PARP1_HUMAN
ID PARP1_HUMAN Reviewed; 1014 AA.
AC P09874; B1ANJ4; Q8IUZ9;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 258.
DE RecName: Full=Poly [ADP-ribose] polymerase 1;
DE Short=PARP-1;
DE EC=2.4.2.30 {ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:7852410};
DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 1 {ECO:0000303|PubMed:29954836};
DE Short=ARTD1 {ECO:0000303|PubMed:29954836};
DE AltName: Full=DNA ADP-ribosyltransferase PARP1 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000269|PubMed:27471034};
DE AltName: Full=NAD(+) ADP-ribosyltransferase 1 {ECO:0000303|Ref.11};
DE Short=ADPRT 1 {ECO:0000303|Ref.11};
DE AltName: Full=Poly[ADP-ribose] synthase 1;
DE AltName: Full=Protein poly-ADP-ribosyltransferase PARP1 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:25043379};
GN Name=PARP1 {ECO:0000312|HGNC:HGNC:270};
GN Synonyms=ADPRT {ECO:0000303|Ref.11}, PPOL;
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].
RC TISSUE=Fibroblast;
RX PubMed=3120710; DOI=10.1016/0006-291x(87)90921-1;
RA Uchida K., Morita T., Sato T., Ogura T., Yamashita R., Noguchi S.,
RA Suzuki H., Nyunoya H., Miwa M., Sugimura T.;
RT "Nucleotide sequence of a full-length cDNA for human fibroblast poly(ADP-
RT ribose) polymerase.";
RL Biochem. Biophys. Res. Commun. 148:617-622(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=2824474; DOI=10.1016/s0021-9258(18)47687-9;
RA Kurosaki T., Ushiro H., Mitsuuchi Y., Suzuki S., Matsuda M., Matsuda Y.,
RA Katunuma N., Kangawa K., Matsuo H., Hirose T., Inayama S., Shizuta Y.;
RT "Primary structure of human poly(ADP-ribose) synthetase as deduced from
RT cDNA sequence.";
RL J. Biol. Chem. 262:15990-15997(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-940.
RX PubMed=2891139; DOI=10.1073/pnas.84.23.8370;
RA Cherney B.W., McBride O.W., Chen D., Alkhatib H., Bhatia K., Hensley P.,
RA Smulson M.E.;
RT "cDNA sequence, protein structure, and chromosomal location of the human
RT gene for poly(ADP-ribose) polymerase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8370-8374(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2513174; DOI=10.1089/dna.1989.8.575;
RA Auer B., Nagl U., Herzog H., Schneider R., Schweiger M.;
RT "Human nuclear NAD+ ADP-ribosyltransferase(polymerizing): organization of
RT the gene.";
RL DNA 8:575-580(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-188; ILE-334; TYR-383;
RP ALA-762 AND ARG-940.
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-762.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-95.
RX PubMed=2125269; DOI=10.1111/j.1432-1033.1990.tb15647.x;
RA Yokoyama Y., Kawamoto T., Mitsuuchi Y., Kurosaki T., Toda K., Ushiro H.,
RA Terashima M., Sumimoto H., Kuribayashi I., Yamamoto Y., Maeda T., Ikeda H.,
RA Sagara Y., Shizuta Y.;
RT "Human poly(ADP-ribose) polymerase gene. Cloning of the promoter region.";
RL Eur. J. Biochem. 194:521-526(1990).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
RX PubMed=2108670; DOI=10.1016/0006-291x(90)92082-b;
RA Ogura T., Nyunoya H., Takahashi-Masutani M., Miwa M., Sugimura T.,
RA Esumi H.;
RT "Characterization of a putative promoter region of the human poly(ADP-
RT ribose) polymerase gene: structural similarity to that of the DNA
RT polymerase beta gene.";
RL Biochem. Biophys. Res. Commun. 167:701-710(1990).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-40.
RA Herzog H., Schneider R., Hirsch-Kauffmann M., Schnitzer D., Schweiger M.;
RT "Human pADPRT is involved in the regulation of its own gene.";
RL Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP PROTEIN SEQUENCE OF 2-10; 35-47; 66-78; 109-119; 183-197; 209-221; 263-282;
RP 453-467; 487-496; 529-548; 552-564; 572-582; 637-654; 668-695; 748-761;
RP 780-796; 803-816 AND 859-903, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION
RP AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Zebisch A., Lilla S., von Kriegsheim A., Lempens A.,
RA Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 166-177 AND 356-367, FUNCTION, INTERACTION WITH EEF1A1
RP AND TXK, PHOSPHORYLATION BY TXK, AND SUBCELLULAR LOCATION.
RX PubMed=17177976; DOI=10.1111/j.1365-2249.2006.03249.x;
RA Maruyama T., Nara K., Yoshikawa H., Suzuki N.;
RT "Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms
RT a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha
RT and regulates interferon-gamma gene transcription in Th1 cells.";
RL Clin. Exp. Immunol. 147:164-175(2007).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 381-420 AND 682-710.
RX PubMed=3121332;
RA Schneider R., Auer B., Kuhne C., Herzog H., Klocker H., Burtscher H.J.,
RA Hirsch-Kauffmann M., Wintersberger U., Schweiger M.;
RT "Isolation of a cDNA clone for human NAD+: protein ADP-
RT ribosyltransferase.";
RL Eur. J. Cell Biol. 44:302-307(1987).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 441-1014.
RX PubMed=3113420; DOI=10.1016/0006-291x(87)90543-2;
RA Suzuki H., Uchida K., Shima H., Sato T., Okamoto T., Kimura T., Miwa M.;
RT "Molecular cloning of cDNA for human poly(ADP-ribose) polymerase and
RT expression of its gene during HL-60 cell differentiation.";
RL Biochem. Biophys. Res. Commun. 146:403-409(1987).
RN [16]
RP ERRATUM OF PUBMED:3113420.
RA Suzuki H., Uchida K., Shima H., Sato T., Okamoto T., Kimura T., Miwa M.;
RL Biochem. Biophys. Res. Commun. 148:1549-1550(1987).
RN [17]
RP ANALYSIS OF ZINC-FINGERS.
RX PubMed=2109322; DOI=10.1073/pnas.87.8.2990;
RA Gradwohl G., Menissier-de Murcia J., Molinete M., Simonin F., Koken M.H.M.,
RA Hoeijmakers J.H.J., de Murcia G.M.;
RT "The second zinc-finger domain of poly(ADP-ribose) polymerase determines
RT specificity for single-stranded breaks in DNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2990-2994(1990).
RN [18]
RP ANALYSIS OF ZINC-FINGERS.
RX PubMed=2123876; DOI=10.1016/s0021-9258(18)45824-3;
RA Ikelima M., Noguchi S., Yamashita R., Ogura T., Sugimura T., Gill D.M.,
RA Miwa M.;
RT "The zinc fingers of human poly(ADP-ribose) polymerase are differentially
RT required for the recognition of DNA breaks and nicks and the consequent
RT enzyme activation. Other structures recognize intact DNA.";
RL J. Biol. Chem. 265:21907-21913(1990).
RN [19]
RP MUTAGENESIS OF CATALYTIC DOMAIN.
RX PubMed=2121735; DOI=10.1016/s0021-9258(17)30651-8;
RA Simonin F., Menissier-de Murcia J., Poch O., Muller S., Gradwohl G.,
RA Molinete M., Penning C., Keith G., de Murcia G.M.;
RT "Expression and site-directed mutagenesis of the catalytic domain of human
RT poly(ADP-ribose)polymerase in Escherichia coli. Lysine 893 is critical for
RT activity.";
RL J. Biol. Chem. 265:19249-19256(1990).
RN [20]
RP NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=1505517; DOI=10.1002/j.1460-2075.1992.tb05404.x;
RA Schreiber V., Molinete M., Boeuf H., de Murcia G.M.,
RA Menissier-de Murcia J.;
RT "The human poly(ADP-ribose) polymerase nuclear localization signal is a
RT bipartite element functionally separate from DNA binding and catalytic
RT activity.";
RL EMBO J. 11:3263-3269(1992).
RN [21]
RP CATALYTIC ACTIVITY, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF HIS-862; GLU-883; GLU-923; GLU-931 AND GLU-988.
RX PubMed=7852410; DOI=10.1074/jbc.270.7.3247;
RA Marsischky G.T., Wilson B.A., Collier R.J.;
RT "Role of glutamic acid 988 of human poly-ADP-ribose polymerase in polymer
RT formation. Evidence for active site similarities to the ADP-ribosylating
RT toxins.";
RL J. Biol. Chem. 270:3247-3254(1995).
RN [22]
RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF LEU-797; ASN-868; MET-890;
RP LYS-893; PHE-897; ASP-899; CYS-908; LEU-926; TYR-986; GLU-988 AND LEU-1003.
