GENERAL INFORMATIONi
Gene namei PYCARD
Synonyms ASC, CARD5, TMS-1
Gene descriptioni PYD and CARD domain containing
Predicted locationi Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi
Chromosome 16
Cytoband p11.2
Chromosome location (bp) 31201486 - 31203450
Number of transcriptsi 3
Ensembl ENSG00000103490 (version 109)
Entrez gene 29108
HGNC HGNC:16608
UniProt Q9ULZ3 (UniProt - Evidence at protein level)
neXtProt NX_Q9ULZ3
GeneCards PYCARD
Antibodypedia PYCARD antibodies


PROTEIN FUNCTION
Protein function (UniProt)i Functions as a key mediator in apoptosis and inflammation 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner 16, 17. 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 18, 19. Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes (NLRP1, NLRP2, NLRP3, NLRP6, AIM2 and probably IFI16) which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35. Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death 36. The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions 37, 38, 39. Clustered PYCARD nucleates the formation of caspase-1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization 40. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1 41. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation 42. May be involved in RIGI-triggered pro-inflammatory responses and inflammasome activation 43. 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 44, 45. 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 46. 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 47, 48. For regulation of NF-kappa-B activating and inhibiting functions have been reported 49. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK 50, 51. 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 52. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA 53. show less
Biological process (UniProt)i Apoptosis, Immunity, Inflammatory response, Innate immunity
Gene summary (Entrez)i 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] show less
PROTEIN INFORMATIONi
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)		 Transmembrane regions
(predicted)
PYCARD-201
ENSP00000247470
ENST00000247470
Q9ULZ3
[Direct mapping] Apoptosis-associated speck-like protein containing a CARD
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000139 [Golgi membrane]
GO:0001773 [myeloid dendritic cell activation]
GO:0002020 [protease binding]
GO:0002218 [activation of innate immune response]
GO:0002221 [pattern recognition receptor signaling pathway]
GO:0002230 [positive regulation of defense response to virus by host]
GO:0002277 [myeloid dendritic cell activation involved in immune response]
GO:0002376 [immune system process]
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:0004197 [cysteine-type endopeptidase activity]
GO:0005138 [interleukin-6 receptor binding]
GO:0005515 [protein binding]
GO:0005523 [tropomyosin binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005739 [mitochondrion]
GO:0005783 [endoplasmic reticulum]
GO:0005794 [Golgi apparatus]
GO:0005829 [cytosol]
GO:0005874 [microtubule]
GO:0006508 [proteolysis]
GO:0006915 [apoptotic process]
GO:0006919 [activation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0006954 [inflammatory response]
GO:0007165 [signal transduction]
GO:0007231 [osmosensory signaling pathway]
GO:0008385 [IkappaB kinase complex]
GO:0008656 [cysteine-type endopeptidase activator activity involved in apoptotic process]
GO:0009617 [response to bacterium]
GO:0010506 [regulation of autophagy]
GO:0010803 [regulation of tumor necrosis factor-mediated signaling pathway]
GO:0016020 [membrane]
GO:0017024 [myosin I binding]
GO:0019899 [enzyme binding]
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:0032090 [Pyrin domain binding]
GO:0032688 [negative regulation of interferon-beta production]
GO:0032722 [positive regulation of chemokine production]
GO:0032729 [positive regulation of interferon-gamma production]
GO:0032731 [positive regulation of interleukin-1 beta production]
GO:0032733 [positive regulation of interleukin-10 production]
GO:0032755 [positive regulation of interleukin-6 production]
GO:0032757 [positive regulation of interleukin-8 production]
GO:0032760 [positive regulation of tumor necrosis factor production]
GO:0032991 [protein-containing complex]
GO:0033209 [tumor necrosis factor-mediated signaling pathway]
GO:0034774 [secretory granule lumen]
GO:0035578 [azurophil granule lumen]
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:0042802 [identical protein binding]
GO:0042803 [protein homodimerization activity]
GO:0042981 [regulation of apoptotic process]
GO:0043025 [neuronal cell body]
GO:0043065 [positive regulation of apoptotic process]
GO:0043087 [regulation of GTPase activity]
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:0043281 [regulation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0044325 [transmembrane transporter binding]
GO:0044351 [macropinocytosis]
GO:0044546 [NLRP3 inflammasome complex assembly]
GO:0045087 [innate immune response]
GO:0046330 [positive regulation of JNK cascade]
GO:0046456 [icosanoid biosynthetic process]
GO:0046983 [protein dimerization activity]
GO:0048583 [regulation of response to stimulus]
GO:0050727 [regulation of inflammatory response]
GO:0050729 [positive regulation of inflammatory response]
GO:0050766 [positive regulation of phagocytosis]
GO:0050829 [defense response to Gram-negative bacterium]
GO:0050830 [defense response to Gram-positive bacterium]
GO:0050870 [positive regulation of T cell activation]
GO:0051091 [positive regulation of DNA-binding transcription factor activity]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051260 [protein homooligomerization]
GO:0051607 [defense response to virus]
GO:0060907 [positive regulation of macrophage cytokine production]
