Homo sapiens Gene: PYCARD
Summary
InnateDB Gene IDBG-28012.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol PYCARD
Gene Name PYD and CARD domain containing
Synonyms
Species Homo sapiens
Ensembl Gene ENSG00000103490
Encoded Proteins
PYD and CARD domain containing
PYD and CARD domain containing
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
PYCARD protein contains CARD and Pyrin domains and is required for assembly of inflammasome.
PYCARD prevents oligomerization of CASP1 mediated by RIPK2 by out-competing RIPK2 for binding, and thus, preventing CASP1 autoactivation. PYCARD also recruits CASP1 into PYCARD-formed cytosolic specks, separating it from RIPK2.
PYCARD directs CASP1 away from RIPK2-mediated NF-kappaB activation, toward CASP1-mediated processing of pro-IL1B by interfering with CASP1-RIPK2 interaction.
PYCARD binds to AIM2 to form a CASP1 and NF-kappaB activating inflammasome.
PYCARD (ASC) splice variant protein (vASC) lacking the PGR domain regulates IL1B release and aggregates differently from intact PYCARD.
PYCARD is a component of the inflammasome and is required for inflammation in acute pancreatitis. (Demonstrated in murine model)
NLRP3/PYCARD inflammasome activation following human respiratory syncytial virus infection is dependent on the activation of TLR2/MYD88/NF-kB and reactive oxygen species/potassium efflux.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Pycard is a component of the inflammasome and is required for inflammation in acute pancreatitis.
[Mus musculus] Nlrp3/Pycard inflammasome activation following human respiratory syncytial virus infection is dependent on the activation of Tlr2/Myd88/NF-kB and reactive oxygen species/potassium efflux. (Demonstrated in human)
[Mus musculus] PYCARD is an essential regulator of inflammatory responses in West Nile virus encephalitis.
[Mus musculus] Phosphorylation of the inflammasome adaptor Pycard (ASC) controls inflammasome activity through the formation of ASC specks. The NLRP3 and AIM2 inflammasomes require Syk and Mapk8 (JNK) for their full activity .
[Mus musculus] Activation of the Nlrp3 inflammasome is detrimental during leishmaniasis. Mice lacking the inflammasome components Nlrp3, Pycard, Casp1 exhibit defective Il1b and Il18 production at the infection site and are resistant to cutaneous Leishmania major infection.
[Mus musculus] Mice lacking Pycard display attenuated pulmonary hypertension and right ventricle remodelling in response to hypoxia and this is accompanied by blunted inflammasome activation.
Entrez Gene
Summary This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 16:31201485-31203450
Strand Reverse strand
Band p11.2
Transcripts
ENST00000247470 ENSP00000247470
ENST00000350605 ENSP00000340441
ENST00000561508 ENSP00000455141
ENST00000565022
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 48 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
Experimentally validated
Total 48 [view]
Protein-Protein 45 [view]
Protein-DNA 3 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 5 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process
GO:0032090 Pyrin domain binding
GO:0042803 protein homodimerization activity
Biological Process
GO:0001773 myeloid dendritic cell activation
GO:0002218 activation of innate immune response
GO:0002277 myeloid dendritic cell activation involved in immune response
GO:0002588 positive regulation of antigen processing and presentation of peptide antigen via MHC class II
GO:0002821 positive regulation of adaptive immune response
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007165 signal transduction
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0030838 positive regulation of actin filament polymerization
GO:0031647 regulation of protein stability
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032688 negative regulation of interferon-beta production
GO:0032729 positive regulation of interferon-gamma production
GO:0032755 positive regulation of interleukin-6 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0042104 positive regulation of activated T cell proliferation
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0042981 regulation of apoptotic process
GO:0043065 positive regulation of apoptotic process
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0044351 macropinocytosis
GO:0045087 innate immune response (InnateDB)
GO:0046330 positive regulation of JNK cascade
GO:0050718 positive regulation of interleukin-1 beta secretion
GO:0050766 positive regulation of phagocytosis
GO:0050829 defense response to Gram-negative bacterium
GO:0050870 positive regulation of T cell activation
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051607 defense response to virus
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0071222 cellular response to lipopolysaccharide
GO:0071347 cellular response to interleukin-1
GO:0071356 cellular response to tumor necrosis factor
GO:0071901 negative regulation of protein serine/threonine kinase activity
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
GO:0090197 positive regulation of chemokine secretion
GO:0090200 positive regulation of release of cytochrome c from mitochondria
GO:2000406 positive regulation of T cell migration
GO:2000484 positive regulation of interleukin-8 secretion
GO:2000778 positive regulation of interleukin-6 secretion
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001181 positive regulation of interleukin-10 secretion
GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005783 endoplasmic reticulum
GO:0005829 cytosol
GO:0008385 IkappaB kinase complex
GO:0072558 NLRP1 inflammasome complex
GO:0072559 NLRP3 inflammasome complex
GO:0097169 AIM2 inflammasome complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Not yet available
Pathways
NETPATH
REACTOME
The AIM2 inflammasome pathway
The NLRP3 inflammasome pathway
Inflammasomes pathway
Innate Immune System pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
Immune System pathway
KEGG
NOD-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
INOH
PID NCI
Direct p53 effectors
Cross-References
SwissProt Q9ULZ3
TrEMBL
UniProt Splice Variant
Entrez Gene 29108
UniGene
RefSeq NM_145182 NM_013258
HUGO HGNC:16608
OMIM 606838
CCDS CCDS10709 CCDS10708
HPRD 06020
IMGT
EMBL AB023416 AF184072 AF184073 AF255794 AF310103 AF384665 AK000211 BC004470 BC013569
GenPept AAF99665 AAG01187 AAG01188 AAG30286 AAH04470 AAH13569 AAK63850 BAA87339 BAA91012
RNA Seq Atlas 29108