RX PubMed=9315851; DOI=10.1021/bi971055p;
RA Rolli V., O'Farrell M., Menissier-de Murcia J., de Murcia G.M.;
RT "Random mutagenesis of the poly(ADP-ribose) polymerase catalytic domain
RT reveals amino acids involved in polymer branching.";
RL Biochemistry 36:12147-12154(1997).
RN [23]
RP INTERACTION WITH POLA1, AND SUBCELLULAR LOCATION.
RX PubMed=9518481; DOI=10.1093/nar/26.8.1891;
RA Dantzer F., Nasheuer H.P., Vonesch J.L., de Murcia G.,
RA Menissier-de Murcia J.;
RT "Functional association of poly(ADP-ribose) polymerase with DNA polymerase
RT alpha-primase complex: a link between DNA strand break detection and DNA
RT replication.";
RL Nucleic Acids Res. 26:1891-1898(1998).
RN [24]
RP PHOSPHORYLATION.
RX PubMed=10467406; DOI=10.1038/sj.onc.1202823;
RA Ariumi Y., Masutani M., Copeland T.D., Mimori T., Sugimura T.,
RA Shimotohno K., Ueda K., Hatanaka M., Noda M.;
RT "Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent
RT protein kinase in vitro.";
RL Oncogene 18:4616-4625(1999).
RN [25]
RP INTERACTION WITH APTX.
RX PubMed=15044383; DOI=10.1093/hmg/ddh122;
RA Gueven N., Becherel O.J., Kijas A.W., Chen P., Howe O., Rudolph J.H.,
RA Gatti R., Date H., Onodera O., Taucher-Scholz G., Lavin M.F.;
RT "Aprataxin, a novel protein that protects against genotoxic stress.";
RL Hum. Mol. Genet. 13:1081-1093(2004).
RN [26]
RP INTERACTION WITH SRY.
RX PubMed=16904257; DOI=10.1016/j.mce.2006.06.008;
RA Li Y., Oh H.J., Lau Y.-F.C.;
RT "The poly(ADP-ribose) polymerase 1 interacts with Sry and modulates its
RT biological functions.";
RL Mol. Cell. Endocrinol. 257:35-46(2006).
RN [27]
RP INTERACTION WITH APLF, AND FUNCTION.
RX PubMed=17396150; DOI=10.1038/sj.emboj.7601663;
RA Kanno S., Kuzuoka H., Sasao S., Hong Z., Lan L., Nakajima S., Yasui A.;
RT "A novel human AP endonuclease with conserved zinc-finger-like motifs
RT involved in DNA strand break responses.";
RL EMBO J. 26:2094-2103(2007).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-179, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [29]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18172500; DOI=10.1038/nature06420;
RA Ahel I., Ahel D., Matsusaka T., Clark A.J., Pines J., Boulton S.J.,
RA West S.C.;
RT "Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint
RT proteins.";
RL Nature 451:81-85(2008).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-368 AND SER-782, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP FUNCTION.
RX PubMed=19344625; DOI=10.1016/j.bcp.2009.02.025;
RA Reinemund J., Seidel K., Steckelings U.M., Zaade D., Klare S., Rompe F.,
RA Katerbaum M., Schacherl J., Li Y., Menk M., Schefe J.H., Goldin-Lang P.,
RA Szabo C., Olah G., Unger T., Funke-Kaiser H.;
RT "Poly(ADP-ribose) polymerase-1 (PARP-1) transcriptionally regulates
RT angiotensin AT2 receptor (AT2R) and AT2R binding protein (ATBP) genes.";
RL Biochem. Pharmacol. 77:1795-1805(2009).
RN [32]
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 [33]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-988, AND ADP-RIBOSYLATION
RP AT ASP-387; GLU-488 AND GLU-491.
RX PubMed=19764761; DOI=10.1021/ja906135d;
RA Tao Z., Gao P., Liu H.W.;
RT "Identification of the ADP-ribosylation sites in the PARP-1
RT automodification domain: analysis and implications.";
RL J. Am. Chem. Soc. 131:14258-14260(2009).
RN [34]
RP INTERACTION WITH RRP1B.
RX PubMed=19710015; DOI=10.1074/jbc.m109.023457;
RA Crawford N.P., Yang H., Mattaini K.R., Hunter K.W.;
RT "The metastasis efficiency modifier ribosomal RNA processing 1 homolog B
RT (RRP1B) is a chromatin-associated factor.";
RL J. Biol. Chem. 284:28660-28673(2009).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-782, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [36]
RP FUNCTION, POLY-ADP-RIBOSYLATION, AND INTERACTION WITH CHD1L.
RX PubMed=19661379; DOI=10.1126/science.1177321;
RA Ahel D., Horejsi Z., Wiechens N., Polo S.E., Garcia-Wilson E., Ahel I.,
RA Flynn H., Skehel M., West S.C., Jackson S.P., Owen-Hughes T., Boulton S.J.;
RT "Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin
RT remodeling enzyme ALC1.";
RL Science 325:1240-1243(2009).
RN [37]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-97; LYS-105; LYS-131; LYS-600 AND
RP LYS-621, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [38]
RP INTERACTION WITH PARP3.
RX PubMed=20064938; DOI=10.1074/jbc.m109.077834;
RA Loseva O., Jemth A.S., Bryant H.E., Schueler H., Lehtioe L., Karlberg T.,
RA Helleday T.;
RT "PARP-3 is a mono-ADP-ribosylase that activates PARP-1 in the absence of
RT DNA.";
RL J. Biol. Chem. 285:8054-8060(2010).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41 AND SER-782, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [40]
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 [41]
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 [42]
RP INTERACTION WITH PUM3.
RX PubMed=21266351; DOI=10.1158/0008-5472.can-10-1831;
RA Chang H.Y., Fan C.C., Chu P.C., Hong B.E., Lee H.J., Chang M.S.;
RT "hPuf-A/KIAA0020 modulates PARP-1 cleavage upon genotoxic stress.";
RL Cancer Res. 71:1126-1134(2011).
RN [43]
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 [44]
RP INTERACTION WITH RNF146, AND SUBCELLULAR LOCATION.
RX PubMed=21799911; DOI=10.1371/journal.pone.0022595;
RA Callow M.G., Tran H., Phu L., Lau T., Lee J., Sandoval W.N., Liu P.S.,
RA Bheddah S., Tao J., Lill J.R., Hongo J.A., Davis D., Kirkpatrick D.S.,
RA Polakis P., Costa M.;
RT "Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt
RT signaling.";
RL PLoS ONE 6:E22595-E22595(2011).
RN [45]
RP FUNCTION, AND ADP-RIBOSYLATION AT LYS-521.
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 [46]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-782, AND IDENTIFICATION BY
RP 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 [47]
RP INTERACTION WITH ZNF423.
RX PubMed=22863007; DOI=10.1016/j.cell.2012.06.028;
RA Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H.,
RA Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J.,
RA Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H.,
RA van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H.,
RA Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A.,
RA Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S.,
RA Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S.,
RA Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C.,
RA Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G.,
RA Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A.,
RA Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R.,
RA Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J.,
RA Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A.,
RA Hildebrandt F.;
RT "Exome capture reveals ZNF423 and CEP164 mutations, linking renal
RT ciliopathies to DNA damage response signaling.";
RL Cell 150:533-548(2012).
RN [48]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=22002106; DOI=10.1074/mcp.m111.013680;
RA Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.;
RT "Systematic analysis of protein pools, isoforms, and modifications
RT affecting turnover and subcellular localization.";
RL Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012).
RN [49]
RP ADP-RIBOSYLATION.
RX PubMed=22753495; DOI=10.1073/pnas.1200583109;
RA Mao Z., Tian X., Van Meter M., Ke Z., Gorbunova V., Seluanov A.;
RT "Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair
RT during replicative senescence.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:11800-11805(2012).
RN [50]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [51]
RP INTERACTION WITH ZNF365.
RX PubMed=23966166; DOI=10.4161/cc.25882;
RA Zhang Y., Park E., Kim C.S., Paik J.H.;
RT "ZNF365 promotes stalled replication forks recovery to maintain genome
RT stability.";
RL Cell Cycle 12:2817-2828(2013).
RN [52]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-41; SER-177; SER-179;
RP SER-185; SER-274; SER-277; SER-782 AND SER-786, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [53]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PARP9.
RX PubMed=23230272; DOI=10.1128/mcb.00990-12;
RA Yan Q., Xu R., Zhu L., Cheng X., Wang Z., Manis J., Shipp M.A.;
RT "BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation,
RT ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and
RT RNF8.";
RL Mol. Cell. Biol. 33:845-857(2013).
RN [54]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [55]
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 [56]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-486; LYS-512 AND LYS-748, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [57]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-203; LYS-486 AND LYS-748, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [58]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-203; LYS-467; LYS-486 AND
RP LYS-512, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [59]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-512, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [60]
RP FUNCTION, CATALYTIC ACTIVITY, AND 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 [61]
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 [62]
RP FUNCTION.
