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Protein

Apoptosis-associated speck-like protein containing a CARD

Gene

Pycard

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 pyrin 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. 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. Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590).5 Publications

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity Source: CACAO
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • activation of innate immune response Source: UniProtKB
  • apoptotic process Source: MGI
  • cellular response to interleukin-1 Source: MGI
  • cellular response to lipopolysaccharide Source: MGI
  • cellular response to tumor necrosis factor Source: MGI
  • defense response to Gram-negative bacterium Source: MGI
  • defense response to virus Source: MGI
  • inflammatory response Source: MGI
  • innate immune response Source: UniProtKB-KW
  • interleukin-1 beta production Source: MGI
  • intrinsic apoptotic signaling pathway by p53 class mediator Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
  • macropinocytosis Source: UniProtKB
  • myeloid dendritic cell activation Source: MGI
  • myeloid dendritic cell activation involved in immune response Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • negative regulation of interferon-beta production Source: MGI
  • negative regulation of NF-kappaB transcription factor activity Source: MGI
  • negative regulation of protein serine/threonine kinase activity Source: MGI
  • positive regulation of actin filament polymerization Source: UniProtKB
  • positive regulation of activated T cell proliferation Source: UniProtKB
  • positive regulation of adaptive immune response Source: MGI
  • positive regulation of antigen processing and presentation of peptide antigen via MHC class II Source: UniProtKB
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of chemokine secretion Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: HGNC
  • positive regulation of defense response to virus by host Source: UniProtKB
  • positive regulation of DNA binding transcription factor activity Source: MGI
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of extrinsic apoptotic signaling pathway Source: MGI
  • positive regulation of interferon-gamma production Source: UniProtKB
  • positive regulation of interleukin-10 secretion Source: MGI
  • positive regulation of interleukin-1 beta secretion Source: UniProtKB
  • positive regulation of interleukin-6 production Source: UniProtKB
  • positive regulation of interleukin-6 secretion Source: MGI
  • positive regulation of interleukin-8 secretion Source: MGI
  • positive regulation of JNK cascade Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of phagocytosis Source: UniProtKB
  • positive regulation of release of cytochrome c from mitochondria Source: MGI
  • positive regulation of T cell activation Source: MGI
  • positive regulation of T cell migration Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: MGI
  • regulation of apoptotic process Source: MGI
  • regulation of autophagy Source: MGI
  • regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • regulation of GTPase activity Source: UniProtKB
  • regulation of inflammatory response Source: MGI
  • regulation of intrinsic apoptotic signaling pathway Source: MGI
  • regulation of protein stability Source: UniProtKB
  • regulation of tumor necrosis factor-mediated signaling pathway Source: MGI
  • response to bacterium Source: MGI
  • tumor necrosis factor-mediated signaling pathway Source: MGI

Keywordsi

Biological processApoptosis, Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-5660668 CLEC7A/inflammasome pathway
R-MMU-6798695 Neutrophil degranulation
R-MMU-844456 The NLRP3 inflammasome

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis-associated speck-like protein containing a CARD
Short name:
mASC
Alternative name(s):
PYD and CARD domain-containing protein
Gene namesi
Name:Pycard
Synonyms:Asc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1931465 Pycard

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

Increased resistance to endotoxic shock and severe defects in caspase-1 activation and interleukin-1 beta and interleukin-18 production in macrophages in response to several pro-inflammatory molecules (PubMed:15190255, PubMed:15507117). Mutants are resitant to vaccinia virus (VACV) but not vesicular somatitis virus (VSV) infection. They show lower viral loads in the lungs compared to wild type mice, they produce higher levels of type I IFN, IL6 and RSAD2/Viperin after VCAV INFECTION (PubMed:28314590).3 Publications

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000646931 – 193Apoptosis-associated speck-like protein containing a CARDAdd BLAST193

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei193PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9EPB4
MaxQBiQ9EPB4
PaxDbiQ9EPB4
PRIDEiQ9EPB4

PTM databases

iPTMnetiQ9EPB4
PhosphoSitePlusiQ9EPB4

Expressioni

Tissue specificityi

Expressed in small intestine, colon, thymus, spleen, brain, heart, skeletal muscle, kidney, lung and liver.

