Protein mono-ADP-ribosyltransferase PARP3

Details

Name
Protein mono-ADP-ribosyltransferase PARP3
Synonyms
  • 2.4.2.-
  • ADP-ribosyltransferase diphtheria toxin-like 3
  • ADPRT-3
  • ADPRT3
  • ADPRTL3
  • ARTD3
  • DNA ADP-ribosyltransferase PARP3
  • hPARP-3
  • IRT1
  • NAD(+) ADP-ribosyltransferase 3
  • pADPRT-3
  • PARP-3
  • Poly [ADP-ribose] polymerase 3
  • Poly[ADP-ribose] synthase 3
Gene Name
PARP3
UniProtKB Entry
Q9Y6F1Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0064489|Protein mono-ADP-ribosyltransferase PARP3
MAPKPKPWVQTEGPEKKKGRQAGREEDPFRSTAEALKAIPAEKRIIRVDPTCPLSSNPGT
QVYEDYNCTLNQTNIENNNNKFYIIQLLQDSNRFFTCWNRWGRVGEVGQSKINHFTRLED
AKKDFEKKFREKTKNNWAERDHFVSHPGKYTLIEVQAEDEAQEAVVKVDRGPVRTVTKRV
QPCSLDPATQKLITNIFSKEMFKNTMALMDLDVKKMPLGKLSKQQIARGFEALEALEEAL
KGPTDGGQSLEELSSHFYTVIPHNFGHSQPPPINSPELLQAKKDMLLVLADIELAQALQA
VSEQEKTVEEVPHPLDRDYQLLKCQLQLLDSGAPEYKVIQTYLEQTGSNHRCPTLQHIWK
VNQEGEEDRFQAHSKLGNRKLLWHGTNMAVVAAILTSGLRIMPHSGGRVGKGIYFASENS
KSAGYVIGMKCGAHHVGYMFLGEVALGREHHINTDNPSLKSPPPGFDSVIARGHTEPDPT
QDTELELDGQQVVVPQGQPVPCPEFSSSTFSQSEYLIYQESQCRLRYLLEVHL
Number of residues
533
Molecular Weight
60088.74
Theoretical pI
6.73
GO Classification
Functions
NAD DNA ADP-ribosyltransferase activity / NAD+- protein-aspartate ADP-ribosyltransferase activity / NAD+- protein-lysine ADP-ribosyltransferase activity / NAD+-protein ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / nucleotidyltransferase activity
Processes
DNA ADP-ribosylation / negative regulation of isotype switching / negative regulation of telomerase RNA reverse transcriptase activity / positive regulation of double-strand break repair via nonhomologous end joining / protein auto-ADP-ribosylation
Components
centrosome / cytoplasm / intercellular bridge / nuclear body / nucleolus / nucleoplasm
General Function
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:16924674, PubMed:19354255, PubMed:20064938, PubMed:21211721, PubMed:21270334, PubMed:23742272, PubMed:24598253, PubMed:25043379, PubMed:28447610). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (PubMed:20064938, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6 (PubMed:16924674, PubMed:24598253). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA (PubMed:27530147). Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ (PubMed:24598253). Suppresses G-quadruplex (G4) structures in response to DNA damage (PubMed:28447610). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (PubMed:16924674). Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks (PubMed:29361132, PubMed:29520010)
Specific Function
catalytic activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0021378|Poly [ADP-ribose] polymerase 3 (PARP3)
ATGTCCCTGCTTTTCTTGGCCATGGCTCCAAAGCCGAAGCCCTGGGTACAGACTGAGGGC
CCTGAGAAGAAGAAGGGCCGGCAGGCAGGAAGGGAGGAGGACCCCTTCCGCTCCACCGCT
GAGGCCCTCAAGGCCATACCCGCAGAGAAGCGCATAATCCGCGTGGATCCAACATGTCCA
CTCAGCAGCAACCCCGGGACCCAGGTGTATGAGGACTACAACTGCACCCTGAACCAGACC
AACATCGAGAACAACAACAACAAGTTCTACATCATCCAGCTGCTCCAAGACAGCAACCGC
TTCTTCACCTGCTGGAACCGCTGGGGCCGTGTGGGAGAGGTCGGCCAGTCAAAGATCAAC
CACTTCACAAGGCTAGAAGATGCAAAGAAGGACTTTGAGAAGAAATTTCGGGAAAAGACC
