PARP2

Last updated
PARP2
Protein PARP2 PDB 1gs0.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PARP2 , ADPRT2, ADPRTL2, ADPRTL3, ARTD2, PARP-2, pADPRT-2, poly(ADP-ribose) polymerase 2
External IDs OMIM: 607725 MGI: 1341112 HomoloGene: 4004 GeneCards: PARP2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001042618
NM_005484

NM_009632

RefSeq (protein)

NP_001036083
NP_005475

NP_033762

Location (UCSC) Chr 14: 20.34 – 20.36 Mb Chr 14: 51.05 – 51.06 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Poly [ADP-ribose] polymerase 2 is an enzyme that in humans is encoded by the PARP2 gene. [5] [6] [7] It is one of the PARP family of enzymes.

Contents

Function

This gene encodes poly(ADP-ribosyl)transferase-like 2 protein, which contains a catalytic domain and is capable of catalyzing a poly(ADP-ribosyl)ation reaction. This protein has a catalytic domain which is homologous to that of poly (ADP-ribosyl) transferase, but lacks an N-terminal DNA binding domain which activates the C-terminal catalytic domain of poly (ADP-ribosyl) transferase. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. Two alternatively spliced transcript variants encoding distinct isoforms have been found. [7]

In the plant species Arabidopsis thaliana, PARP2 plays more significant roles than PARP1 in protective responses to DNA damage and bacterial pathogenesis. [8] The plant PARP2 carries N-terminal SAP DNA binding motifs rather than the Zn-finger DNA binding motifs of plant and animal PARP1 proteins. [8]

PARP inhibitor drugs

Some PARP inhibitor anti-cancer drugs (primarily aimed at PARP1) also inhibit PARP2, e.g. niraparib.

Interactions

PARP2 has been shown to interact with XRCC1. [9]

PARP2 also interacts with HPF1. [10] [11] [12]

PARP2 binds to and bridges blunt DNA ends. [12] [13] [14]

Related Research Articles

<span class="mw-page-title-main">Poly (ADP-ribose) polymerase</span> Family of proteins

Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.

<span class="mw-page-title-main">XRCC1</span> Protein

DNA repair protein XRCC1, also known as X-ray repair cross-complementing protein 1, is a protein that in humans is encoded by the XRCC1 gene. XRCC1 is involved in DNA repair, where it complexes with DNA ligase III.

<span class="mw-page-title-main">ADP-ribosylation</span> Addition of one or more ADP-ribose moieties to a protein.

ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. Improper ADP-ribosylation has been implicated in some forms of cancer. It is also the basis for the toxicity of bacterial compounds such as cholera toxin, diphtheria toxin, and others.

<span class="mw-page-title-main">PARP1</span> Mammalian protein found in Homo sapiens

Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene. It is the most abundant of the PARP family of enzymes, accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus, but cytosolic fraction of this protein was also reported.

<span class="mw-page-title-main">Tankyrase</span> Enzyme

Tankyrase, also known as tankyrase 1, is an enzyme that in humans is encoded by the TNKS gene. It inhibits the binding of TERF1 to telomeric DNA. Tankyrase attracts substantial interest in cancer research through its interaction with AXIN1 and AXIN2, which are negative regulators of pro-oncogenic β-catenin signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and thus such inhibitors are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers.

<span class="mw-page-title-main">NMNAT1</span> Protein-coding gene in the species Homo sapiens

Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is an enzyme that in humans is encoded by the nmnat1 gene. It is a member of the nicotinamide-nucleotide adenylyltransferases (NMNATs) which catalyze nicotinamide adenine dinucleotide (NAD) synthesis.

<span class="mw-page-title-main">PARP4</span> Enzyme

Poly [ADP-ribose] polymerase 4 is an enzyme that in humans is encoded by the PARP4 gene.

<span class="mw-page-title-main">PARP3</span> Protein-coding gene in the species Homo sapiens

Poly [ADP-ribose] polymerase 3 is an enzyme that in humans is encoded by the PARP3 gene.

<span class="mw-page-title-main">Tankyrase 2</span> Protein-coding gene in the species Homo sapiens

Tankyrase-2 is an enzyme that in humans is encoded by the TNKS2 gene.

<span class="mw-page-title-main">ADP-ribosylhydrolase 3</span> Protein-coding gene in the species Homo sapiens

(ADP-ribosyl)hydrolase 3 (ARH3) is an enzyme that in humans is encoded by the ADPRHL2 gene (also called ADPRS). This enzyme reverses the proteins’ post-translational addition of ADP-ribose to serine residues as part of the DNA damage response The enzyme is also known to cleave poly(ADP-ribose) polymers, 1''-O-acetyl-ADP-ribose and alpha-NAD+

<span class="mw-page-title-main">PARP8</span> Protein-coding gene in the species Homo sapiens

Poly [ADP-ribose] polymerase 8 is an enzyme that in humans is encoded by the PARP8 gene.

<span class="mw-page-title-main">TIPARP</span> Protein-coding gene in the species Homo sapiens

TCDD-inducible poly [ADP-ribose] polymerase is an enzyme that in humans is encoded by the TIPARP gene.

<span class="mw-page-title-main">PARP10</span> Protein-coding gene in the species Homo sapiens

Poly [ADP-ribose] polymerase 10 is an enzyme that in humans is encoded by the PARP10 gene.

<span class="mw-page-title-main">PARP inhibitor</span> Pharmacological enzyme inhibitors of poly (ADP-ribose) polymerases

PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP).

