Pyrin

Pyrin also known as "cryopyrin" or marenostrin (lat.: mare nostrum for Mediterranean) ,is a protein encoded by the MEFV gene (MEFV is the acronym for "Mediterranean fever gene") located on chromosome 16p13.3.

The gene product pyrin is an important modulator of innate immunity.

Mutations in the MEFV gene, the "pyrin gene", lead to functional impairments of the protein and to the triggering of a systemic inflammatory reaction.

Pyrin is involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. It is involved in the autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1 and ATG8 family members.

Pyrin recognizes specific autophagy targets, coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. It acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, thus preventing excessive IL1B- and IL18-mediated inflammation.

However, pyrin may also positively impact the inflammatory pathway by acting as an innate immune system sensor that triggers PYCARD/ASC stain formation, caspase-1 activation (see caspases below), and IL1B and IL18 production.

Pyrin is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation. Recruits PSTPIP1to inflammasomes and is required for PSTPIP1 ol igomerization.