PADI4
PADI4 (peptidyl arginine deiminase 4, also known as PAD, PDI4, PDI5 and PADI5) is a member of the protein arginine deiminase family. It catalyses the conversion of arginine residues in proteins to citrulline, notably on histones, and contributes to chromatin regulation and neutrophil responses. Browse Assay Genie's current range of PADI4 research reagents below, or read on for the biology behind the target.
PADI4 catalyses the citrullination, or deimination, of arginine residues in proteins. Its best-characterised substrates are histones: it citrullinates histone H1 at Arg-54, histone H3 at Arg-2, Arg-8, Arg-17 and/or Arg-26, and histone H4 at Arg-3, placing it at the centre of the histone code. Citrullination of histone H3 prevents its methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullination of H1 at Arg-54 displaces H1 from chromatin and causes global chromatin decondensation, which promotes pluripotency and stem cell maintenance.
In neutrophils, the same H1 modification drives profound chromatin decondensation during the innate immune response to infection. PADI4 is also involved in forming neutrophil extracellular traps (NETs). It citrullinates histone H3, initiating chromatin decondensation and nuclear membrane rupture. NETs are made mainly of DNA fibres, and neutrophils release them to trap pathogens during inflammation. PADI4 also citrullinates the transcriptional coactivator EP300/P300 at Arg-2142, which favours its interaction with NCOA2/GRIP1.
The PADI4 gene belongs to a family of genes encoding enzymes that convert arginine to citrulline, and the protein is localised to the cytoplasm, nucleus and cytoplasmic granules. According to NCBI Gene, it may play a role in granulocyte and macrophage development, linking it to inflammation and immune response. Earlier names include peptidyl arginine deiminase, type IV and type V. Mouse and rat both have a Padi4 ortholog, and related family members include PADI2 and PADI6.
PADI4 citrullinates histones H1, H3 and H4, and H3 citrullination blocks methylation by CARM1 and PRMT1, making it a key enzyme for studying chromatin regulation.
Citrullination of histone H1 at Arg-54 displaces H1 and decondenses chromatin, promoting pluripotency and stem cell maintenance.
PADI4 mediates histone H3 citrullination and chromatin decondensation needed for neutrophil extracellular trap formation during the innate response to infection.
The gene may influence granulocyte and macrophage development, making PADI4 relevant to studies of inflammation and immune response.
PADI4 converts arginine residues in proteins to citrulline. Its substrates include histones H1, H3 and H4, and EP300. Through these modifications it regulates chromatin decondensation, transcription, stem cell maintenance and the formation of neutrophil extracellular traps during infection.
PADI4 is also called PAD, PDI4, PDI5 and PADI5. Earlier HGNC names were peptidyl arginine deiminase, type IV and type V. UniProt lists the protein as protein-arginine deiminase type-4, and it carries the enzyme classification EC 3.5.3.15.
Mouse and rat each have a Padi4 ortholog, and the human gene sits within a family of arginine-to-citrulline converting enzymes that includes PADI2 and PADI6. Check the datasheet of any product for its validated reactivity.
Other peptidyl arginine deiminase family members with research reagents at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UM07; product specifications from Assay Genie datasheets.