GO:0061702 [inflammasome complex]
GO:0070269 [pyroptosis]
GO:0070374 [positive regulation of ERK1 and ERK2 cascade]
GO:0070700 [BMP receptor binding]
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:0072558 [NLRP1 inflammasome complex]
GO:0072559 [NLRP3 inflammasome complex]
GO:0090200 [positive regulation of release of cytochrome c from mitochondria]
GO:0097153 [cysteine-type endopeptidase activity involved in apoptotic process]
GO:0097169 [AIM2 inflammasome complex]
GO:0097202 [activation of cysteine-type endopeptidase activity]
GO:0098542 [defense response to other organism]
GO:0140738 [NLRP6 inflammasome complex]
GO:1900016 [negative regulation of cytokine production involved in inflammatory response]
GO:2000406 [positive regulation of T cell migration]
GO:2001056 [positive regulation of cysteine-type endopeptidase activity]
GO:2001238 [positive regulation of extrinsic apoptotic signaling pathway]
GO:2001242 [regulation of intrinsic apoptotic signaling pathway]
Show all
 195 aa
21.6 kDa 		No 0
PYCARD-202
ENSP00000340441
ENST00000350605
Q9ULZ3
[Direct mapping] Apoptosis-associated speck-like protein containing a CARD
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0000139 [Golgi membrane]
GO:0001773 [myeloid dendritic cell activation]
GO:0002020 [protease binding]
GO:0002218 [activation of innate immune response]
GO:0002221 [pattern recognition receptor signaling pathway]
GO:0002277 [myeloid dendritic cell activation involved in immune response]
GO:0002376 [immune system process]
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:0004197 [cysteine-type endopeptidase activity]
GO:0005138 [interleukin-6 receptor binding]
GO:0005515 [protein binding]
GO:0005523 [tropomyosin binding]
GO:0005576 [extracellular region]
GO:0005634 [nucleus]
GO:0005654 [nucleoplasm]
GO:0005730 [nucleolus]
GO:0005737 [cytoplasm]
GO:0005739 [mitochondrion]
GO:0005783 [endoplasmic reticulum]
GO:0005794 [Golgi apparatus]
GO:0005829 [cytosol]
GO:0005874 [microtubule]
GO:0006508 [proteolysis]
GO:0006915 [apoptotic process]
GO:0006919 [activation of cysteine-type endopeptidase activity involved in apoptotic process]
GO:0006954 [inflammatory response]
GO:0007165 [signal transduction]
GO:0007231 [osmosensory signaling pathway]
GO:0008385 [IkappaB kinase complex]
GO:0008656 [cysteine-type endopeptidase activator activity involved in apoptotic process]
GO:0010803 [regulation of tumor necrosis factor-mediated signaling pathway]
GO:0016020 [membrane]
GO:0017024 [myosin I binding]
GO:0019899 [enzyme binding]
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:0032090 [Pyrin domain binding]
GO:0032688 [negative regulation of interferon-beta production]
GO:0032722 [positive regulation of chemokine production]
GO:0032729 [positive regulation of interferon-gamma production]
GO:0032731 [positive regulation of interleukin-1 beta production]
GO:0032733 [positive regulation of interleukin-10 production]
GO:0032755 [positive regulation of interleukin-6 production]
GO:0032757 [positive regulation of interleukin-8 production]
GO:0032760 [positive regulation of tumor necrosis factor production]
GO:0032991 [protein-containing complex]
GO:0033209 [tumor necrosis factor-mediated signaling pathway]
GO:0034774 [secretory granule lumen]
GO:0035578 [azurophil granule lumen]
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:0042802 [identical protein binding]
GO:0042803 [protein homodimerization activity]
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:0044546 [NLRP3 inflammasome complex assembly]
GO:0045087 [innate immune response]
GO:0046330 [positive regulation of JNK cascade]
GO:0046456 [icosanoid biosynthetic process]
GO:0046983 [protein dimerization activity]
GO:0048583 [regulation of response to stimulus]
GO:0050729 [positive regulation of inflammatory response]
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 DNA-binding transcription factor activity]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051260 [protein homooligomerization]
GO:0051607 [defense response to virus]
GO:0061702 [inflammasome complex]
GO:0070269 [pyroptosis]
GO:0070374 [positive regulation of ERK1 and ERK2 cascade]
GO:0070700 [BMP receptor binding]
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:0072558 [NLRP1 inflammasome complex]
GO:0072559 [NLRP3 inflammasome complex]
GO:0090200 [positive regulation of release of cytochrome c from mitochondria]
GO:0097153 [cysteine-type endopeptidase activity involved in apoptotic process]
GO:0097169 [AIM2 inflammasome complex]
GO:0098542 [defense response to other organism]
GO:0140738 [NLRP6 inflammasome complex]
GO:1900016 [negative regulation of cytokine production involved in inflammatory response]
GO:2000406 [positive regulation of T cell migration]
GO:2001056 [positive regulation of cysteine-type endopeptidase activity]
GO:2001238 [positive regulation of extrinsic apoptotic signaling pathway]
GO:2001242 [regulation of intrinsic apoptotic signaling pathway]
Show all
 176 aa
20 kDa 		No 0
PYCARD-203
ENSP00000455141
ENST00000561508
H3BP42
[Direct mapping] Apoptosis-associated speck-like protein-containing a CARD
Show all
Predicted intracellular proteins
   Intracellular proteins predicted by MDM and MDSEC
Protein evidence (Ezkurdia et al 2014)
Show all
GO:0002376 [immune system process]
GO:0004197 [cysteine-type endopeptidase activity]
GO:0005737 [cytoplasm]
GO:0005829 [cytosol]
GO:0006508 [proteolysis]
GO:0007165 [signal transduction]
GO:0032731 [positive regulation of interleukin-1 beta production]
GO:0032991 [protein-containing complex]
GO:0048583 [regulation of response to stimulus]
GO:0098542 [defense response to other organism]
Show all
 125 aa
13.5 kDa 		No 0

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