Reactome: A Curated Pathway Database

PSTPIP1 binds Pyrin (R-HSA-879221) [Homo sapiens]


Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) is a pyrin-binding protein, involved in regulation of the actin cytoskeleton (Li et al. 1998) and suggested as a regulator of inflammasome activation (Khare et al. 2010). A naturally occurring mutation of PSTPIP1 where Y344 is replaced by F blocks tyrosine phosphorylation and reduces pyrin binding. Mutations of PSTPIP1 that increase pyrin binding are associated with the inflammatory syndrome pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA). Expression of PSTPIP1 with these mutations in THP-11 cells resulted in substantially increased caspase-1 activation and IL-1beta secretion. PSTPIP1 binding to pyrin is believed to promote the unmasking of its PYD domain and enhance interactions with ASC, facilitating ASC oligomerization and caspase-1 recruitment (Yu et al. 2007).

Additional Information
Compartment cytosol
Literature References
pubMedId Title Journal Year
14595024 Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway Proc Natl Acad Sci U S A 2003