Recombinant Mouse Apoptosis-associated speck-like protein containing a CARD (Pycard)

Function

Functions as a key mediator in apoptosis and inflammation (PubMed:32424362, PubMed:34678144). Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner (By similarity). Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3 (By similarity). Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes (NLRP2, NLRP3, NLRP6 and AIM2) which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:15190255, PubMed:15507117, PubMed:21892172, PubMed:22555457, PubMed:32424362, PubMed:34678144). Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death (By similarity). The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions (By similarity). Clustered PYCARD nucleates the formation of caspase-1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization (By similarity). In the NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1 (By similarity). In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation (By similarity). May be involved in RIGI-triggered pro-inflammatory responses and inflammasome activation (By similarity). In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8 (PubMed:22555457). In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form (By similarity). Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways (By similarity). For regulation of NF-kappa-B activating and inhibiting functions have been reported (By similarity). Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK (By similarity). Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing (By similarity). Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590)

Subcellular Location

Cytoplasm; Inflammasome; Endoplasmic reticulum; Mitochondrion; Nucleus

Tissue Specificity

Expressed in small intestine, colon, thymus, spleen, brain, heart, skeletal muscle, kidney, lung and liver

Subunit

Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta secretion (By similarity). Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height (By similarity). Component of several inflammasomes containing one pattern recognition receptor/sensor, such as NLRP2, NLRP3, NLRP6, NLRC4, AIM2, MEFV or NOD2, and probably NLRC4 or NLRP12 (PubMed:32424362, PubMed: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 (By similarity). 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 (By similarity). Interacts with NLRP3; the interaction requires the homooligomerization of NLRP3 (PubMed:30487600). Interacts with NLRP2, NLRC4, MEFV, CARD16, AIM2, NOD2, RIGI, RIPK2, PYDC1, PYDC2, NLRP10, CHUK, IKBKB and BAX (By similarity). Interacts with CASP8 (PubMed:22555457). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (PubMed:34471287). Interacts with FAM120A; this interaction inhibits inflammasome activation (By similarity)

• Masumoto J. et al. Murine ortholog of ASC, a CARD-containing protein, self-associates and exhibits restricted distribution in developing mouse embryos. — Exp. Cell Res. (2001)
• Martinon F. et al. Pycard a PYD and CARD containing molecule. (SEP-)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Yamamoto M. et al. ASC is essential for LPS-induced activation of procaspase-1 independently of TLR-associated signal adaptor molecules. — Genes Cells (2004)
• Mariathasan S. et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. — Nature (2004)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Ippagunta S.K. et al. The inflammasome adaptor ASC regulates the function of adaptive immune cells by controlling Dock2-mediated Rac activation and actin polymerization. — Nat. Immunol. (2011)