======= PYCARD =======
== Gene Information ==
* **Official Symbol**: PYCARD
* **Official Name**: PYD and CARD domain containing
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=29108|29108]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q9ULZ3|Q9ULZ3]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=PYCARD&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PYCARD|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/606838|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: 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. [provided by RefSeq, Jul 2008].
* **UniProt Summary**: 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 (PubMed:28314590). {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:21487011, ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:28314590}.
|PAAD DAPIN|
|CARD|
|myosin I binding|
|Pyrin domain binding|
|positive regulation of antigen processing and presentation of peptide antigen via MHC class II|
|positive regulation of antigen processing and presentation of peptide antigen|
|positive regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II|
|AIM2 inflammasome complex|
|myeloid dendritic cell activation involved in immune response|
|NLRP1 inflammasome complex|
|regulation of antigen processing and presentation of peptide antigen via MHC class II|
|regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II|
|regulation of antigen processing and presentation of peptide antigen|
|positive regulation of interleukin-10 secretion|
|interleukin-6 receptor binding|
|NLRP3 inflammasome complex|
|macropinocytosis|
|IkappaB kinase complex|
|positive regulation of antigen processing and presentation|
|regulation of interleukin-10 secretion|
|BMP receptor binding|
|pinocytosis|
|negative regulation of interferon-beta production|
|activation of cysteine-type endopeptidase activity|
|positive regulation of chemokine secretion|
|cysteine-type endopeptidase activity involved in apoptotic process|
|tropomyosin binding|
|positive regulation of interleukin-8 secretion|
|interleukin-1 beta production|
|regulation of chemokine secretion|
|cysteine-type endopeptidase activator activity involved in apoptotic process|
|interleukin-1 production|
|negative regulation of cytokine production involved in inflammatory response|
|regulation of antigen processing and presentation|
|positive regulation of activated T cell proliferation|
|myeloid dendritic cell activation|
|regulation of interleukin-8 secretion|
|positive regulation of defense response to virus by host|
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|positive regulation of release of cytochrome c from mitochondria|
|positive regulation of T cell migration|
|positive regulation of interleukin-6 secretion|
|positive regulation of interleukin-1 beta secretion|
|regulation of activated T cell proliferation|
|positive regulation of interleukin-10 production|
|positive regulation of lymphocyte migration|
|regulation of defense response to virus by host|
|positive regulation of interleukin-1 secretion|
|regulation of cytokine production involved in inflammatory response|
|zymogen activation|
|negative regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of T cell migration|
|negative regulation of type I interferon production|
|regulation of interleukin-1 beta secretion|
|regulation of interferon-beta production|
|regulation of release of cytochrome c from mitochondria|
|positive regulation of extrinsic apoptotic signaling pathway|
|positive regulation of interleukin-8 production|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|positive regulation of interleukin-1 beta production|
|regulation of interleukin-10 production|
|regulation of interleukin-1 secretion|
|positive regulation of chemokine production|
|regulation of tumor necrosis factor-mediated signaling pathway|
|positive regulation of interleukin-1 production|
|regulation of lymphocyte migration|
|positive regulation of interferon-gamma production|
|positive regulation of phagocytosis|
|regulation of interleukin-8 production|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|regulation of defense response to virus|
|regulation of chemokine production|
|regulation of interleukin-1 beta production|
|negative regulation of NF-kappaB transcription factor activity|
|defense response to Gram-negative bacterium|
|positive regulation of tumor necrosis factor production|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of tumor necrosis factor superfamily cytokine production|
|azurophil granule lumen|
|positive regulation of actin filament polymerization|
|positive regulation of interleukin-6 production|
|regulation of interleukin-1 production|
|positive regulation of T cell proliferation|
|regulation of phagocytosis|
|regulation of interferon-gamma production|
|protease binding|
|positive regulation of adaptive immune response|
|positive regulation of mitochondrion organization|
|secretory granule lumen|
|tumor necrosis factor-mediated signaling pathway|
|signal transduction by p53 class mediator|
|ion channel binding|
|regulation of type I interferon production|
|positive regulation of protein polymerization|
|positive regulation of leukocyte migration|
|positive regulation of lymphocyte proliferation|
|positive regulation of mononuclear cell proliferation|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|negative regulation of protein serine/threonine kinase activity|
|negative regulation of inflammatory response|
|positive regulation of leukocyte proliferation|
|positive regulation of cytokine secretion|
|positive regulation of JNK cascade|
|regulation of interleukin-6 production|
|regulation of tumor necrosis factor production|
|intrinsic apoptotic signaling pathway|
|cytokine production|
|positive regulation of cysteine-type endopeptidase activity|
|regulation of tumor necrosis factor superfamily cytokine production|
|positive regulation of NF-kappaB transcription factor activity|
|regulation of extrinsic apoptotic signaling pathway|
|regulation of T cell proliferation|
|protein processing|
|protein dimerization activity|
|regulation of intrinsic apoptotic signaling pathway|
|negative regulation of DNA-binding transcription factor activity|
|regulation of adaptive immune response|
|regulation of cytokine-mediated signaling pathway|
|regulation of actin filament polymerization|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|positive regulation of endopeptidase activity|
|positive regulation of apoptotic signaling pathway|
|cellular response to interleukin-1|
|regulation of response to cytokine stimulus|
|regulation of mitochondrion organization|
|regulation of actin polymerization or depolymerization|
|regulation of actin filament length|
|cellular response to lipopolysaccharide|
|regulation of JNK cascade|
|positive regulation of peptidase activity|
|defense response to virus|
