ASC_BOVIN
ID ASC_BOVIN Reviewed; 195 AA.
AC Q8HXK9;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Apoptosis-associated speck-like protein containing a CARD;
DE AltName: Full=PYD and CARD domain-containing protein;
GN Name=PYCARD; Synonyms=ASC;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Masumoto J., Sagara J., Taniguchi S.;
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Functions as key mediator in apoptosis and inflammation.
CC Promotes caspase-mediated apoptosis involving predominantly caspase-8
CC and also caspase-9 in a probable cell type-specific manner. Involved in
CC activation of the mitochondrial apoptotic pathway, promotes caspase-8-
CC dependent proteolytic maturation of BID independently of FADD in
CC certain cell types and also mediates mitochondrial translocation of BAX
CC and activates BAX-dependent apoptosis coupled to activation of caspase-
CC 9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent
CC inflammatory form of cell death and is the major constituent of the ASC
CC pyroptosome which forms upon potassium depletion and rapidly recruits
CC and activates caspase-1. In innate immune response, acts as an integral
CC adapter in the assembly of the inflammasome which activates caspase-1
CC leading to processing and secretion of pro-inflammatory cytokines. The
CC function as activating adapter in different types of inflammasomes is
CC mediated by the pyrin and CARD domains and their homotypic
CC interactions. Required for recruitment of caspase-1 to inflammasomes
CC containing certain pattern recognition receptors, such as NLRP2, NLRP3,
CC NLRP6, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes
CC seems not be required but facilitates the processing of procaspase-1.
CC In cooperation with NOD2 involved in an inflammasome activated by
CC bacterial muramyl dipeptide leading to caspase-1 activation. May be
CC involved in DDX58-triggered pro-inflammatory responses and inflammasome
CC activation. In collaboration with AIM2 which detects cytosolic double-
CC stranded DNA may also be involved in a caspase-1-independent cell death
CC that involves caspase-8. In adaptive immunity may be involved in
CC maturation of dendritic cells to stimulate T-cell immunity and in
CC cytoskeletal rearrangements coupled to chemotaxis and antigen uptake
CC may be involved in post-transcriptional regulation of the guanine
CC nucleotide exchange factor DOCK2; the latter function is proposed to
CC involve the nuclear form. Also involved in transcriptional activation
CC of cytokines and chemokines independent of the inflammasome; this
CC function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling
CC pathways. For regulation of NF-kappa-B activating and inhibiting
CC functions have been reported. Modulates NF-kappa-B induction at the
CC level of the IKK complex by inhibiting kinase activity of CHUK and
CC IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby
CC down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation
CC and activating interleukin-1 beta processing (By similarity). Modulates
CC host resistance to DNA virus infection, probably by inducing the
CC cleavage of and inactivating CGAS in presence of cytoplasmic double-
CC stranded DNA (By similarity). {ECO:0000250|UniProtKB:Q9EPB4,
CC ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- SUBUNIT: Self-associates; enforced oligomerization induces apoptosis,
CC NF-kappa-B regulation and interleukin-1 beta secretion. Homooligomers
CC can form disk-like particles of approximately 12 nm diameter and
CC approximately 1 nm height. Component of several inflammasomes
CC containing one pattern recognition receptor/sensor, such as NLRP1,
CC NLRP2, NLRP3, NLRP6, NLRC4, AIM2, MEFV or NOD2, and probably NLRC4,
CC NLRP12 or IFI16. Major component of the ASC pyroptosome, a 1-2 um
CC supramolecular assembly (one per macrophage cell) which consists of
CC oligomerized PYCARD dimers and CASP1. Interacts with CASP1 (precursor
CC form); the interaction induces activation of CASP1 leading to the
CC processing of interleukin-1 beta; PYCARD competes with RIPK2 for
CC binding to CASP1. Interacts with NLRP3; the interaction requires the
CC homooligomerization of NLRP3. Interacts with NLRP2, NLRC4, MEFV,
CC CARD16, AIM2, IFI16, NOD2, DDX58, RIPK2, PYDC1, PYDC2, NLRP10, CASP8,
CC CHUK, IKBKB and BAX. Component of the AIM2 PANoptosome complex, a
CC multiprotein complex that drives inflammatory cell death (PANoptosis).
