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PYCARD

This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants encoding different isoforms have been found for this gene.
Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Kupffer cells, Proximal enterocytes, Hofbauer cells, Paneth cells, Macrophages)

Immune cell specificity

Group enriched (neutrophil, non-classical monocyte, intermediate monocyte, classical monocyte, eosinophil, myeloid DC, plasmacytoid DC, basophil)

Cell line specificity

Cell line enhanced (MCF7, NB-4, THP-1, U-937)

Interaction

Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta secretion (PubMed:15641782, 17599095, 33420028, 33420033). Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height (PubMed:15641782, 17599095). Next to isoform 1, also isoform 2 and isoform 3 may be involved in oligomerization leading to functional regulation (Probable). Component of several inflammasomes containing one pattern recognition receptor/sensor, such as NLRP1, NLRP2, NLRP3, NLRP6, NLRC4, AIM2, MEFV or NOD2, and probably NLRC4, NLRP12 or IFI16 (PubMed:11374873, 12191486, 15030775, 15456791, 19158676, 30674671, 34678144). Major component of the ASC pyroptosome, a 1-2 um supramolecular assembly (one per macrophage cell) which consists of oligomerized PYCARD dimers and CASP1 (PubMed:17599095). Interacts with CASP1 (precursor form); the interaction induces activation of CASP1 leading to the processing of interleukin-1 beta; PYCARD competes with RIPK2 for binding to CASP1 (PubMed:11967258, 14634131, 16585594, 17599095, 33420033). Interacts with NLRP3; the interaction requires the homooligomerization of NLRP3 (PubMed:11786556, 15030775, 15020601, 34341353). Interacts with NLRP2, NLRC4, MEFV, CARD16, AIM2, IFI16, NOD2, DDX58, RIPK2, PYDC1, PYDC2, NLRP10, CASP8, CHUK, IKBKB and BAX (PubMed:11374873, 11498534, 12486103, 12646168, 12656673, 15456791, 14730312, 15096476, 17178784, 17339483, 18362139, 19158675, 19158676, 19915568, 21575908). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity).

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