|cellular response to molecule of bacterial origin|
|regulation of leukocyte migration|
|positive regulation of supramolecular fiber organization|
|response to interleukin-1|
|positive regulation of T cell activation|
|regulation of cytokine secretion|
|negative regulation of defense response|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|positive regulation of ERK1 and ERK2 cascade|
|cellular response to biotic stimulus|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of leukocyte cell-cell adhesion|
|positive regulation of cytoskeleton organization|
|regulation of leukocyte proliferation|
|regulation of protein polymerization|
|negative regulation of protein kinase activity|
|protein maturation|
|regulation of stress-activated MAPK cascade|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of stress-activated protein kinase signaling cascade|
|cellular response to tumor necrosis factor|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of kinase activity|
|positive regulation of protein complex assembly|
|positive regulation of cell-cell adhesion|
|activation of innate immune response|
|regulation of actin filament organization|
|positive regulation of DNA-binding transcription factor activity|
|response to tumor necrosis factor|
|positive regulation of protein secretion|
|negative regulation of cytokine production|
|negative regulation of transferase activity|
|response to virus|
|apoptotic signaling pathway|
|regulation of protein stability|
|positive regulation of peptide secretion|
|regulation of ERK1 and ERK2 cascade|
|regulation of leukocyte cell-cell adhesion|
|response to lipopolysaccharide|
|regulation of T cell activation|
|response to molecule of bacterial origin|
|defense response to bacterium|
|regulation of autophagy|
|regulation of inflammatory response|
|protein homooligomerization|
|positive regulation of innate immune response|
|regulation of actin cytoskeleton organization|
|enzyme binding|
|regulation of supramolecular fiber organization|
|positive regulation of proteolysis|
|positive regulation of lymphocyte activation|
|positive regulation of response to biotic stimulus|
|negative regulation of response to external stimulus|
|neuronal cell body|
|regulation of cellular component size|
|regulation of actin filament-based process|
|regulation of apoptotic signaling pathway|
|regulation of cell-cell adhesion|
|positive regulation of secretion by cell|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|negative regulation of protein phosphorylation|
|regulation of endopeptidase activity|
|positive regulation of cell activation|
|positive regulation of protein transport|
|regulation of DNA-binding transcription factor activity|
|positive regulation of secretion|
|regulation of peptidase activity|
|negative regulation of phosphorylation|
|positive regulation of cytokine production|
|regulation of protein complex assembly|
|regulation of innate immune response|
|positive regulation of establishment of protein localization|
|regulation of protein secretion|
|regulation of immune effector process|
|positive regulation of defense response|
|regulation of GTPase activity|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|regulation of peptide secretion|
|neutrophil mediated immunity|
|inflammatory response|
|positive regulation of cell migration|
|neutrophil activation|
|granulocyte activation|
|negative regulation of intracellular signal transduction|
|positive regulation of multi-organism process|
|leukocyte degranulation|
|regulation of anatomical structure size|
|regulation of lymphocyte activation|
|regulation of protein serine/threonine kinase activity|
|myeloid leukocyte mediated immunity|
|protein complex oligomerization|
|positive regulation of cellular component biogenesis|
|cellular response to lipid|
|positive regulation of cell motility|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|positive regulation of cellular component movement|
|regulation of cytoskeleton organization|
|positive regulation of MAPK cascade|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|endocytosis|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|myeloid leukocyte activation|
|negative regulation of protein modification process|
|protein-containing complex|
|positive regulation of response to external stimulus|
|regulation of leukocyte activation|
|Golgi membrane|
|positive regulation of organelle organization|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|activation of immune response|
|regulation of cell activation|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|cytokine-mediated signaling pathway|
|import into cell|
|regulation of cell adhesion|
|response to bacterium|
|regulation of cytokine production|
|positive regulation of cell death|
|regulated exocytosis|
|regulation of protein transport|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of MAPK cascade|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|positive regulation of hydrolase activity|
|cellular response to DNA damage stimulus|
|regulation of multi-organism process|
|negative regulation of catalytic activity|
|exocytosis|
|regulation of protein kinase activity|
|regulation of secretion|
|regulation of cellular catabolic process|
|regulation of cell migration|
|response to lipid|
|nucleolus|
|positive regulation of immune response|
|regulation of kinase activity|
|protein homodimerization activity|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|apoptotic process|
|leukocyte activation|
|defense response to other organism|
|regulation of cellular component biogenesis|
|regulation of transferase activity|
|regulation of locomotion|
|positive regulation of transport|
|regulation of catabolic process|
|regulation of cellular component movement|
|secretion by cell|
|cellular response to cytokine stimulus|
|endoplasmic reticulum|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|export from cell|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|identical protein binding|
|cell activation|
|immune effector process|
|cell death|
|regulation of response to external stimulus|
|response to cytokine|
|negative regulation of protein metabolic process|
|secretion|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|regulation of immune response|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|proteolysis|
|regulation of hydrolase activity|
|regulation of organelle organization|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|regulation of apoptotic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|immune response|
|extracellular region|
|vesicle-mediated transport|
|gene expression|
\\
=== CRISPR Data ===
No hits were found.
^Gene^Correlation^
|[[:human genes:h:hgc6.3|HGC6.3]]|0.583|
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 8432
* **Expression level (log2 read counts)**: 2.47
{{:chemogenomics:nalm6 dist.png?nolink |}}