Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)

Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) is a cytoskeletal adaptor protein highly expressed in hematopoietic tissues and diverse immune lineages[2][3]. It contains an N-terminal F-BAR domain mediating membrane and actin interactions, and a C-terminal SH3 domain for protein-protein interactions[2]. PSTPIP1 binds PEST-type protein tyrosine phosphatases (PTPN12/PTP-PEST, PTPN18, PTPN22/LYP), coupling them to actin cytoskeletal regulators including WASP and the kinase c-Abl, and directing c-Abl dephosphorylation[1][2][3]. It also interacts with pyrin (MEFV gene product), modifying inflammasome assembly and regulating IL-1β secretion[1][2]. Mutations in PSTPIP1’s coiled-coil region (notably A230T, E250Q) are causative for PAPA syndrome, a rare monogenic autoinflammatory disorder characterized by pyogenic sterile arthritis, pyoderma gangrenosum, and acne, and are linked to hyperactivation of the inflammatory response via excess IL-1β signaling[1][2][3].

Other names

CD2-binding protein 1CD2BP1PEST phosphatase-interacting protein 1PAPAPAPASH-PIPCD2BP1LCD2BP1S

Not applicable/currently no direct drugs, but protein-protein disruption may theoretically block pathological signaling