Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PYCARD (PYD and CARD domain containing)

Written2014-07Jeffrey H Dunn, Mayumi Fujita
Department of Dermatology, University of Colorado Denver, SOM, Aurora, CO, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)TMS-1
CARD5
ASC
Other aliasTMS
TMS1
HGNC (Hugo) PYCARD
LocusID (NCBI) 29108
Atlas_Id 712
Location 16p11.2  [Link to chromosome band 16p11]
Location_base_pair Starts at 31201486 and ends at 31202776 bp from pter ( according to hg19-Feb_2009)  [Mapping PYCARD.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Description 3 exons spanning 1.4 kb, with a CpG island surrounding exon 1 (Conway et al., 2000; Gerhard et al., 2004; Ota et al., 2004). Exon 1 encodes a pyrin domain (PYD), exon 2 encodes a proline and glycine-rich (PGR) domain, and exon 3 encodes a caspase recruitment domain (CARD) (Masumoto et al., 1999; Matsushita et al., 2009).

Protein

Description PYCARD is composed of two protein-protein interaction domains: an N-terminal pyrin domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are structurally independent six-helix bundle motifs connected by a 23-residue proline and glycine-rich (PGR) linker domain (Martinon et al., 2000; Bertin et al., 2001; de Alba, 2009; Matsushita et al., 2009).
There are 4 transcripts (splice variants) including the canonical PYCARD (PYCARD1) (Matsushita et al., 2009; Bryan et al., 2010). Correlating to four transcript splice variants are four protein isoforms. In addition to the canonical PYCARD protein (also known as isoform 1, fASC), three additional isoforms display unique capabilities with respect to their function as part of the inflammasome, with one of the isoforms even showing an inhibitory effect. Isoforms 1 and 2 are the activating isoforms of ASC and co-localize with intracellular nucleotide oligomerization domain-like receptors (NLRs) and caspase-1. Isoform 2 (also known as ASC-b, vASC) lacks a PGR domain and may not be needed for caspase activation but is involved in direct regulation of IL-1β processing. The inhibitory isoform (isoform 3, ASC-c) co-localizes only with caspase-1, but not with NLRP3. Isoform 4 (ASC-d) does not co-localize with NLRP3 or with caspase-1 and lacks the ability to function as an inflammasome adaptor. It may not be a functional protein product and its precise function and relation to PYCARD is unknown (Matsushita et al., 2009; Bryan et al., 2010).
PYD is also known as the domain in apoptosis and interferon response (DAPIN) or the pyrin, AIM, ASC death-domain-like (PAAD) domain. It is an 80-100 residue domain with alpha-helical secondary structure located on the N-terminus of the protein. Like CARD, it is a member of the death domain-fold superfamily of proteins. Strong dipole moments in PYD suggest that electrostatic interactions play an important role for the binding between PYDs. The function of PYD is to bind other PYD-containing proteins and is also associated with domains such as CARD, leucine-rich repeat (LRR), dual specificity spore lysis A (splA) protein kinase and ryanodine receptor (SPRY), caspase, or zinc-finger B-box (Martinon et al., 2001; Pawlowski et al., 2001; Liepinsh et al., 2003).
CARD is a subclass of protein motif known as the death fold, which features an arrangement of six to seven antiparallel alpha helices with a hydrophobic core and an outer face composed of charged residues. The CARD structure of PYCARD reveals two distinctive characteristics; helix 1 is not fragmented as in all other known CARDs; and it demonstrates a uniform distribution of positive and negative charges, whereas these are commonly separated into two areas in other death domains (de Alba, 2009).
CARD mediates the interaction between adaptor proteins participating in apoptosis by regulating caspases. CARD-containing proteins are also involved in inflammation through their regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The mechanisms by which CARDs activate caspases and NF-κB involve the assembly of multi-protein complexes, which can facilitate dimerization or serve as scaffolds on which proteases and kinases are assembled and activated. Domains associated with CARD include: PYD, Apoptotic protease activating factor-1 (Apaf-1) domains [including LRR, Tryptophan-Aspartic acid (WD or beta-transducin) repeats, nucleotide binding and oligomerization (NB-ARC or NOD) domains and ATPase domains], sarcoma (Src) tyrosine kinase proto-oncogene homology domains, death domain (DD) and the proform of caspases (e.g., CASP-9) (Hofmann et al., 1997; Bouchier-Hayes and Martin, 2002; Reed et al., 2004).
The PGR linker adopts a residual structure in order to maintain a back-to-back orientation of the PYD and CARD domains, which avoids steric interference of one domain with the binding site of the other. NMR relaxation experiments show that the linker is flexible despite the residual structure (de Alba, 2009).
Expression Silencing of PYCARD correlates with hypermethylation of the CpG island surrounding exon 1. Breast cancer cell lines exhibit complete methylation of PYCARD and do not express PYCARD mRNA, whereas overexpression of PYCARD inhibits the growth of breast cancer cells (Conway et al., 2000).
In normal fibroblasts, the CpG island of the PYCARD gene is composed of an unmethylated domain with distinct 5-prime and 3-prime boundaries. De novo or aberrant methylation of the PYCARD CpG island in cells is accompanied by localized hypoacetylation of histone H3 and H4 and gene silencing (Stimson and Vertino, 2002).
Localisation Cytoplasm, endoplasmic reticulum, mitochondrion, nucleus.
PYCARD forms hollow spherical aggregates near the perinuclear space of apoptotic cells (McConnell and Vertino, 2000). PYCARD also tends to self-aggregate during in vitro apoptosis induced by retinoids, etoposide and other anti-tumor drugs (Masumoto et al., 1999).
PYCARD is localized primarily in the nucleus in resting monocytes/macrophages but rapidly redistributes to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria upon pathogen infection and subsequent inflammasome activation (Bryan et al., 2009; Zhou et al., 2011).
Function PYCARD is known to interact with a variety of inflammatory and cell death-related genes including NLRs (NLRP1-14, NLRC4 [IL-1β converting enzyme protease-activating factor (IPAF)], Absent in Melanoma 2 (AIM2); caspase-1, caspase-2, caspase-3, caspase-5, caspase-8, caspase-9, caspase-12; pyrin; pyrin-only protein (POP) 1 and pyrin-only protein (POP) 2; cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A); AP-1; serum response factor. There are 75 genes known to be induced by PYCARD. A large proportion of them are related to transcription (23%), inflammation (21%), or cell death (16%) (Hasegawa et al., 2009).

Inflammation
PYCARD is an adaptor protein involved in the structure and function of inflammasomes. Inflammasomes are pattern recognition receptors characteristically composed of an NLR, ASC and caspase-1 and are responsible for production of pro-inflammatory cytokines, in particular IL-1β and IL-18. There are several subtypes of inflammasomes that recognize a diverse array of microbial, endogenous, and environmental danger signals (Agostini et al., 2004; Mariathasan et al., 2004; Muruve et al., 2008; Fernandes-Alnemri et al., 2009; Hornung et al., 2009; Zhou et al., 2011; Dunn et al., 2012).
Mounting evidence indicates that inflammasomes and PYCARD also elicit non-overlapping inflammatory functions. PYCARD interaction with NLRC4 regulates both apoptosis via caspase-8 and NF-κB activation via PYD. PYCARD can inhibit or activate NF-κB through PYD interactions with the NF-κB IKK complex (Stehlik et al., 2002; Masumoto et al., 2003; Sarkar et al., 2006; Fernandes-Alnemri et al., 2007; Hasegawa et al., 2009; Hornung et al., 2009; Taxman et al., 2011).
PYCARD is also associated with inflammasome-independent transcriptional activation of cytokines and chemokines via activator protein-1 (AP-1), NF-κB, mitogen activated protein kinase (MAPK) and caspase-8 (Taxman et al., 2006). In pathogen-infected cells, PYCARD regulates MAPK phosphorylation by pathogens and Toll-like receptor (TLR) agonists via suppression of the dual-specificity phosphatase (DUSP10/MKP5), and independent of caspase-1 and IL-1β; thus demonstrating a function for ASC that is distinct from the inflammasome in modulating MAPK activity and chemokine expression (Taxman et al., 2011).

Adaptive immunity
PYCARD may play an inflammasome-independent role in driving dendritic cells to stimulate T-cell priming for the induction of antigen-specific cellular and humoral immunity. Dendritic cell maturation stimuli activate caspase-1 in human dendritic cells. Inhibition of PYCARD and cathepsin B markedly diminishes the capacity of mature dendritic cells to stimulate antigen-specific T cells. The defective ability of PYCARD or cathepsin B-deficient dendritic cells to stimulate T cells is independent of inflammasome-mediated processing of inflammatory cytokines or priming of dendritic cells with pre-processed lipopolysaccharide (Guo and Dhodapkar, 2012).
On the other hand, PYCARD may also play an inflammasome-independent role in antigen-specific inflammatory disease. Mice genetically modified to lack both PYCARD alleles [ASC (-/-)] are protected from collagen-induced arthritis, whereas mice lacking Nlrp3 and caspase-1 are susceptible to collagen-induced arthritis. This may result from an inability of dendritic cells to facilitate antigen-specific activation of lymphocytes in mice lacking PYCARD. Furthermore, antigen-induced proliferation of purified T cells lacking PYCARD [ASC (-/-)] is restored upon incubation with wild type dendritic cells, but not when cultured with ASC (-/-) dendritic cells (Ippagunta et al., 2010).

