Poly [ADP-ribose] polymerase 1
UniProtKB accession: P26446
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Go to UniProtKB: P26446
UniProtKB description: Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (By similarity). Mediates glutamate, aspartate, serine, histidine or tyrosine 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 (By similarity). Specificity for the different amino acids is conferred by interacting factors, such as hpf1 and nmnat1 (By similarity). Following interaction with hpf1, catalyzes serine ADP-ribosylation of target proteins; hpf1 confers serine specificity by completing the parp1 active site. Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with hpf1 (By similarity). Following interaction with nmnat1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; nmnat1 confers glutamate and aspartate specificity (By similarity). Parp1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits hpf1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair. Mediates the poly-ADP-ribosylation of a number of proteins. In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (By similarity). Parp1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (By similarity). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II. Acts both as a positive and negative regulator of transcription elongation, depending on the context (By similarity). Poly-ADP-ribose chains generated by parp1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos. Also acts as a negative regulator of the cGAS-STING pathway by mediating poly-ADP-ribosylation and inactivation of cgas. Acts as a negative regulator of adipogenesis by catalyzing poly ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) (By similarity).
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