Developmental stagei

Strongly expressed at E9.5 in the telencephalon, thalamic areas of the diencephalon, heart and liver.

Gene expression databases

BgeeiENSMUSG00000030793
CleanExiMM_PYCARD
ExpressionAtlasiQ9EPB4 baseline and differential
GenevisibleiQ9EPB4 MM

Interactioni

Subunit structurei

Self-associates; enforced oligomerization induces apoptosis, NF-kappa-B regulation and interleukin-1 beta secretion. Homooligomers can form disk-like particles of approximately 12 nm diameter and approximately 1 nm height. 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.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi211743, 3 interactors
DIPiDIP-27619N
IntActiQ9EPB4, 10 interactors
MINTiQ9EPB4
STRINGi10090.ENSMUSP00000033056

Structurei

3D structure databases

ProteinModelPortaliQ9EPB4
SMRiQ9EPB4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 91PyrinPROSITE-ProRule annotationAdd BLAST91
Domaini105 – 193CARDPROSITE-ProRule annotationAdd BLAST89

Domaini

The CARD domain mediates interaction with CASP1 and NLRC4.By similarity
The pyrin domain mediates homotypic interactions with pyrin domains of proteins such as of NLRP3, PYDC1, PYDC2 and AIM2.By similarity

Phylogenomic databases

eggNOGiENOG410J02A Eukaryota
ENOG4111XEQ LUCA
GeneTreeiENSGT00440000033973
HOGENOMiHOG000034090
HOVERGENiHBG018739
InParanoidiQ9EPB4
KOiK12799
OMAiAWNLTCK
OrthoDBiEOG091G0OWO
PhylomeDBiQ9EPB4
TreeFamiTF337882

Family and domain databases

CDDicd08330 CARD_ASC_NALP1, 1 hit
InterProiView protein in InterPro
IPR001315 CARD
IPR033516 CARD8/ASC/NALP1_CARD
IPR004020 DAPIN
IPR011029 DEATH-like_dom_sf
PfamiView protein in Pfam
PF00619 CARD, 1 hit
PF02758 PYRIN, 1 hit
SMARTiView protein in SMART
SM01289 PYRIN, 1 hit
SUPFAMiSSF47986 SSF47986, 2 hits
PROSITEiView protein in PROSITE
PS50209 CARD, 1 hit
PS50824 DAPIN, 1 hit

Sequencei

Sequence statusi: Complete.

Q9EPB4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRARDAILD ALENLSGDEL KKFKMKLLTV QLREGYGRIP RGALLQMDAI
60 70 80 90 100
DLTDKLVSYY LESYGLELTM TVLRDMGLQE LAEQLQTTKE ESGAVAAAAS
110 120 130 140 150
VPAQSTARTG HFVDQHRQAL IARVTEVDGV LDALHGSVLT EGQYQAVRAE
160 170 180 190
TTSQDKMRKL FSFVPSWNLT CKDSLLQALK EIHPYLVMDL EQS
Length:193
Mass (Da):21,459
Last modified:March 1, 2001 - v1
Checksum:i2A4EA40194870B31
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti159K → E in BAB31341 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB032249 mRNA Translation: BAB16609.1
AF310104 mRNA Translation: AAG30287.1
AK009852 mRNA Translation: BAB26543.1
AK007742 mRNA Translation: BAB25229.1
AK018682 mRNA Translation: BAB31341.1
BC008252 mRNA Translation: AAH08252.1
CCDSiCCDS21888.1
RefSeqiNP_075747.3, NM_023258.4
UniGeneiMm.24163

Genome annotation databases

EnsembliENSMUST00000033056; ENSMUSP00000033056; ENSMUSG00000030793
GeneIDi66824
KEGGimmu:66824
UCSCiuc009jxu.2 mouse

Similar proteinsi

Entry informationi

Entry nameiASC_MOUSE
AccessioniPrimary (citable) accession number: Q9EPB4
Secondary accession number(s): Q9D2W9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 162 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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