Cell death (apoptosis, pyroptosis, necrosis)
PYCARD promotes caspase-mediated inhibition of cellular proliferation, DNA fragmentation and apoptosis via caspases including caspase-2/3/8 and 9 to activate the mitochondrial apoptotic pathway. The mechanism likely involves mitochondrial translocation of BAX, proteolytic maturation of BID and upregulation of the p53 response to cell stress or genotoxic insult (McConnell and Vertino, 2000; Ohtsuka et al., 2004; Hasegawa et al., 2007). PYCARD may also increase the susceptibility of leukemia cell lines to apoptotic stimuli by anticancer drugs (Masumoto et al., 1999).
PYCARD is involved in macrophage pyropoptosis (inflammatory cell death) which is characterized by potassium efflux and/or decreased intracellular potassium. The interaction of AIM2 with PYCARD leads to the formation of the pyroptosome, which induces pyroptotic cell death in response to cytoplasmic DNA in cells containing caspase-1 (Fernandes-Alnemri et al., 2007; Fernandes-Alnemri et al., 2009).
PYCARD also mediates cellular necrosis (pyronecrosis) in concert with NLRP3 and cathespin to cause programmed necrotic cell death that is independent from pyroptosis and does not require caspase-1 (Willingham et al., 2007; Satoh et al., 2013).

Implicated in

Note
  
Entity Cancer
  
  
Entity Anti-cancer immunity
Note ATP released by dying tumor cells activates P2RX7 receptors on dendritic cells, which triggers NLRP3/ASC (PYCARD)/ caspase-1 inflammasome-dependent IL-1β production and subsequent dendritic cell-mediated priming of tumor antigen-specific CD8+ T-cell production of IFN-γ (Aymeric et al., 2010).
  
  
Entity Melanoma
Note ASC has a dual role in melanoma progression via differential regulation of NF-κB activity and IL-1β processing. In primary melanoma, relatively high levels of ASC expression inhibit NF-κB activity and IL-1β transcription, with net inhibition of tumorigenesis. In metastatic melanoma, however, aberrant methylation results in decreased levels of ASC. The relative paucity of ASC protein in these cells, as well as assembly of a constitutionally active ASC-dependent inflammasome, may result competition among various pathways for a limited supply of ASC, with a net result of decreased inhibition of NF-κB, a positive feedback loop of IL-1 signalling and a pro-tumorigenic effect (Guan et al., 2003; Okamoto et al., 2010; Liu et al., 2013).
  
  
Entity Skin squamous cell carcinoma
Note ASC expression is reduced in squamous cell carcinoma. Tissue-specific analysis of a murine model of squamous cell carcinoma reveals that ASC has opposing functions: ASC acts as an inflammasome-independent p53-dependent tumor suppressor in keratinocytes while functioning as an inflammasome-dependent tumor promoter in dendritic cells (Drexler et al., 2012).
  
  
Entity Colorectal cancer
Note ASC expression sensitizes colorectal cancer cells to chemotherapeutic agents, resulting in inflammasome-independent cell death via mitochondrial reactive oxygen species and janus-kinase signalling. Methylation and silencing of ASC in colorectal cancer cells confers resistence to cell death by DNA-damaging chermotherapeutics (Riojas et al., 2007; Hong et al., 2013). NLRP3/ASC-dependent caspase-1 activity is critical for IL-18-mediated IFN-γ-dependent STAT1 tumor suppression of colorectal cancer triggered by chronic inflammation (Allen et al., 2010; Dupaul-Chicoine et al., 2010; Zaki et al., 2010). On the other hand ASC-dependent caspase-1 activity has a tumorigenic effect via IL-6 and STAT3 in response to microbial induction of aryl hydrocarbon receptors in the cecum (Ikuta et al., 2013).
  
  
Entity Breast cancer
Note Epigenetic silencing of TMS1 (PYCARD, ASC) results in failure of breast cancer cells to undergo BIM- and caspase-8-dependent apoptosis (anoikis) after detachment from the extra-cellular matrix (Parsons and Vertino, 2006; Parsons et al., 2009).
  
  
Entity Prostate cancer
Note Interferons induce expression of the cytosolic DNA-sensing AIM2/ASC inflammasome in normal human prostate cells. AIM2 mRNA levels are higher in benign prostate hyperplasia (BPH) cells than in normal prostate tissue. AIM2 mRNA levels are lower, however, in prostate cancer cells relative to BPH cells (Ponomareva et al., 2013).
Aberrant methylation and reduced expression of ASC occurs in prostate cancer cell lines and is associated with more aggressive disease (Collard et al., 2006; Das et al., 2006).
  
  
Entity Glioblastoma
Note Glioblastoma astrocytes aberrantly methylate ASC resulting in decreased ASC expression relative to normal human brain tissue. Decreased ASC expression may be associated with decreased patient survival and progression from grade III to grade IV glioma (Stone et al., 2004).
  
  
Entity Lung cancer
Note Hypermethylation of the ASC promoter with reduced ASC expression occurs in primary lung cancer and is correlated with progression and metastasis of human lung adenocarcinoma. ASC hypermethylation in sputum DNA correlates with a high risk of lung cancer (Machida et al., 2006).
  
  
Entity Promyelocytic leukemia
Note Promyelocytic leukemia protein (PML) limits ASC function and relegates ASC to the nucleus, limiting inflammasome activation and IL-1β production in bone marrow macrophages (Dowling et al., 2014). Another study, using a genetically distinct murine model, found that PML enhances NLRP3 inflammasome assembly and production of IL-1β, but did not specifically examine interactions between PML and ASC (Lo et al., 2013).
  
  
Entity Inflammatory diseases
  
  
Entity Atopic dermatitis
Note Downregulation of NLRP3/ASC inflammasome function in atopic dermatitis may predispose patients to Staphylococcus aureus superinfection (Niebuhr et al., 2014).
  
  
Entity Psoriasis
Note AIM2, ASC, caspase-1, and caspase-5 expression is upregulated in psoriatic skin lesions (Dombrowski et al., 2011; Kopfnagel et al., 2011; Salskov-Iversen et al., 2011).
  
  
Entity Contact dermatitis
Note Ultraviolet (UV) light triggers cutaneous production of uric acid with demonstrated effects on the NLRP3/ASC/caspase-1 inflammasome and varying impact on immunity and carcinogenesis. The NLRP3/ASC inflammasome contributes to a caspase-dependent IL-1β hypersensitivity response (Watanabe et al., 2007). Allopurinol (a xanthine oxidase inhibitor of uric acid production) prevents UV-induced NLRP3 upregulation but not UV-induced ASC downregulation (Leighton et al., 2013).
  
  
Entity Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome
Note Alterations in ASC as well as upstream and downstream components of the inflammasome pathway are involved in a variety of inflammatory skin diseases. Hereditary mutations in proline serine threonine phosphatase-interacting protein [PSTPIP1, or CD2-binding protein 1 (CD2BP1)], which regulates pyrin and is involved in filament organization, may activate NLRP3-independent ASC/caspase-1 activity, resulting in the persistent IL-1β secretion implicated in PAPA syndrome (Shoham et al., 2003; Waite et al., 2009).
  
  
Entity Familial mediterranean fever
Note Similar to the PAPA syndrome, gain of function mutations in the pyrin-encoding MEFV gene result in ASC-dependent, NLRP3-independent, caspase-1-mediated activation of IL-1β (Waite et al., 2009; Chae et al., 2011; Franchi and Núñez, 2011).
  
  
Entity Inflammatory bowel disease
Note ASC triggers caspase-driven enteric neuronal cell death in response to inflammatory driven ATP activation of P2X7R and pannexin channels (Gulbransen et al., 2012). Alterations in the NLRP6 inflammasome pathway including ASC, caspase-1 and IL-18 may contribute to the etiology of human inflammatory bowel disease (Elinav et al., 2011).
  
  
Entity Metabolic diseases including: gout, rheumatoid arthritis, diabetes mellitus and atherosclerosis
Note Macrophages, TLRs, NLRs and other components of the innate immune system play a role in the etiology of a variety of metabolic inflammatory diseases. Dysregulated ATP, lipid, urate and glucose metabolism disrupts microtubule polymerization, inflammasome assembly and proinflammatory cytokine production. Tubulin polymerization is critical for mitochondrial transport and inflammasome assembly by allowing for juxtaposition of ASC with NLRP3 in the cytosol (Martinon et al., 2006; Griffith et al., 2009; Ippagunta et al., 2010; Wen et al., 2011; Lu et al., 2012; Wen et al., 2012; Akira et al., 2013; Benetti et al., 2013; Grant and Dixit, 2013; Jourdan et al., 2013; Lee et al., 2013).
  
