PADI4
entrez
23569
canonical
uniprot
Q9UM07
canonical
ensembl
ENSG00000159339
resolver
ensembl
ENSG00000280908
resolver
ensp
ENSP00000364597
resolver
ensp
ENSP00000487021
resolver
enst
ENST00000375448
resolver
enst
ENST00000628229
resolver
genesymbol
PADI4
resolver
genesymbol_syn
PAD4
resolver
genesymbol_syn
PADI5
resolver
genesymbol_syn
PDI5
resolver
hgnc
HGNC:18368
resolver
uniprot
A8K392
resolver
uniprot
B2RBW0
resolver
uniprot
Q5VTZ8
resolver
uniprot
Q70SX4
resolver
uniprot_entry
PADI4_HUMAN
resolver
uniprot_sec
A8K392
resolver
uniprot_sec
B2RBW0
resolver
uniprot_sec
Q5VTZ8
resolver
uniprot_sec
Q70SX4
resolver
activity_regulation
ACTIVITY REGULATION: Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family (PubMed:17002273). Incorporation of a carboxylate ortho to the backbone amide of Cl-amidine results in inhibitors with increased specificity for PADI4: N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) (PubMed:21882827). Strongly and specifically inhibited by Thr-Asp-F-amidine (TDFA); other members of the family are not inhibited (PubMed:22004374). Specifically inhibited by GSK215 small molecule; inhibiting formation of neutrophil extracellular traps (NETs) (PubMed:25622091). {ECO:0000269|PubMed:17002273, ECO:0000269|PubMed:21882827, ECO:0000269|PubMed:22004374, ECO:0000269|PubMed:25622091}.
uniprot
proteins
amino_acid_sequence
MAQGTLIRVTPEQPTHAVCVLGTLTQLDICSSAPEDCTSFSINASPGVVVDIAHGPPAKKKSTGSSTWPLDPGVEVTLTMKVASGSTGDQKVQISYYGPKTPPVKALLYLTGVEISLCADITRTGKVKPTRAVKDQRTWTWGPCGQGAILLVNCDRDNLESSAMDCEDDEVLDSEDLQDMSLMTLSTKTPKDFFTNHTLVLHVARSEMDKVRVFQATRGKLSSKCSVVLGPKWPSHYLMVPGGKHNMDFYVEALAFPDTDFPGLITLTISLLDTSNLELPEAVVFQDSVVFRVAPWIMTPNTQPPQEVYACSIFENEDFLKSVTTLAMKAKCKLTICPEEENMDDQWMQDEMEIGYIQAPHKTLPVVFDSPRNRGLKEFPIKRVMGPDFGYVTRGPQTGGISGLDSFGNLEVSPPVTVRGKEYPLGRILFGDSCYPSNDSRQMHQALQDFLSAQQVQAPVKLYSDWLSVGHVDEFLSFVPAPDRKGFRLLLASPRSCYKLFQEQQNEGHGEALLFEGIKKKKQQKIKNILSNKTLREHNSFVERCIDWNRELLKRELGLAESDIIDIPQLFKLKEFSKAEAFFPNMVNMLVLGKHLGIPKPFGPVINGRCCLEEKVCSLLEPLGLQCTFINDFFTYHIRHGEVHCGTNVRRKPFSFKWWNMVP
uniprot
proteins
disease_involvement
DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:12833157}. Note=The gene represented in this entry may be involved in disease pathogenesis. The association to rheumatoid arthritis was initially thought to result from increased citrullination of target proteins (PubMed:12833157). However, variants that have been associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not affect the catalytic activity or the citrullination activity of PADI4, suggesting that these variants may affect the mRNA stability rather than the protein (PubMed:21245532). {ECO:0000269|PubMed:12833157, ECO:0000269|PubMed:21245532}.
uniprot
proteins
ec_number
3.5.3.15
uniprot
proteins
function
FUNCTION: Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:19153223, PubMed:21245532, PubMed:25622091). Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci) (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci (PubMed:18209087). Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription (PubMed:15345777). Involved for the formation of neutrophil extracellular traps (NETs) by mediating citrullination of histone H3 and initiating decondensation of chromatin and nuclear membrane rupture (PubMed:19153223, PubMed:25622091, PubMed:28574339, PubMed:32170015). NETs are mainly composed of DNA fibers and are released by neutrophils to trap pathogens during inflammation (PubMed:19153223). Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1 (PubMed:15731352). {ECO:0000269|PubMed:15339660, ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15731352, ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:18209087, ECO:0000269|PubMed:19153223, ECO:0000269|PubMed:21245532, ECO:0000269|PubMed:25622091, ECO:0000269|PubMed:28574339, ECO:0000269|PubMed:32170015}.
uniprot
proteins
mass_dalton
74079
uniprot
proteins
mutagenesis
MUTAGEN 59..61; /note="KKK->AAA: Abolished nuclear localization, preventing chromatin decondensation and formation of neutrophil extracellular traps."; /evidence="ECO:0000269|PubMed:32170015"; MUTAGEN 346; /note="Q->A: Impaired binding of TDFAInhibitor."; /evidence="ECO:0000269|PubMed:21882827"; MUTAGEN 374; /note="R->A: Strongly reduces enzymatic activity."; /evidence="ECO:0000269|PubMed:15247907, ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:21882827"; MUTAGEN 374; /note="R->Q: Impaired binding of TDFAInhibitor."; /evidence="ECO:0000269|PubMed:15247907, ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:21882827"; MUTAGEN 639; /note="R->Q: Impaired binding of TDFAInhibitor."; /evidence="ECO:0000269|PubMed:21882827"; MUTAGEN 645; /note="C->AS: Abolishes enzymatic activity. Prevents chromatin decondensation and formation of neutrophil extracellular traps."; /evidence="ECO:0000269|PubMed:15247907, ECO:0000269|PubMed:19153223, ECO:0000269|PubMed:25622091, ECO:0000269|PubMed:32170015
uniprot
proteins
post_translational_modification
PTM: Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme. {ECO:0000269|PubMed:20201080}.
uniprot
proteins
protein_family
Protein arginine deiminase family
uniprot
proteins
pubmed
10488123
uniprot
proteins
pubmed
11435484
uniprot
proteins
pubmed
12833157
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15087120
uniprot
proteins
pubmed
15247907
uniprot
proteins
pubmed
15338034
uniprot
proteins
pubmed
15339660
uniprot
proteins
pubmed
15345777
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15629448
uniprot
proteins
pubmed
15731352
uniprot
proteins
pubmed
16567635
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17002273
uniprot
proteins
pubmed
18209087
uniprot
proteins
pubmed
19153223
uniprot
proteins
pubmed
20201080
uniprot
proteins
pubmed
21245532
uniprot
proteins
pubmed
21882827
uniprot
proteins
pubmed
22004374
uniprot
proteins
pubmed
25622091
uniprot
proteins
pubmed
28574339
uniprot
proteins
pubmed
32170015
uniprot
proteins
sequence_length
663
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15629448}. Nucleus {ECO:0000269|PubMed:15629448, ECO:0000269|PubMed:32170015}. Cytoplasmic granule {ECO:0000269|PubMed:11435484}. Note=Cytoplasmic granules of eosinophils and neutrophils. {ECO:0000269|PubMed:11435484}.
uniprot
proteins