ID:ASC_HUMAN DESCRIPTION: RecName: Full=Apoptosis-associated speck-like protein containing a CARD; Short=hASC; AltName: Full=Caspase recruitment domain-containing protein 5; AltName: Full=PYD and CARD domain-containing protein; AltName: Full=Target of methylation-induced silencing 1; 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. SUBUNIT: 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. INTERACTION: O14862:AIM2; NbExp=4; IntAct=EBI-751215, EBI-6253193; Q07812:BAX; NbExp=7; IntAct=EBI-751215, EBI-516580; Q9C000:NLRP1; NbExp=5; IntAct=EBI-751215, EBI-1220518; Q96P20:NLRP3; NbExp=4; IntAct=EBI-751215, EBI-6253230; SUBCELLULAR LOCATION: 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). 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 Burkitt's 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. 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). DOMAIN: The CARD domain mediates interaction with CASP1 and NLRC4 (PubMed:14634131 and PubMed:11967258). PTM: Phosphorylated. MISCELLANEOUS: In breast tumorigenesis, methylation-mediated silencing may affect genes and proteins that act as positive mediators of cell death. SIMILARITY: Contains 1 CARD domain. SIMILARITY: Contains 1 DAPIN domain. SEQUENCE CAUTION: Sequence=BAA91012.1; Type=Frameshift; Positions=4;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9ULZ3
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0002020 protease binding GO:0005138 interleukin-6 receptor binding GO:0005515 protein binding GO:0005523 tropomyosin binding GO:0008656 cysteine-type endopeptidase activator activity involved in apoptotic process GO:0017024 myosin I binding GO:0019899 enzyme binding GO:0032090 Pyrin domain binding GO:0042802 identical protein binding GO:0042803 protein homodimerization activity GO:0070700 BMP receptor binding GO:0097153 cysteine-type endopeptidase activity involved in apoptotic process
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: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:0006915 apoptotic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006954 inflammatory response 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: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:0043312 neutrophil degranulation GO:0044351 macropinocytosis GO:0045087 innate immune response 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
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