  
Entity Infectious diseases
  
  
Entity Anthrax
Note Anthrax lethal toxin triggers the formation of ASC-dependent NLRC4, NLRP3 and AIM2, but not NLRP1-dependent processing of caspase-1 with subsequent autoproteolysis and IL-1β secretion in murine macrophages (Nour et al., 2009; Lu et al., 2012; Van Opdenbosch et al., 2014). The 7-desacetoxy-6,7-dehydrogedunin (7DG) small molecule has been shown to protect macrophages from anthrax lethal toxin. 7DG inhibits protein kinase R, which is has a role in ASC assembly, caspase-1 activation and macrophage pyroptosis (Hett et al., 2013).
  
  
Entity Chlamydia trachomatis
Note Chlamydia trachomatis, an obligate intracellular bacteria, triggers secretion of IL-1β secretion in human trophoblasts via Nod1 but independent of Nalp3 (NLRP3) inflammasomes (Kavathas et al., 2013). Murine macrophages lacking ASC display prolonged courses of infection with Chlamydia muridarum, associated with reduced IL-18 production as well as T cell recruitment and proliferation but exhibit normal levels of IL-1β secretion and no change oviduct pathology, suggesting ASC has an IL-1-independent role in adaptive immunity during genital chlamydial infection (Nagarajan et al., 2012). Cervical epithelial cells, however, are the preferred host medium for Chlamydia trachomatis and these cells do not normally produce IL-1β. Infection by Chlamydia trachomatis activates NLRP3/ASC/caspase-1 which instead alters lipid metabolism by caspase mediated fragmentation of the Golgi apparatus diversion of Golgi lipids to the Chlamydia intracellular inclusion. This provides an optimal growth environment for intracellular chlamydia and blocking casapase-1 in these cells can inhibit chlamydial infection by ~60% (Abdul-Sater et al., 2009).
  
  
Entity Chlamydia pneumonia
Note Chlamydia pneumonia is a significant cause of atypical pneumonia and inflammatory diseases including asthma and COPD, infects alveolar macrophages. IL-1β secretion depends on Chlamydia pneumonia entry into murine macrophages with subsequent protein synthesis resulting in mitochondrial dysfunction, NLRP3/ASC/Caspase-1 activation, and IL-1β secretion. This suggests an important role for ASC in clearing Chlamydia pneumonia infection as well as chronic inflammatory diseases affecting the airway (He et al., 2010; Shimada et al., 2011).
  
  
Entity Escherichia coli
Note Enterohemorrhagic E. coli (EHEC) O157:H7 enterohemolysin (Ehx) triggers NLRP3/ASC/caspase-1-dependent production of IL-1 in THP-1 macrophages (Zhang et al., 2012). As with salmonella, double-stranded RNA-dependent protein kinase (PKR, EIF2AK2) interacts with ASC and other inflammasome components including NLRP3, NLRP1, NLRC4 and AIM2 to trigger caspase-1-dependent IL-1β production and pryopoptosis in E. coli-infected macrophages IL-1β (Lu et al., 2012). Extracellular infection, however, requires ATP co-stimulation of the P2X7 receptor and potassium efflux for NLRC4/ASC-driven caspase-1 activation in macrophages (Franchi et al., 2007a).
  
  
Entity HSV
Note The nuclear promyelocytic leukemia (PML) protein limits formation of cytosolic ASC dimers in HSV-infected bone marrow macrophages with subsequent decreases in IL-1β secretion (Dowling et al., 2014).
  
  
Entity Legionella
Note Legionella avoids caspase-1 activation through downregulation of NLRC4 and ASC expression through an unknown mechanism (Abdelaziz et al., 2011; Pereira et al., 2011).
  
  
Entity Listeria
Note The AIM2/ASC inflammasome senses cytosolic double strand DNA from intracellular viruses and bacteria including Listeria and triggers caspase-1-dependent maturation of IL-1β and IL-18 (Franchi et al., 2007a; Jin et al., 2013).
  
  
Entity Malaria
Note Malaria is characterized by cyclical fevers and associated with high levels of IL-1β and other cytokines. Mice infected with plasmodium demonstrate caspase-1 activation dependent on ASC, NLRP3 and other inflammasome components. Pro-IL-1β production depends on secondary stimulation with LPS, IFN-γ or TNF-R1. Uric acid release during malaria infection may further augment host response via NLRP3 inflammasome activation. As a result of caspase-1 activation in plasmodium-infected mice, microbial stimulus results in extremely high levels of IL-1β and sensitivity to septic shock. IL-1R antagonist prevents bacterial-induced lethality in rodents. Peripheral blood monocytes in febrile malaria patients display activated caspase-1 and produce large amounts of IL-1β after stimulation with LPS, suggesting that NLRP3/ASC-dependent activation of caspase-1 is crucial to production of systemic IL-1β and hypersensitivity to sepsis during malaria infection (Ataide et al., 2014).
  
  
Entity Pseudomonas
Note Pseudomonas aeruginosa increases expression of human pattern recognition receptors including TLR2 and TLR4, proinflammatory cytokines including IL-1 and IFN-γ, and inflammasome components NLRP3, NLRC4 and ASC compared with control donor corneas. Putative molecules triggering this response are the bacterial pilus protein type IV pilin, as well as several type III secretion apparatus proteins (Franchi et al., 2007b; Arlehamn and Evans, 2011; Karthikeyan et al., 2013).
  
  
Entity Salmonella
Note ASC forms a complex with NLRP3, NLRC4, caspase-1, caspase-8 and pro-IL-1 in S. typhimurium-infected THP-1 macrophages (Broz et al., 2010; Man et al., 2013; Man et al., 2014). The nuclear promyelocytic leukemia (PML) protein limits formation of cytosolic ASC dimers in S. typhimurium-infected bone marrow macrophages with subsequent decreases in IL-1β and IL-18 secretion but no effect on pyroptotic cell death (Dowling et al., 2014). Double-stranded RNA-dependent protein kinase (PKR, EIF2AK2) interacts with ASC and other inflammasome components including NLRP3, NLRP1, NLRC4 and AIM2 to trigger caspase-1-dependent IL-1β production and pryopoptosis in S. typhimurium-infected macrophages (Lu et al., 2012). Salmonella flagellin and type III secretion proteins promotes potassium-efflux independent ASC oligomerization and NLRC4 inflammasome-dependent caspase-1 activation (Franchi et al., 2007a; Hwang et al., 2012).
  
  
Entity Schistosoma mansoni
Note Schistosoma infection activates the Dectin-2 receptor, which triggers NLRP3/ASC-dependent IL-1β secretion as well with subsequent alteration of the adaptive immune reponse, increased granuloma formation and liver disease (Ritter et al., 2010).
  
  
Entity Shigella
Note Shigella type III secretion proteins induce NLRC4/ASC/caspase-1-dependent processing of IL-1β and pyroptosome formation in macrophages (Suzuki et al., 2007; Willingham et al., 2007; Suzuki et al., 2014).
  
  
Entity Streptococcus pneumonia
Note ASC is involved in controlling pneumococcus infection via several putative downstream intermediates including IL-17, GM-CSF and adaptive immune regulatory genes (van Lieshout et al., 2014). ASC regulates systemic inflammatory responses to pneumococcal meningitis infection via caspase-1, IL-1, IL-18 and IFN-γ (Fang et al., 2011; Geldhoff et al., 2013). Bacterial keratitis caused by S. pneumonia pneumolysin triggers increased expression of inflammasome components NLRP3, NLRC4 and ASC compared with control donor corneas (Karthikeyan et al., 2013).
  
  
Entity Streptococcus pyogenes
Note ASC and NLP3 is necessary for caspase-1-dependent IL-1β secretion (but not pro-IL-1β expression) in response to S. Pyogenes infection. Caspase-1 activation activation in response to streptolysin O pore-forming toxin also depdends on NF-κB but not on P2X7R or TLR signaling (Harder et al., 2009).
  
  
Entity Tuberculosis
Note Mycobacterium tuberculosis infection induces NLRP3/ASC-dependent IL-1β secretion and apoptosis in bone marrow derived dendritic cells (Abdalla et al., 2012).
  
  
Entity West Nile virus
Note ASC is critical for clearance of west nile virus infection via secretion of IL-1β, IL-6, IFN-γ, and IFN-α as well as increased levels of IgM, suggesting a role for ASC in coordinating innate as well as adaptive immune reponses to west nile virus infection (Kumar et al., 2013).
  
  
Entity Vaccine adjuvent
Note ASC has an NLRP3/caspase-1-independent role in mediating antigen-specific immunity to oil-in-water adjuvent H5N1 influenza vaccine via B-cell antigen-specific antibody production and dendritic cell inflammatory cytokine release (Ellebedy et al., 2011).
  