RX PubMed=27257257; DOI=10.1126/science.aad9335;
RA Wright R.H., Lioutas A., Le Dily F., Soronellas D., Pohl A., Bonet J.,
RA Nacht A.S., Samino S., Font-Mateu J., Vicent G.P., Wierer M., Trabado M.A.,
RA Schelhorn C., Carolis C., Macias M.J., Yanes O., Oliva B., Beato M.;
RT "ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for
RT chromatin remodeling.";
RL Science 352:1221-1225(2016).
RN [63]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH HPF1, ADP-RIBOSYLATION AT
RP SER-499; SER-507 AND SER-519, AND MUTAGENESIS OF SER-499; SER-507 AND
RP SER-519.
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 [64]
RP INTERACTION WITH CHD1L, AND MUTAGENESIS OF GLU-988.
RX PubMed=29220653; DOI=10.1016/j.molcel.2017.11.019;
RA Singh H.R., Nardozza A.P., Moeller I.R., Knobloch G., Kistemaker H.A.V.,
RA Hassler M., Harrer N., Blessing C., Eustermann S., Kotthoff C., Huet S.,
RA Mueller-Planitz F., Filippov D.V., Timinszky G., Rand K.D., Ladurner A.G.;
RT "A Poly-ADP-Ribose trigger releases the auto-inhibition of a chromatin
RT remodeling oncogene.";
RL Mol. Cell 68:860-871(2017).
RN [65]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-192; LYS-203; LYS-249; LYS-467;
RP LYS-486; LYS-512; LYS-528 AND LYS-748, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [66]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30257210; DOI=10.1016/j.celrep.2018.08.092;
RA Bartlett E., Bonfiglio J.J., Prokhorova E., Colby T., Zobel F., Ahel I.,
RA Matic I.;
RT "Interplay of histone marks with serine ADP-ribosylation.";
RL Cell Rep. 24:3488-3502(2018).
RN [67]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH HPF1, AND ADP-RIBOSYLATION
RP AT SER-499; SER-504; SER-507 AND SER-519.
RX PubMed=29954836; DOI=10.15252/embr.201745310;
RA Leslie Pedrioli D.M., Leutert M., Bilan V., Nowak K., Gunasekera K.,
RA Ferrari E., Imhof R., Malmstroem L., Hottiger M.O.;
RT "Comprehensive ADP-ribosylome analysis identifies tyrosine as an ADP-ribose
RT acceptor site.";
RL EMBO Rep. 19:0-0(2018).
RN [68]
RP FUNCTION, AND INTERACTION WITH CGAS AND TIMELESS.
RX PubMed=30356214; DOI=10.1038/s41586-018-0629-6;
RA Liu H., Zhang H., Wu X., Ma D., Wu J., Wang L., Jiang Y., Fei Y., Zhu C.,
RA Tan R., Jungblut P., Pei G., Dorhoi A., Yan Q., Zhang F., Zheng R., Liu S.,
RA Liang H., Liu Z., Yang H., Chen J., Wang P., Tang T., Peng W., Hu Z.,
RA Xu Z., Huang X., Wang J., Li H., Zhou Y., Liu F., Yan D., Kaufmann S.H.E.,
RA Chen C., Mao Z., Ge B.;
RT "Nuclear cGAS suppresses DNA repair and promotes tumorigenesis.";
RL Nature 563:131-136(2018).
RN [69]
RP INTERACTION WITH KHDC3L.
RX PubMed=31609975; DOI=10.1371/journal.pbio.3000468;
RA Zhang W., Chen Z., Zhang D., Zhao B., Liu L., Xie Z., Yao Y., Zheng P.;
RT "KHDC3L mutation causes recurrent pregnancy loss by inducing genomic
RT instability of human early embryonic cells.";
RL PLoS Biol. 17:e3000468-e3000468(2019).
RN [70]
RP FUNCTION, CATALYTIC ACTIVITY, AND ADP-RIBOSYLATION AT SER-499.
RX PubMed=33186521; DOI=10.1016/j.cell.2020.09.055;
RA Bonfiglio J.J., Leidecker O., Dauben H., Longarini E.J., Colby T.,
RA San Segundo-Acosta P., Perez K.A., Matic I.;
RT "An HPF1/PARP1-based chemical biology strategy for exploring ADP-
RT ribosylation.";
RL Cell 183:1086-1102(2020).
RN [71]
RP ADP-RIBOSYLATION AT LYS-521, AND SUBCELLULAR LOCATION.
RX PubMed=27568560; DOI=10.1016/j.celrep.2016.08.006;
RA Van Meter M., Simon M., Tombline G., May A., Morello T.D., Hubbard B.P.,
RA Bredbenner K., Park R., Sinclair D.A., Bohr V.A., Gorbunova V.,
RA Seluanov A.;
RT "JNK phosphorylates SIRT6 to stimulate DNA double-strand break repair in
RT response to oxidative stress by recruiting PARP1 to DNA Breaks.";
RL Cell Rep. 16:2641-2650(2016).
RN [72]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, INTERACTION WITH HPF1, AND
RP MUTAGENESIS OF HIS-826; GLU-988 AND 1013-LEU-TRP-1014.
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 [73]
RP STRUCTURE BY NMR OF 1-93 AND 385-643.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first ZF-PARP domain, of the BRCT domain and of
RT the WGR domain of human poly(ADP-ribose)polymerase-1.";
RL Submitted (APR-2007) to the PDB data bank.
RN [74] {ECO:0007744|PDB:4XHU}
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 661-1014 IN COMPLEX WITH
RP TIMELESS, FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TIMELESS,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 490-VAL--VAL-493; 850-PRO-PHE-851
RP AND ASP-993.
RX PubMed=26344098; DOI=10.1016/j.molcel.2015.07.031;
RA Xie S., Mortusewicz O., Ma H.T., Herr P., Poon R.Y., Helleday T., Qian C.;
RT "Timeless interacts with PARP-1 to promote homologous recombination
RT repair.";
RL Mol. Cell 60:163-176(2015).
RN [75]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-488.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Poly-ADP-ribosyltransferase that mediates poly-ADP-
CC ribosylation of proteins and plays a key role in DNA repair
CC (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379,
CC PubMed:21680843, PubMed:23230272, PubMed:25043379, PubMed:33186521,
CC PubMed:32028527, PubMed:26344098). Mediates glutamate, aspartate,
CC serine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl
CC group of NAD(+) is transferred to the acceptor carboxyl group of target
CC residues and further ADP-ribosyl groups are transferred to the 2'-
CC position of the terminal adenosine moiety, building up a polymer with
CC an average chain length of 20-30 units (PubMed:7852410, PubMed:9315851,
CC PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836).
CC Serine ADP-ribosylation of proteins constitutes the primary form of
CC ADP-ribosylation of proteins in response to DNA damage
CC (PubMed:33186521). Mainly mediates glutamate and aspartate ADP-
CC ribosylation of target proteins in absence of HPF1 (PubMed:19764761,
CC PubMed:25043379). Following interaction with HPF1, catalyzes serine
CC ADP-ribosylation of target proteins; HPF1 conferring serine specificity
CC by completing the PARP1 active site (PubMed:28190768, PubMed:29954836,
CC PubMed:33186521, PubMed:32028527). Also catalyzes tyrosine ADP-
CC ribosylation of target proteins following interaction with HPF1
CC (PubMed:30257210, PubMed:29954836). PARP1 initiates the repair of DNA
CC breaks: recognizes and binds DNA breaks within chromatin and recruits
CC HPF1, licensing serine ADP-ribosylation of target proteins, such as
CC histones, thereby promoting decompaction of chromatin and the
CC recruitment of repair factors leading to the reparation of DNA strand
CC breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625,
CC PubMed:19661379, PubMed:23230272, PubMed:27067600). In addition to base
CC excision repair (BER) pathway, also involved in double-strand breaks
CC (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites
CC and promotes homologous recombination repair by mediating poly-ADP-
CC ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly(ADP-
CC ribosyl)ation of a number of proteins, including itself, APLF and CHFR
CC (PubMed:17396150, PubMed:19764761). In addition to proteins, also able
CC to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break
CC termini containing terminal phosphates and a 2'-OH group in single- and
CC double-stranded DNA, respectively (PubMed:27471034). Required for PARP9
CC and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-
CC dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and
CC specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA
CC damage sites (PubMed:23230272). Acts as a regulator of transcription:
CC positively regulates the transcription of MTUS1 and negatively
CC regulates the transcription of MTUS2/TIP150 (PubMed:19344625). Plays a
CC role in the positive regulation of IFNG transcription in T-helper 1
CC cells as part of an IFNG promoter-binding complex with TXK and EEF1A1
CC (PubMed:17177976). Involved in the synthesis of ATP in the nucleus,
CC together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP
CC generation is required for extensive chromatin remodeling events that
CC are energy-consuming (PubMed:27257257). {ECO:0000269|PubMed:17177976,
CC ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18172500,
CC ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379,
CC ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:21680843,
CC ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:25043379,
CC ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:27067600,
CC ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034,
CC ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836,
CC ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214,
CC ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:33186521,
CC ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.
