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Details on Person UniProt:Q9UGN5 PARP2
| Class:Id | ReferenceGeneProduct:62066 |
|---|---|
| _chainChangeLog | chain:1-583 added on Fri February 6 2015 |
| _displayName | UniProt:Q9UGN5 PARP2 |
| _timestamp | 2025-02-21 18:59:49 |
| chain | chain:1-583 |
| checksum | 5B7AE8AE531836AF |
| comment | 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).CATALYTIC ACTIVITY NAD(+) + (ADP-D-ribosyl)n-acceptor = nicotinamide + (ADP-D-ribosyl)n+1-acceptor + H(+).CATALYTIC ACTIVITY L-seryl-[protein] + NAD(+) = O-(ADP-D-ribosyl)-L-seryl-[protein] + nicotinamide + H(+)CATALYTIC ACTIVITY L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + nicotinamideCATALYTIC ACTIVITY L-glutamyl-[protein] + NAD(+) = 5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + nicotinamideACTIVITY REGULATION ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism (PubMed:34108479). In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding (PubMed:34108479). Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition (PubMed:34108479). Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences (PubMed:33275888). CHD1L promotes PARP2 removal from chromatin (PubMed:33275888). ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination (PubMed:35349716). PARPi molecules (niraparib, talazoparib, and, to a lesser extent, olaparib) also trap PARP2 at DNA damage sites (PubMed:33275888, PubMed:35349716).SUBUNIT Component of a base excision repair (BER) complex, containing at least XRCC1, PARP1, POLB and LRIG3 (By similarity). Homo- and heterodimer with PARP1 (PubMed:20092359). Interacts (via the PARP catalytic domain) with HPF1 (PubMed:27067600, PubMed:28190768, PubMed:32028527, PubMed:32939087, PubMed:33141820, PubMed:34108479). Interacts with core nucleosomes (PubMed:32939087, PubMed:33141820).INTERACTION Recruited to DNA damage sites in a PARP1-dependent process: recognizes and binds poly-ADP-ribose chains produced by PARP1 at DNA damage sites via its N-terminus, leading to its recruitment.ALTERNATIVE PRODUCTS Widely expressed, mainly in actively dividing tissues (PubMed:10364231). The highest levels are in the brain, heart, pancreas, skeletal muscle and testis; also detected in kidney, liver, lung, placenta, ovary and spleen; levels are low in leukocytes, colon, small intestine, prostate and thymus (PubMed:10364231).DOMAIN The N-terminal region (NTR) recognizes and binds poly-ADP-ribose chains produced by PARP1, leading to its recruitment to DNA damage sites.DOMAIN The N-terminal disordered region does not act as a key DNA-binding domain (PubMed:26704974). The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage (PubMed:26704974).DOMAIN The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation (PubMed:30321391, PubMed:32939087, PubMed:33141820). The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins (PubMed:32939087).DOMAIN The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal (PubMed:34108479). Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition (PubMed:34108479).PTM Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP2-HPF1 complex from chromatin (PubMed:32939087, PubMed:34108479). Poly-ADP-ribosylated by PARP1 (By similarity).PTM Acetylation reduces DNA binding and enzymatic activity.PTM Proteolytically cleaved by caspase-8 (CASP8) in response to apoptosis, leading to its inactivation.SIMILARITY Belongs to the ARTD/PARP family.SEQUENCE CAUTION Catalysis - Issue 235 of April 2021 |
| description | recommendedName: fullName evidence="32"Poly [ADP-ribose] polymerase 2 shortName evidence="30"PARP-2 shortName evidence="30"hPARP-2 ecNumber evidence="8 14 15 17"2.4.2.30 alternativeName: fullName evidence="31"ADP-ribosyltransferase diphtheria toxin-like 2 shortName evidence="31"ARTD2 alternativeName: fullName evidence="32"DNA ADP-ribosyltransferase PARP2 ecNumber evidence="11"2.4.2.- alternativeName: NAD(+) ADP-ribosyltransferase 2 shortName: ADPRT-2 alternativeName: fullName evidence="27"Poly[ADP-ribose] synthase 2 shortName evidence="27"pADPRT-2 alternativeName: fullName evidence="32"Protein poly-ADP-ribosyltransferase PARP2 ecNumber evidence="8 17"2.4.2.- |
| geneName | PARP2 ADPRT2 ADPRTL2 |
| identifier | Q9UGN5 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation ADP-ribosylation Allosteric enzyme Alternative splicing Chromosome DNA damage DNA repair DNA-binding Glycosyltransferase NAD Nucleotidyltransferase Nucleus Phosphoprotein Proteomics identification Reference proteome Transferase |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | PARP2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962157] ENSEMBL:ENSG00000129484 PARP2 [Homo sapiens] |
| secondaryIdentifier | PARP2_HUMAN Q8TEU4 Q9NUV2 Q9UMR4 Q9Y6C8 |
| sequenceLength | 583 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:152402] UniProt:Q9UGN5-2 PARP2 [Homo sapiens] [ReferenceIsoform:415348] UniProt:Q9UGN5-1 PARP2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:174874] PARP2 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:5651715] PAR-PARP2 [nucleoplasm] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:5651711] L-glutamyl-5-poly(ADP-ribose) at unknown position |
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No pathways have been reviewed or authored by UniProt:Q9UGN5 PARP2 (62066)
