CPLM-021036

Genbank Nucleotide ID

Apoptosis-associated speck-like protein containing a CARD

Protein Synonyms/Alias

mASC; PYD and CARD domain-containing protein

Mus musculus (Mouse)

Position	Peptide	Type	References
21	NLSGDELKKFKMKLL	acetylation	[1]

[1] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
Simon GM, Cheng J, Gordon JI.
Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]

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. 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 105 193 CARD.

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; ISS:UniProtKB.
GO:0005829; C:cytosol; IDA:MGI.
GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
GO:0005576; C:extracellular region; IDA:MGI.
GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
GO:0072559; C:NLRP3 inflammasome complex; ISS:UniProtKB.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0016505; F:apoptotic protease activator activity; ISO:MGI.
GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
GO:0042803; F:protein homodimerization activity; ISS:HGNC.
GO:0032090; F:Pyrin domain binding; ISS:HGNC.
GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
GO:0002218; P:activation of innate immune response; IMP:UniProtKB.
GO:0006917; P:induction of apoptosis; ISO:MGI.
GO:0006954; P:inflammatory response; IMP:MGI.
GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO:0032611; P:interleukin-1 beta production; IGI:MGI.
GO:0044351; P:macropinocytosis; IMP:UniProtKB.
GO:0002277; P:myeloid dendritic cell activation involved in immune response; IMP:UniProtKB.
GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
GO:0042104; P:positive regulation of activated T cell proliferation; IMP:UniProtKB.
GO:0002588; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class II; IMP:UniProtKB.
GO:0090197; P:positive regulation of chemokine secretion; IMP:UniProtKB.
GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
GO:0032729; P:positive regulation of interferon-gamma production; IMP:UniProtKB.
GO:0050718; P:positive regulation of interleukin-1 beta secretion; IMP:UniProtKB.
GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
GO:0050766; P:positive regulation of phagocytosis; IMP:UniProtKB.
GO:2000406; P:positive regulation of T cell migration; IMP:UniProtKB.
GO:0006508; P:proteolysis; IEA:InterPro.
GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
GO:0032314; P:regulation of Rac GTPase activity; IMP:UniProtKB.

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

PF00619; CARD
PF02758; PYRIN

PS50209; CARD
PS50824; DAPIN