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:18172500, ECO:0000269|PubMed:19764761,
CC ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098,
CC ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:7852410};
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:27067600,
CC ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:33186521,
CC ECO:0000305|PubMed:29954836};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58233;
CC Evidence={ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:32028527,
CC ECO:0000269|PubMed:33186521, ECO:0000305|PubMed:29954836};
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:19764761, ECO:0000269|PubMed:25043379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54425;
CC Evidence={ECO:0000269|PubMed:19764761, 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:19764761, ECO:0000269|PubMed:25043379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58225;
CC Evidence={ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:25043379};
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:0000305|PubMed:29954836,
CC ECO:0000305|PubMed:30257210};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58237;
CC Evidence={ECO:0000305|PubMed:29954836, ECO:0000305|PubMed:30257210};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=130 uM for NAD(+) {ECO:0000269|PubMed:7852410};
CC Note=kcat is 390 sec(-1) for NAD(+). {ECO:0000269|PubMed:7852410};
CC -!- SUBUNIT: Homo- and heterodimer with PARP2. Interacts with APTX
CC (PubMed:15044383). Component of a base excision repair (BER) complex,
CC containing at least XRCC1, PARP1, PARP2, POLB and LRIG3 (By
CC similarity). Interacts with SRY (PubMed:16904257). The SWAP complex
CC consists of NPM1, NCL, PARP1 and SWAP70 (By similarity). Interacts with
CC TIAM2 (By similarity). Interacts with PARP3; leading to activate PARP1
CC in absence of DNA (PubMed:20064938). Interacts (when poly-ADP-
CC ribosylated) with CHD1L (via macro domain) (PubMed:19661379,
CC PubMed:29220653). Interacts with the DNA polymerase alpha catalytic
CC subunit POLA1; this interaction functions as part of the control of
CC replication fork progression (PubMed:9518481). Interacts with EEF1A1
CC and TXK (PubMed:17177976). Interacts with RNF4 (PubMed:19779455).
CC Interacts with RNF146 (PubMed:21799911). Interacts with ZNF423
CC (PubMed:22863007). Interacts with APLF (PubMed:17396150). Interacts
CC with SNAI1 (via zinc fingers); the interaction requires SNAI1 to be
CC poly-ADP-ribosylated and non-phosphorylated (active) by GSK3B
CC (PubMed:21577210). Interacts (when poly-ADP-ribosylated) with PARP9
CC (PubMed:23230272). 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
CC (PubMed:21266351). Interacts (via the PARP catalytic domain) with HPF1
CC (PubMed:27067600, PubMed:28190768, PubMed:29954836, PubMed:32028527).
CC Interacts with ZNF365 (PubMed:23966166). Interacts with RRP1B
CC (PubMed:19710015). Interacts with TIMELESS; the interaction is direct
CC (PubMed:26344098). Interacts with CGAS; leading to impede the formation
CC of the PARP1-TIMELESS complex (PubMed:30356214). Interacts with KHDC3L,
CC the interaction is increased following the formation of DNA double-
CC strand breaks (PubMed:31609975). {ECO:0000250|UniProtKB:P11103,
CC ECO:0000250|UniProtKB:P27008, ECO:0000269|PubMed:15044383,
CC ECO:0000269|PubMed:16904257, ECO:0000269|PubMed:17177976,
CC ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:19661379,
CC ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:19779455,
CC ECO:0000269|PubMed:20064938, ECO:0000269|PubMed:21266351,
CC ECO:0000269|PubMed:21577210, ECO:0000269|PubMed:21799911,
CC ECO:0000269|PubMed:22863007, ECO:0000269|PubMed:23230272,
CC ECO:0000269|PubMed:23966166, ECO:0000269|PubMed:26344098,
CC ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:28190768,
CC ECO:0000269|PubMed:29220653, ECO:0000269|PubMed:29954836,
CC ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31609975,
CC ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:9518481}.
CC -!- INTERACTION:
CC P09874; Q8IW19: APLF; NbExp=8; IntAct=EBI-355676, EBI-1256044;
CC P09874; Q7Z2E3: APTX; NbExp=8; IntAct=EBI-355676, EBI-847814;
CC P09874; P42574: CASP3; NbExp=2; IntAct=EBI-355676, EBI-524064;
CC P09874; P49715: CEBPA; NbExp=2; IntAct=EBI-355676, EBI-1172054;
CC P09874; Q86WJ1-1: CHD1L; NbExp=3; IntAct=EBI-355676, EBI-15797018;
CC P09874; P26358: DNMT1; NbExp=6; IntAct=EBI-355676, EBI-719459;
CC P09874; Q01094: E2F1; NbExp=3; IntAct=EBI-355676, EBI-448924;
CC P09874; P11308: ERG; NbExp=7; IntAct=EBI-355676, EBI-79704;
CC P09874; P09429: HMGB1; NbExp=2; IntAct=EBI-355676, EBI-389432;
CC P09874; Q13007: IL24; NbExp=2; IntAct=EBI-355676, EBI-3915542;
CC P09874; Q9Y530: OARD1; NbExp=5; IntAct=EBI-355676, EBI-8502288;
CC P09874; P09874: PARP1; NbExp=3; IntAct=EBI-355676, EBI-355676;
CC P09874; Q8N2W9: PIAS4; NbExp=5; IntAct=EBI-355676, EBI-473160;
CC P09874; P46063: RECQL; NbExp=8; IntAct=EBI-355676, EBI-2823728;
CC P09874; Q9NTX7: RNF146; NbExp=4; IntAct=EBI-355676, EBI-722397;
CC P09874; Q14684-1: RRP1B; NbExp=4; IntAct=EBI-355676, EBI-5280110;
CC P09874; O95863: SNAI1; NbExp=10; IntAct=EBI-355676, EBI-1045459;
CC P09874; P63165: SUMO1; NbExp=2; IntAct=EBI-355676, EBI-80140;
CC P09874; P04637: TP53; NbExp=3; IntAct=EBI-355676, EBI-366083;
CC P09874; P0CG48: UBC; NbExp=2; IntAct=EBI-355676, EBI-3390054;
CC P09874; Q14191: WRN; NbExp=8; IntAct=EBI-355676, EBI-368417;
CC P09874; P18887: XRCC1; NbExp=6; IntAct=EBI-355676, EBI-947466;
CC P09874; P54577: YARS1; NbExp=5; IntAct=EBI-355676, EBI-1048893;
CC P09874; Q2M1K9: ZNF423; NbExp=2; IntAct=EBI-355676, EBI-950016;
CC P09874; Q02085: Snai1; Xeno; NbExp=3; IntAct=EBI-355676, EBI-6049807;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17177976,
CC ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:23230272}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:9518481}. Chromosome
CC {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26344098,
CC ECO:0000269|PubMed:27568560}. Note=Localizes to sites of DNA damage.
CC {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26344098,
CC ECO:0000269|PubMed:27568560}.
CC -!- DOMAIN: The N-terminal disordered region does not act as a key DNA-
CC binding domain. The WGR and PARP catalytic domains function together to
CC recruit PARP1 to sites of DNA breaks. The N-terminal disordered region
CC is only required for activation on specific types of DNA damage.
CC {ECO:0000250|UniProtKB:Q9UGN5}.
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 -!- PTM: Poly-ADP-ribosylated on glutamate and aspartate residues by
CC autocatalysis (PubMed:19764761). Poly-ADP-ribosylated by PARP2; poly-
CC ADP-ribosylation mediates the recruitment of CHD1L to DNA damage sites
CC (PubMed:19661379). ADP-ribosylated on serine by autocatalysis; serine
CC ADP-ribosylation takes place following interaction with HPF1
CC (PubMed:28190768). Auto poly-ADP-ribosylated on serine residues,
CC leading to dissociation of the PARP1-HPF1 complex from chromatin (By
CC similarity). Mono-ADP-ribosylated at Lys-521 by SIRT6 in response to
CC oxidative stress, promoting recruitment to double-strand breaks (DSBs)
CC sites (PubMed:21680843, PubMed:22753495, PubMed:27568560).
CC {ECO:0000250|UniProtKB:Q9UGN5, ECO:0000269|PubMed:19661379,
CC ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:21680843,
CC ECO:0000269|PubMed:22753495, ECO:0000269|PubMed:27568560,
CC ECO:0000269|PubMed:28190768}.
CC -!- PTM: Phosphorylated by PRKDC (PubMed:10467406). Phosphorylated by TXK
CC (PubMed:17177976). {ECO:0000269|PubMed:10467406,
CC ECO:0000269|PubMed:17177976}.
CC -!- PTM: S-nitrosylated, leading to inhibit transcription regulation
CC activity. {ECO:0000250|UniProtKB:P11103}.
CC -!- SIMILARITY: Belongs to the ARTD/PARP family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/adprt/";
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; M18112; AAA60137.1; -; mRNA.
