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Aliases for PYCARD Gene

Aliases for PYCARD Gene

  • PYD And CARD Domain Containing 2 3
  • TMS1 3 4 6
  • ASC 3 4 6
  • Caspase Recruitment Domain-Containing Protein 5 3 4
  • Target Of Methylation-Induced Silencing 1 3 4
  • CARD5 3 4
  • Apoptosis-Associated Speck-Like Protein Containing A CARD 3
  • PYD And CARD Domain-Containing Protein 4
  • TMS-1 3
  • HASC 4
  • TMS 3

External Ids for PYCARD Gene

Previous GeneCards Identifiers for PYCARD Gene

  • GC16M031249
  • GC16M031120
  • GC16M028774

Summaries for PYCARD Gene

Entrez Gene Summary for PYCARD Gene

  • 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]

GeneCards Summary for PYCARD Gene

PYCARD (PYD And CARD Domain Containing) is a Protein Coding gene. Diseases associated with PYCARD include cryopyrin-associated periodic syndrome and cinca syndrome. Among its related pathways are Salmonella infection (KEGG) and Direct p53 effectors. GO annotations related to this gene include protein homodimerization activity and cysteine-type endopeptidase activator activity involved in apoptotic process. An important paralog of this gene is PYDC1.

UniProtKB/Swiss-Prot for PYCARD Gene

  • 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 DAPIN 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.

Gene Wiki entry for PYCARD Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PYCARD Gene

Genomics for PYCARD Gene

Regulatory Elements for PYCARD Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for PYCARD Gene

Start:
31,201,485 bp from pter
End:
31,203,450 bp from pter
Size:
1,966 bases
Orientation:
Minus strand

Genomic View for PYCARD Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for PYCARD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PYCARD Gene

Proteins for PYCARD Gene

  • Protein details for PYCARD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9ULZ3-ASC_HUMAN
    Recommended name:
    Apoptosis-associated speck-like protein containing a CARD
    Protein Accession:
    Q9ULZ3
    Secondary Accessions:
    • Q96D12
    • Q9BSZ5
    • Q9HBD0
    • Q9NXJ8

    Protein attributes for PYCARD Gene

    Size:
    195 amino acids
    Molecular mass:
    21627 Da
    Quaternary structure:
    • Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta seceretion. Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height. Next to isorm 1 also isoform 2 and isoform 3 may be involved in oligomerization leading to functional regulation. Component of several inflammasomes containing one pattern recognition receptor/sensor, such as NLRP1, NLRP2, NLRP3, AIM2, MEFV or NOD2, and probably NLRC4, NLRP12 or IFI16. Major component of the ASC pyroptosome, a 1-2 um supramolecular assembly (one per macrophage cell) which consists of oligomerized PYCARD dimers and CASP1. Interacts with CASP1 (precursor form); the interaction induces activation of CASP1 leading to the processing of interleukin-1 beta; PYCARD competes with RIPK2 for binding to CASP1. Interacts with NLRP3; the interaction requires the homooligomerization of NLRP3. Interacts with NLRP2, NLRC4, MEFV, CARD16, AIM2, IFI16, NOD2, DDX58, RIPK2, PYDC1, PYDC2, NLRP10, CASP8, CHUK, IKBKB and BAX.
    Miscellaneous:
    • In breast tumorigenesis, methylation-mediated silencing may affect genes and proteins that act as positive mediators of cell death
    SequenceCaution:
    • Sequence=BAA91012.1; Type=Frameshift; Positions=4; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PYCARD Gene

    Alternative splice isoforms for PYCARD Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PYCARD Gene

Proteomics data for PYCARD Gene at MOPED

Post-translational modifications for PYCARD Gene

Other Protein References for PYCARD Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for PYCARD (PYCARD)

No data available for DME Specific Peptides for PYCARD Gene

Domains for PYCARD Gene

Protein Domains for PYCARD Gene

Suggested Antigen Peptide Sequences for PYCARD Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9ULZ3

UniProtKB/Swiss-Prot:

ASC_HUMAN :
  • Q9ULZ3
Domain:
  • The DAPIN domain mediates homotypic interactions with DAPIN domains of proteins such as of NLRP3, PYDC1 and AIM2 (PubMed:11786556, PubMed:12656673, PubMed:19158676 and PubMed:19158675).
  • The CARD domain mediates interaction with CASP1 and NLRC4 (PubMed:14634131 and PubMed:11967258).
  • Contains 1 CARD domain.
  • Contains 1 DAPIN domain.
genes like me logo Genes that share domains with PYCARD: view

No data available for Gene Families for PYCARD Gene

Function for PYCARD Gene

Molecular function for PYCARD Gene

UniProtKB/Swiss-Prot Function: 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 DAPIN 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.

