PARP2
entrez
10038
canonical
uniprot
Q9UGN5
canonical
ensembl
ENSG00000129484
resolver
ensembl
ENSG00000291803
resolver
ensp
ENSP00000250416
resolver
ensp
ENSP00000392972
resolver
ensp
ENSP00000723968
resolver
genesymbol
PARP2
resolver
genesymbol_syn
ADPRT2
resolver
genesymbol_syn
ADPRTL2
resolver
hgnc
HGNC:272
resolver
uniprot
Q8TEU4
resolver
uniprot
Q9NUV2
resolver
uniprot
Q9UMR4
resolver
uniprot
Q9Y6C8
resolver
uniprot_entry
PARP2_HUMAN
resolver
uniprot_sec
Q8TEU4
resolver
uniprot_sec
Q9NUV2
resolver
uniprot_sec
Q9UMR4
resolver
uniprot_sec
Q9Y6C8
resolver
activity_regulation
ACTIVITY 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). {ECO:0000269|PubMed:33275888, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:35349716}.
uniprot
proteins
amino_acid_sequence
MAARRRRSTGGGRARALNESKRVNNGNTAPEDSSPAKKTRRCQRQESKKMPVAGGKANKDRTEDKQDGMPGRSWASKRVSESVKALLLKGKAPVDPECTAKVGKAHVYCEGNDVYDVMLNQTNLQFNNNKYYLIQLLEDDAQRNFSVWMRWGRVGKMGQHSLVACSGNLNKAKEIFQKKFLDKTKNNWEDREKFEKVPGKYDMLQMDYATNTQDEEETKKEESLKSPLKPESQLDLRVQELIKLICNVQAMEEMMMEMKYNTKKAPLGKLTVAQIKAGYQSLKKIEDCIRAGQHGRALMEACNEFYTRIPHDFGLRTPPLIRTQKELSEKIQLLEALGDIEIAIKLVKTELQSPEHPLDQHYRNLHCALRPLDHESYEFKVISQYLQSTHAPTHSDYTMTLLDLFEVEKDGEKEAFREDLHNRMLLWHGSRMSNWVGILSHGLRIAPPEAPITGYMFGKGIYFADMSSKSANYCFASRLKNTGLLLLSEVALGQCNELLEANPKAEGLLQGKHSTKGLGKMAPSSAHFVTLNGSTVPLGPASDTGILNPDGYTLNYNEYIVYNPNQVRMRYLLKVQFNFLQLW
uniprot
proteins
ec_number
2.4.2.-
uniprot
proteins
ec_number
2.4.2.30
uniprot
proteins
function
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). {ECO:0000269|PubMed:10364231, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29361132, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266}.
uniprot
proteins
mass_dalton
66206
uniprot
proteins
mutagenesis
MUTAGEN 21..22; /note="KR->AA: Reduced localization to the nucleus. Abolished localization to the nucleus; when associated with 37-A-A-38."; /evidence="ECO:0000269|PubMed:26704974"; MUTAGEN 37..38; /note="KK->AA: Reduced localization to the nucleus. Abolished localization to the nucleus; when associated with 21-A-A-22."; /evidence="ECO:0000269|PubMed:26704974"; MUTAGEN 125..126; /note="QF->RD: In PARP2-QFRD mutant; induces conformational change that bridges nucleosomes by binding to linker DNA ends and promotes interaction with HPF1."; /evidence="ECO:0000269|PubMed:33141820"; MUTAGEN 127; /note="N->A: Decreased poly [ADP-ribose] polymerase activity. Impaired formation of a complex with damaged DNA."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 128; /note="N->A: Does not affect poly [ADP-ribose] polymerase activity."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 129; /note="N->A: Reduced recruitment to DNA damage sites. Abolished DNA-induced ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:26704974, ECO:0000269|PubMed:34108479"; MUTAGEN 130; /note="K->A: Decreased poly [ADP-ribose] polymerase activity."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 132; /note="Y->F: Decreased poly [ADP-ribose] polymerase activity."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 151; /note="W->A: Decreased poly [ADP-ribose] polymerase activity. Impaired formation of a complex with damaged DNA."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 153; /note="R->A: Abolished formation of a complex with core nucleosome and HPF1, leading to abolished ability to catalyze serine ADP-ribosylation of histones. Abolished DNA-induced ADP-ribosyltransferase activity. Abolished trapping at DNA damage sites upon binding to PARP inhibitors (PARPi)."; /evidence="ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:35349716"; MUTAGEN 154; /note="V->A: Abolished formation of a complex with core nucleosome and HPF1, leading to abolished ability to catalyze serine ADP-ribosylation of histones."; /evidence="ECO:0000269|PubMed:32939087"; MUTAGEN 159; /note="Q->A: Decreased poly [ADP-ribose] polymerase activity."