DR EMBL; J03473; AAB59447.1; -; mRNA.
DR EMBL; M32721; AAA60155.1; -; mRNA.
DR EMBL; M29786; AAA51663.1; -; Genomic_DNA.
DR EMBL; M29545; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29766; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29767; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29768; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29769; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29770; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29771; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29772; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29773; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29774; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29775; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29776; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29777; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29778; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29779; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29780; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29781; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29783; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29784; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29785; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29544; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; M29782; AAA51663.1; JOINED; Genomic_DNA.
DR EMBL; AF524947; AAM75364.1; -; Genomic_DNA.
DR EMBL; AL359704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359742; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69783.1; -; Genomic_DNA.
DR EMBL; BC037545; AAH37545.1; -; mRNA.
DR EMBL; X56140; CAA39606.1; -; Genomic_DNA.
DR EMBL; X56141; CAA39606.1; JOINED; Genomic_DNA.
DR EMBL; X16674; CAA34663.1; -; Genomic_DNA.
DR EMBL; M60436; AAA60000.1; -; Genomic_DNA.
DR EMBL; M17081; AAA51599.1; ALT_SEQ; mRNA.
DR CCDS; CCDS1554.1; -.
DR PIR; A29725; A29725.
DR RefSeq; NP_001609.2; NM_001618.3.
DR PDB; 1UK0; X-ray; 3.00 A; A/B=662-1011.
DR PDB; 1UK1; X-ray; 3.00 A; A/B=662-1011.
DR PDB; 1WOK; X-ray; 3.00 A; A/B/C/D=662-1011.
DR PDB; 2COK; NMR; -; A=387-486.
DR PDB; 2CR9; NMR; -; A=518-643.
DR PDB; 2CS2; NMR; -; A=103-223.
DR PDB; 2DMJ; NMR; -; A=1-93.
DR PDB; 2JVN; NMR; -; A=233-358.
DR PDB; 2L30; NMR; -; A=1-108.
DR PDB; 2L31; NMR; -; A=103-214.
DR PDB; 2N8A; NMR; -; A=1-214.
DR PDB; 2RCW; X-ray; 2.80 A; A=662-1011.
DR PDB; 2RD6; X-ray; 2.30 A; A=662-1011.
DR PDB; 2RIQ; X-ray; 1.70 A; A=216-366.
DR PDB; 3GJW; X-ray; 2.30 A; A=662-1011.
DR PDB; 3GN7; X-ray; 2.50 A; A=662-1011.
DR PDB; 3L3L; X-ray; 2.50 A; A=662-1011.
DR PDB; 3L3M; X-ray; 2.50 A; A=662-1011.
DR PDB; 3OD8; X-ray; 2.40 A; A/B/C/D/E/F/G/H=2-96.
DR PDB; 3ODA; X-ray; 2.64 A; A/B/C/D/E/F/G/H=2-96.
DR PDB; 3ODC; X-ray; 2.80 A; A/B=105-206.
DR PDB; 3ODE; X-ray; 2.95 A; A/B=105-206.
DR PDB; 4AV1; X-ray; 3.10 A; A/B/C/D=5-202.
DR PDB; 4DQY; X-ray; 3.25 A; A/D=1-96, B/E=216-366, C/F=518-1014.
DR PDB; 4GV7; X-ray; 2.89 A; A/B/C/D=662-1011.
DR PDB; 4HHY; X-ray; 2.36 A; A/B/C/D=660-1011.
DR PDB; 4HHZ; X-ray; 2.72 A; A/B/C/D=660-1011.
DR PDB; 4L6S; X-ray; 2.20 A; A/B=662-1011.
DR PDB; 4OPX; X-ray; 3.31 A; A/D=1-97, A/D=207-366, C/F=518-1014.
DR PDB; 4OQA; X-ray; 3.65 A; A/D=1-97, A/D=207-366, C/F=518-1014.
DR PDB; 4OQB; X-ray; 3.36 A; A/D=1-97, A/D=207-366, C/F=518-1014.
DR PDB; 4PJT; X-ray; 2.35 A; A/B/C/D=662-1011.
DR PDB; 4R5W; X-ray; 2.84 A; A/B=662-1011.
DR PDB; 4R6E; X-ray; 2.20 A; A/B/C/D=662-1011.
DR PDB; 4RV6; X-ray; 3.19 A; A/B/C/D=662-1011.
DR PDB; 4UND; X-ray; 2.20 A; A/B=662-1011.
DR PDB; 4UXB; X-ray; 3.22 A; A/B=662-1011.
DR PDB; 4XHU; X-ray; 2.09 A; A/C=661-1014.
DR PDB; 4ZZZ; X-ray; 1.90 A; A/B=655-1014.
DR PDB; 5A00; X-ray; 2.75 A; A=655-1014.
DR PDB; 5DS3; X-ray; 2.60 A; A=788-1012.
DR PDB; 5HA9; X-ray; 4.01 A; A/B=662-1011.
DR PDB; 5KPN; X-ray; 2.30 A; A/B=662-1011.
DR PDB; 5KPO; X-ray; 2.65 A; A/B=662-1011.
DR PDB; 5KPP; X-ray; 2.33 A; A/B=662-1011.
DR PDB; 5KPQ; X-ray; 2.55 A; A/B=662-1011.
DR PDB; 5WRQ; X-ray; 2.65 A; A/B=662-1011.
DR PDB; 5WRY; X-ray; 2.30 A; A/B=662-1011.
DR PDB; 5WRZ; X-ray; 2.20 A; A/B=662-1011.
DR PDB; 5WS0; X-ray; 2.60 A; A/B=662-1011.
DR PDB; 5WS1; X-ray; 1.90 A; A/B=662-1011.
DR PDB; 5WTC; X-ray; 2.20 A; A/B=662-1011.
DR PDB; 5XSR; X-ray; 2.30 A; A=662-1011.
DR PDB; 5XST; X-ray; 2.30 A; A=662-1010.
DR PDB; 5XSU; X-ray; 2.40 A; A/B/C/D=662-1011.
DR PDB; 6BHV; X-ray; 2.30 A; A/B/C/D=788-1012.
DR PDB; 6GHK; X-ray; 2.28 A; A/B=662-1011.
DR PDB; 6M3I; X-ray; 1.98 A; B=788-1014.
DR PDB; 6NRF; X-ray; 2.00 A; A=788-1012.
DR PDB; 6NRG; X-ray; 1.70 A; A=788-1012.
DR PDB; 6NRH; X-ray; 1.50 A; A=788-1012.
DR PDB; 6NRI; X-ray; 2.20 A; A=788-1012.
DR PDB; 6NRJ; X-ray; 1.65 A; A=788-1012.
DR PDB; 6NTU; X-ray; 1.80 A; A=788-1012.
DR PDB; 6VKK; X-ray; 2.10 A; A/B/C/D=661-1011.
DR PDB; 6VKO; X-ray; 2.80 A; A/B/C/D=661-1011.
DR PDB; 6VKQ; X-ray; 2.90 A; A/B/C/D=661-1011.
DR PDB; 6XVW; X-ray; 2.00 A; A/B=663-1014.
DR PDB; 7AAA; X-ray; 1.74 A; A/B=662-1011.
DR PDB; 7AAB; X-ray; 2.80 A; A/B=662-1011.
DR PDB; 7AAC; X-ray; 1.59 A; A/B=662-1011.
DR PDB; 7AAD; X-ray; 2.21 A; A/B=662-1011.
DR PDB; 7CMW; X-ray; 2.70 A; A/B=662-1011.
DR PDB; 7KK2; X-ray; 1.70 A; A/B=662-1011.
DR PDB; 7KK3; X-ray; 2.06 A; A/B/C/D=662-1011.
DR PDB; 7KK4; X-ray; 1.96 A; A/B=662-1011.
DR PDB; 7KK5; X-ray; 1.70 A; A/B/C/D=662-1011.
DR PDB; 7KK6; X-ray; 2.06 A; A/B=662-1011.
DR PDB; 7ONR; X-ray; 2.05 A; A/B=662-1011.
DR PDB; 7ONS; X-ray; 1.97 A; A/B=662-1011.
DR PDB; 7ONT; X-ray; 1.85 A; A/B=662-1011.
DR PDB; 7SCY; EM; 4.10 A; K=385-492.
DR PDB; 7SCZ; EM; 3.50 A; K=385-492.
DR PDBsum; 1UK0; -.
DR PDBsum; 1UK1; -.
DR PDBsum; 1WOK; -.
DR PDBsum; 2COK; -.
DR PDBsum; 2CR9; -.
DR PDBsum; 2CS2; -.
DR PDBsum; 2DMJ; -.
DR PDBsum; 2JVN; -.
DR PDBsum; 2L30; -.
DR PDBsum; 2L31; -.
DR PDBsum; 2N8A; -.
DR PDBsum; 2RCW; -.
DR PDBsum; 2RD6; -.
DR PDBsum; 2RIQ; -.
DR PDBsum; 3GJW; -.