Bibliography

Mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11-independent IL-1b and IL-18 secretion but not to pyroptosis.
Abdalla H, Srinivasan L, Shah S, Mayer-Barber KD, Sher A, Sutterwala FS, Briken V.
PLoS One. 2012;7(7):e40722. doi: 10.1371/journal.pone.0040722. Epub 2012 Jul 24.
PMID 22911706
 
Apoptosis-associated speck-like protein (ASC) controls Legionella pneumophila infection in human monocytes.
Abdelaziz DH, Gavrilin MA, Akhter A, Caution K, Kotrange S, Khweek AA, Abdulrahman BA, Grandhi J, Hassan ZA, Marsh C, Wewers MD, Amer AO.
J Biol Chem. 2011 Feb 4;286(5):3203-8. doi: 10.1074/jbc.M110.197681. Epub 2010 Nov 19.
PMID 21097506
 
Inflammasome-dependent caspase-1 activation in cervical epithelial cells stimulates growth of the intracellular pathogen Chlamydia trachomatis.
Abdul-Sater AA, Koo E, Hacker G, Ojcius DM.
J Biol Chem. 2009 Sep 25;284(39):26789-96. doi: 10.1074/jbc.M109.026823. Epub 2009 Jul 31.
PMID 19648107
 
NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder.
Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J.
Immunity. 2004 Mar;20(3):319-25.
PMID 15030775
 
Macrophages control innate inflammation.
Akira S, Misawa T, Satoh T, Saitoh T.
Diabetes Obes Metab. 2013 Sep;15 Suppl 3:10-8. doi: 10.1111/dom.12151. (REVIEW)
PMID 24003916
 
The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer.
Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP.
J Exp Med. 2010 May 10;207(5):1045-56. doi: 10.1084/jem.20100050. Epub 2010 Apr 12.
PMID 20385749
 
Pseudomonas aeruginosa pilin activates the inflammasome.
Arlehamn CS, Evans TJ.
Cell Microbiol. 2011 Mar;13(3):388-401. doi: 10.1111/j.1462-5822.2010.01541.x. Epub 2010 Nov 3.
PMID 20955240
 
Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.
Ataide MA, Andrade WA, Zamboni DS, Wang D, Souza Mdo C, Franklin BS, Elian S, Martins FS, Pereira D, Reed G, Fitzgerald KA, Golenbock DT, Gazzinelli RT.
PLoS Pathog. 2014 Jan;10(1):e1003885. doi: 10.1371/journal.ppat.1003885. Epub 2014 Jan 16.
PMID 24453977
 
Tumor cell death and ATP release prime dendritic cells and efficient anticancer immunity.
Aymeric L, Apetoh L, Ghiringhelli F, Tesniere A, Martins I, Kroemer G, Smyth MJ, Zitvogel L.
Cancer Res. 2010 Feb 1;70(3):855-8. doi: 10.1158/0008-5472.CAN-09-3566. Epub 2010 Jan 19.
PMID 20086177
 
The NLRP3 Inflammasome as a novel player of the intercellular crosstalk in metabolic disorders.
Benetti E, Chiazza F, Patel NS, Collino M.
Mediators Inflamm. 2013;2013:678627. doi: 10.1155/2013/678627. Epub 2013 Jun 13. (REVIEW)
PMID 23843683
 
CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B.
Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES.
J Biol Chem. 2001 Apr 13;276(15):11877-82. Epub 2001 Jan 12.
PMID 11278692
 
CARD games in apoptosis and immunity.
Bouchier-Hayes L, Martin SJ.
EMBO Rep. 2002 Jul;3(7):616-21. (REVIEW)
PMID 12101092
 
Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing.
Broz P, von Moltke J, Jones JW, Vance RE, Monack DM.
Cell Host Microbe. 2010 Dec 16;8(6):471-83. doi: 10.1016/j.chom.2010.11.007.
PMID 21147462
 
Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC) regulates inflammasomes.
Bryan NB, Dorfleutner A, Kramer SJ, Yun C, Rojanasakul Y, Stehlik C.
J Inflamm (Lond). 2010 May 18;7:23. doi: 10.1186/1476-9255-7-23.
PMID 20482797
 
Gain-of-function Pyrin mutations induce NLRP3 protein-independent interleukin-1b activation and severe autoinflammation in mice.
Chae JJ, Cho YH, Lee GS, Cheng J, Liu PP, Feigenbaum L, Katz SI, Kastner DL.
Immunity. 2011 May 27;34(5):755-68. doi: 10.1016/j.immuni.2011.02.020. Epub 2011 May 19.
PMID 21600797
 
Methylation of the ASC gene promoter is associated with aggressive prostate cancer.
Collard RL, Harya NS, Monzon FA, Maier CE, O'Keefe DS.
Prostate. 2006 May 15;66(7):687-95.
PMID 16425203
 
TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers.
Conway KE, McConnell BB, Bowring CE, Donald CD, Warren ST, Vertino PM.
Cancer Res. 2000 Nov 15;60(22):6236-42.
PMID 11103776
 
Methylation mediated silencing of TMS1/ASC gene in prostate cancer.
Das PM, Ramachandran K, Vanwert J, Ferdinand L, Gopisetty G, Reis IM, Singal R.
Mol Cancer. 2006 Jul 18;5:28.
PMID 16848908
 
Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions.
Dombrowski Y, Peric M, Koglin S, Kammerbauer C, Goss C, Anz D, Simanski M, Glaser R, Harder J, Hornung V, Gallo RL, Ruzicka T, Besch R, Schauber J.
Sci Transl Med. 2011 May 11;3(82):82ra38. doi: 10.1126/scitranslmed.3002001.
PMID 21562230
 
Promyelocytic leukemia protein interacts with the apoptosis-associated speck-like protein to limit inflammasome activation.
Dowling JK, Becker CE, Bourke NM, Corr SC, Connolly DJ, Quinn SR, Pandolfi PP, Mansell A, O'Neill LA.
J Biol Chem. 2014 Mar 7;289(10):6429-37. doi: 10.1074/jbc.M113.539692. Epub 2014 Jan 9.
PMID 24407287
 
Tissue-specific opposing functions of the inflammasome adaptor ASC in the regulation of epithelial skin carcinogenesis.
Drexler SK, Bonsignore L, Masin M, Tardivel A, Jackstadt R, Hermeking H, Schneider P, Gross O, Tschopp J, Yazdi AS.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18384-9. doi: 10.1073/pnas.1209171109. Epub 2012 Oct 22.
PMID 23090995
 
Inflammasomes as molecular mediators of inflammation and cancer: potential role in melanoma.
Dunn JH, Ellis LZ, Fujita M.
Cancer Lett. 2012 Jan 1;314(1):24-33. doi: 10.1016/j.canlet.2011.10.001. Epub 2011 Oct 12. (REVIEW)
PMID 22050907
 
Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases.
Dupaul-Chicoine J, Yeretssian G, Doiron K, Bergstrom KS, McIntire CR, LeBlanc PM, Meunier C, Turbide C, Gros P, Beauchemin N, Vallance BA, Saleh M.
Immunity. 2010 Mar 26;32(3):367-78. doi: 10.1016/j.immuni.2010.02.012. Epub 2010 Mar 11.
PMID 20226691
 
NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis.
Elinav E, Strowig T, Kau AL, Henao-Mejia J, Thaiss CA, Booth CJ, Peaper DR, Bertin J, Eisenbarth SC, Gordon JI, Flavell RA.
Cell. 2011 May 27;145(5):745-57. doi: 10.1016/j.cell.2011.04.022. Epub 2011 May 12.
PMID 21565393
 
Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59.
Ellebedy AH, Lupfer C, Ghoneim HE, DeBeauchamp J, Kanneganti TD, Webby RJ.
Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2927-32. doi: 10.1073/pnas.1012455108. Epub 2011 Jan 26.
PMID 21270336
 
Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection.
Fang R, Tsuchiya K, Kawamura I, Shen Y, Hara H, Sakai S, Yamamoto T, Fernandes-Alnemri T, Yang R, Hernandez-Cuellar E, Dewamitta SR, Xu Y, Qu H, Alnemri ES, Mitsuyama M.
J Immunol. 2011 Nov 1;187(9):4890-9. doi: 10.4049/jimmunol.1100381. Epub 2011 Sep 28.
PMID 21957143
 
AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA.
Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES.
Nature. 2009 Mar 26;458(7237):509-13. doi: 10.1038/nature07710. Epub 2009 Jan 21.
PMID 19158676
 
Differential requirement of P2X7 receptor and intracellular K+ for caspase-1 activation induced by intracellular and extracellular bacteria.
Franchi L, Kanneganti TD, Dubyak GR, Nunez G.
J Biol Chem. 2007a Jun 29;282(26):18810-8. Epub 2007 May 9.
PMID 17491021
 
A new twist on the PYRIN Mediterranean coast.
Franchi L, Nunez G.
Immunity. 2011 May 27;34(5):695-7. doi: 10.1016/j.immuni.2011.05.004.
PMID 21616439
 
Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation.
Franchi L, Stoolman J, Kanneganti TD, Verma A, Ramphal R, Nunez G.
Eur J Immunol. 2007b Nov;37(11):3030-9.
PMID 17935074
 
Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis.
Geldhoff M, Mook-Kanamori BB, Brouwer MC, Troost D, Leemans JC, Flavell RA, Van der Ende A, Van der Poll T, Van de Beek D.
BMC Infect Dis. 2013 Jul 31;13:358. doi: 10.1186/1471-2334-13-358.
PMID 23902681
 
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J; MGC Project Team.
Genome Res. 2004 Oct;14(10B):2121-7.
PMID 15489334
 
Mechanisms of disease: inflammasome activation and the development of type 2 diabetes.
Grant RW, Dixit VD.
Front Immunol. 2013 Mar 8;4:50. doi: 10.3389/fimmu.2013.00050. eCollection 2013.
PMID 23483669
 
Pure Hemozoin is inflammatory in vivo and activates the NALP3 inflammasome via release of uric acid.
Griffith JW, Sun T, McIntosh MT, Bucala R.
J Immunol. 2009 Oct 15;183(8):5208-20. doi: 10.4049/jimmunol.0713552. Epub 2009 Sep 25.
PMID 19783673
 
ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma.
Guan X, Sagara J, Yokoyama T, Koganehira Y, Oguchi M, Saida T, Taniguchi S.
Int J Cancer. 2003 Nov 1;107(2):202-8.
PMID 12949795
 
Activation of neuronal P2X7 receptor-pannexin-1 mediates death of enteric neurons during colitis.
Gulbransen BD, Bashashati M, Hirota SA, Gui X, Roberts JA, MacDonald JA, Muruve DA, McKay DM, Beck PL, Mawe GM, Thompson RJ, Sharkey KA.
Nat Med. 2012 Mar 18;18(4):600-4. doi: 10.1038/nm.2679.
PMID 22426419
 
Central and overlapping role of Cathepsin B and inflammasome adaptor ASC in antigen presenting function of human dendritic cells.
Guo X, Dhodapkar KM.
Hum Immunol. 2012 Sep;73(9):871-8. doi: 10.1016/j.humimm.2012.06.008. Epub 2012 Jun 22.
PMID 22732093
 
Activation of the Nlrp3 inflammasome by Streptococcus pyogenes requires streptolysin O and NF-kappa B activation but proceeds independently of TLR signaling and P2X7 receptor.
Harder J, Franchi L, Munoz-Planillo R, Park JH, Reimer T, Nunez G.
J Immunol. 2009 Nov 1;183(9):5823-9. doi: 10.4049/jimmunol.0900444. Epub 2009 Oct 7.
PMID 19812205
 
Mechanism and repertoire of ASC-mediated gene expression.
Hasegawa M, Imamura R, Motani K, Nishiuchi T, Matsumoto N, Kinoshita T, Suda T.
J Immunol. 2009 Jun 15;182(12):7655-62. doi: 10.4049/jimmunol.0800448.
PMID 19494289
 
Inflammation and fibrosis during Chlamydia pneumoniae infection is regulated by IL-1 and the NLRP3/ASC inflammasome.
He X, Mekasha S, Mavrogiorgos N, Fitzgerald KA, Lien E, Ingalls RR.
J Immunol. 2010 May 15;184(10):5743-54. doi: 10.4049/jimmunol.0903937. Epub 2010 Apr 14.
PMID 20393140
 
Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis.
Hett EC, Slater LH, Mark KG, Kawate T, Monks BG, Stutz A, Latz E, Hung DT.
Nat Chem Biol. 2013 Jun;9(6):398-405. doi: 10.1038/nchembio.1236. Epub 2013 Apr 21.
PMID 23603659
 
The CARD domain: a new apoptotic signalling motif.
Hofmann K, Bucher P, Tschopp J.
Trends Biochem Sci. 1997 May;22(5):155-6.
PMID 9175472
 
Restoration of ASC expression sensitizes colorectal cancer cells to genotoxic stress-induced caspase-independent cell death.
Hong S, Hwang I, Lee YS, Park S, Lee WK, Fernandes-Alnemri T, Alnemri ES, Kim YS, Yu JW.
Cancer Lett. 2013 May 1;331(2):183-91. doi: 10.1016/j.canlet.2012.12.020. Epub 2013 Jan 12.
PMID 23321501
 
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC.
Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E, Fitzgerald KA.
Nature. 2009 Mar 26;458(7237):514-8. doi: 10.1038/nature07725. Epub 2009 Jan 21.
PMID 19158675
 
Caspase recruitment domain-containing sensors and adaptors in intestinal innate immunity.
Hruz P, Eckmann L.
Curr Opin Gastroenterol. 2008 Mar;24(2):108-14. doi: 10.1097/MOG.0b013e3282f50fdf. (REVIEW)
PMID 18301258
 
Salmonella Promotes ASC Oligomerization-dependent Caspase-1 Activation.
Hwang I, Park S, Hong S, Kim EH, Yu JW.
Immune Netw. 2012 Dec;12(6):284-90. doi: 10.4110/in.2012.12.6.284. Epub 2012 Dec 31.
PMID 23396959
 
ASC-associated inflammation promotes cecal tumorigenesis in aryl hydrocarbon receptor-deficient mice.
Ikuta T, Kobayashi Y, Kitazawa M, Shiizaki K, Itano N, Noda T, Pettersson S, Poellinger L, Fujii-Kuriyama Y, Taniguchi S, Kawajiri K.
Carcinogenesis. 2013 Jul;34(7):1620-7. doi: 10.1093/carcin/bgt083. Epub 2013 Mar 1.
PMID 23455376
 
Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis.
Ippagunta SK, Brand DD, Luo J, Boyd KL, Calabrese C, Stienstra R, Van de Veerdonk FL, Netea MG, Joosten LA, Lamkanfi M, Kanneganti TD.
J Biol Chem. 2010 Apr 16;285(16):12454-62. doi: 10.1074/jbc.M109.093252. Epub 2010 Feb 22.
PMID 20177071
 
Structure of the absent in melanoma 2 (AIM2) pyrin domain provides insights into the mechanisms of AIM2 autoinhibition and inflammasome assembly.
Jin T, Perry A, Smith P, Jiang J, Xiao TS.
J Biol Chem. 2013 May 10;288(19):13225-35. doi: 10.1074/jbc.M113.468033. Epub 2013 Mar 25.
PMID 23530044
 
Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes.
Jourdan T, Godlewski G, Cinar R, Bertola A, Szanda G, Liu J, Tam J, Han T, Mukhopadhyay B, Skarulis MC, Ju C, Aouadi M, Czech MP, Kunos G.
Nat Med. 2013 Sep;19(9):1132-40. doi: 10.1038/nm.3265. Epub 2013 Aug 18.
PMID 23955712
 
Host response and bacterial virulence factor expression in Pseudomonas aeruginosa and Streptococcus pneumoniae corneal ulcers.
Karthikeyan RS, Priya JL, Leal SM Jr, Toska J, Rietsch A, Prajna V, Pearlman E, Lalitha P.
PLoS One. 2013 Jun 4;8(6):e64867. doi: 10.1371/journal.pone.0064867. Print 2013.
PMID 23750216
 
Nod1, but not the ASC inflammasome, contributes to induction of IL-1b secretion in human trophoblasts after sensing of Chlamydia trachomatis.
Kavathas PB, Boeras CM, Mulla MJ, Abrahams VM.
Mucosal Immunol. 2013 Mar;6(2):235-43. doi: 10.1038/mi.2012.63. Epub 2012 Jul 4.
PMID 22763410
 
Human keratinocytes express AIM2 and respond to dsDNA with IL-1b secretion.
Kopfnagel V, Wittmann M, Werfel T.
Exp Dermatol. 2011 Dec;20(12):1027-9. doi: 10.1111/j.1600-0625.2011.01382.x.
PMID 22092578
 
Inflammasome adaptor protein Apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in west Nile virus encephalitis.
Kumar M, Roe K, Orillo B, Muruve DA, Nerurkar VR, Gale M Jr, Verma S.
J Virol. 2013 Apr;87(7):3655-67. doi: 10.1128/JVI.02667-12. Epub 2013 Jan 9.
PMID 23302887
 
Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes.
Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK.
Diabetes. 2013 Jan;62(1):194-204. doi: 10.2337/db12-0420. Epub 2012 Oct 18.
PMID 23086037
 
Inhibition of UV-induced uric acid production using allopurinol prevents suppression of the contact hypersensitivity response.
Leighton S, Kok LF, Halliday GM, Byrne SN.
Exp Dermatol. 2013 Mar;22(3):189-94. doi: 10.1111/exd.12096. Epub 2013 Feb 6.
PMID 23387472
 
The death-domain fold of the ASC PYRIN domain, presenting a basis for PYRIN/PYRIN recognition.
Liepinsh E, Barbals R, Dahl E, Sharipo A, Staub E, Otting G.
J Mol Biol. 2003 Oct 3;332(5):1155-63.
PMID 14499617
 
