HPF1
entrez
54969
canonical
uniprot
Q9NWY4
canonical
ensembl
ENSG00000056050
resolver
ensp
ENSP00000406598
resolver
enst
ENST00000393381
resolver
genesymbol
HPF1
resolver
genesymbol_syn
C4orf27
resolver
hgnc
HGNC:26051
resolver
uniprot_entry
HPF1_HUMAN
resolver
amino_acid_sequence
MVGGGGKRRPGGEGPQCEKTTDVKKSKFCEADVSSDLRKEVENHYKLSLPEDFYHFWKFCEELDPEKPSDSLSASLGLQLVGPYDILAGKHKTKKKSTGLNFNLHWRFYYDPPEFQTIIIGDNKTQYHMGYFRDSPDEFPVYVGINEAKKNCIIVPNGDNVFAAVKLFLTKKLREITDKKKINLLKNIDEKLTEAARELGYSLEQRTVKMKQRDKKVVTKTFHGAGLVVPVDKNDVGYRELPETDADLKRICKTIVEAASDEERLKAFAPIQEMMTFVQFANDECDYGMGLELGMDLFCYGSHYFHKVAGQLLPLAYNLLKRNLFAEIIEEHLANRSQENIDQLAA
uniprot
proteins
function
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). {ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29480802, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32939087, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34108479, ECO:0000269|PubMed:34210965, ECO:0000269|PubMed:34486521, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266}.
uniprot
proteins
mass_dalton
39436
uniprot
proteins
mutagenesis
MUTAGEN 149..150; /note="KK->EE: Abolished interaction with PARP2, leading to destabilize the PARP2-nucleosome complex."; /evidence="ECO:0000269|PubMed:32939087"; MUTAGEN 179..181; /note="KKK->EEE: Abolished interaction with PARP2, leading to destabilize the PARP2-nucleosome complex."; /evidence="ECO:0000269|PubMed:32939087"; MUTAGEN 238..239; /note="YR->AA: Loss of ability to bind PARP1 and histones. Abolishes PARP1 ability to mediate ADP-ribosylation."; /evidence="ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:28190768"; MUTAGEN 239; /note="R->A: Strongly reduced serine ADP-ribosylation by PARP1 and PARP2. Decreases PARP1 ability to mediate tyrosine ADP-ribosylation. Promotes auto-ADP-ribosylation of PARP1."; /evidence="ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:33589610"; MUTAGEN 243; /note="E->A: Does not affect serine ADP-ribosylation by PARP1 and PARP2."; /evidence="ECO:0000269|PubMed:32028527"; MUTAGEN 268; /note="F->S: Promotes auto-ADP-ribosylation of PARP1. Abolished interaction with PARP1."; /evidence="ECO:0000269|PubMed:33589610"; MUTAGEN 280; /note="F->A: Promotes auto-ADP-ribosylation of PARP1."; /evidence="ECO:0000269|PubMed:33589610"; MUTAGEN 283; /note="D->A: Strongly reduced serine ADP-ribosylation by PARP1 and PARP2."; /evidence="ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:33683197"; MUTAGEN 283; /note="D->H: Promotes auto-ADP-ribosylation of PARP1. Abolished interaction with PARP1."; /evidence="ECO:0000269|PubMed:33589610"; MUTAGEN 284; /note="E->A: Abolished serine ADP-ribosylation by PARP1 and PARP2."; /evidence="ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197"; MUTAGEN 285; /note="C->H: Promotes auto-ADP-ribosylation of PARP1."; /evidence="ECO:0000269|PubMed:33589610"; MUTAGEN 286; /note="D->A: Strongly reduced serine ADP-ribosylation by PARP1 and PARP2."; /evidence="ECO:0000269|PubMed:32028527"; MUTAGEN 292; /note="E->A: Does not affect serine ADP-ribosylation of histones."; /evidence="ECO:0000269|PubMed:33683197"; MUTAGEN 303; /note="H->Q: Does not affect serine ADP-ribosylation of histones."; /evidence="ECO:0000269|PubMed:33683197"; MUTAGEN 307; /note="K->S: Promotes auto-ADP-ribosylation of PARP1."; /evidence="ECO:0000269|PubMed:33589610
uniprot
proteins
protein_family
HPF1 family
uniprot
proteins
pubmed
11230166
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
27067600
uniprot
proteins
pubmed
28190768
uniprot
proteins
pubmed
29480802
uniprot
proteins
pubmed
29954836
uniprot
proteins
pubmed
30257210
uniprot
proteins
pubmed
32028527
uniprot
proteins
pubmed
32939087
uniprot
proteins
pubmed
33141820
uniprot
proteins
pubmed
33186521
uniprot
proteins
pubmed
33589610
uniprot
proteins
pubmed
33683197
uniprot
proteins
pubmed
34108479
uniprot
proteins
pubmed
34210965
uniprot
proteins
pubmed
34486521
uniprot
proteins
pubmed
34625544
uniprot
proteins
pubmed
34732825
uniprot
proteins
pubmed
34795260
uniprot
proteins
pubmed
34874266
uniprot
proteins
sequence_length
346
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:32939087}. Nucleus {ECO:0000269|PubMed:27067600}. Note=Localizes to DNA damage sites; chromatin localization is dependent on PARP1 and PARP2. {ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:32939087}.
uniprot
proteins