AAGAACAACTGGGCAGAGCGGGACCACTTTGTGTCTCACCCGGGCAAGTACACACTTATC
GAAGTACAGGCAGAGGATGAGGCCCAGGAAGCTGTGGTGAAGGTGGACAGAGGCCCAGTG
AGGACTGTGACTAAGCGGGTGCAGCCCTGCTCCCTGGACCCAGCCACGCAGAAGCTCATC
ACTAACATCTTCAGCAAGGAGATGTTCAAGAACACCATGGCCCTCATGGACCTGGATGTG
AAGAAGATGCCCCTGGGAAAGCTGAGCAAGCAACAGATTGCACGGGGTTTCGAGGCCTTG
GAGGCGCTGGAGGAGGCCCTGAAAGGCCCCACGGATGGTGGCCAAAGCCTGGAGGAGCTG
TCCTCACACTTTTACACCGTCATCCCGCACAACTTCGGCCACAGCCAGCCCCCGCCCATC
AATTCCCCTGAGCTTCTGCAGGCCAAGAAGGACATGCTGCTGGTGCTGGCGGACATCGAG
CTGGCCCAGGCCCTGCAGGCAGTCTCTGAGCAGGAGAAGACGGTGGAGGAGGTGCCACAC
CCCCTGGACCGAGACTACCAGCTTCTCAAGTGCCAGCTGCAGCTGCTAGACTCTGGAGCA
CCTGAGTACAAGGTGATACAGACCTACTTAGAACAGACTGGCAGCAACCACAGGTGCCCT
ACACTTCAACACATCTGGAAAGTAAACCAAGAAGGGGAGGAAGACAGATTCCAGGCCCAC
TCCAAACTGGGTAATCGGAAGCTGCTGTGGCATGGCACCAACATGGCCGTGGTGGCCGCC
ATCCTCACTAGTGGGCTCCGCATCATGCCACATTCTGGTGGGCGTGTTGGCAAGGGCATC
TACTTTGCCTCAGAGAACAGCAAGTCAGCTGGATATGTTATTGGCATGAAGTGTGGGGCC
CACCATGTCGGCTACATGTTCCTGGGTGAGGTGGCCCTGGGCAGAGAGCACCATATCAAC
ACGGACAACCCCAGCTTGAAGAGCCCACCTCCTGGCTTCGACAGTGTCATTGCCCGAGGC
CACACCGAGCCTGATCCGACCCAGGACACTGAGTTGGAGCTGGATGGCCAGCAAGTGGTG
GTGCCCCAGGGCCAGCCTGTGCCCTGCCCAGAGTTCAGCAGCTCCACATTCTCCCAGAGC
GAGTACCTCATCTACCAGGAGAGCCAGTGTCGCCTGCGCTACCTGCTGGAGGTCCACCTC
TGA
Chromosome Location
3
Locus
3p21.2
External Identifiers
ResourceLink
UniProtKB IDQ9Y6F1
UniProtKB Entry NamePARP3_HUMAN
GenBank Protein ID29788060
GenBank Gene IDY16836
GeneCard IDPARP3
HGNC IDHGNC:273
PDB ID(s)2EOC, 3C49, 3C4H, 3CE0, 3FHB, 4GV0, 4GV2, 4GV4, 4L6Z, 4L70, 4L7L, 4L7N, 4L7O, 4L7P, 4L7R, 4L7U
KEGG IDhsa:10039
IUPHAR/Guide To Pharmacology ID2864
NCBI Gene ID10039
General References
  1. 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]
  2. Augustin A, Spenlehauer C, Dumond H, Menissier-De Murcia J, Piel M, Schmit AC, Apiou F, Vonesch JL, Kock M, Bornens M, De Murcia G: PARP-3 localizes preferentially to the daughter centriole and interferes with the G1/S cell cycle progression. J Cell Sci. 2003 Apr 15;116(Pt 8):1551-62. [Article]
  3. Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA: The DNA sequence, annotation and analysis of human chromosome 3. Nature. 2006 Apr 27;440(7088):1194-8. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  6. Rouleau M, McDonald D, Gagne P, Ouellet ME, Droit A, Hunter JM, Dutertre S, Prigent C, Hendzel MJ, Poirier GG: PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery. J Cell Biochem. 2007 Feb 1;100(2):385-401. [Article]
  7. 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]

Associated Data

Bio-Entities
Bio-EntityType
Protein mono-ADP-ribosyltransferase PARP3 (Humans)protein
primary
Poly [ADP-ribose] polymerases (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
2-methyl-3,5,7,8-tetrahydro-4H-thiopyrano[4,3-d]pyrimidin-4-oneexperimentalunknowntargetDetails
4-[3-(1,4-diazepan-1-ylcarbonyl)-4-fluorobenzyl]phthalazin-1(2H)-oneexperimentalunknowntargetDetails
N~2~,N~2~-DIMETHYL-N~1~-(6-OXO-5,6-DIHYDROPHENANTHRIDIN-2-YL)GLYCINAMIDEexperimentalunknowntargetDetails
OlaparibapprovedyestargetinhibitorDetails
Rucaparibapproved, investigationalyestargetinhibitorDetails