Gene Ontology (GO) - Molecular Function for PYCARD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 24407287
GO:0005138 interleukin-6 receptor binding IPI 24407287
GO:0005515 protein binding IPI 11786556
GO:0005523 tropomyosin binding IPI 24407287
GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process NAS 12019269
genes like me logo Genes that share ontologies with PYCARD: view
genes like me logo Genes that share phenotypes with PYCARD: view

Animal Models for PYCARD Gene

MGI Knock Outs for PYCARD:

Animal Model Products

CRISPR Products

miRNA for PYCARD Gene

miRTarBase miRNAs that target PYCARD

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PYCARD

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for PYCARD Gene

Localization for PYCARD Gene

Subcellular locations from UniProtKB/Swiss-Prot for PYCARD Gene

Cytoplasm. Endoplasmic reticulum. Mitochondrion. Nucleus. Note=Upstream of caspase activation, a redistribution from the cytoplasm to the aggregates occurs. These appear as hollow, perinuclear spherical, ball-like structures. Upon NLRP3 inflammasome activation redistributes to the perinuclear space localizing to endoplasmic reticulum and mitochondria. Localized primarily to the nucleus in resting monocytes/macrophages and rapidly redistributed to the cytoplasm upon pathogen infection. Localized to large cytoplasmic aggregate appearing as a speck containing AIM2, PYCARD, CASP8 and bacterial DNA after infection with Francisella tularensis (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for PYCARD Gene COMPARTMENTS Subcellular localization image for PYCARD gene
Compartment Confidence
endoplasmic reticulum 5
mitochondrion 5
nucleus 5
cytosol 4
extracellular 2

Gene Ontology (GO) - Cellular Components for PYCARD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005634 nucleus ISS --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm NAS 12019269
GO:0005739 mitochondrion IDA 14730312
genes like me logo Genes that share ontologies with PYCARD: view

Pathways for PYCARD Gene

genes like me logo Genes that share pathways with PYCARD: view

Pathways by source for PYCARD Gene

PCR Array Products

Gene Ontology (GO) - Biological Process for PYCARD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001773 myeloid dendritic cell activation IMP 22732093
GO:0002218 activation of innate immune response IDA 21575908
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS --
GO:0002230 positive regulation of defense response to virus by host IEA --
GO:0002277 myeloid dendritic cell activation involved in immune response ISS --
genes like me logo Genes that share ontologies with PYCARD: view

Compounds for PYCARD Gene

(1) Novoseek inferred chemical compound relationships for PYCARD Gene

Compound -log(P) Hits PubMed IDs
5-aza-2deoxycytidine 64 5
genes like me logo Genes that share compounds with PYCARD: view

Transcripts for PYCARD Gene

Unigene Clusters for PYCARD Gene

PYD and CARD domain containing:
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for PYCARD

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for PYCARD Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b
SP1: -
SP2: - -
SP3:
SP4:

Relevant External Links for PYCARD Gene

GeneLoc Exon Structure for
PYCARD
ECgene alternative splicing isoforms for
PYCARD

Expression for PYCARD Gene

mRNA expression in normal human tissues for PYCARD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PYCARD Gene

This gene is overexpressed in Whole Blood (18.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for PYCARD Gene

SOURCE GeneReport for Unigene cluster for PYCARD Gene Hs.499094

mRNA Expression by UniProt/SwissProt for PYCARD Gene

Q9ULZ3-ASC_HUMAN
Tissue specificity: Widely expressed at low levels. Detected in peripheral blood leukocytes, lung, small intestine, spleen, thymus, colon and at lower levels in placenta, liver and kidney. Very low expression in skeletal muscle, heart and brain. Detected in the leukemia cell lines HL-60 and U-937, but not in Jurkat T-cell lymphoma and Daudi Burkitts lymphoma. Detected in the melanoma cell line WM35, but not in WM793. Not detected in HeLa cervical carcinoma cells and MOLT-4 lymphocytic leukemia cells
genes like me logo Genes that share expressions with PYCARD: view

In Situ Assay Products

Orthologs for PYCARD Gene

This gene was present in the common ancestor of chordates.

