UniprotKB/SwissProt ID: Q9NWY4 (Q9NWY4)
Gene Name:
HPF1
Organism: Homo sapiens (Human)
Function: Cofactor for serine ADP-ribosylation that confers serine specificity on PARP1 and PARP2 and plays a key role in DNA damage response (PubMed:28190768, PubMed:29480802, PubMed:29954836, PubMed:32028527, PubMed:32939087, PubMed:33186521, PubMed:33589610, PubMed:33683197, PubMed:34108479, PubMed:34210965, PubMed:34486521, PubMed:34625544, PubMed:34732825, PubMed:34795260, PubMed:34874266). Initiates the repair of double-strand DNA breaks: recruited to DNA damage sites by PARP1 and PARP2 and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues, licensing serine ADP-ribosylation of target proteins (PubMed:28190768, PubMed:29480802, PubMed:29954836, PubMed:32028527, PubMed:32939087, PubMed:33589610, PubMed:33683197, PubMed:34486521, PubMed:34625544, PubMed:34732825, PubMed:34795260, PubMed:34874266). Serine ADP-ribosylation of target proteins, such as histones, promotes decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:27067600, PubMed:28190768, PubMed:32939087, PubMed:33589610). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). HPF1 acts by completing the active site of PARP1 and PARP2: forms a composite active site composed of residues from HPF1 and PARP1 or PARP2 (PubMed:32028527, PubMed:33589610). While HPF1 promotes the initiation of serine ADP-ribosylation, it restricts the polymerase activity of PARP1 and PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1 (PubMed:29954836, PubMed:30257210)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Chromosome. Nucleus
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