Poly [ADP-ribose] polymerase 2

Details

Name
Poly [ADP-ribose] polymerase 2
Synonyms
  • 2.4.2.30
  • ADP-ribosyltransferase diphtheria toxin-like 2
  • ADPRT-2
  • ADPRT2
  • ADPRTL2
  • ARTD2
  • DNA ADP-ribosyltransferase PARP2
  • hPARP-2
  • NAD(+) ADP-ribosyltransferase 2
  • pADPRT-2
  • PARP-2
  • Poly[ADP-ribose] synthase 2
  • Protein poly-ADP-ribosyltransferase PARP2
Gene Name
PARP2
UniProtKB Entry
Q9UGN5Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0007286|Poly [ADP-ribose] polymerase 2
MAARRRRSTGGGRARALNESKRVNNGNTAPEDSSPAKKTRRCQRQESKKMPVAGGKANKD
RTEDKQDGMPGRSWASKRVSESVKALLLKGKAPVDPECTAKVGKAHVYCEGNDVYDVMLN
QTNLQFNNNKYYLIQLLEDDAQRNFSVWMRWGRVGKMGQHSLVACSGNLNKAKEIFQKKF
LDKTKNNWEDREKFEKVPGKYDMLQMDYATNTQDEEETKKEESLKSPLKPESQLDLRVQE
LIKLICNVQAMEEMMMEMKYNTKKAPLGKLTVAQIKAGYQSLKKIEDCIRAGQHGRALME
ACNEFYTRIPHDFGLRTPPLIRTQKELSEKIQLLEALGDIEIAIKLVKTELQSPEHPLDQ
HYRNLHCALRPLDHESYEFKVISQYLQSTHAPTHSDYTMTLLDLFEVEKDGEKEAFREDL
HNRMLLWHGSRMSNWVGILSHGLRIAPPEAPITGYMFGKGIYFADMSSKSANYCFASRLK
NTGLLLLSEVALGQCNELLEANPKAEGLLQGKHSTKGLGKMAPSSAHFVTLNGSTVPLGP
ASDTGILNPDGYTLNYNEYIVYNPNQVRMRYLLKVQFNFLQLW
Number of residues
583
Molecular Weight
66205.31
Theoretical pI
9.22
GO Classification
Functions
chromatin binding / damaged DNA binding / NAD DNA ADP-ribosyltransferase activity / NAD+- protein-aspartate ADP-ribosyltransferase activity / NAD+-protein ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / NAD+-protein-serine ADP-ribosyltransferase activity / nucleosome binding / nucleotidyltransferase activity / poly-ADP-D-ribose binding / poly-ADP-D-ribose modification-dependent protein binding
Processes
decidualization / DNA ADP-ribosylation / DNA damage response / DNA repair-dependent chromatin remodeling / double-strand break repair / hippocampal neuron apoptotic process / positive regulation of cell growth involved in cardiac muscle cell development / protein auto-ADP-ribosylation / protein poly-ADP-ribosylation / response to oxygen-glucose deprivation
Components
site of DNA damage
General Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, PubMed:32028527, PubMed:32939087, PubMed:34108479, PubMed:34486521, PubMed:34874266). Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:25043379, PubMed:30104678, PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (PubMed:28190768, PubMed:32028527, PubMed:34108479, PubMed:34486521, PubMed:34874266). PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:10364231, PubMed:32939087, PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (PubMed:30104678). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex (PubMed:27471034, PubMed:29361132)
Specific Function
Chromatin binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0012648|Poly [ADP-ribose] polymerase 2 (PARP2)
ATGGCGGCGCGGCGGCGACGGAGCACCGGCGGCGGCAGGGCGAGAGCATTAAATGAAAGC
AAAAGAGTTAATAATGGCAACACGGCTCCAGAAGACTCTTCCCCTGCCAAGAAAACTCGT
AGATGCCAGAGACAGGAGTCGAAAAAGATGCCTGTGGCTGGAGGAAAAGCTAATAAGGAC
AGGACAGAAGACAAGCAAGATGAATCTGTGAAGGCCTTGCTGTTAAAGGGCAAAGCTCCT
GTGGACCCAGAGTGTACAGCCAAGGTGGGGAAGGCTCATGTGTATTGTGAAGGAAATGAT
GTCTATGATGTCATGCTAAATCAGACCAATCTCCAGTTCAACAACAACAAGTACTATCTG
ATTCAGCTATTAGAAGATGATGCCCAGAGGAACTTCAGTGTTTGGATGAGATGGGGCCGA
GTTGGGAAAATGGGACAGCACAGCCTGGTGGCTTGTTCAGGCAATCTCAACAAGGCCAAG
GAAATCTTTCAGAAGAAATTCCTTGACAAAACGAAAAACAATTGGGAAGATCGAGAAAAG
TTTGAGAAGGTGCCTGGAAAATATGATATGCTACAGATGGACTATGCCACCAATACTCAG
GATGAAGAGGAAACAAAGAAAGAGGAATCTCTTAAATCTCCCTTGAAGCCAGAGTCACAG
