Poly [ADP-ribose] polymerase 2
Also known as: ADPRT2, ADPRTL2, PARP2
Function
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair. 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. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1. Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site. 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. HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains. Specifically mediates formation of branched poly-ADP-ribosylation. Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF. In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates at DNA strand breaks termini in nicked duplex.
Classification
- Family (Pfam)
- PF00644 PARP, PF02877 PARP_reg, PF05406 WGR
- InterPro
- ARTD/PARP, Poly(ADP-ribose)pol_cat_dom, Poly(ADP-ribose)pol_reg_dom, Poly(ADP-ribose)pol_reg_dom_sf, WGR_dom_sf, WGR_domain
- Functional cluster
- Zinc-Finger & Chromatin Regulatory Proteins
Experimental structures · PDB · 26
- 3KCZ X-ray 2.00A
- 3KJD X-ray 1.95A
- 4PJV X-ray 2.50A
- 4TVJ X-ray 2.10A
- 4ZZX X-ray 1.65A
- 4ZZY X-ray 2.20A
- 5D5K X-ray 1.90A
- 5DSY X-ray 2.70A
- 6F1K X-ray 2.20A
- 6F5B X-ray 2.80A
- 6F5F X-ray 2.98A
- 6TX3 X-ray 2.96A
- … and 14 more
A predicted model is available from AlphaFold.
Gene Ontology · 24
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0090734 site of DNA damage
- GO:0003682 chromatin binding
- GO:0003684 damaged DNA binding
- GO:0140294 NAD DNA ADP-ribosyltransferase activity
- GO:0003950 NAD+ poly-ADP-ribosyltransferase activity
- GO:1990404 NAD+-protein mono-ADP-ribosyltransferase activity
- GO:0140806 NAD+-protein-aspartate ADP-ribosyltransferase activity
- GO:0140807 NAD+-protein-glutamate ADP-ribosyltransferase activity
- GO:0140805 NAD+-protein-serine ADP-ribosyltransferase activity
- GO:0031491 nucleosome binding
- GO:0016779 nucleotidyltransferase activity
- GO:0072572 poly-ADP-D-ribose binding
- GO:0160004 poly-ADP-D-ribose modification-dependent protein binding
- GO:0046697 decidualization
- GO:0030592 DNA ADP-ribosylation
- GO:0006974 DNA damage response
- GO:0006281 DNA repair
- GO:0140861 DNA repair-dependent chromatin remodeling
- GO:0006302 double-strand break repair
- GO:0070213 protein auto-ADP-ribosylation
- GO:0070212 protein poly-ADP-ribosylation
Drugs targeting this protein · 12
- NIRAPARIB inhibitor
- RUCAPARIB inhibitor
- TALAZOPARIB TOSYLATE inhibitor
- TALAZOPARIB inhibitor
- E-7016 inhibitor
- 2X-121 inhibitor
- RUCAPARIB CAMSYLATE inhibitor
- NIRAPARIB TOSYLATE MONOHYDRATE inhibitor
- PAMIPARIB inhibitor
- SENAPARIB inhibitor
- VELIPARIB inhibitor
- OLAPARIB inhibitor
Related proteins · sequence + function similarity
- Poly [ADP-ribose] polymerase 2 0.99
- Protein mono-ADP-ribosyltransferase PARP3 0.88
- Protein mono-ADP-ribosyltransferase PARP3 0.85
- Protein mono-ADP-ribosyltransferase PARP3 0.77
- Poly [ADP-ribose] polymerase 2-B 0.76
- Poly [ADP-ribose] polymerase 2 0.70
- Poly [ADP-ribose] polymerase 1 0.67
- Poly [ADP-ribose] polymerase 2 0.64
- Poly [ADP-ribose] polymerase 2-A 0.63
- Poly [ADP-ribose] polymerase 1 0.63
- Poly [ADP-ribose] polymerase 1 0.63
- Poly [ADP-ribose] polymerase 1 0.63
Co-cited proteins · studied together in the literature
- Poly [ADP-ribose] polymerase 2 3 shared papers
- Histone PARylation factor 1 10 shared papers
- Protein mono-ADP-ribosyltransferase PARP3 4 shared papers
- Poly [ADP-ribose] polymerase 1 11 shared papers
- ATP-dependent chromatin remodeler CHD1L 3 shared papers
- Histone PARylation factor 1 1 shared papers
- Histone H4 2 shared papers
- Aprataxin and PNK-like factor 1 shared papers
- Histone H2A type 1 2 shared papers
- Poly [ADP-ribose] polymerase 1 1 shared papers
- Histone H2B 1.1 2 shared papers
- Protein mono-ADP-ribosyltransferase PARP8 2 shared papers
Literature · 28 cited papers
- PARP inhibitors trap PARP2 and alter the mode of recruitment of PARP2 at DNA damage sites. Nucleic Acids Res. · 2022
- Serine ADP-ribosylation marks nucleosomes for ALC1-dependent chromatin remodeling. Elife · 2021
- HPF1 dynamically controls the PARP1/2 balance between initiating and elongating ADP-ribose modifications. Nat. Commun. · 2021
- Dual function of HPF1 in the modulation of PARP1 and PARP2 activities. Commun. Biol. · 2021
- Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome. Elife · 2021
- Activation of PARP2/ARTD2 by DNA damage induces conformational changes relieving enzyme autoinhibition. Nat. Commun. · 2021
- The oncogenic helicase ALC1 regulates PARP inhibitor potency by trapping PARP2 at DNA breaks. Mol. Cell · 2020
- Bridging of nucleosome-proximal DNA double-strand breaks by PARP2 enhances its interaction with HPF1. PLoS ONE · 2020
- Bridging of DNA breaks activates PARP2-HPF1 to modify chromatin. Nature · 2020
- HPF1 completes the PARP active site for DNA damage-induced ADP-ribosylation. Nature · 2020
- Structural basis for DNA break recognition by ARTD2/PARP2. Nucleic Acids Res. · 2018
- PARP2 mediates branched poly ADP-ribosylation in response to DNA damage. Nat. Commun. · 2018
- … and 16 more in the literature graph