Orthologs for PYCARD Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PYCARD 35
  • 99.32 (n)
  • 98.97 (a)
PYCARD 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PYCARD 35
  • 81.54 (n)
  • 75.38 (a)
PYCARD 36
  • 75 (a)
OneToOne
dog
(Canis familiaris)
Mammalia PYCARD 35
  • 77.84 (n)
  • 77.32 (a)
PYCARD 36
  • 69 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Pycard 35
  • 74.27 (n)
  • 72.54 (a)
Pycard 16
Pycard 36
  • 72 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 51 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 57 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Pycard 35
  • 74.09 (n)
  • 70.47 (a)
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 44 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100491802 35
  • 58.62 (n)
  • 50 (a)
zebrafish
(Danio rerio)
Actinopterygii pycard 36
  • 30 (a)
OneToMany
Species with no ortholog for PYCARD:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PYCARD Gene

ENSEMBL:
Gene Tree for PYCARD (if available)
TreeFam:
Gene Tree for PYCARD (if available)

Paralogs for PYCARD Gene

Paralogs for PYCARD Gene

Selected SIMAP similar genes for PYCARD Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with PYCARD: view

Variants for PYCARD Gene

Sequence variations from dbSNP and Humsavar for PYCARD Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs13339393 -- 31,204,662(+) tttta(A/C)aattt upstream-variant-2KB
rs34483141 -- 31,204,195(-) GTCTC(-/A)AAACT upstream-variant-2KB
rs111901353 -- 31,204,320(+) CTGAA(A/C)CCGTG upstream-variant-2KB
rs112701104 -- 31,204,665(+) TAAAA(-/T)TTTTA upstream-variant-2KB
rs144514436 -- 31,204,471(+) GCCTT(G/T)TTGTT upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for PYCARD Gene

Variant ID Type Subtype PubMed ID
nsv905729 CNV Loss 21882294
dgv2670n71 CNV Loss 21882294
dgv2672n71 CNV Loss 21882294

Relevant External Links for PYCARD Gene

HapMap Linkage Disequilibrium report
PYCARD
Human Gene Mutation Database (HGMD)
PYCARD

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PYCARD Gene

Disorders for PYCARD Gene

(10) Novoseek inferred disease relationships for PYCARD Gene

Disease -log(P) Hits PubMed IDs
cancer 39.3 10
breast cancer 35.1 16
tumors 32.9 12
inflammation 18.9 4
ovarian cancer 12.9 5

Relevant External Links for PYCARD

Genetic Association Database (GAD)
PYCARD
Human Genome Epidemiology (HuGE) Navigator
PYCARD
genes like me logo Genes that share disorders with PYCARD: view

No data available for UniProtKB/Swiss-Prot for PYCARD Gene

Publications for PYCARD Gene

  1. ASC, a novel 22-kDa protein, aggregates during apoptosis of human promyelocytic leukemia HL-60 cells. (PMID: 10567338) Masumoto J. … Sagara J. (J. Biol. Chem. 1999) 3 4 23
  2. TMS1, a novel proapoptotic caspase recruitment domain protein, is a target of methylation-induced gene silencing in human breast cancers. (PMID: 11103776) Conway K.E. … Vertino P.M. (Cancer Res. 2000) 3 4 23
  3. Activation of a caspase-9-mediated apoptotic pathway by subcellular redistribution of the novel caspase recruitment domain protein TMS1. (PMID: 11103777) McConnell B.B. … Vertino P.M. (Cancer Res. 2000) 3 4 23
  4. Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. (PMID: 11498534) Richards N. … Gumucio D.L. (J. Biol. Chem. 2001) 3 4 23
  5. The PAAD/PYRIN-only protein POP1/ASC2 is a modulator of ASC-mediated nuclear-factor-kappa B and pro-caspase-1 regulation. (PMID: 12656673) Stehlik C. … Reed J.C. (Biochem. J. 2003) 3 4 23

Products for PYCARD Gene

Sources for PYCARD Gene

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