Names & Taxonomy
- Uniprot ID:
- Q9UM07
- Entry Name:
- PADI4_HUMAN
- Status:
- reviewed
- Protein Names:
- Protein-arginine deiminase type-4 (EC 3.5.3.15) (HL-60 PAD) (Peptidylarginine deiminase IV) (Protein-arginine deiminase type IV)
- Gene Names:
- PADI4 PAD4 PADI5 PDI5
- Gene Names Primary:
- PADI4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 663
- Sequence:
- MAQGTLIRVTPEQPTHAVCVLGTLTQLDICSSAPEDCTSFSINASPGVVVDIAHGPPAKKKSTGSSTWPLDPGVEVTLTMKVASGSTGDQKVQISYYGPKTPPVKALLYLTGVEISLCADITRTGKVKPTRAVKDQRTWTWGPCGQGAILLVNCDRDNLESSAMDCEDDEVLDSEDLQDMSLMTLSTKTPKDFFTNHTLVLHVARSEMDKVRVFQATRGKLSSKCSVVLGPKWPSHYLMVPGGKHNMDFYVEALAFPDTDFPGLITLTISLLDTSNLELPEAVVFQDSVVFRVAPWIMTPNTQPPQEVYACSIFENEDFLKSVTTLAMKAKCKLTICPEEENMDDQWMQDEMEIGYIQAPHKTLPVVFDSPRNRGLKEFPIKRVMGPDFGYVTRGPQTGGISGLDSFGNLEVSPPVTVRGKEYPLGRILFGDSCYPSNDSRQMHQALQDFLSAQQVQAPVKLYSDWLSVGHVDEFLSFVPAPDRKGFRLLLASPRSCYKLFQEQQNEGHGEALLFEGIKKKKQQKIKNILSNKTLREHNSFVERCIDWNRELLKRELGLAESDIIDIPQLFKLKEFSKAEAFFPNMVNMLVLGKHLGIPKPFGPVINGRCCLEEKVCSLLEPLGLQCTFINDFFTYHIRHGEVHCGTNVRRKPFSFKWWNMVP
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm. Nucleus. Cytoplasmic granule. Note=Cytoplasmic granules of eosinophils and neutrophils.
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. 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). 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. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.
- Catalytic Activity:
- Protein L-arginine + H(2)O = protein L-citrulline + NH(3).
- Cofactor:
- COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.055 mM for fibrinogen
- Enzyme Regulation:
- ENZYME 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).
- Active Site:
- ACT_SITE 350 350
- Cross Reference Drug Bank:
- DB00207 DB00254 DB00155 DB01082 DB00759
- Gene Ontology Go:
- cytoplasm
nucleoplasm
nucleus
arginine deiminase activity
calcium ion binding
protein-arginine deiminase activity
cellular protein modification process
chromatin modification
chromatin organization
chromatin remodeling
histone citrullination
histone H3-R26 citrullination
innate immune response
nucleosome assembly
protein citrullination
regulation of transcription, DNA-templated
stem cell population maintenance
transcription, DNA-templated - Gene Ontology Biological Process:
- cellular protein modification process
chromatin modification
chromatin organization
chromatin remodeling
histone citrullination
histone H3-R26 citrullination
innate immune response
nucleosome assembly
protein citrullination
regulation of transcription, DNA-templated
stem cell population maintenance
transcription, DNA-templated - Gene Ontology Molecular Function:
- arginine deiminase activity
calcium ion binding
protein-arginine deiminase activity - Gene Ontology Cellular Component:
- cytoplasm
nucleoplasm
nucleus - Keywords:
- 3D-structure
Calcium
Chromatin regulator
Citrullination
Complete proteome
Cytoplasm
Hydrolase
Immunity
Innate immunity
Metal-binding
Nucleus
Polymorphism
Reference proteome
Transcription
Transcription regulation - Interacts With:
- Q6LES2