DR PDBsum; 3GN7; -.
DR PDBsum; 3L3L; -.
DR PDBsum; 3L3M; -.
DR PDBsum; 3OD8; -.
DR PDBsum; 3ODA; -.
DR PDBsum; 3ODC; -.
DR PDBsum; 3ODE; -.
DR PDBsum; 4AV1; -.
DR PDBsum; 4DQY; -.
DR PDBsum; 4GV7; -.
DR PDBsum; 4HHY; -.
DR PDBsum; 4HHZ; -.
DR PDBsum; 4L6S; -.
DR PDBsum; 4OPX; -.
DR PDBsum; 4OQA; -.
DR PDBsum; 4OQB; -.
DR PDBsum; 4PJT; -.
DR PDBsum; 4R5W; -.
DR PDBsum; 4R6E; -.
DR PDBsum; 4RV6; -.
DR PDBsum; 4UND; -.
DR PDBsum; 4UXB; -.
DR PDBsum; 4XHU; -.
DR PDBsum; 4ZZZ; -.
DR PDBsum; 5A00; -.
DR PDBsum; 5DS3; -.
DR PDBsum; 5HA9; -.
DR PDBsum; 5KPN; -.
DR PDBsum; 5KPO; -.
DR PDBsum; 5KPP; -.
DR PDBsum; 5KPQ; -.
DR PDBsum; 5WRQ; -.
DR PDBsum; 5WRY; -.
DR PDBsum; 5WRZ; -.
DR PDBsum; 5WS0; -.
DR PDBsum; 5WS1; -.
DR PDBsum; 5WTC; -.
DR PDBsum; 5XSR; -.
DR PDBsum; 5XST; -.
DR PDBsum; 5XSU; -.
DR PDBsum; 6BHV; -.
DR PDBsum; 6GHK; -.
DR PDBsum; 6M3I; -.
DR PDBsum; 6NRF; -.
DR PDBsum; 6NRG; -.
DR PDBsum; 6NRH; -.
DR PDBsum; 6NRI; -.
DR PDBsum; 6NRJ; -.
DR PDBsum; 6NTU; -.
DR PDBsum; 6VKK; -.
DR PDBsum; 6VKO; -.
DR PDBsum; 6VKQ; -.
DR PDBsum; 6XVW; -.
DR PDBsum; 7AAA; -.
DR PDBsum; 7AAB; -.
DR PDBsum; 7AAC; -.
DR PDBsum; 7AAD; -.
DR PDBsum; 7CMW; -.
DR PDBsum; 7KK2; -.
DR PDBsum; 7KK3; -.
DR PDBsum; 7KK4; -.
DR PDBsum; 7KK5; -.
DR PDBsum; 7KK6; -.
DR PDBsum; 7ONR; -.
DR PDBsum; 7ONS; -.
DR PDBsum; 7ONT; -.
DR PDBsum; 7SCY; -.
DR PDBsum; 7SCZ; -.
DR AlphaFoldDB; P09874; -.
DR BMRB; P09874; -.
DR SMR; P09874; -.
DR BioGRID; 106652; 759.
DR CORUM; P09874; -.
DR DIP; DIP-38N; -.
DR ELM; P09874; -.
DR IntAct; P09874; 173.
DR MINT; P09874; -.
DR STRING; 9606.ENSP00000355759; -.
DR BindingDB; P09874; -.
DR ChEMBL; CHEMBL3105; -.
DR DrugBank; DB04010; 2-(3'-Methoxyphenyl) Benzimidazole-4-Carboxamide.
DR DrugBank; DB03509; 2-(4-Chlorophenyl)-5-Quinoxalinecarboxamide.
DR DrugBank; DB03072; 2-{3-[4-(4-Fluorophenyl)-3,6-Dihydro-1(2h)-Pyridinyl]Propyl}-8-Methyl-4(3h)-Quinazolinone.
DR DrugBank; DB03722; 3,4-Dihydro-5-Methyl-Isoquinolinone.
DR DrugBank; DB03073; 3-Methoxybenzamide.
DR DrugBank; DB07787; 5-FLUORO-1-[4-(4-PHENYL-3,6-DIHYDROPYRIDIN-1(2H)-YL)BUTYL]QUINAZOLINE-2,4(1H,3H)-DIONE.
DR DrugBank; DB07096; 6-AMINO-BENZO[DE]ISOQUINOLINE-1,3-DIONE.
DR DrugBank; DB07330; A-620223.
DR DrugBank; DB02498; Carba-nicotinamide-adenine-dinucleotide.
DR DrugBank; DB13877; Iniparib.
DR DrugBank; DB02701; Nicotinamide.
DR DrugBank; DB11793; Niraparib.
DR DrugBank; DB02690; NU1025.
DR DrugBank; DB09074; Olaparib.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB11760; Talazoparib.
DR DrugBank; DB00277; Theophylline.
DR DrugBank; DB07232; Veliparib.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P09874; -.
DR GuidetoPHARMACOLOGY; 2771; -.
DR GlyGen; P09874; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P09874; -.
DR MetOSite; P09874; -.
DR PhosphoSitePlus; P09874; -.
DR SwissPalm; P09874; -.
DR BioMuta; PARP1; -.
DR DMDM; 130781; -.
DR SWISS-2DPAGE; P09874; -.
DR CPTAC; CPTAC-3240; -.
DR CPTAC; CPTAC-3241; -.
DR CPTAC; CPTAC-556; -.
DR CPTAC; CPTAC-557; -.
DR EPD; P09874; -.
DR jPOST; P09874; -.
DR MassIVE; P09874; -.
DR MaxQB; P09874; -.
DR PaxDb; P09874; -.
DR PeptideAtlas; P09874; -.
DR PRIDE; P09874; -.
DR ProteomicsDB; 52271; -.
DR Antibodypedia; 3545; 1935 antibodies from 50 providers.
DR CPTC; P09874; 1 antibody.
DR DNASU; 142; -.
DR Ensembl; ENST00000366794.10; ENSP00000355759.5; ENSG00000143799.14.
DR GeneID; 142; -.
DR KEGG; hsa:142; -.
DR MANE-Select; ENST00000366794.10; ENSP00000355759.5; NM_001618.4; NP_001609.2.
DR UCSC; uc001hqd.5; human.
DR CTD; 142; -.
DR DisGeNET; 142; -.
DR GeneCards; PARP1; -.
DR HGNC; HGNC:270; PARP1.
DR HPA; ENSG00000143799; Low tissue specificity.
DR MIM; 173870; gene.
DR neXtProt; NX_P09874; -.
DR OpenTargets; ENSG00000143799; -.
DR PharmGKB; PA32; -.
DR VEuPathDB; HostDB:ENSG00000143799; -.
DR eggNOG; KOG1037; Eukaryota.
DR GeneTree; ENSGT00940000156058; -.
DR HOGENOM; CLU_004841_0_0_1; -.
DR InParanoid; P09874; -.
DR OMA; RSAMMEF; -.
DR OrthoDB; 909382at2759; -.
DR PhylomeDB; P09874; -.
DR TreeFam; TF316616; -.
DR BRENDA; 2.4.2.30; 2681.
DR PathwayCommons; P09874; -.
DR Reactome; R-HSA-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-192814; vRNA Synthesis.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
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; P09874; -.
DR SIGNOR; P09874; -.
DR BioGRID-ORCS; 142; 31 hits in 1084 CRISPR screens.
DR ChiTaRS; PARP1; human.
DR EvolutionaryTrace; P09874; -.
DR GeneWiki; PARP1; -.
DR GenomeRNAi; 142; -.
DR Pharos; P09874; Tclin.
DR PRO; PR:P09874; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P09874; protein.
DR Bgee; ENSG00000143799; Expressed in ventricular zone and 210 other tissues.
DR ExpressionAtlas; P09874; baseline and differential.
DR Genevisible; P09874; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0032993; C:protein-DNA complex; IDA:CAFA.
DR GO; GO:0090734; C:site of DNA damage; IMP:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0051287; F:NAD binding; IEA:Ensembl.
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:0030331; F:nuclear estrogen receptor binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0070412; F:R-SMAD binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:1990966; P:ATP generation from poly-ADP-D-ribose; IDA:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:MGI.
DR GO; GO:0034644; P:cellular response to UV; IMP:BHF-UCL.
DR GO; GO:0071294; P:cellular response to zinc ion; IEA:Ensembl.
DR GO; GO:0030592; P:DNA ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; TAS:UniProtKB.
DR GO; GO:0032042; P:mitochondrial DNA metabolic process; IMP:MGI.
DR GO; GO:0043504; P:mitochondrial DNA repair; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; IMP:MGI.
DR GO; GO:2001170; P:negative regulation of ATP biosynthetic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1904357; P:negative regulation of telomere maintenance via telomere lengthening; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:Reactome.
DR GO; GO:0018424; P:peptidyl-glutamic acid poly-ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0018312; P:peptidyl-serine ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:1904762; P:positive regulation of myofibroblast differentiation; IEA:Ensembl.
