Citrullination

The immune system can attack citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS).

Thus, arginine's positive charge (at physiological pH) is removed, altering the protein's tertiary structure.

The reaction uses one water molecule and yields ammonia as a side-product: PADs are found in chordates but not in lower animals.

PAD1 expression has been detected in epidermis and the uterus, and it acts in citrullination of keratin and filaggrin, key components of keratinocytes.

[4] PAD2 is expressed at a high level in the central nervous system (CNS), including the eye and brain, as well as skeletal muscle and the spleen.

[5] PAD2 has also been shown to interact with vimentin in skeletal muscle and macrophages, causing the filaments to disassemble, suggesting a role in apoptosis.

In early CNS development of the embryo, MBP deimination plays a major role in myelin assembly.

Citrullination of trichohyalin allows it to bind and cross-link keratin filaments, directing growth of the wool fiber.

The presence of anti-citrullinated protein antibody is a standard test for rheumatoid arthritis, and it is associated with more severe disease.

Citrullinated proteins are also found in the cellular debris accompanying the destruction of cells in alzheimer disease, and after smoking cigarettes.

[18][19] Another approach is to utilize the neutral loss of isocyanic acid (HNCO) from citrulline residues when submitted to low energy collision induced dissociation fragmentation in mass spectrometers.