CC {ECO:0000250|UniProtKB:Q9EPB4, ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9ULZ3}.
CC Inflammasome {ECO:0000250|UniProtKB:Q9ULZ3}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9ULZ3}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9ULZ3}. Nucleus {ECO:0000250|UniProtKB:Q9ULZ3}.
CC Note=Upstream of caspase activation, a redistribution from the
CC cytoplasm to the aggregates occurs. These appear as hollow, perinuclear
CC spherical, ball-like structures. Upon NLRP3 inflammasome activation
CC redistributes to the perinuclear space localizing to endoplasmic
CC reticulum and mitochondria. Localized primarily to the nucleus in
CC resting monocytes/macrophages and rapidly redistributed to the
CC cytoplasm upon pathogen infection (By similarity). Localized to large
CC cytoplasmic aggregate appearing as a speck containing AIM2, PYCARD,
CC CASP8 and bacterial DNA after infection with Francisella tularensis (By
CC similarity). {ECO:0000250|UniProtKB:Q9EPB4,
CC ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- DOMAIN: The CARD domain mediates interaction with CASP1 and NLRC4.
CC {ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- DOMAIN: The pyrin domain mediates homotypic interactions with pyrin
CC domains of proteins such as of NLRP3, PYDC1, PYDC2 and AIM2.
CC {ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- PTM: 'Lys-63'-linked polyubiquitination by TRAF3 is critical for speck
CC formation and inflammasome activation. {ECO:0000250|UniProtKB:Q9ULZ3}.
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DR EMBL; AB050006; BAC43753.1; -; mRNA.
DR EMBL; BC102385; AAI02386.1; -; mRNA.
DR RefSeq; NP_777155.1; NM_174730.2.
DR AlphaFoldDB; Q8HXK9; -.
DR SMR; Q8HXK9; -.
DR STRING; 9913.ENSBTAP00000027359; -.
DR PaxDb; Q8HXK9; -.
DR PeptideAtlas; Q8HXK9; -.
DR PRIDE; Q8HXK9; -.
DR GeneID; 282846; -.
DR KEGG; bta:282846; -.
DR CTD; 29108; -.
DR eggNOG; ENOG502S3G5; Eukaryota.
DR InParanoid; Q8HXK9; -.
DR OrthoDB; 1494108at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0097169; C:AIM2 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:HGNC-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0072559; C:NLRP3 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0140738; C:NLRP6 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:HGNC-UCL.
DR GO; GO:0032090; F:Pyrin domain binding; ISS:HGNC-UCL.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0002277; P:myeloid dendritic cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0002588; P:positive regulation of antigen processing and presentation of peptide antigen via MHC class II; ISS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:HGNC-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:HGNC-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:2000406; P:positive regulation of T cell migration; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR CDD; cd08330; CARD_ASC_NALP1; 1.
DR Gene3D; 1.10.533.10; -; 2.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR033516; CARD8/ASC/NALP1_CARD.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002398; Pept_C14.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR SUPFAM; SSF47986; SSF47986; 2.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS50824; DAPIN; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Endoplasmic reticulum; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Isopeptide bond; Mitochondrion;
KW Nucleus; Phosphoprotein; Reference proteome; Tumor suppressor;
KW Ubl conjugation.
FT CHAIN 1..195
FT /note="Apoptosis-associated speck-like protein containing a
FT CARD"
FT /id="PRO_0000245585"
FT DOMAIN 1..91
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 107..195
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EPB4"
FT CROSSLNK 174
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9ULZ3"
SQ SEQUENCE 195 AA; 21917 MW; 7C9D4BD8DBA9A9E8 CRC64;
MGCTRDAILD ALENLTADEL KKFKMKLLSV PLREGYGRIP RGTLLPLDAV DLTDKLVSYY
LEAYGAELTA LVLRDMGMQE VAEQLQETMS KGPRNVLAEV RDPLQKTAKP GLHFVDQHRA
ALIARVTVVD GVLDALYGKV LTEEQYQAVR AERTSSDKMR KLFSFSPAWN MTCKDLLLQA
LRDTQPYLVD DLEQS
