Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002395
UniProt IDQ9ULZ3
Primary gene name(s)PYCARD
Synonym gene name(s)ASC, CARD5, TMS1
Protein nameApoptosis-associated speck-like protein containing a CARD
Protein functionFunctions 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. 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. {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:21487011, ECO:0000269|PubMed:22732093}.
Subcellular locationCytoplasm. 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}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9ULZ3
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
activation of innate immune response [GO:0002218];
apoptotic process [GO:0006915];
cellular response to interleukin-1 [GO:0071347];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to tumor necrosis factor [GO:0071356];
defense response to Gram-negative bacterium [GO:0050829];
defense response to virus [GO:0051607];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
intrinsic apoptotic signaling pathway by p53 class mediator [GO:0072332];
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771];
macropinocytosis [GO:0044351];
myeloid dendritic cell activation [GO:0001773];
myeloid dendritic cell activation involved in immune response [GO:0002277];
negative regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043124];
negative regulation of interferon-beta production [GO:0032688];
negative regulation of NF-kappaB transcription factor activity [GO:0032088];
negative regulation of protein serine/threonine kinase activity [GO:0071901];
positive regulation of actin filament polymerization [GO:0030838];
positive regulation of activated T cell proliferation [GO:0042104];
positive regulation of adaptive immune response [GO:0002821];
positive regulation of antigen processing and presentation of peptide antigen via MHC class II [GO:0002588];
positive regulation of apoptotic process [GO:0043065];
positive regulation of chemokine secretion [GO:0090197];
positive regulation of cysteine-type endopeptidase activity [GO:2001056];
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of extrinsic apoptotic signaling pathway [GO:2001238];
positive regulation of interferon-gamma production [GO:0032729];
positive regulation of interleukin-10 secretion [GO:2001181];
positive regulation of interleukin-1 beta secretion [GO:0050718];
positive regulation of interleukin-6 production [GO:0032755];
positive regulation of interleukin-6 secretion [GO:2000778];
positive regulation of interleukin-8 secretion [GO:2000484];
positive regulation of JNK cascade [GO:0046330];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of phagocytosis [GO:0050766];
positive regulation of release of cytochrome c from mitochondria [GO:0090200];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of T cell activation [GO:0050870];
positive regulation of T cell migration [GO:2000406];
positive regulation of tumor necrosis factor production [GO:0032760];
regulation of intrinsic apoptotic signaling pathway [GO:2001242];
regulation of protein stability [GO:0031647];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
signal transduction [GO:0007165];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
BMP receptor binding [GO:0070700];
cysteine-type endopeptidase activator activity involved in apoptotic process [GO:0008656];
cysteine-type endopeptidase activity involved in apoptotic process [GO:0097153];
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
interleukin-6 receptor binding [GO:0005138];
myosin I binding [GO:0017024];
protease binding [GO:0002020];
protein homodimerization activity [GO:0042803];
Pyrin domain binding [GO:0032090];
tropomyosin binding [GO:0005523]
Gene Ontology
(Cellular Component)
Complete annatation
AIM2 inflammasome complex [GO:0097169];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
IkappaB kinase complex [GO:0008385];
mitochondrion [GO:0005739];
NLRP1 inflammasome complex [GO:0072558];
NLRP3 inflammasome complex [GO:0072559];
nucleolus [GO:0005730];
nucleus [GO:0005634]
Protein-protein interaction118876
Phylogenetic treeQ9ULZ3
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-3.9691972103771300
AZA vs. DISU-0.6738777393016540.09299454669149210.627213219512123
AZA vs. IL70.008184869409207640.9792322315619380.999311006273513
AZA vs. SAHA-0.8941273345913970.007538961725065190.0812536395741867
DISU vs. CD33.28563810247541.88737914186277e-149.11870294373056e-13
DISU vs. IL70.6710380240233240.1314534850050860.47467131374922
DISU vs. SAHA-0.2178480121295690.6328632156619660.885131669008137
DMSO vs. AZA-0.1231397640297750.6075450764038691
DMSO vs. CD33.8389633467352300
DMSO vs. DISU0.5497724908267210.1613344116495890.667942193285523
DMSO vs. IL70.1382658408100470.6497026591814780.925034717336681
DMSO vs. SAHA-0.7761375855240950.01651563935251190.124765514126169
HIV vs. Mock in Activation0.07712034145744170.9101564317107950.999983755607037
HIV vs. Mock in Latency-0.04449635883380890.8145942212823840.999834320637052
IL7 vs. CD33.9821482241104700
SAHA vs. CD33.054293292562779.43689570931383e-154.11023174391212e-13
SAHA vs. IL7-0.9038899337362290.01816764299562270.0944993273002127
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.195517 0.184854
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
221666_s_at 1.74 No upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1UCP NMR - A=1-91.
2KN6 NMR - A=1-195.
3J63 EM 3.8Å A/B/C/D/E/F/G/H/I/J/K/L/M/N/O=1-91.
5H8O X-ray 4.2Å B=115-195.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa05132 Salmonella infection - Homo sapiens (human)
hsa05133 Pertussis - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
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