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 183; /note="K->A: Decreased poly [ADP-ribose] polymerase activity. Impaired formation of a complex with damaged DNA."; /evidence="ECO:0000269|PubMed:30321391"; MUTAGEN 201; /note="Y->A: Reduced DNA-induced ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:34108479"; MUTAGEN 201; /note="Y->F: Reduced recruitment to DNA damage sites. Decreased poly [ADP-ribose] polymerase activity."; /evidence="ECO:0000269|PubMed:26704974, ECO:0000269|PubMed:30321391"; MUTAGEN 286; /note="E->A,R: Increased DNA-induced ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:34108479"; MUTAGEN 338; /note="G->A: Does not affect DNA-induced ADP-ribosyltransferase activity."; /evidence="ECO:0000269|PubMed:34108479"; MUTAGEN 394; /note="H->A: Strongly reduced serine ADP-ribosylation, caused by abolished interaction with HPF1."; /evidence="ECO:0000269|PubMed:32028527"; MUTAGEN 428; /note="H->A: Abolished trapping at DNA damage sites upon binding to PARP inhibitors (PARPi)."; /evidence="ECO:0000269|PubMed:35349716"; MUTAGEN 558; /note="E->A: Abolished poly [ADP-ribose] polymerase activity without affecting localization to DNA damage sites."; /evidence="ECO:0000269|PubMed:26704974, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:33275888"; MUTAGEN 582..583; /note="LW->EE: Strongly reduced serine ADP-ribosylation, caused by abolished interaction with HPF1."; /evidence="ECO:0000269|PubMed:32028527
uniprot
proteins
post_translational_modification
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). {ECO:0000250|UniProtKB:O88554, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:34108479}.; PTM: Acetylation reduces DNA binding and enzymatic activity. {ECO:0000250|UniProtKB:O88554}.; PTM: Proteolytically cleaved by caspase-8 (CASP8) in response to apoptosis, leading to its inactivation. {ECO:0000250|UniProtKB:O88554}.
uniprot
proteins
protein_family
ARTD/PARP family
uniprot
proteins
pubmed
10329013
uniprot
proteins
pubmed
10338144
uniprot
proteins
pubmed
10364231
uniprot
proteins
pubmed
11948190
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
20092359
uniprot
proteins
pubmed
20106667
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
25043379
uniprot
proteins
pubmed
26626480
uniprot
proteins
pubmed
26704974
uniprot
proteins
pubmed
27067600
uniprot
proteins
pubmed
27471034
uniprot
proteins
pubmed
28190768
uniprot
proteins
pubmed
29361132
uniprot
proteins
pubmed
30104678
uniprot
proteins
pubmed
30321391
uniprot
proteins
pubmed
32028527
uniprot
proteins
pubmed
32939087
uniprot
proteins
pubmed
33141820
uniprot
proteins
pubmed
33275888
uniprot
proteins
pubmed
34108479
uniprot
proteins
pubmed
34486521
uniprot
proteins
pubmed
34732825
uniprot
proteins
pubmed
34795260
uniprot
proteins
pubmed
34874266
uniprot
proteins
pubmed
35349716
uniprot
proteins
sequence_length
583
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10364231, ECO:0000269|PubMed:26704974}. Chromosome {ECO:0000269|PubMed:26704974, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33141820, ECO:0000269|PubMed:35349716}. Note=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. {ECO:0000269|PubMed:26704974, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30321391, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33141820, ECO:0000269|PubMed:35349716}.
uniprot
proteins