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FLASH GENE
Symbol PYCARD contributors: mct - updated : 06-09-2019
HGNC name PYD and CARD domain containing
HGNC id 16608
Location 16p11.2      Physical location : 31.212.808 - 31.214.251
Synonym name
  • apoptosis-associated speck-like protein containning a CARD
  • target of methylation induced silencing 1
  • caspase recruitment domain-containing protein 5
  • Synonym symbol(s) TMS1, ASC, CARD5, TMS, TMS-1, MGC10332
    DNA
    TYPE functioning gene
    STRUCTURE 1.29 kb     3 Exon(s)
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • promoter is embedded within a CpG island that is unmethylated in normal cells and is spanned by three DNase I-hypersensitive sites (HS)
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 782 21 195 - 2000 11103776
  • a 3 exons variant
  • having exon 1a, containing and longer than exons 1b & 1c
  • 2 splicing 725 19 176 - 2000 11103776
  • a 2 exons variant
  • having exon 1a, containing and longer than exons 1b & 1c
  • lacking exon 2
  • - splicing 763 14 135 - 2000 11103776
  • a 4 exons variant
  • having exons 1b & 1c, included in and longer than exon 1a
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
    Lymphoid/Immunethymus   lowly
     tonsils   highly
    Nervousbrain   lowly
    Reproductivefemale systembreast   
     male systemprostate  moderately
    Respiratorylung   moderately
     respiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Epithelialbarrier/liningretinal pigment epithelium (RPE)  
    cell lineage
    cell lines leukemia and melanoma cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal PYD (Pyrin-PAAD-Dapin) domain
  • separated by a flexible linker of the CARD domain
  • C terminal caspase recruitment motif domain (CARD), which are protein interaction domains of the death fold superfamily
  • HOMOLOGY
    interspecies homolog to rattus Pycard (70.47 pc)
    homolog to murine Pycard (72.02 pc)
    Homologene
    FAMILY CARD containing adaptor protein family
    CATEGORY adaptor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text moving in cells undergoing apoptosis from the cytoplasm to the perinuclear periphery
    basic FUNCTION
  • involved in methylation-mediated silencing
  • promoting the assembly of large signaling complexes in the inflammatory and apototic signaling pathway
  • involved in the caspase-1 signaling pathway by mediating the assembly of a caspase-1-inflammasome signaling complex in response to pro-inflammatory cytokine stimulation
  • essential adaptor protein in the formation of a multiprotein complex that activates procaspase-1
  • adaptor molecule important in the induction of apoptosis and inflammatory response
  • proapoptotic signaling factor that is subject to epigenetic silencing in human breast and other cancers
  • acts as an essential adapter for inflammasome integrity, and oligomerizes into functional supramolecular assemblies
  • mediates distinct forms of cell death in different cell types
  • having a function that is distinct from the inflammasome in modulating MAPK activity and chemokine expression
  • has important roles in both inflammasome-dependent and inflammasome-independent signaling cascades
  • connects pathogen/danger sensors such as NLRP3 and NLRC4 with caspases and is involved in inflammation and cell death
  • contributes to innate immunity through the assembly of inflammasome complexes that activate the cysteine protease caspase-1
  • shapes adaptive immunity independently of inflammasomes by modulating DOCK2-dependent RAC1 activation and actin polymerization in dendritic cells and lymphocytes
  • plays a key role in inflammasome assembly
  • key component of multimeric protein complexes that mediate inflammation and host defence
  • central role of CARDs in the formation of PYCARD signalling platforms, providing an important tool for investigation of CARD-dependent networks
  • inflammasome adaptor PYCARD contributes to innate immunity through the activation of CASP1
  • during inflammasome assembly, activated receptors of the NLR or PYHIN family recruit the adaptor protein PYCARD and initiate polymerization of its pyrin domain (PYD) into filaments
  • suppresses cancer metastasis and progression via the modulation of cytoskeletal remodeling and the SRC-CASP8 signaling pathway
  • contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, CASP1 )
  • is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals
  • assembles into filaments with integral participation of its two Death Domains, PYD and CARD
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling signal transduction
  • inflammasome pathway, including NLRP6, PYCARD, CASP1, and IL18
  • a component
  • component of inflammatory and apoptotic complexes i.e. with CASP1, CASP5, DEFCAP
  • central component of the inflammasome that is responsible for processing of mature IL1B from pro-IL1B
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating CASP9 mediated apoptotic pathway by cellular redistribution of ASC
  • interacting with PYDC1
  • DUSP10 is a novel PYCARD target
  • CASP1 interacting with PYCARD, AIM2 and NLRP3 (PYCARD inflammasomes, including AIM2 and NLRP3, are critical for CASP1 activation induced by S. pneumoniae)
  • PYCARD interacts with NLRP3 via a homotypic PYD interaction and recruits procaspase-1 via a homotypic caspase recruitment domain interaction
  • PYCARD specks recruit and activate CASP1, which induces maturation of the cytokine IL1B and pyroptotic cell death
  • CHUK controls the inflammasome at the level of the adaptor PYCARD, which interacts with CHUK in the nucleus of resting macrophages in an CHUK kinase-dependent manner
  • MAVS is required for the optimal activation of apoptosis-associated specklike protein (PYCARD)-dependent inflammasome
  • BTK physically interacts with PYCARD and NLRP3
  • PTK2B, but not PTK2, could directly phosphorylate PYCARD at Tyr146, and only the phosphorylated PYCARD could participate in speck formation and trigger IL1B secretion
  • PYCARD induces apoptosis via activation of CASP9 by enhancing gap junction-mediated intercellular communication
  • deubiquitinating enzyme USP50 binds to the PYCARD protein and subsequently regulates the inflammasome signaling pathway by deubiquitinating the lysine 63-linked polyubiquitination of PYCARD
  • endogenous NLRC3 interacts with both PYCARD and pro-caspase-1 but not with NLRP3, disrupts PYCARD speck formation through its CARD, and impairs the PYCARD and pro-caspase-1 interaction
  • NLRP3 can initiate PYCARD polymerization simply by increasing the local concentration of PYCARD above a supercritical level
  • PYCARD is a critical downstream target of PYCARD-AS1
  • cell & other
    REGULATION
    Other hypermethylated and silenced in cells overexpressing DNA cytosine 5 methyltransferase 1 (DNMT1)
    methylation mediated silencing of ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture
    in response to LPS stimulation, PYCARD expression is correlated with IL-8 secretion
    phosphorylation of PYCARD controls inflammasome activity through the formation of PYCARD specks
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral imprinting      
    aberrantly methylated and silenced in breast cancer cells and melanoma
    tumoral imprinting   --low  
    low expressed by hypermethylation in epithelial ovarian cancer
    tumoral        
    selectively down-regulated in the aberrant epithelial cells filling the lumen of the breast duct in a subset of primary ductal carcinoma in situ
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • NLRP6 expression and PYCARD methylation may represent unique molecular markers of carcinogenesis
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    promising target for cancer therapy
    ANIMAL & CELL MODELS
  • Pycard-/- mice had fewer myelin oligodendrocyte glycoprotein-specific T cells in the draining lymph nodes and CNS
  • Pycard-deficient mice showed defective antigen presentation by dendritic cells (DCs) and lymphocyte migration due to impaired actin polymerization mediated by the small GTPase Rac1