ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32939087}; 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:0000269|PubMed:32028527, CC ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479, CC ECO:0000305|PubMed:28190768}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58233; CC Evidence={ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, CC ECO:0000269|PubMed:34108479, ECO:0000305|PubMed:28190768}; 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:25043379}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54425; CC Evidence={ECO:0000269|PubMed:25043379}; 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:25043379}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58225; CC Evidence={ECO:0000269|PubMed:25043379}; CC -!- ACTIVITY REGULATION: ADP-ribosyltransferase activity is regulated via CC an allosteric activation mechanism (PubMed:34108479). In absence of CC activation signal, PARP2 is autoinhibited by the PARP alpha-helical CC domain (also named HD region), which prevents effective NAD(+)-binding CC (PubMed:34108479). Activity is highly stimulated by signals, which CC unfold the PARP alpha-helical domain, relieving autoinhibition CC (PubMed:34108479). Poly-ADP-ribosyltransferase activity is tightly CC regulated and PARP2 is removed from damaged chromatin following initial CC poly-ADP-ribosylation of chromatin to avoid prolonged residence CC (trapping) that has cytotoxic consequences (PubMed:33275888). CHD1L CC promotes PARP2 removal from chromatin (PubMed:33275888). ADP- CC ribosyltransferase activity is inhibited by a number of PARP inhibitors CC (PARPi) compounds, that are used the treatment of breast or ovarian CC cancers that have defects in DNA repair by homologous recombination CC (PubMed:35349716). PARPi molecules (niraparib, talazoparib, and, to a CC lesser extent, olaparib) also trap PARP2 at DNA damage sites CC (PubMed:33275888, PubMed:35349716). {ECO:0000269|PubMed:33275888, CC ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:35349716}. CC -!- SUBUNIT: Component of a base excision repair (BER) complex, containing CC at least XRCC1, PARP1, POLB and LRIG3 (By similarity). Homo- and CC heterodimer with PARP1 (PubMed:20092359). Interacts (via the PARP CC catalytic domain) with HPF1 (PubMed:27067600, PubMed:28190768, CC PubMed:32028527, PubMed:32939087, PubMed:33141820, PubMed:34108479). CC Interacts with core nucleosomes (PubMed:32939087, PubMed:33141820). CC {ECO:0000250|UniProtKB:O88554, ECO:0000269|PubMed:20092359, CC ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:28190768, CC ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, CC ECO:0000269|PubMed:33141820, ECO:0000269|PubMed:34108479}. CC -!- INTERACTION: CC Q9UGN5; Q00688: FKBP3; NbExp=2; IntAct=EBI-2795348, EBI-1044081; CC Q9UGN5; Q99469: STAC; NbExp=2; IntAct=EBI-2795348, EBI-2652799; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10364231, CC ECO:0000269|PubMed:26704974}. Chromosome {ECO:0000269|PubMed:26704974, CC ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, CC ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33141820, CC ECO:0000269|PubMed:35349716}. Note=Recruited to DNA damage sites in a CC PARP1-dependent process: recognizes and binds poly-ADP-ribose chains CC produced by PARP1 at DNA damage sites via its N-terminus, leading to CC its recruitment. {ECO:0000269|PubMed:26704974, CC ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, CC ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33141820, CC ECO:0000269|PubMed:35349716}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UGN5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UGN5-2; Sequence=VSP_004537; CC -!- TISSUE SPECIFICITY: Widely expressed, mainly in actively dividing CC tissues (PubMed:10364231). The highest levels are in the brain, heart, CC pancreas, skeletal muscle and testis; also detected in kidney, liver, CC lung, placenta, ovary and spleen; levels are low in leukocytes, colon, CC small intestine, prostate and thymus (PubMed:10364231). CC {ECO:0000269|PubMed:10364231}. CC -!