PAD4

Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1

PAD4 Related Areas

Enzyme>>Other>>PAD4/PADI4

PAD4 Alternative Names

PAD4, PADI4, PAD, PADI5, PDI4, PDI5 [Homo sapiens]

PADI4, RP23-48K5.5, Pdi4 [Mus musculus]

Summaries for PAD4

Entrez Gene summary for PAD4:

This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response.

OMIM - description for PAD4:

Peptidylarginine deiminases (PADs; EC 3.5.3.15), such as PADI4, make up a family of posttranslational modification enzymes that convert arginine residues to citrulline residues in the presence of calcium ion (Nakashima et al., 1999).

Wikipedia summary for PAD4:

Peptidyl arginine deiminase, type IV, also known as PADI4, is a human protein which in humans is encoded by the PADI4 gene

Human PAD4 Protein General Information

 

• Protein names: Recommended name: Protein-arginine deiminase type-4
• Sequence length: 663 AA.
• Sequence similarities: Belongs to the protein arginine deiminase family.
• Subcellular location: Cytoplasm. Nucleus. Cytoplasmic granule. Note: Cytoplasmic granules of eosinophils and neutrophils.
• Tissue specificity: Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes.
• Involvement in disease: Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:180300]. It is a systemic 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. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context

General information above from UniProt

Function for PAD4 Protein

UniProtKB:

Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1

Genatlas:

• PAD4 may be playing a role in granulocyte and macrophage development leading to inflammation and immune response
• PAD4 may be mediating gene expression by regulating arginine methylation and citrullination in histones
• catalyzing the post-translational citrullination of proteins
• PAD4 plays a role in the regulation of TP53 target gene expression
• citrullinated the histone chaperone protein, nucleophosmin (NPM1), at the arginine 197, and citrullination of NPM1 by PADI4 resulted in its translocation from the nucleoli to the nucleoplasm
• PAD4 promotes the deimination of arginine residues in histones and may regulate transcription in the context of the chromatin
• converts peptidyl arginine to citrulline in histone H3 and can repress gene expression
• catalyze the hydrolysis of peptidyl-arginine to form peptidyl-citrulline, and play important roles in a variety of cell signaling pathways, including apoptosis, differentiation, and transcriptional regulation
• autodeimination of PADI4 alters protein-protein interactions but not activit

Homology for human PAD4

• ortholog to rattus padi4
• ortholog to murine Padi4

Phenotype Information for PAD4

• Gene/Locus: PADI4, PADI5, PAD
• Phenotype:

  {Rheumatoid arthritis, susceptibility to}

Phenotype Information for PAD4 from OMIM (Online Mendelian Inheritance in Man)