DR GO; GO:1901216; P:positive regulation of neuron death; IEA:Ensembl.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IEA:Ensembl.
DR GO; GO:0006471; P:protein ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0070213; P:protein auto-ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IEA:Ensembl.
DR GO; GO:0036211; P:protein modification process; IMP:MGI.
DR GO; GO:0070212; P:protein poly-ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0050790; P:regulation of catalytic activity; IDA:BHF-UCL.
DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl.
DR GO; GO:1903376; P:regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI.
DR GO; GO:0010990; P:regulation of SMAD protein complex assembly; IEA:Ensembl.
DR GO; GO:1904044; P:response to aldosterone; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl.
DR GO; GO:0000723; P:telomere maintenance; TAS:BHF-UCL.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR Gene3D; 1.20.142.10; -; 1.
DR Gene3D; 2.20.25.630; -; 1.
DR Gene3D; 3.30.1740.10; -; 2.
DR Gene3D; 3.40.50.10190; -; 1.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR012982; PADR1.
DR InterPro; IPR038650; PADR1_dom_sf.
DR InterPro; IPR008288; PARP.
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 Pfam; PF00533; BRCT; 1.
DR Pfam; PF08063; PADR1; 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; SSF142921; SSF142921; 1.
DR SUPFAM; SSF47587; SSF47587; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR PROSITE; PS50172; BRCT; 1.
DR PROSITE; PS51060; PARP_ALPHA_HD; 1.
DR PROSITE; PS51059; PARP_CATALYTIC; 1.
DR PROSITE; PS00347; PARP_ZN_FINGER_1; 2.
DR PROSITE; PS50064; PARP_ZN_FINGER_2; 2.
DR PROSITE; PS51977; WGR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Chromosome;
KW Direct protein sequencing; DNA damage; DNA repair; DNA-binding;
KW Glycosyltransferase; Isopeptide bond; Metal-binding; NAD;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.12, ECO:0007744|PubMed:22814378"
FT CHAIN 2..1014
FT /note="Poly [ADP-ribose] polymerase 1"
FT /id="PRO_0000211320"
FT DOMAIN 385..476
FT /note="BRCT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 542..638
FT /note="WGR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01321"
FT DOMAIN 662..779
FT /note="PARP alpha-helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00398"
FT DOMAIN 788..1014
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 198..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 361..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..524
FT /note="Automodification domain"
FT /evidence="ECO:0000303|PubMed:19764761"
FT MOTIF 207..209
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:1505517"
FT MOTIF 221..226
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:1505517"
FT COMPBIAS 366..385
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 988
FT /note="For poly [ADP-ribose] polymerase activity"
FT /evidence="ECO:0000305|PubMed:32028527,
FT ECO:0000305|PubMed:7852410, ECO:0000305|PubMed:9315851"
FT BINDING 862..864
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UGN5"
FT BINDING 871
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UGN5"
FT BINDING 878
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UGN5"
FT BINDING 904
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q9UGN5"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.12, ECO:0007744|PubMed:22814378"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 97
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 131
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 179
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 368
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 387
FT /note="PolyADP-ribosyl aspartic acid"
FT /evidence="ECO:0000269|PubMed:19764761"
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 471
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:0000269|PubMed:19764761"
FT MOD_RES 491
FT /note="PolyADP-ribosyl glutamic acid"
FT /evidence="ECO:0000269|PubMed:19764761"
FT MOD_RES 499
FT /note="ADP-ribosylserine"
FT /evidence="ECO:0000269|PubMed:28190768,
FT ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:33186521"
FT MOD_RES 504
FT /note="ADP-ribosylserine"
FT /evidence="ECO:0000269|PubMed:29954836"
FT MOD_RES 507
FT /note="ADP-ribosylserine"
FT /evidence="ECO:0000269|PubMed:28190768,
FT ECO:0000269|PubMed:29954836"
FT MOD_RES 513
FT /note="PolyADP-ribosyl glutamic acid"
FT /evidence="ECO:0000255"
FT MOD_RES 514
FT /note="PolyADP-ribosyl glutamic acid"
FT /evidence="ECO:0000255"
FT MOD_RES 519
FT /note="ADP-ribosylserine"
FT /evidence="ECO:0000269|PubMed:28190768,
FT ECO:0000269|PubMed:29954836"
FT MOD_RES 520
FT /note="PolyADP-ribosyl glutamic acid"
FT /evidence="ECO:0000255"
FT MOD_RES 521
FT /note="N6-(ADP-ribosyl)lysine"
FT /evidence="ECO:0000269|PubMed:21680843,
FT ECO:0000269|PubMed:27568560"
FT MOD_RES 600
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 621
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 192
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 203
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 203
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 249
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 467
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 512
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 528
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 748
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 748
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VARIANT 54
FT /note="F -> L (in dbSNP:rs3738708)"
FT /id="VAR_050460"
FT VARIANT 188
FT /note="A -> T (in dbSNP:rs1805409)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_014714"
FT VARIANT 334
FT /note="V -> I (in dbSNP:rs3219057)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_019171"
FT VARIANT 377
FT /note="P -> S (in dbSNP:rs2230484)"
FT /id="VAR_050461"
FT VARIANT 383
FT /note="S -> Y (in dbSNP:rs3219062)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_019172"
FT VARIANT 488
FT /note="E -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035852"
FT VARIANT 762
FT /note="V -> A (in dbSNP:rs1136410)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_014715"
FT VARIANT 940
FT /note="K -> R (in dbSNP:rs3219145)"
FT /evidence="ECO:0000269|PubMed:2891139, ECO:0000269|Ref.5"
FT /id="VAR_019173"
FT MUTAGEN 490..493
FT /note="VEVV->GEVQ: Strongly reduced interaction with
FT TIMELESS."
FT /evidence="ECO:0000269|PubMed:26344098"
FT MUTAGEN 499
FT /note="S->A: Abolishes automodification on serine following
FT interaction with HPF1; when associated with A-507 and A-
FT 519."
FT /evidence="ECO:0000269|PubMed:28190768"
FT MUTAGEN 507
FT /note="S->A: Abolishes automodification on serine following
FT interaction with HPF1; when associated with A-499 and A-
FT 519."
FT /evidence="ECO:0000269|PubMed:28190768"
FT MUTAGEN 519
FT /note="S->A: Abolishes automodification on serine following
FT interaction with HPF1; when associated with A-499 and A-
FT 507."
FT /evidence="ECO:0000269|PubMed:28190768"
FT MUTAGEN 797
FT /note="L->P: 1.5% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 826
FT /note="H->A: Strongly reduced serine ADP-ribosylation,
FT caused by abolished interaction with HPF1."
FT /evidence="ECO:0000269|PubMed:32028527"
FT MUTAGEN 850..851
FT /note="Missing: Abolished interaction with TIMELESS."
FT /evidence="ECO:0000269|PubMed:26344098"
FT MUTAGEN 862
FT /note="H->A: Poly-ADP-ribosyltransferase activity is
FT impaired while mono-ADP-ribosyltransferase activity is not
FT affected; produces a mixture of short and mono ADP-ribose
FT chains."
FT /evidence="ECO:0000269|PubMed:7852410"
FT MUTAGEN 868
FT /note="N->S: 4% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 883
FT /note="E->Q: Does not affect ADP-ribosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:7852410"
FT MUTAGEN 890
FT /note="M->V: <0.5% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 893
FT /note="K->I: Abolishes enzymatic activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 897
FT /note="F->S: 10% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 899
FT /note="D->N: 0.6% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 908
FT /note="C->R: <0.5% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 923
FT /note="E->Q: Does not affect ADP-ribosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:7852410"
FT MUTAGEN 926
FT /note="L->F: 1.5% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 931
FT /note="E->Q: Does not affect ADP-ribosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:7852410"
FT MUTAGEN 986
FT /note="Y->H: 14% of wild-type activity and increased
FT branching 15-fold."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 988
FT /note="E->A,D,Q,K: Poly-ADP-ribosyltransferase activity is
FT inhibited while mono-ADP-ribosyltransferase activity is not
FT affected; only monomers are added. Disrupts interaction
FT with CHD1L."
FT /evidence="ECO:0000269|PubMed:29220653,
FT ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:7852410,
FT ECO:0000269|PubMed:9315851"
FT MUTAGEN 993
FT /note="D->G: Abolished interaction with TIMELESS."
FT /evidence="ECO:0000269|PubMed:26344098"
FT MUTAGEN 1003
FT /note="L->P: 1.5% of wild-type activity."
FT /evidence="ECO:0000269|PubMed:9315851"
FT MUTAGEN 1013..1014
FT /note="LW->EE: Strongly reduced serine ADP-ribosylation,
FT caused by abolished interaction with HPF1."