CTAGATCTTCGGGTACAGGAGTTAATAAAGTTGATCTGTAATGTTCAGGCCATGGAAGAA
ATGATGATGGAAATGAAGTATAATACCAAGAAAGCCCCACTTGGGAAGCTGACAGTGGCA
CAAATCAAGGCAGGTTACCAGTCTCTTAAGAAGATTGAGGATTGTATTCGGGCTGGCCAG
CATGGACGAGCTCTCATGGAAGCATGCAATGAATTCTACACCAGGATTCCGCATGACTTT
GGACTCCGTACTCCTCCACTAATCCGGACACAGAAGGAACTGTCAGAAAAAATACAATTA
CTAGAGGCTTTGGGAGACATTGAAATTGCTATTAAGCTGGTGAAAACAGAGCTACAAAGC
CCAGAACACCCATTGGACCAACACTATAGAAACCTACATTGTGCCTTGCGCCCCCTTGAC
CATGAAAGTTATGAGTTCAAAGTGATTTCCCAGTACCTACAATCTACCCATGCTCCCACA
CACAGCGACTATACCATGACCTTGCTGGATTTGTTTGAAGTGGAGAAGGATGGTGAGAAA
GAAGCCTTCAGAGAGGACCTTCATAACAGGATGCTTCTATGGCATGGTTCCAGGATGAGT
AACTGGGTGGGAATCTTGAGCCATGGGCTTCGAATTGCCCCACCTGAAGCTCCCATCACA
GGTTACATGTTTGGGAAAGGAATCTACTTTGCTGACATGTCTTCCAAGAGTGCCAATTAC
TGCTTTGCCTCTCGCCTAAAGAATACAGGACTGCTGCTCTTATCAGAGGTAGCTCTAGGT
CAGTGTAATGAACTACTAGAGGCCAATCCTAAGGCCGAAGGATTGCTTCAAGGTAAACAT
AGCACCAAGGGGCTGGGCAAGATGGCTCCCAGTTCTGCCCACTTCGTCACCCTGAATGGG
AGTACAGTGCCATTAGGACCAGCAAGTGACACAGGAATTCTGAATCCAGATGGTTATACC
CTCAACTACAATGAATATATTGTATATAACCCCAACCAGGTCCGTATGCGGTACCTTTTA
AAGGTTCAGTTTAATTTCCTTCAGCTGTGGTGA
Chromosome Location
14
Locus
14q11.2
External Identifiers
ResourceLink
UniProtKB IDQ9UGN5
UniProtKB Entry NamePARP2_HUMAN
GenBank Protein ID6688130
GenBank Gene IDAJ236912
GeneCard IDPARP2
HGNC IDHGNC:272
PDB ID(s)3KCZ, 3KJD, 4PJV, 4TVJ, 4ZZX, 4ZZY, 5D5K, 5DSY, 6F1K, 6F5B, 6F5F, 6TX3, 6USJ, 6X0L, 6X0M, 6X0N, 7AEO, 7R59, 8HE8
KEGG IDhsa:10038
IUPHAR/Guide To Pharmacology ID2772
NCBI Gene ID10038
General References
  1. Ame JC, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Menissier-de Murcia J, de Murcia G: PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999 Jun 18;274(25):17860-8. [Article]
  2. Johansson M: A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues. Genomics. 1999 May 1;57(3):442-5. [Article]
  3. Berghammer H, Ebner M, Marksteiner R, Auer B: pADPRT-2: a novel mammalian polymerizing(ADP-ribosyl)transferase gene related to truncated pADPRT homologues in plants and Caenorhabditis elegans. FEBS Lett. 1999 Apr 23;449(2-3):259-63. [Article]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  5. Schreiber V, Ame JC, Dolle P, Schultz I, Rinaldi B, Fraulob V, Menissier-de Murcia J, de Murcia G: Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. J Biol Chem. 2002 Jun 21;277(25):23028-36. Epub 2002 Apr 10. [Article]
  6. Hottiger MO, Hassa PO, Luscher B, Schuler H, Koch-Nolte F: Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem Sci. 2010 Apr;35(4):208-19. doi: 10.1016/j.tibs.2009.12.003. Epub 2010 Jan 26. [Article]
  7. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  8. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  9. Karlberg T, Hammarstrom M, Schutz P, Svensson L, Schuler H: Crystal structure of the catalytic domain of human PARP2 in complex with PARP inhibitor ABT-888. Biochemistry. 2010 Feb 16;49(6):1056-8. doi: 10.1021/bi902079y. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Poly [ADP-ribose] polymerase 2 (Humans)protein
primary
Poly [ADP-ribose] polymerases (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
VeliparibinvestigationalunknowntargetDetails
OlaparibapprovedyestargetinhibitorDetails
Rucaparibapproved, investigationalyestargetinhibitorDetails
Niraparibapproved, investigationalyestargetinhibitorDetails
Talazoparibapproved, investigationalyestargetinhibitorDetails
2X-121investigationalyestargetinhibitorDetails