CPLM-023200

Genbank Nucleotide ID

Apoptosis-associated speck-like protein containing a CARD

Protein Synonyms/Alias

hASC; Caspase recruitment domain-containing protein 5; PYD and CARD domain-containing protein; Target of methylation-induced silencing 1

Homo sapiens (Human)

Position	Peptide	Type	References
21	NLTAEELKKFKLKLL	acetylation	[1]
109	APPQSAAKPGLHFID	ubiquitination	[2, 3]

[1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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.

DOMAIN 1 91 DAPIN.
DOMAIN 107 195 CARD.

3D-structure; Alternative splicing; Apoptosis; Complete proteome; Cytoplasm; Endoplasmic reticulum; Immunity; Inflammatory response; Innate immunity; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome; Tumor suppressor.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0097169; C:AIM2 inflammasome complex; IDA:UniProtKB.
GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
GO:0008385; C:IkappaB kinase complex; TAS:HGNC.
GO:0005739; C:mitochondrion; IDA:UniProtKB.
GO:0072558; C:NLRP1 inflammasome complex; IDA:UniProtKB.
GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB.
GO:0005634; C:nucleus; ISS:UniProtKB.
GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; NAS:UniProtKB.
GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
GO:0042803; F:protein homodimerization activity; IDA:HGNC.
GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
GO:0051607; P:defense response to virus; IDA:UniProtKB.
GO:0006917; P:induction of apoptosis; TAS:ProtInc.
GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO:0045087; P:innate immune response; TAS:Reactome.
GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:UniProtKB.
GO:0044351; P:macropinocytosis; ISS:UniProtKB.
GO:0002277; P:myeloid dendritic cell activation involved in immune response; ISS:UniProtKB.
GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
GO:0032688; P:negative regulation of interferon-beta production; IMP:UniProtKB.
GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
GO:0035872; P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway; TAS:Reactome.
GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
GO:0002821; P:positive regulation of adaptive immune response; IMP:UniProtKB.
GO:0002588; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class II; ISS:UniProtKB.
GO:0090197; P:positive regulation of chemokine secretion; IMP:UniProtKB.
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IDA:UniProtKB.
GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
GO:0050718; P:positive regulation of interleukin-1 beta secretion; IDA:HGNC.
GO:2001181; P:positive regulation of interleukin-10 secretion; IMP:UniProtKB.
GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
GO:2000778; P:positive regulation of interleukin-6 secretion; IMP:UniProtKB.
GO:2000484; P:positive regulation of interleukin-8 secretion; IMP:UniProtKB.
GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB.
GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB.
GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
GO:0006508; P:proteolysis; IEA:InterPro.
GO:2001242; P:regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IMP:UniProtKB.
GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:HGNC.

IPR001315; CARD.
IPR004020; DAPIN.
IPR011029; DEATH-like_dom.
IPR002398; Pept_C14_p45.

PF00619; CARD
PF02758; PYRIN

PS50209; CARD
PS50824; DAPIN