- DOMAIN: The N-terminal region (NTR) recognizes and binds poly-ADP- CC ribose chains produced by PARP1, leading to its recruitment to DNA CC damage sites. {ECO:0000269|PubMed:30104678}. CC -!- DOMAIN: The N-terminal disordered region does not act as a key DNA- CC binding domain (PubMed:26704974). The WGR and PARP catalytic domains CC function together to recruit PARP2 to sites of DNA breaks. The N- CC terminal disordered region is only required for activation on specific CC types of DNA damage (PubMed:26704974). {ECO:0000269|PubMed:26704974}. CC -!- DOMAIN: The WGR domain bridges two nucleosomes, with the broken DNA CC aligned in a position suitable for ligation (PubMed:30321391, CC PubMed:32939087, PubMed:33141820). The bridging induces structural CC changes in PARP2 that signal the recognition of a DNA break to the CC catalytic domain of PARP2, promoting HPF1 recruitment and subsequent CC activation of PARP2, licensing serine ADP-ribosylation of target CC proteins (PubMed:32939087). {ECO:0000269|PubMed:30321391, CC ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33141820}. CC -!- DOMAIN: The PARP alpha-helical domain (also named HD region) prevents CC effective NAD(+)-binding in absence of activation signal CC (PubMed:34108479). Binding to damaged DNA unfolds the PARP alpha- CC helical domain, relieving autoinhibition (PubMed:34108479). CC {ECO:0000269|PubMed:34108479}. CC -!- PTM: Auto poly-ADP-ribosylated on serine residues, leading to CC dissociation of the PARP2-HPF1 complex from chromatin (PubMed:32939087, CC PubMed:34108479). Poly-ADP-ribosylated by PARP1 (By similarity). CC {ECO:0000250|UniProtKB:O88554, ECO:0000269|PubMed:32939087, CC ECO:0000269|PubMed:34108479}. CC -!- PTM: Acetylation reduces DNA binding and enzymatic activity. CC {ECO:0000250|UniProtKB:O88554}. CC -!- PTM: Proteolytically cleaved by caspase-8 (CASP8) in response to CC apoptosis, leading to its inactivation. {ECO:0000250|UniProtKB:O88554}. CC -!- SIMILARITY: Belongs to the ARTD/PARP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD29857.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAL77437.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAB41505.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/adprtl2/"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Catalysis - Issue 235 of CC April 2021; CC URL="https://web.expasy.org/spotlight/back_issues/235/"; 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; AJ236912; CAB65088.1; -; mRNA. DR EMBL; AF085734; AAD29857.1; ALT_INIT; mRNA. DR EMBL; AJ236876; CAB41505.2; ALT_INIT; mRNA. DR EMBL; AK001980; BAA92017.1; ALT_TERM; mRNA. DR EMBL; AF479321; AAL77437.1; ALT_SEQ; Genomic_DNA. DR CCDS; CCDS41910.1; -. [Q9UGN5-1] DR CCDS; CCDS45077.1; -. [Q9UGN5-2] DR RefSeq; NP_001036083.1; NM_001042618.1. [Q9UGN5-2] DR RefSeq; NP_005475.2; NM_005484.3. [Q9UGN5-1] DR PDB; 3KCZ; X-ray; 2.00 A; A/B=235-579. DR PDB; 3KJD; X-ray; 1.95 A; A/B=235-579. DR PDB; 4PJV; X-ray; 2.50 A; A/B=235-579. DR PDB; 4TVJ; X-ray; 2.10 A; A/B=235-579. DR PDB; 4ZZX; X-ray; 1.65 A; A/B=223-583. DR PDB; 4ZZY; X-ray; 2.20 A; A=223-583. DR PDB; 5D5K; X-ray; 1.90 A; B=1-91. DR PDB; 5DSY; X-ray; 2.70 A; A/B/C/D=348-583. DR PDB; 6F1K; X-ray; 2.20 A; A=90-218. DR PDB; 6F5B; X-ray; 2.80 A; A/B=90-218. DR PDB; 6F5F; X-ray; 2.98 A; A/B/C/D=90-218. DR PDB; 6TX3; X-ray; 2.96 A; B=323-583. DR PDB; 6USJ; EM; 10.50 A; U/V=1-583. DR PDB; 6X0L; EM; 3.90 A; P/R=1-583. DR PDB; 6X0M; EM; 6.30 A; P/p=1-583. DR PDB; 6X0N; EM; 10.00 A; P/R=1-583. DR PDB; 7AEO; X-ray; 2.80 A; A=90-583. DR PDB; 7R59; X-ray; 2.00 A; A=235-583. DR PDB; 8HE8; X-ray; 3.05 A; A/B/C=231-581. DR PDBsum; 3KCZ; -. DR PDBsum; 3KJD; -. DR PDBsum; 4PJV; -. DR PDBsum; 