<span class="mw-page-title-main">ADP-ribosylhydrolase</span>

In molecular biology, the (ADP-ribosyl)hydrolase (ARH) family contains enzymes which catalyses the hydrolysis of ADP-ribosyl modifications from proteins, nucleic acids and small molecules.

<span class="mw-page-title-main">Macro domain</span>

In molecular biology, the Macro domain or A1pp domain is a module of about 180 amino acids which can bind ADP-ribose, an NAD metabolite, or related ligands. Binding to ADP-ribose can be either covalent or non-covalent: in certain cases it is believed to bind non-covalently, while in other cases it appears to bind both non-covalently through a zinc finger motif, and covalently through a separate region of the protein.

<span class="mw-page-title-main">LIG3</span> Protein-coding gene in the species Homo sapiens

DNA ligase 3 is an enzyme that, in humans, is encoded by the LIG3 gene. The human LIG3 gene encodes ATP-dependent DNA ligases that seal interruptions in the phosphodiester backbone of duplex DNA.

<span class="mw-page-title-main">ADP-ribosylhydrolase 1</span>

(ADP-ribosyl)hydrolase 1, also termed [Protein ADP-ribosylarginine] hydrolase and protein-Nω-(ADP-D-ribosyl)-L-arginine ADP-ribosylhydrolase (EC 3.2.2.19), is an enzyme that in humans is encoded by the ADPRH gene. This enzyme is a specific mono(ADP-ribosyl)hydrolase that catalyses the removal of an ADP-ribosyl modification from target arginine residues of protein substrates. The chemical reactions can formally be described as follows:

<span class="mw-page-title-main">DNA polymerase alpha subunit 2</span> Protein-coding gene in the species Homo sapiens

DNA polymerase alpha subunit 2 is an enzyme that in humans is encoded by the POLA2 gene.

Parthanatos is a form of programmed cell death that is distinct from other cell death processes such as necrosis and apoptosis. While necrosis is caused by acute cell injury resulting in traumatic cell death and apoptosis is a highly controlled process signalled by apoptotic intracellular signals, parthanatos is caused by the accumulation of Poly(ADP ribose) (PAR) and the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria. Parthanatos is also known as PARP-1 dependent cell death. PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes nuclear translocation of AIF. Parthanatos is involved in diseases that afflict hundreds of millions of people worldwide. Well known diseases involving parthanatos include Parkinson's disease, stroke, heart attack, and diabetes. It also has potential use as a treatment for ameliorating disease and various medical conditions such as diabetes and obesity.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000129484 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000036023 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Johansson M (May 1999). "A human poly(ADP-ribose) polymerase gene family (ADPRTL): cDNA cloning of two novel poly(ADP-ribose) polymerase homologues". Genomics. 57 (3): 442–5. doi:10.1006/geno.1999.5799. PMID   10329013.
  6. Yélamos J, Schreiber V, Dantzer F (April 2008). "Toward specific functions of poly(ADP-ribose) polymerase-2". Trends in Molecular Medicine. 14 (4): 169–78. doi:10.1016/j.molmed.2008.02.003. PMID   18353725.
  7. 1 2 "Entrez Gene: PARP2 poly (ADP-ribose) polymerase family, member 2".
  8. 1 2 Song J, Keppler BD, Wise RR, Bent AF (May 2015). "PARP2 Is the Predominant Poly(ADP-Ribose) Polymerase in Arabidopsis DNA Damage and Immune Responses". PLOS Genetics. 11 (5): e1005200. doi: 10.1371/journal.pgen.1005200 . PMC   4423837 . PMID   25950582.
  9. Schreiber V, Amé JC, Dollé P, Schultz I, Rinaldi B, Fraulob V, Ménissier-de Murcia J, de Murcia G (June 2002). "Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1". The Journal of Biological Chemistry. 277 (25): 23028–36. doi: 10.1074/jbc.M202390200 . PMID   11948190.
  10. Gibbs-Seymour I, Fontana P, Rack JG, Ahel I (5 May 2016). "HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates PARP-1 ADP-Ribosylation Activity". Molecular Cell. 62 (3): 432–442. doi:10.1016/j.molcel.2016.03.008. PMC   4858568 . PMID   27067600.
  11. Suskiewicz MJ, Zobel F, Ogden TE, Fontana P, Ariza A, Yang JC, Zhu K, Bracken L, Hawthorne WJ, Ahel D, Neuhaus D, Ahel I (March 2020). "HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation". Nature. 579 (7800): 598–602. Bibcode:2020Natur.579..598S. doi:10.1038/s41586-020-2013-6. PMC   7104379 . PMID   32028527.
  12. 1 2 Gaullier G, Roberts G, Muthurajan UM, Bowerman S, Rudolph J, Mahadevan J, Jha A, Rae PS, Luger K (3 November 2020). "Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1". PLOS ONE. 15 (11): e0240932. Bibcode:2020PLoSO..1540932G. doi: 10.1371/journal.pone.0240932 . PMC   7608914 . PMID   33141820.
  13. Obaji E, Haikarainen T, Lehtiö L (14 December 2018). "Structural basis for DNA break recognition by ARTD2/PARP2". Nucleic Acids Research. 46 (22): 12154–12165. doi:10.1093/nar/gky927. PMC   6294510 . PMID   30321391.
  14. Bilokapic S, Suskiewicz MJ, Ahel I, Halic M (September 2020). "Bridging of DNA breaks activates PARP2-HPF1 to modify chromatin". Nature. 585 (7826): 609–613. Bibcode:2020Natur.585..609B. doi:10.1038/s41586-020-2725-7. PMC   7529888 . PMID   32939087.

Further reading