Dual role of apoptosis-associated speck-like protein containing a CARD (ASC) in tumorigenesis of human melanoma.
Liu W, Luo Y, Dunn JH, Norris DA, Dinarello CA, Fujita M.
J Invest Dermatol. 2013 Feb;133(2):518-27. doi: 10.1038/jid.2012.317. Epub 2012 Aug 30.
PMID 22931929
 
Selective inhibition of the NLRP3 inflammasome by targeting to promyelocytic leukemia protein in mouse and human.
Lo YH, Huang YW, Wu YH, Tsai CS, Lin YC, Mo ST, Kuo WC, Chuang YT, Jiang ST, Shih HM, Lai MZ.
Blood. 2013 Apr 18;121(16):3185-94. doi: 10.1182/blood-2012-05-432104. Epub 2013 Feb 21.
PMID 23430110
 
Novel role of PKR in inflammasome activation and HMGB1 release.
Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundback P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ.
Nature. 2012 Aug 30;488(7413):670-4. doi: 10.1038/nature11290.
PMID 22801494
 
Hypermethylation of ASC/TMS1 is a sputum marker for late-stage lung cancer.
Machida EO, Brock MV, Hooker CM, Nakayama J, Ishida A, Amano J, Picchi MA, Belinsky SA, Herman JG, Taniguchi S, Baylin SB.
Cancer Res. 2006 Jun 15;66(12):6210-8.
PMID 16778195
 
Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex.
Man SM, Hopkins LJ, Nugent E, Cox S, Gluck IM, Tourlomousis P, Wright JA, Cicuta P, Monie TP, Bryant CE.
Proc Natl Acad Sci U S A. 2014 May 20;111(20):7403-8. doi: 10.1073/pnas.1402911111. Epub 2014 May 6.
PMID 24803432
 
Salmonella infection induces recruitment of Caspase-8 to the inflammasome to modulate IL-1b production.
Man SM, Tourlomousis P, Hopkins L, Monie TP, Fitzgerald KA, Bryant CE.
J Immunol. 2013 Nov 15;191(10):5239-46. doi: 10.4049/jimmunol.1301581. Epub 2013 Oct 11.
PMID 24123685
 
Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf.
Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S, Dixit VM.
Nature. 2004 Jul 8;430(6996):213-8. Epub 2004 Jun 9.
PMID 15190255
 
Gout-associated uric acid crystals activate the NALP3 inflammasome.
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J.
Nature. 2006 Mar 9;440(7081):237-41. Epub 2006 Jan 11.
PMID 16407889
 
ASC is an activating adaptor for NF-kappa B and caspase-8-dependent apoptosis.
Masumoto J, Dowds TA, Schaner P, Chen FF, Ogura Y, Li M, Zhu L, Katsuyama T, Sagara J, Taniguchi S, Gumucio DL, Nunez G, Inohara N.
Biochem Biophys Res Commun. 2003 Mar 28;303(1):69-73.
PMID 12646168
 
A splice variant of ASC regulates IL-1beta release and aggregates differently from intact ASC.
Matsushita K, Takeoka M, Sagara J, Itano N, Kurose Y, Nakamura A, Taniguchi S.
Mediators Inflamm. 2009;2009:287387. doi: 10.1155/2009/287387. Epub 2009 Sep 15.
PMID 19759850
 
Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1.
McConnell BB, Vertino PM.
Cancer Res. 2000 Nov 15;60(22):6243-7.
PMID 11103777
 
The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response.
Muruve DA, Petrilli V, Zaiss AK, White LR, Clark SA, Ross PJ, Parks RJ, Tschopp J.
Nature. 2008 Mar 6;452(7183):103-7. doi: 10.1038/nature06664. Epub 2008 Feb 20.
PMID 18288107
 
Significant role of IL-1 signaling, but limited role of inflammasome activation, in oviduct pathology during Chlamydia muridarum genital infection.
Nagarajan UM, Sikes JD, Yeruva L, Prantner D.
J Immunol. 2012 Mar 15;188(6):2866-75. doi: 10.4049/jimmunol.1103461. Epub 2012 Feb 13.
PMID 22331066
 
Impaired NLRP3 inflammasome expression and function in atopic dermatitis due to Th2 milieu.
Niebuhr M, Baumert K, Heratizadeh A, Satzger I, Werfel T.
Allergy. 2014 Aug;69(8):1058-67. doi: 10.1111/all.12428. Epub 2014 Jun 4.
PMID 24894535
 
Anthrax lethal toxin triggers the formation of a membrane-associated inflammasome complex in murine macrophages.
Nour AM, Yeung YG, Santambrogio L, Boyden ED, Stanley ER, Brojatsch J.
Infect Immun. 2009 Mar;77(3):1262-71. doi: 10.1128/IAI.01032-08. Epub 2009 Jan 5.
PMID 19124602
 
ASC is a Bax adaptor and regulates the p53-Bax mitochondrial apoptosis pathway.
Ohtsuka T, Ryu H, Minamishima YA, Macip S, Sagara J, Nakayama KI, Aaronson SA, Lee SW.
Nat Cell Biol. 2004 Feb;6(2):121-8. Epub 2004 Jan 18.
PMID 14730312
 
Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase-1 processing and secretion of interleukin-1beta.
Okamoto M, Liu W, Luo Y, Tanaka A, Cai X, Norris DA, Dinarello CA, Fujita M.
J Biol Chem. 2010 Feb 26;285(9):6477-88. doi: 10.1074/jbc.M109.064907. Epub 2009 Dec 28.
PMID 20038581
 
Complete sequencing and characterization of 21,243 full-length human cDNAs.
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S.
Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21.
PMID 14702039
 
Silencing of TMS1/ASC promotes resistance to anoikis in breast epithelial cells.
Parsons MJ, Patel P, Brat DJ, Colbert L, Vertino PM.
Cancer Res. 2009 Mar 1;69(5):1706-11. doi: 10.1158/0008-5472.CAN-08-2351. Epub 2009 Feb 17.
PMID 19223547
 
PAAD - a new protein domain associated with apoptosis, cancer and autoimmune diseases.
Pawlowski K, Pio F, Chu Z, Reed JC, Godzik A.
Trends Biochem Sci. 2001 Feb;26(2):85-7.
PMID 11166558
 
The Nlrc4 Inflammasome Contributes to Restriction of Pulmonary Infection by Flagellated Legionella spp. that Trigger Pyroptosis.
Pereira MS, Marques GG, Dellama JE, Zamboni DS.
Front Microbiol. 2011 Feb 15;2:33. doi: 10.3389/fmicb.2011.00033. eCollection 2011.
PMID 21687424
 
AIM2, an IFN-inducible cytosolic DNA sensor, in the development of benign prostate hyperplasia and prostate cancer.
Ponomareva L, Liu H, Duan X, Dickerson E, Shen H, Panchanathan R, Choubey D.
Mol Cancer Res. 2013 Oct;11(10):1193-202. doi: 10.1158/1541-7786.MCR-13-0145. Epub 2013 Jul 17.
PMID 23864729
 
The domains of apoptosis: a genomics perspective.
Reed JC, Doctor KS, Godzik A.
Sci STKE. 2004 Jun 22;2004(239):re9. (REVIEW)
PMID 15226512
 
Methylation-induced silencing of ASC/TMS1, a pro-apoptotic gene, is a late-stage event in colorectal cancer.
Riojas MA, Guo M, Glockner SC, Machida EO, Baylin SB, Ahuja N.
Cancer Biol Ther. 2007 Nov;6(11):1710-6. Epub 2007 Aug 3.
PMID 17986858
 
Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses.
Ritter M, Gross O, Kays S, Ruland J, Nimmerjahn F, Saijo S, Tschopp J, Layland LE, Prazeres da Costa C.
Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20459-64. doi: 10.1073/pnas.1010337107. Epub 2010 Nov 8.
PMID 21059925
 
Caspase-5 expression is upregulated in lesional psoriatic skin.
Salskov-Iversen ML, Johansen C, Kragballe K, Iversen L.
J Invest Dermatol. 2011 Mar;131(3):670-6. doi: 10.1038/jid.2010.370. Epub 2010 Dec 30.
PMID 21191419
 
ASC directs NF-kappaB activation by regulating receptor interacting protein-2 (RIP2) caspase-1 interactions.
Sarkar A, Duncan M, Hart J, Hertlein E, Guttridge DC, Wewers MD.
J Immunol. 2006 Apr 15;176(8):4979-86.
PMID 16585594
 
NLRP3 activation induces ASC-dependent programmed necrotic cell death, which leads to neutrophilic inflammation.
Satoh T, Kambe N, Matsue H.
Cell Death Dis. 2013 May 23;4:e644. doi: 10.1038/cddis.2013.169.
PMID 23703389
 