4TVJ; -. DR PDBsum; 4ZZX; -. DR PDBsum; 4ZZY; -. DR PDBsum; 5D5K; -. DR PDBsum; 5DSY; -. DR PDBsum; 6F1K; -. DR PDBsum; 6F5B; -. DR PDBsum; 6F5F; -. DR PDBsum; 6TX3; -. DR PDBsum; 6USJ; -. DR PDBsum; 6X0L; -. DR PDBsum; 6X0M; -. DR PDBsum; 6X0N; -. DR PDBsum; 7AEO; -. DR PDBsum; 7R59; -. DR PDBsum; 8HE8; -. DR AlphaFoldDB; Q9UGN5; -. DR EMDB; EMD-20864; -. DR EMDB; EMD-21978; -. DR EMDB; EMD-21979; -. DR EMDB; EMD-21980; -. DR SMR; Q9UGN5; -. DR BioGRID; 115350; 125. DR DIP; DIP-48934N; -. DR IntAct; Q9UGN5; 90. DR MINT; Q9UGN5; -. DR STRING; 9606.ENSP00000250416; -. DR BindingDB; Q9UGN5; -. DR ChEMBL; CHEMBL5366; -. DR DrugBank; DB11793; Niraparib. DR DrugBank; DB09074; Olaparib. DR DrugBank; DB12332; Rucaparib. DR DrugBank; DB11760; Talazoparib. DR DrugBank; DB07232; Veliparib. DR DrugCentral; Q9UGN5; -. DR GuidetoPHARMACOLOGY; 2772; -. DR GlyGen; Q9UGN5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UGN5; -. DR PhosphoSitePlus; Q9UGN5; -. DR BioMuta; PARP2; -. DR DMDM; 17380230; -. DR EPD; Q9UGN5; -. DR jPOST; Q9UGN5; -. DR MassIVE; Q9UGN5; -. DR MaxQB; Q9UGN5; -. DR PaxDb; 9606-ENSP00000250416; -. DR PeptideAtlas; Q9UGN5; -. DR ProteomicsDB; 84250; -. [Q9UGN5-1] DR ProteomicsDB; 84251; -. [Q9UGN5-2] DR Pumba; Q9UGN5; -. DR Antibodypedia; 4794; 343 antibodies from 38 providers. DR DNASU; 10038; -. DR Ensembl; ENST00000250416.9; ENSP00000250416.5; ENSG00000129484.14. [Q9UGN5-1] DR Ensembl; ENST00000429687.8; ENSP00000392972.3; ENSG00000129484.14. [Q9UGN5-2] DR Ensembl; ENST00000708822.1; ENSP00000517361.1; ENSG00000291803.1. [Q9UGN5-2] DR Ensembl; ENST00000708823.1; ENSP00000517362.1; ENSG00000291803.1. [Q9UGN5-1] DR GeneID; 10038; -. DR KEGG; hsa:10038; -. DR MANE-Select; ENST00000429687.8; ENSP00000392972.3; NM_001042618.2; NP_001036083.1. [Q9UGN5-2] DR UCSC; uc001vxc.4; human. [Q9UGN5-1] DR AGR; HGNC:272; -. DR CTD; 10038; -. DR DisGeNET; 10038; -. DR GeneCards; PARP2; -. DR HGNC; HGNC:272; PARP2. DR HPA; ENSG00000129484; Low tissue specificity. DR MIM; 607725; gene. DR neXtProt; NX_Q9UGN5; -. DR OpenTargets; ENSG00000129484; -. DR PharmGKB; PA24592; -. DR VEuPathDB; HostDB:ENSG00000129484; -. DR eggNOG; KOG1037; Eukaryota. DR GeneTree; ENSGT00940000158452; -. DR HOGENOM; CLU_004841_2_2_1; -. DR InParanoid; Q9UGN5; -. DR OMA; QGENDRF; -. DR OrthoDB; 5481368at2759; -. DR PhylomeDB; Q9UGN5; -. DR TreeFam; TF315407; -. DR BRENDA; 2.4.2.30; 2681. DR PathwayCommons; Q9UGN5; -. DR Reactome; R-HSA-110362; POLB-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ). DR Reactome; R-HSA-5696394; DNA Damage Recognition in GG-NER. DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER. DR Reactome; R-HSA-5696400; Dual Incision in GG-NER. DR SignaLink; Q9UGN5; -. DR SIGNOR; Q9UGN5; -. DR BioGRID-ORCS; 10038; 13 hits in 1169 CRISPR screens. DR ChiTaRS; PARP2; human. DR EvolutionaryTrace; Q9UGN5; -. DR GeneWiki; PARP2; -. DR GenomeRNAi; 10038; -. DR Pharos; Q9UGN5; Tclin. DR PRO; PR:Q9UGN5; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q9UGN5; Protein. DR Bgee; ENSG00000129484; Expressed in cerebellar hemisphere and 202 other cell types or tissues. DR ExpressionAtlas; Q9UGN5; baseline and differential. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0090734; C:site of DNA damage; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0140294; F:NAD DNA ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0140806; F:NAD+- protein-aspartate ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:1990404; F:NAD+-protein ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0140807; F:NAD+-protein-glutamate ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0140805; F:NAD+-protein-serine ADP-ribosyltransferase activity; IDA:UniProtKB. DR GO; GO:0031491; F:nucleosome binding; IDA:UniProtKB. DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0072572; F:poly-ADP-D-ribose binding; IDA:UniProtKB. DR