PYCARD a protein that functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. 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. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. Isoform 2 may have a regulating effect on the function as inflammasome adapter. Isoform 3 seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. 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. 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. 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. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. 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. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA. Widely expressed at low levels. Detected in peripheral blood leukocytes, lung, small intestine, spleen, thymus, colon and at lower levels in placenta, liver and kidney. Very low expression in skeletal muscle, heart and brain. Expressed in lung epithelial cells. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold; Tumor suppressor
Chromosomal Location of Human Ortholog: 7|7 F3
Cellular Component:  AIM2 inflammasome complex; cytoplasm; cytosol; endoplasmic reticulum; extracellular region; Golgi membrane; mitochondrion; neuronal cell body; NLRP1 inflammasome complex; NLRP3 inflammasome complex; nucleolus; nucleus; protein-containing complex
Molecular Function:  BMP receptor binding; cysteine-type endopeptidase activity; cysteine-type endopeptidase activity involved in apoptotic process; enzyme binding; identical protein binding; interleukin-6 receptor binding; ion channel binding; myosin I binding; peptidase activator activity involved in apoptotic process; protease binding; protein binding; protein dimerization activity; protein homodimerization activity; Pyrin domain binding; tropomyosin binding
Biological Process:  activation of cysteine-type endopeptidase activity; activation of cysteine-type endopeptidase activity involved in apoptotic process; activation of innate immune response; apoptotic process; cellular response to interleukin-1; cellular response to lipopolysaccharide; cellular response to tumor necrosis factor; defense response to Gram-negative bacterium; defense response to virus; immune system process; inflammatory response; innate immune response; interleukin-1 beta production; intrinsic apoptotic signaling pathway by p53 class mediator; intrinsic apoptotic signaling pathway in response to DNA damage; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; macropinocytosis; myeloid dendritic cell activation; myeloid dendritic cell activation involved in immune response; negative regulation of cytokine production involved in inflammatory response; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of interferon-beta production; negative regulation of NF-kappaB transcription factor activity; negative regulation of protein serine/threonine kinase activity; positive regulation of actin filament polymerization; positive regulation of activated T cell proliferation; positive regulation of adaptive immune response; positive regulation of antigen processing and presentation of peptide antigen via MHC class II; positive regulation of apoptotic process; positive regulation of chemokine secretion; positive regulation of cysteine-type endopeptidase activity; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of defense response to virus by host; positive regulation of DNA-binding transcription factor activity; positive regulation of ERK1 and ERK2 cascade; positive regulation of extrinsic apoptotic signaling pathway; positive regulation of interferon-gamma production; positive regulation of interleukin-1 beta secretion; positive regulation of interleukin-10 secretion; positive regulation of interleukin-6 production; positive regulation of interleukin-6 secretion; positive regulation of interleukin-8 secretion; positive regulation of JNK cascade; positive regulation of NF-kappaB transcription factor activity; positive regulation of phagocytosis; positive regulation of release of cytochrome c from mitochondria; positive regulation of T cell activation; positive regulation of T cell migration; positive regulation of tumor necrosis factor production; protein homooligomerization; regulation of apoptotic process; regulation of autophagy; regulation of cysteine-type endopeptidase activity involved in apoptotic process; regulation of GTPase activity; regulation of inflammatory response; regulation of intrinsic apoptotic signaling pathway; regulation of protein stability; regulation of tumor necrosis factor-mediated signaling pathway; response to bacterium; tumor necrosis factor-mediated signaling pathway
Reference #:  Q9EPB4 (UniProtKB)
Alt. Names/Synonyms: 9130417A21Rik; Apoptosis-associated speck-like protein containing a CARD; Asc; CARD5; mASC; OTTMUSP00000030782; Pycard; PYD and CARD domain containing; PYD and CARD domain-containing protein; TMS-; TMS-1; TNS1
Gene Symbols: Pycard
Molecular weight: 21,459 Da
Basal Isoelectric point: 5.26  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene