PTPN22 is located on chromosome 1 and codes for the lymphoid specific tyrosine phosphatase protein, Lyp. This protein is comprised of 807 amino acids, and contains an N-terminal protein tyrosine phosphatase (PTP) domain and four proline-rich motifs (P1–4) in the C-terminal region. Lyp has a major role in regulation of the Src family of tyrosine kinases (SFKs). SFKs serve as molecular switches that regulate a variety of cellular events including cell growth, division, differentiation and programmed death. The P1 proline-rich motif of Lyp is important for its interaction with the C-terminal Src tyrosine kinase (CSK), a negative regulatory kinase [28]. Csk phosphorylates C-terminal tyrosines in SFKs, and the Lyp-CSK interaction destabilizes the kinase domains of SFKs through tyrosine dephosphorylation. The well established PTPN22 polymorphism (rs2476601) encodes the amino acid substitution of arginine to tryptophan at position 620 (R620W) which disrupts the Lyp-Csk interaction and therefore has been the main focus of many research studies [26].
