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.

PYD and CARD domain containing

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, acts as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:25847972).
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, NLRP6, AIM2 and probably IFI16 (PubMed:15030775, PubMed:17349957, PubMed:19158676, PubMed:19158675, PubMed:30674671, PubMed:34678144).
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 pro-inflammatory responses and inflammasome activation. 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).
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.

Activation of cysteine-type endopeptidase activityIEA:Ensembl
Activation of cysteine-type endopeptidase activity involved in apoptotic process1 PublicationNAS:UniProtKB
Activation of innate immune responseManual Assertion Based On ExperimentIDA:UniProtKB
Apoptotic processManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to interleukin-1Manual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to lipopolysaccharideManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to tumor necrosis factorManual Assertion Based On ExperimentIDA:UniProtKB
Defense response to Gram-negative bacteriumManual Assertion Based On ExperimentIMP:UniProtKB
Defense response to Gram-positive bacteriumIEA:Ensembl
Defense response to virusManual Assertion Based On ExperimentIDA:UniProtKB
Icosanoid biosynthetic process1 PublicationIC:ComplexPortal
Inflammatory responseIEA:UniProtKB-KW
Innate immune responseIEA:UniProtKB-KW
Intrinsic apoptotic signaling pathway by p53 class mediatorManual Assertion Based On ExperimentIMP:UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatorManual Assertion Based On ExperimentIMP:UniProtKB
MacropinocytosisISS:UniProtKB
Myeloid dendritic cell activationManual Assertion Based On ExperimentIMP:UniProtKB
Myeloid dendritic cell activation involved in immune responseISS:UniProtKB
Negative regulation of cytokine production involved in inflammatory responseManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of interferon-beta productionManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Osmosensory signaling pathway1 PublicationIC:ComplexPortal
Pattern recognition receptor signaling pathway4 PublicationsIC:ComplexPortal
Positive regulation of actin filament polymerizationISS:UniProtKB
Positive regulation of activated T cell proliferationISS:UniProtKB
Positive regulation of adaptive immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of antigen processing and presentation of peptide antigen via MHC class IIISS:UniProtKB
Positive regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of chemokine productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of cysteine-type endopeptidase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:HGNC-UCL
Positive regulation of defense response to virus by hostIEA:Ensembl
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of inflammatory responseManual Assertion Based On ExperimentIDA:ComplexPortal
Positive regulation of interferon-gamma productionISS:UniProtKB
Positive regulation of interleukin-1 beta productionManual Assertion Based On ExperimentIDA:HGNC-UCL
Positive regulation of interleukin-10 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of interleukin-6 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of JNK cascadeManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of macrophage cytokine productionIEA:Ensembl
Positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of phagocytosisISS:UniProtKB
Positive regulation of release of cytochrome c from mitochondriaManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of T cell activationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of T cell migrationISS:UniProtKB
Positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIMP:UniProtKB
Protein homooligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Pyroptosis4 PublicationsIC:ComplexPortal
Regulation of autophagyIEA:Ensembl
Regulation of GTPase activityIEA:Ensembl
Regulation of intrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of protein stabilityISS:UniProtKB
Regulation of tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Signal transduction1 PublicationNAS:UniProtKB
Tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIDA:HGNC-UCL

Cytoplasm
Inflammasome
Endoplasmic reticulum
Mitochondrion
Nucleus
Upstream of caspase activation, a redistribution from the cytoplasm to the aggregates occurs. These appear as hollow, perinuclear spherical, ball-like structures (PubMed:11103777, PubMed:12191486, PubMed:15030775).
Upon NLRP3 inflammasome activation redistributes to the perinuclear space localizing to endoplasmic reticulum and mitochondria (PubMed:12191486, PubMed:15030775).
Localized primarily to the nucleus in resting monocytes/macrophages and rapidly redistributed to the cytoplasm upon pathogen infection (PubMed:19234215).
Localized to large cytoplasmic aggregate appearing as a speck containing AIM2, PYCARD, CASP8 and bacterial DNA after infection with Francisella tularensis (By similarity).
Golgi apparatus membrane
(Microbial infection) Upon HRSV infection, the protein is mainly located in lipid rafts in the Golgi membrane.

Phosphorylated.
'Lys-63'-linked polyubiquitination by TRAF3 is critical for speck formation and inflammasome activation.