GO; GO:0160004; F:poly-ADP-D-ribose modification-dependent protein binding; IDA:UniProt. DR GO; GO:0006284; P:base-excision repair; IEA:Ensembl. DR GO; GO:0046697; P:decidualization; ISS:UniProtKB. DR GO; GO:0030592; P:DNA ADP-ribosylation; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProt. DR GO; GO:0006281; P:DNA repair; IDA:UniProt. DR GO; GO:0140861; P:DNA repair-dependent chromatin remodeling; IDA:UniProtKB. DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0110088; P:hippocampal neuron apoptotic process; IEA:Ensembl. DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0070213; P:protein auto-ADP-ribosylation; IDA:UniProtKB. DR GO; GO:0070212; P:protein poly-ADP-ribosylation; IDA:UniProtKB. DR GO; GO:0090649; P:response to oxygen-glucose deprivation; IEA:Ensembl. DR CDD; cd22252; PARP2_NTR; 1. DR CDD; cd01437; parp_like; 1. DR CDD; cd08003; WGR_PARP2_like; 1. DR Gene3D; 3.90.228.10; -; 1. DR Gene3D; 1.20.142.10; Poly(ADP-ribose) polymerase, regulatory domain; 1. DR Gene3D; 2.20.140.10; WGR domain; 1. 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 PANTHER; PTHR10459; DNA LIGASE; 1. DR PANTHER; PTHR10459:SF60; POLY [ADP-RIBOSE] POLYMERASE 2; 1. DR Pfam; PF00644; PARP; 1. DR Pfam; PF02877; PARP_reg; 1. DR Pfam; PF05406; WGR; 1. DR SMART; SM00773; WGR; 1. DR SUPFAM; SSF56399; ADP-ribosylation; 1. DR SUPFAM; SSF47587; Domain of poly(ADP-ribose) polymerase; 1. DR SUPFAM; SSF142921; WGR domain-like; 1. DR PROSITE; PS51060; PARP_ALPHA_HD; 1. DR PROSITE; PS51059; PARP_CATALYTIC; 1. DR PROSITE; PS51977; WGR; 1. DR Genevisible; Q9UGN5; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ADP-ribosylation; Allosteric enzyme; KW Alternative splicing; Chromosome; DNA damage; DNA repair; DNA-binding; KW Glycosyltransferase; NAD; Nucleotidyltransferase; Nucleus; Phosphoprotein; KW Reference proteome; Transferase. FT CHAIN 1..583 FT /note="Poly [ADP-ribose] polymerase 2" FT /id="PRO_0000211327" FT DOMAIN 104..201 FT /note="WGR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01321" FT DOMAIN 231..348 FT /note="PARP alpha-helical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00398" FT DOMAIN 356..583 FT /note="PARP catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00397" FT REGION 1..103 FT /note="N-terminal region (NTR)" FT /evidence="ECO:0000305|PubMed:30104678" FT REGION 1..77 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 21..22 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:26704974" FT MOTIF 35..40 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:26704974" FT COMPBIAS 34..71 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 558 FT /note="For poly [ADP-ribose] polymerase activity" FT /evidence="ECO:0000305|PubMed:26704974, FT ECO:0000305|PubMed:30104678, ECO:0000305|PubMed:32028527" FT BINDING 428..430 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:32028527, FT ECO:0007744|PDB:6TX3" FT BINDING 437 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:32028527, FT ECO:0007744|PDB:6TX3" FT BINDING 444 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:32028527, FT ECO:0007744|PDB:6TX3" FT BINDING 470 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|PubMed:32028527, FT ECO:0007744|PDB:6TX3" FT SITE 207..208 FT /note="Cleavage; by caspase-8" FT /evidence="ECO:0000250|UniProtKB:O88554" FT MOD_RES 37 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O88554" FT MOD_RES 38 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O88554" FT MOD_RES 226 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 232 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT VAR_SEQ 68..80 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10364231" FT /id="VSP_004537" FT VARIANT 161 FT /note="S -> N (in dbSNP:rs3093905)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019174" FT VARIANT 168 FT /note="N -> S (in dbSNP:rs3093906)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019175" FT