PADI4
GeneName
PADI4
Summary
PADI4, also known as PAD4 or PDI5, is a 74kDa enzyme that is predominantly expressed in immune cells and various tissues, including the cytoplasm and nucleus. It functions as a protein-arginine deiminase, catalysing the conversion of arginine residues in proteins to citrulline, a process known as deimination. This post-translational modification plays a vital role in chromatin organisation and nucleosome assembly, influencing gene expression and cellular responses. PADI4 is also involved in the innate immune response, where it modulates the activity of histones through its histone arginine deiminase activity, affecting chromatin remodelling and stem cell maintenance.
Importance
PADI4 is relevant to: - Autoimmune diseases, such as rheumatoid arthritis, due to its role in the modification of histones and subsequent regulation of gene expression in immune cells. - Cancer biology, as it may influence tumour progression through its effects on chromatin dynamics and gene regulation. - Epigenetic research, given its involvement in post-translational modifications that impact chromatin structure and function. - Developmental biology, particularly in stem cell maintenance and differentiation processes.
Top Products
For researchers investigating PADI4, we recommend two excellent primary antibodies. The first is the well-cited Anti-PADI4 / PAD4 antibody [OTI4H5] (ab128086), a monoclonal antibody that has garnered 43 citations, highlighting its reliability in the field. This antibody is versatile, suitable for a range of applications including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). Additionally, we offer the recombinant antibody, Anti-PADI4 / PAD4 antibody [EPR26687-49] (ab315269). This product also supports WB, IHC, ICC, and FC, making it a great choice for those seeking the consistency that recombinant antibodies provide. Together, these antibodies offer robust options for studying PADI4 in various experimental contexts. The Recombinant human PADI4 / PAD4 protein ELISA Kit (ab196393), supported by 2 citations, is an excellent option for researchers looking to accurately measure PADI4 levels in their experiments.
Abcam Product Citation Summary
The data indicates that the PADI4 target has been studied in human cell extracts using western blotting. This suggests a focus on the role of PADI4 in human biology, potentially in relation to various diseases or cellular processes.
Abcam Product Citation Table
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:21245532). 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). Required for the formation of neutrophil extracellular traps (NETs); NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription (PubMed:15345777). Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1 (PubMed:15731352).
Involvement in disease
Rheumatoid arthritis
RA
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.
None
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).
Post-translational modifications
Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.
Sequence Similarities
Belongs to the protein arginine deiminase family.
Tissue Specificity
Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes.
Cellular localization
- Cytoplasm
- Nucleus
- Cytoplasmic granule
- Cytoplasmic granules of eosinophils and neutrophils.
Alternative names
PAD4, PADI5, PDI5, PADI4, Protein-arginine deiminase type-4, HL-60 PAD, Peptidylarginine deiminase IV, Protein-arginine deiminase type IV