PARP2_HUMAN
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 03-AUG-2022, entry version 201.
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: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 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 [15] {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 [16] {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 [17] {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 [18] {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 [19] {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).
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:32028527,
CC PubMed:32939087). 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:30321391). Serine ADP-
CC ribosylation of proteins constitutes the primary form of ADP-
CC ribosylation of proteins in response to DNA damage (PubMed:32939087).
CC Mediates glutamate and aspartate ADP-ribosylation of target proteins in
CC absence of HPF1 (PubMed:25043379). Following interaction with HPF1,
CC catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring
CC serine specificity by completing the PARP2 active site
CC (PubMed:28190768, PubMed:32028527). 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). In
CC addition to proteins, also able to ADP-ribosylate DNA: preferentially
CC acts on 5'-terminal phosphates at DNA strand breaks termini in nicked
CC duplex (PubMed:27471034). {ECO:0000269|PubMed:10364231,
CC ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:27471034,
CC ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:30321391,
CC ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087}.
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:30321391,
CC 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:0000305|PubMed:28190768};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58233;
CC Evidence={ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087,
CC 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 -!- 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). Interacts with core
CC 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}.
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:30321391, ECO:0000269|PubMed:32939087,
CC ECO:0000269|PubMed:33141820}. Note=Recruited to DNA damage sites.
CC {ECO:0000269|PubMed:26704974, ECO:0000269|PubMed:30321391,
CC ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33141820}.
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 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 -!- PTM: Auto poly-ADP-ribosylated on serine residues, leading to
CC dissociation of the PARP2-HPF1 complex from chromatin
CC (PubMed:32939087). Poly-ADP-ribosylated by PARP1 (By similarity).
CC {ECO:0000250|UniProtKB:O88554, ECO:0000269|PubMed:32939087}.
CC -!- PTM: Acetylation reduces DNA binding and enzymatic activity.
CC {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/";
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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 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 AlphaFoldDB; Q9UGN5; -.
DR SMR; Q9UGN5; -.
DR BioGRID; 115350; 114.
DR DIP; DIP-48934N; -.
DR IntAct; Q9UGN5; 88.
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; Q9UGN5; -.
DR PeptideAtlas; Q9UGN5; -.
DR PRIDE; Q9UGN5; -.
DR ProteomicsDB; 84250; -. [Q9UGN5-1]
DR ProteomicsDB; 84251; -. [Q9UGN5-2]
DR Antibodypedia; 4794; 312 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 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 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; SANYCCP; -.
DR OrthoDB; 909382at2759; -.
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; 12 hits in 1084 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 200 other tissues.
DR ExpressionAtlas; Q9UGN5; baseline and differential.
DR Genevisible; Q9UGN5; HS.
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:0003677; F:DNA binding; IEA:UniProtKB-KW.
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:1990404; F:NAD+-protein ADP-ribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0031491; F:nucleosome binding; IDA:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IEA:Ensembl.
DR GO; GO:0030592; P:DNA ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0016570; P:histone modification; IDA:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0018312; P:peptidyl-serine ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0006471; P:protein ADP-ribosylation; TAS:ProtInc.
DR GO; GO:0070213; P:protein auto-ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0070212; P:protein poly-ADP-ribosylation; IDA:UniProtKB.
DR Gene3D; 1.20.142.10; -; 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 Pfam; PF00644; PARP; 1.
DR Pfam; PF02877; PARP_reg; 1.
DR Pfam; PF05406; WGR; 1.
DR SMART; SM00773; WGR; 1.
DR SUPFAM; SSF142921; SSF142921; 1.
DR SUPFAM; SSF47587; SSF47587; 1.
DR PROSITE; PS51060; PARP_ALPHA_HD; 1.
DR PROSITE; PS51059; PARP_CATALYTIC; 1.
DR PROSITE; PS51977; WGR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing;
KW Chromosome; DNA damage; DNA repair; DNA-binding; Glycosyltransferase; NAD;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW 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..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: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 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 /evidence="ECO:0000269|PubMed:26704974"
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."
FT /evidence="ECO:0000269|PubMed:30321391,
FT ECO:0000269|PubMed:32939087"
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->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 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 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 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