VARIANT 235 FT /note="D -> G (in dbSNP:rs3093921)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019176" FT VARIANT 285 FT /note="I -> V (in dbSNP:rs3093925)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019177" FT VARIANT 296 FT /note="R -> Q (in dbSNP:rs3093926)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_019178" FT VARIANT 331 FT /note="I -> T (in dbSNP:rs2275010)" FT /id="VAR_050462" FT MUTAGEN 21..22 FT /note="KR->AA: Reduced localization to the nucleus. FT Abolished localization to the nucleus; when associated with FT 37-A-A-38." FT /evidence="ECO:0000269|PubMed:26704974" FT MUTAGEN 37..38 FT /note="KK->AA: Reduced localization to the nucleus. FT Abolished localization to the nucleus; when associated with FT 21-A-A-22." FT /evidence="ECO:0000269|PubMed:26704974" FT MUTAGEN 125..126 FT /note="QF->RD: In PARP2-QFRD mutant; induces conformational FT change that bridges nucleosomes by binding to linker DNA FT ends and promotes interaction with HPF1." FT /evidence="ECO:0000269|PubMed:33141820" FT MUTAGEN 127 FT /note="N->A: Decreased poly [ADP-ribose] polymerase FT activity. Impaired formation of a complex with damaged FT DNA." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 128 FT /note="N->A: Does not affect poly [ADP-ribose] polymerase FT activity." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 129 FT /note="N->A: Reduced recruitment to DNA damage sites. FT Abolished DNA-induced ADP-ribosyltransferase activity." FT /evidence="ECO:0000269|PubMed:26704974, FT ECO:0000269|PubMed:34108479" FT MUTAGEN 130 FT /note="K->A: Decreased poly [ADP-ribose] polymerase FT activity." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 132 FT /note="Y->F: Decreased poly [ADP-ribose] polymerase FT activity." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 151 FT /note="W->A: Decreased poly [ADP-ribose] polymerase FT activity. Impaired formation of a complex with damaged FT DNA." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 153 FT /note="R->A: Abolished formation of a complex with core FT nucleosome and HPF1, leading to abolished ability to FT catalyze serine ADP-ribosylation of histones. Abolished FT DNA-induced ADP-ribosyltransferase activity. Abolished FT trapping at DNA damage sites upon binding to PARP FT inhibitors (PARPi)." FT /evidence="ECO:0000269|PubMed:30321391, FT ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479, FT ECO:0000269|PubMed:35349716" FT MUTAGEN 154 FT /note="V->A: Abolished formation of a complex with core FT nucleosome and HPF1, leading to abolished ability to FT catalyze serine ADP-ribosylation of histones." FT /evidence="ECO:0000269|PubMed:32939087" FT MUTAGEN 159 FT /note="Q->A: Decreased poly [ADP-ribose] polymerase FT activity." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 183 FT /note="K->A: Decreased poly [ADP-ribose] polymerase FT activity. Impaired formation of a complex with damaged FT DNA." FT /evidence="ECO:0000269|PubMed:30321391" FT MUTAGEN 201 FT /note="Y->A: Reduced DNA-induced ADP-ribosyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:34108479" FT MUTAGEN 201 FT /note="Y->F: Reduced recruitment to DNA damage sites. FT Decreased poly [ADP-ribose] polymerase activity." FT /evidence="ECO:0000269|PubMed:26704974, FT ECO:0000269|PubMed:30321391" FT MUTAGEN 286 FT /note="E->A,R: Increased DNA-induced ADP-ribosyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:34108479" FT MUTAGEN 338 FT /note="G->A: Does not affect DNA-induced FT ADP-ribosyltransferase activity." FT /evidence="ECO:0000269|PubMed:34108479" FT MUTAGEN 394 FT /note="H->A: Strongly reduced serine ADP-ribosylation, FT caused by abolished interaction with HPF1." FT /evidence="ECO:0000269|PubMed:32028527" FT MUTAGEN 428 FT /note="H->A: Abolished trapping at DNA damage sites upon FT binding to PARP inhibitors (PARPi)." FT /evidence="ECO:0000269|PubMed:35349716" FT