Caspase-1 dependent IL-1b secretion is critical for host defense in a mouse model of Chlamydia pneumoniae lung infection.
Shimada K, Crother TR, Karlin J, Chen S, Chiba N, Ramanujan VK, Vergnes L, Ojcius DM, Arditi M.
PLoS One. 2011;6(6):e21477. doi: 10.1371/journal.pone.0021477. Epub 2011 Jun 23.
PMID 21731762
 
Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.
Shoham NG, Centola M, Mansfield E, Hull KM, Wood G, Wise CA, Kastner DL.
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13501-6. Epub 2003 Oct 31.
PMID 14595024
 
The PAAD/PYRIN-family protein ASC is a dual regulator of a conserved step in nuclear factor kappaB activation pathways.
Stehlik C, Fiorentino L, Dorfleutner A, Bruey JM, Ariza EM, Sagara J, Reed JC.
J Exp Med. 2002 Dec 16;196(12):1605-15.
PMID 12486103
 
Methylation-mediated silencing of TMS1/ASC is accompanied by histone hypoacetylation and CpG island-localized changes in chromatin architecture.
Stimson KM, Vertino PM.
J Biol Chem. 2002 Feb 15;277(7):4951-8. Epub 2001 Dec 3.
PMID 11733524
 
Aberrant methylation and down-regulation of TMS1/ASC in human glioblastoma.
Stone AR, Bobo W, Brat DJ, Devi NS, Van Meir EG, Vertino PM.
Am J Pathol. 2004 Oct;165(4):1151-61.
PMID 15466382
 
Shigella type III secretion protein MxiI is recognized by Naip2 to induce Nlrc4 inflammasome activation independently of Pkcd.
Suzuki S, Franchi L, He Y, Munoz-Planillo R, Mimuro H, Suzuki T, Sasakawa C, Nunez G.
PLoS Pathog. 2014 Feb 6;10(2):e1003926. doi: 10.1371/journal.ppat.1003926. eCollection 2014.
PMID 24516390
 
Differential regulation of caspase-1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella-infected macrophages.
Suzuki T, Franchi L, Toma C, Ashida H, Ogawa M, Yoshikawa Y, Mimuro H, Inohara N, Sasakawa C, Nuez G.
PLoS Pathog. 2007 Aug 10;3(8):e111.
PMID 17696608
 
The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated protein kinase (MAPK), and chemokine induction independent of the inflammasome.
Taxman DJ, Holley-Guthrie EA, Huang MT, Moore CB, Bergstralh DT, Allen IC, Lei Y, Gris D, Ting JP.
J Biol Chem. 2011 Jun 3;286(22):19605-16. doi: 10.1074/jbc.M111.221077. Epub 2011 Apr 12.
PMID 21487011
 
Cutting edge: ASC mediates the induction of multiple cytokines by Porphyromonas gingivalis via caspase-1-dependent and -independent pathways.
Taxman DJ, Zhang J, Champagne C, Bergstralh DT, Iocca HA, Lich JD, Ting JP.
J Immunol. 2006 Oct 1;177(7):4252-6.
PMID 16982856
 
Activation of the NLRP1b inflammasome independently of ASC-mediated caspase-1 autoproteolysis and speck formation.
Van Opdenbosch N, Gurung P, Vande Walle L, Fossoul A, Kanneganti TD, Lamkanfi M.
Nat Commun. 2014;5:3209. doi: 10.1038/ncomms4209.
PMID 24492532
 
Pyrin Modulates the Intracellular Distribution of PSTPIP1.
Waite AL, Schaner P, Richards N, Balci-Peynircioglu B, Masters SL, Brydges SD, Fox M, Hong A, Yilmaz E, Kastner DL, Reinherz EL, Gumucio DL.
PLoS One. 2009 Jul 7;4(7):e6147. doi: 10.1371/journal.pone.0006147.
PMID 19584923
 
Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity.
Watanabe H, Gaide O, Petrilli V, Martinon F, Contassot E, Roques S, Kummer JA, Tschopp J, French LE.
J Invest Dermatol. 2007 Aug;127(8):1956-63. Epub 2007 Apr 12.
PMID 17429439
 
Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling.
Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP.
Nat Immunol. 2011 May;12(5):408-15. doi: 10.1038/ni.2022. Epub 2011 Apr 10.
PMID 21478880
 
A role for the NLRP3 inflammasome in metabolic diseases--did Warburg miss inflammation?
Wen H, Ting JP, O'Neill LA.
Nat Immunol. 2012 Mar 19;13(4):352-7. doi: 10.1038/ni.2228. (REVIEW)
PMID 22430788
 
Microbial pathogen-induced necrotic cell death mediated by the inflammasome components CIAS1/cryopyrin/NLRP3 and ASC.
Willingham SB, Bergstralh DT, O'Connor W, Morrison AC, Taxman DJ, Duncan JA, Barnoy S, Venkatesan MM, Flavell RA, Deshmukh M, Hoffman HM, Ting JP.
Cell Host Microbe. 2007 Sep 13;2(3):147-59.
PMID 18005730
 
IL-18 production downstream of the Nlrp3 inflammasome confers protection against colorectal tumor formation.
Zaki MH, Vogel P, Body-Malapel M, Lamkanfi M, Kanneganti TD.
J Immunol. 2010 Oct 15;185(8):4912-20. doi: 10.4049/jimmunol.1002046. Epub 2010 Sep 20.
PMID 20855874
 
Enterohemorrhagic Escherichia coli specific enterohemolysin induced IL-1? in human macrophages and EHEC-induced IL-1b required activation of NLRP3 inflammasome.
Zhang X, Cheng Y, Xiong Y, Ye C, Zheng H, Sun H, Zhao H, Ren Z, Xu J.
PLoS One. 2012;7(11):e50288. doi: 10.1371/journal.pone.0050288. Epub 2012 Nov 27.
PMID 23209696
 
A role for mitochondria in NLRP3 inflammasome activation.
Zhou R, Yazdi AS, Menu P, Tschopp J.
Nature. 2011 Jan 13;469(7329):221-5. doi: 10.1038/nature09663. Epub 2010 Dec 1.
PMID 21124315
 
Structure and interdomain dynamics of apoptosis-associated speck-like protein containing a CARD (ASC).
de Alba E.
J Biol Chem. 2009 Nov 20;284(47):32932-41. doi: 10.1074/jbc.M109.024273. Epub 2009 Sep 15.
PMID 19759015
 
NLRP3 and ASC differentially affect the lung transcriptome during pneumococcal pneumonia.
van Lieshout MH, Scicluna BP, Florquin S, van der Poll T.
Am J Respir Cell Mol Biol. 2014 Apr;50(4):699-712. doi: 10.1165/rcmb.2013-0015OC.
PMID 24164497
 

Citation

This paper should be referenced as such :
JH Dunn, M Fujita
PYCARD (PYD, CARD domain containing)
Atlas Genet Cytogenet Oncol Haematol. 2015;19(4):291-301.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PYCARDID712ch16p12.html


