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The protein tyrosine phosphatase PTPN22 (PTP22, LYP, PEP, formerly PTPN8) is a genetic variant that confers risk of developing diverse human autoimmune diseases such as type 1 diabetes and rheumatoid arthritis. The minor allele of a missense SNP in PTPN22 encodes a hematopoietic-specific protein tyrosine phosphatase also known as "Lyp." The risk allele is present in about 17% of Caucasian individuals from the general population and in approximately 28% of Caucasian individuals with rheumatoid arthritis; it is thought to disrupt the P1 proline-rich motif that is important for interaction with the Src homology-3 (SH3) domain of CSK (cytoplasmic tyrosine kinase), potentially altering the normal functions of these proteins as negative regulators of T cell activation. The interaction between CSK and PTPN22 is highly specific and it is speculated that PTPN22 may be an effector and/or regulator of CSK in T cells and other hematopoietic cells.
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