MUTAGEN 558 FT /note="E->A: Abolished poly [ADP-ribose] polymerase FT activity without affecting localization to DNA damage FT sites." FT /evidence="ECO:0000269|PubMed:26704974, FT ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:33275888" FT MUTAGEN 582..583 FT /note="LW->EE: Strongly reduced serine ADP-ribosylation, FT caused by abolished interaction with HPF1." FT /evidence="ECO:0000269|PubMed:32028527" FT CONFLICT 447 FT /note="P -> H (in Ref. 2; AAD29857)" FT /evidence="ECO:0000305" FT CONFLICT 481 FT /note="N -> H (in Ref. 4; BAA92017)" FT /evidence="ECO:0000305" FT TURN 99..104 FT /evidence="ECO:0007829|PDB:6F1K" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:6F1K" FT STRAND 116..123 FT /evidence="ECO:0007829|PDB:6F1K" FT TURN 124..127 FT /evidence="ECO:0007829|PDB:6F1K" FT STRAND 128..143 FT /evidence="ECO:0007829|PDB:6F1K" FT STRAND 145..153 FT /evidence="ECO:0007829|PDB:6F1K" FT STRAND 159..166 FT /evidence="ECO:0007829|PDB:6F1K" FT HELIX 169..184 FT /evidence="ECO:0007829|PDB:6F1K" FT HELIX 188..193 FT /evidence="ECO:0007829|PDB:6F1K" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:6F1K" FT HELIX 236..245 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 248..257 FT /evidence="ECO:0007829|PDB:4ZZX" FT TURN 262..264 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 267..269 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 272..290 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 296..308 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 324..346 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 357..365 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 367..371 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 377..388 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 397..409 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 412..415 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 423..429 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 435..441 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 452..454 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 459..466 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 467..471 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 472..474 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 478..480 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 482..491 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 494..500 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 505..508 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 514..517 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 519..523 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 525..527 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 529..531 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 534..536 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 541..543 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 549..551 FT /evidence="ECO:0007829|PDB:3KJD" FT STRAND 554..556 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 558..563 FT /evidence="ECO:0007829|PDB:4ZZX" FT HELIX 564..566 FT /evidence="ECO:0007829|PDB:4ZZX" FT STRAND 567..579 FT /evidence="ECO:0007829|PDB:4ZZX" SQ SEQUENCE 583 AA; 66206 MW; 5B7AE8AE531836AF CRC64; MAARRRRSTG GGRARALNES KRVNNGNTAP EDSSPAKKTR RCQRQESKKM PVAGGKANKD RTEDKQDGMP GRSWASKRVS ESVKALLLKG KAPVDPECTA KVGKAHVYCE GNDVYDVMLN QTNLQFNNNK YYLIQLLEDD AQRNFSVWMR WGRVGKMGQH SLVACSGNLN KAKEIFQKKF LDKTKNNWED REKFEKVPGK YDMLQMDYAT NTQDEEETKK EESLKSPLKP ESQLDLRVQE LIKLICNVQA MEEMMMEMKY NTKKAPLGKL TVAQIKAGYQ SLKKIEDCIR AGQHGRALME ACNEFYTRIP HDFGLRTPPL IRTQKELSEK IQLLEALGDI EIAIKLVKTE LQSPEHPLDQ HYRNLHCALR PLDHESYEFK VISQYLQSTH APTHSDYTMT LLDLFEVEKD GEKEAFREDL HNRMLLWHGS RMSNWVGILS HGLRIAPPEA PITGYMFGKG IYFADMSSKS ANYCFASRLK NTGLLLLSEV ALGQCNELLE ANPKAEGLLQ GKHSTKGLGK MAPSSAHFVT LNGSTVPLGP ASDTGILNPD GYTLNYNEYI VYNPNQVRMR YLLKVQFNFL QLW //