FT /evidence="ECO:0000269|PubMed:32028527"
FT CONFLICT 17
FT /note="G -> E (in Ref. 2; AAB59447)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="E -> Q (in Ref. 1; AAA60137)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="E -> K (in Ref. 2; AAB59447)"
FT /evidence="ECO:0000305"
FT CONFLICT 613
FT /note="H -> Q (in Ref. 3; AAA60155)"
FT /evidence="ECO:0000305"
FT CONFLICT 827
FT /note="N -> S (in Ref. 3; AAA60155)"
FT /evidence="ECO:0000305"
FT CONFLICT 908
FT /note="C -> Y (in Ref. 3; AAA60155)"
FT /evidence="ECO:0000305"
FT CONFLICT 980
FT /note="N -> I (in Ref. 3; AAA60155)"
FT /evidence="ECO:0000305"
FT TURN 2..5
FT /evidence="ECO:0007829|PDB:2L30"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:3OD8"
FT STRAND 15..17
FT /evidence="ECO:0007829|PDB:3OD8"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:3OD8"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:2L30"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:3OD8"
FT STRAND 42..53
FT /evidence="ECO:0007829|PDB:3OD8"
FT HELIX 54..59
FT /evidence="ECO:0007829|PDB:3OD8"
FT HELIX 67..70
FT /evidence="ECO:0007829|PDB:3OD8"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:3OD8"
FT HELIX 79..90
FT /evidence="ECO:0007829|PDB:3OD8"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:2N8A"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:3ODC"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:3ODC"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:3ODC"
FT STRAND 137..145
FT /evidence="ECO:0007829|PDB:3ODC"
FT STRAND 148..158
FT /evidence="ECO:0007829|PDB:3ODC"
FT HELIX 160..165
FT /evidence="ECO:0007829|PDB:3ODC"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:3ODC"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:3ODC"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:3ODC"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:3ODC"
FT HELIX 189..198
FT /evidence="ECO:0007829|PDB:3ODC"
FT TURN 204..206
FT /evidence="ECO:0007829|PDB:2L31"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:2N8A"
FT HELIX 226..255
FT /evidence="ECO:0007829|PDB:2RIQ"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:2RIQ"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:2JVN"
FT HELIX 276..289
FT /evidence="ECO:0007829|PDB:2RIQ"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:2RIQ"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:2RIQ"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:2RIQ"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:2RIQ"
FT STRAND 324..327
FT /evidence="ECO:0007829|PDB:2RIQ"
FT HELIX 337..340
FT /evidence="ECO:0007829|PDB:2RIQ"
FT HELIX 342..347
FT /evidence="ECO:0007829|PDB:2RIQ"
FT TURN 389..392
FT /evidence="ECO:0007829|PDB:7SCZ"
FT STRAND 394..397
FT /evidence="ECO:0007829|PDB:7SCZ"
FT HELIX 405..414
FT /evidence="ECO:0007829|PDB:7SCZ"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:7SCZ"
FT STRAND 427..431
FT /evidence="ECO:0007829|PDB:7SCZ"
FT HELIX 434..438
FT /evidence="ECO:0007829|PDB:7SCZ"
FT HELIX 441..448
FT /evidence="ECO:0007829|PDB:7SCZ"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:7SCZ"
FT HELIX 458..464
FT /evidence="ECO:0007829|PDB:7SCZ"
FT HELIX 469..472
FT /evidence="ECO:0007829|PDB:7SCZ"
FT TURN 473..475
FT /evidence="ECO:0007829|PDB:7SCZ"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:4DQY"
FT TURN 540..542
FT /evidence="ECO:0007829|PDB:4DQY"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:2CR9"
FT STRAND 551..560
FT /evidence="ECO:0007829|PDB:4DQY"
FT TURN 562..564
FT /evidence="ECO:0007829|PDB:4DQY"
FT STRAND 567..573
FT /evidence="ECO:0007829|PDB:4DQY"
FT TURN 578..581
FT /evidence="ECO:0007829|PDB:2CR9"
FT STRAND 585..591
FT /evidence="ECO:0007829|PDB:4DQY"
FT STRAND 597..602
FT /evidence="ECO:0007829|PDB:4DQY"
FT HELIX 608..622
FT /evidence="ECO:0007829|PDB:4DQY"
FT STRAND 639..641
FT /evidence="ECO:0007829|PDB:4DQY"
FT HELIX 667..676
FT /evidence="ECO:0007829|PDB:7AAC"
FT HELIX 679..688
FT /evidence="ECO:0007829|PDB:7AAC"
FT TURN 693..695
FT /evidence="ECO:0007829|PDB:7AAC"
FT HELIX 698..700
FT /evidence="ECO:0007829|PDB:7AAC"
FT HELIX 703..721
FT /evidence="ECO:0007829|PDB:7AAC"
FT HELIX 726..739
FT /evidence="ECO:0007829|PDB:7AAC"
FT STRAND 745..747
FT /evidence="ECO:0007829|PDB:7ONS"
FT STRAND 752..754
FT /evidence="ECO:0007829|PDB:1UK0"
FT HELIX 755..779
FT /evidence="ECO:0007829|PDB:7AAC"
FT STRAND 785..787
FT /evidence="ECO:0007829|PDB:4R6E"
FT HELIX 790..796
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 799..803
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 806..808
FT /evidence="ECO:0007829|PDB:2RCW"
FT HELIX 809..820
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 824..826
FT /evidence="ECO:0007829|PDB:7AAC"
FT STRAND 829..841
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 844..848
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 849..851
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 853..855
FT /evidence="ECO:0007829|PDB:3GN7"
FT STRAND 857..863
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 866..868
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 869..875
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 882..884
FT /evidence="ECO:0007829|PDB:6VKQ"
FT HELIX 886..888
FT /evidence="ECO:0007829|PDB:7AAC"
FT STRAND 889..891
FT /evidence="ECO:0007829|PDB:1WOK"
FT STRAND 893..900
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 901..905
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 906..908
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 912..914
FT /evidence="ECO:0007829|PDB:7KK5"
FT STRAND 916..925
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 928..934
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 938..940
FT /evidence="ECO:0007829|PDB:6VKK"
FT STRAND 947..950
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 952..956
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 958..960
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 962..964
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 967..969
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 974..976
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 983..986
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 988..993
FT /evidence="ECO:0007829|PDB:6NRH"
FT HELIX 994..996
FT /evidence="ECO:0007829|PDB:6NRH"
FT STRAND 997..1009
FT /evidence="ECO:0007829|PDB:6NRH"
SQ SEQUENCE 1014 AA; 113084 MW; 6A5FC01EB91C046B CRC64;
MAESSDKLYR VEYAKSGRAS CKKCSESIPK DSLRMAIMVQ SPMFDGKVPH WYHFSCFWKV
GHSIRHPDVE VDGFSELRWD DQQKVKKTAE AGGVTGKGQD GIGSKAEKTL GDFAAEYAKS
NRSTCKGCME KIEKGQVRLS KKMVDPEKPQ LGMIDRWYHP GCFVKNREEL GFRPEYSASQ
LKGFSLLATE DKEALKKQLP GVKSEGKRKG DEVDGVDEVA KKKSKKEKDK DSKLEKALKA
QNDLIWNIKD ELKKVCSTND LKELLIFNKQ QVPSGESAIL DRVADGMVFG ALLPCEECSG
QLVFKSDAYY CTGDVTAWTK CMVKTQTPNR KEWVTPKEFR EISYLKKLKV KKQDRIFPPE
TSASVAATPP PSTASAPAAV NSSASADKPL SNMKILTLGK LSRNKDEVKA MIEKLGGKLT
GTANKASLCI STKKEVEKMN KKMEEVKEAN IRVVSEDFLQ DVSASTKSLQ ELFLAHILSP
WGAEVKAEPV EVVAPRGKSG AALSKKSKGQ VKEEGINKSE KRMKLTLKGG AAVDPDSGLE
HSAHVLEKGG KVFSATLGLV DIVKGTNSYY KLQLLEDDKE NRYWIFRSWG RVGTVIGSNK
LEQMPSKEDA IEHFMKLYEE KTGNAWHSKN FTKYPKKFYP LEIDYGQDEE AVKKLTVNPG
TKSKLPKPVQ DLIKMIFDVE SMKKAMVEYE IDLQKMPLGK LSKRQIQAAY SILSEVQQAV
SQGSSDSQIL DLSNRFYTLI PHDFGMKKPP LLNNADSVQA KVEMLDNLLD IEVAYSLLRG
GSDDSSKDPI DVNYEKLKTD IKVVDRDSEE AEIIRKYVKN THATTHNAYD LEVIDIFKIE
REGECQRYKP FKQLHNRRLL WHGSRTTNFA GILSQGLRIA PPEAPVTGYM FGKGIYFADM
VSKSANYCHT SQGDPIGLIL LGEVALGNMY ELKHASHISK LPKGKHSVKG LGKTTPDPSA
NISLDGVDVP LGTGISSGVN DTSLLYNEYI VYDIAQVNLK YLLKLKFNFK TSLW