External links

Nomenclature
HGNC (Hugo)PYCARD   16608
Cards
AtlasPYCARDID712ch16p12
Entrez_Gene (NCBI)PYCARD  29108  PYD and CARD domain containing
AliasesASC; CARD5; TMS; TMS-1; 
TMS1
GeneCards (Weizmann)PYCARD
Ensembl hg19 (Hinxton)ENSG00000103490 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000103490 [Gene_View]  chr16:31201486-31202776 [Contig_View]  PYCARD [Vega]
ICGC DataPortalENSG00000103490
TCGA cBioPortalPYCARD
AceView (NCBI)PYCARD
Genatlas (Paris)PYCARD
WikiGenes29108
SOURCE (Princeton)PYCARD
Genetics Home Reference (NIH)PYCARD
Genomic and cartography
GoldenPath hg38 (UCSC)PYCARD  -     chr16:31201486-31202776 -  16p11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PYCARD  -     16p11.2   [Description]    (hg19-Feb_2009)
EnsemblPYCARD - 16p11.2 [CytoView hg19]  PYCARD - 16p11.2 [CytoView hg38]
Mapping of homologs : NCBIPYCARD [Mapview hg19]  PYCARD [Mapview hg38]
OMIM606838   
Gene and transcription
Genbank (Entrez)AB023416 AF184073 AF255794 AF310103 AF384665
RefSeq transcript (Entrez)NM_013258 NM_145182 NM_145183
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PYCARD
Cluster EST : UnigeneHs.499094 [ NCBI ]
CGAP (NCI)Hs.499094
Alternative Splicing GalleryENSG00000103490
Gene ExpressionPYCARD [ NCBI-GEO ]   PYCARD [ EBI - ARRAY_EXPRESS ]   PYCARD [ SEEK ]   PYCARD [ MEM ]
Gene Expression Viewer (FireBrowse)PYCARD [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)29108
GTEX Portal (Tissue expression)PYCARD
Human Protein AtlasENSG00000103490-PYCARD [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9ULZ3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9ULZ3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9ULZ3
Splice isoforms : SwissVarQ9ULZ3
PhosPhoSitePlusQ9ULZ3
Domaine pattern : Prosite (Expaxy)CARD (PS50209)    DAPIN (PS50824)   
Domains : Interpro (EBI)CARD    CARD8/ASC/NALP1_CARD    DAPIN    DEATH-like_dom   
Domain families : Pfam (Sanger)CARD (PF00619)    PYRIN (PF02758)   
Domain families : Pfam (NCBI)pfam00619    pfam02758   
Domain families : Smart (EMBL)PYRIN (SM01289)  
Conserved Domain (NCBI)PYCARD
DMDM Disease mutations29108
Blocks (Seattle)PYCARD
PDB (SRS)1UCP    2KN6    3J63    5H8O   
PDB (PDBSum)1UCP    2KN6    3J63    5H8O   
PDB (IMB)1UCP    2KN6    3J63    5H8O   
PDB (RSDB)1UCP    2KN6    3J63    5H8O   
Structural Biology KnowledgeBase1UCP    2KN6    3J63    5H8O   
SCOP (Structural Classification of Proteins)1UCP    2KN6    3J63    5H8O   
CATH (Classification of proteins structures)1UCP    2KN6    3J63    5H8O   
SuperfamilyQ9ULZ3
Human Protein Atlas [tissue]ENSG00000103490-PYCARD [tissue]
Peptide AtlasQ9ULZ3
HPRD06020
IPIIPI00001699   IPI00221360   IPI00221362   
Protein Interaction databases
DIP (DOE-UCLA)Q9ULZ3
IntAct (EBI)Q9ULZ3
FunCoupENSG00000103490
BioGRIDPYCARD
STRING (EMBL)PYCARD
ZODIACPYCARD
Ontologies - Pathways
QuickGOQ9ULZ3
Ontology : AmiGOmyeloid dendritic cell activation  protease binding  activation of innate immune response  myeloid dendritic cell activation involved in immune response  positive regulation of antigen processing and presentation of peptide antigen via MHC class II  positive regulation of adaptive immune response  interleukin-6 receptor binding  protein binding  tropomyosin binding  extracellular region  nucleus  nucleus  nucleolus  cytoplasm  cytoplasm  mitochondrion  endoplasmic reticulum  cytosol  cytosol  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  inflammatory response  signal transduction  IkappaB kinase complex  IkappaB kinase complex  cysteine-type endopeptidase activator activity involved in apoptotic process  regulation of tumor necrosis factor-mediated signaling pathway  myosin I binding  enzyme binding  positive regulation of actin filament polymerization  regulation of protein stability  negative regulation of NF-kappaB transcription factor activity  Pyrin domain binding  negative regulation of interferon-beta production  positive regulation of interferon-gamma production  positive regulation of interleukin-6 production  positive regulation of tumor necrosis factor production  tumor necrosis factor-mediated signaling pathway  secretory granule lumen  azurophil granule lumen  positive regulation of activated T cell proliferation  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  negative regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  neutrophil degranulation  macropinocytosis  innate immune response  positive regulation of JNK cascade  positive regulation of interleukin-1 beta secretion  positive regulation of phagocytosis  defense response to Gram-negative bacterium  positive regulation of T cell activation  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  defense response to virus  positive regulation of ERK1 and ERK2 cascade  BMP receptor binding  cellular response to lipopolysaccharide  cellular response to interleukin-1  cellular response to tumor necrosis factor  negative regulation of protein serine/threonine kinase activity  intrinsic apoptotic signaling pathway by p53 class mediator  NLRP1 inflammasome complex  NLRP3 inflammasome complex  positive regulation of chemokine secretion  positive regulation of release of cytochrome c from mitochondria  cysteine-type endopeptidase activity involved in apoptotic process  AIM2 inflammasome complex  positive regulation of T cell migration  positive regulation of interleukin-8 secretion  positive regulation of interleukin-6 secretion  positive regulation of cysteine-type endopeptidase activity  positive regulation of interleukin-10 secretion  positive regulation of extrinsic apoptotic signaling pathway  regulation of intrinsic apoptotic signaling pathway  
Ontology : EGO-EBImyeloid dendritic cell activation  protease binding  activation of innate immune response  myeloid dendritic cell activation involved in immune response  positive regulation of antigen processing and presentation of peptide antigen via MHC class II  positive regulation of adaptive immune response  interleukin-6 receptor binding  protein binding  tropomyosin binding  extracellular region  nucleus  nucleus  nucleolus  cytoplasm  cytoplasm  mitochondrion  endoplasmic reticulum  cytosol  cytosol  apoptotic process  activation of cysteine-type endopeptidase activity involved in apoptotic process  inflammatory response  signal transduction  IkappaB kinase complex  IkappaB kinase complex  cysteine-type endopeptidase activator activity involved in apoptotic process  regulation of tumor necrosis factor-mediated signaling pathway  myosin I binding  enzyme binding  positive regulation of actin filament polymerization  regulation of protein stability  negative regulation of NF-kappaB transcription factor activity  Pyrin domain binding  negative regulation of interferon-beta production  positive regulation of interferon-gamma production  positive regulation of interleukin-6 production  positive regulation of tumor necrosis factor production  tumor necrosis factor-mediated signaling pathway  secretory granule lumen  azurophil granule lumen  positive regulation of activated T cell proliferation  intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  identical protein binding  protein homodimerization activity  positive regulation of apoptotic process  negative regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of cysteine-type endopeptidase activity involved in apoptotic process  neutrophil degranulation  macropinocytosis  innate immune response  positive regulation of JNK cascade  positive regulation of interleukin-1 beta secretion  positive regulation of phagocytosis  defense response to Gram-negative bacterium  positive regulation of T cell activation  positive regulation of sequence-specific DNA binding transcription factor activity  positive regulation of NF-kappaB transcription factor activity  defense response to virus  positive regulation of ERK1 and ERK2 cascade  BMP receptor binding  cellular response to lipopolysaccharide  cellular response to interleukin-1  cellular response to tumor necrosis factor  negative regulation of protein serine/threonine kinase activity  intrinsic apoptotic signaling pathway by p53 class mediator  NLRP1 inflammasome complex  NLRP3 inflammasome complex  positive regulation of chemokine secretion  positive regulation of release of cytochrome c from mitochondria  cysteine-type endopeptidase activity involved in apoptotic process  AIM2 inflammasome complex  positive regulation of T cell migration  positive regulation of interleukin-8 secretion  positive regulation of interleukin-6 secretion  positive regulation of cysteine-type endopeptidase activity  positive regulation of interleukin-10 secretion  positive regulation of extrinsic apoptotic signaling pathway  regulation of intrinsic apoptotic signaling pathway  
Pathways : KEGGNOD-like receptor signaling pathway    Cytosolic DNA-sensing pathway    Salmonella infection    Pertussis    Legionellosis    Influenza A   
REACTOMEQ9ULZ3 [protein]
REACTOME PathwaysR-HSA-844615 [pathway]   
NDEx NetworkPYCARD
Atlas of Cancer Signalling NetworkPYCARD
Wikipedia pathwaysPYCARD
Orthology - Evolution
OrthoDB29108
GeneTree (enSembl)ENSG00000103490
Phylogenetic Trees/Animal Genes : TreeFamPYCARD
HOVERGENQ9ULZ3
HOGENOMQ9ULZ3
Homologs : HomoloGenePYCARD
Homology/Alignments : Family Browser (UCSC)PYCARD
Gene fusions - Rearrangements
Tumor Fusion PortalPYCARD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPYCARD [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PYCARD
dbVarPYCARD
ClinVarPYCARD
1000_GenomesPYCARD 
Exome Variant ServerPYCARD
ExAC (Exome Aggregation Consortium)ENSG00000103490
GNOMAD BrowserENSG00000103490
Genetic variants : HAPMAP29108
Genomic Variants (DGV)PYCARD [DGVbeta]
DECIPHERPYCARD [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPYCARD 
Mutations
ICGC Data PortalPYCARD 
TCGA Data PortalPYCARD 
Broad Tumor PortalPYCARD
OASIS PortalPYCARD [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPYCARD  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPYCARD
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PYCARD
DgiDB (Drug Gene Interaction Database)PYCARD
DoCM (Curated mutations)PYCARD (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PYCARD (select a term)
intoGenPYCARD
NCG5 (London)PYCARD
Cancer3DPYCARD(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606838   
Orphanet
DisGeNETPYCARD
MedgenPYCARD
Genetic Testing Registry PYCARD
NextProtQ9ULZ3 [Medical]
TSGene29108
GENETestsPYCARD
Target ValidationPYCARD
Huge Navigator PYCARD [HugePedia]
snp3D : Map Gene to Disease29108
BioCentury BCIQPYCARD
ClinGenPYCARD
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD29108
Chemical/Pharm GKB GenePA134950175
Clinical trialPYCARD
Miscellaneous
canSAR (ICR)PYCARD (select the gene name)
Probes
Litterature
PubMed122 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePYCARD
EVEXPYCARD
GoPubMedPYCARD
iHOPPYCARD
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Nov 21 15:00:48 CET 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.