ASC_DANRE
ID ASC_DANRE Reviewed; 203 AA.
AC Q9I9N6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 118.
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, asc1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10917738; DOI=10.1038/sj.cdd.4400679;
RA Inohara N., Nunez G.;
RT "Genes with homology to mammalian apoptosis regulators identified in
RT zebrafish.";
RL Cell Death Differ. 7:509-510(2000).
RN [2]
RP FUNCTION, SELF-ASSOCIATION, INTERACTION WITH CASPA, SUBCELLULAR LOCATION,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=12464617; DOI=10.1074/jbc.m203944200;
RA Masumoto J., Zhou W., Chen F.F., Su F., Kuwada J.Y., Hidaka E.,
RA Katsuyama T., Sagara J., Taniguchi S., Ngo-Hazelett P., Postlethwait J.H.,
RA Nunez G., Inohara N.;
RT "Caspy, a zebrafish caspase, activated by ASC oligomerization is required
RT for pharyngeal arch development.";
RL J. Biol. Chem. 278:4268-4276(2003).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=29123523; DOI=10.3389/fimmu.2017.01375;
RA Tyrkalska S.D., Candel S., Perez-Oliva A.B., Valera A., Alcaraz-Perez F.,
RA Garcia-Moreno D., Cayuela M.L., Mulero V.;
RT "Identification of an Evolutionarily Conserved Ankyrin Domain-Containing
RT Protein, Caiap, Which Regulates Inflammasome-Dependent Resistance to
RT Bacterial Infection.";
RL Front. Immunol. 8:1375-1375(2017).
RN [4]
RP FUNCTION, IDENTIFICATION IN NLRP1 INFLAMMASOME, INTERACTION WITH CASPA AND
RP CASPB, SUBCELLULAR LOCATION, AND INDUCTION BY E.TARDA.
RX PubMed=30150286; DOI=10.4049/jimmunol.1800498;
RA Li J.Y., Gao K., Shao T., Fan D.D., Hu C.B., Sun C.C., Dong W.R., Lin A.F.,
RA Xiang L.X., Shao J.Z.;
RT "Characterization of an NLRP1 Inflammasome from Zebrafish Reveals a Unique
RT Sequential Activation Mechanism Underlying Inflammatory Caspases in Ancient
RT Vertebrates.";
RL J. Immunol. 201:1946-1966(2018).
RN [5] {ECO:0007744|PDB:5GPP, ECO:0007744|PDB:5GPQ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 3-88, SUBUNIT, INTERACTION WITH
RP CASPA AND NLP3X1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND MUTAGENESIS OF GLN-10; GLU-14; ASP-19; ARG-22; ASP-47 AND
RP ASP-50.
RX PubMed=29791979; DOI=10.1111/febs.14514;
RA Li Y., Huang Y., Cao X., Yin X., Jin X., Liu S., Jiang J., Jiang W.,
RA Xiao T.S., Zhou R., Cai G., Hu B., Jin T.;
RT "Functional and structural characterization of zebrafish ASC.";
RL FEBS J. 285:2691-2707(2018).
CC -!- FUNCTION: Functions as key mediator in apoptosis and inflammation
CC (PubMed:12464617). Promotes caspase-mediated apoptosis
CC (PubMed:12464617). Induces proteolytic processing of caspa and caspa-
CC dependent apoptosis (PubMed:12464617). In innate immune response acts
CC as an integral adapter in the assembly of NLRP1 inflammasomes which
CC activate caspases caspa and caspb leading to processing and secretion
CC of the pro-inflammatory cytokine il1b (PubMed:30150286). The function
CC as activating adapter in different types of inflammasomes is mediated
CC by the pyrin and CARD domains and their homotypic interactions
CC (PubMed:30150286). Also involved in transcriptional activation of
CC cytokines and chemokines independent of the inflammasome.
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:30150286}.
CC -!- SUBUNIT: Self-associates (via pyrin and CARD domains) (PubMed:12464617,
CC PubMed:29791979). Interacts (via pyrin domain) with caspa (via pyrin
CC domain) (PubMed:12464617, PubMed:30150286, PubMed:29791979). Interacts
CC with caspb; the interaction only occurs in the presence of nlrp1
CC (PubMed:30150286). Component of NLRP1 inflammasomes (PubMed:30150286).
CC Inflammasomes are supramolecular complexes that assemble in the cytosol
CC in response to pathogens and other damage-associated signals and play
CC critical roles in innate immunity and inflammation (PubMed:30150286).
CC The NLRP1 inflammasome is composed of the signal sensor nlrp1, and the
CC adapter pycard (asc), which recruit effector pro-inflammatory caspases
CC caspa and/or caspb (PubMed:30150286). The interaction between nlrp1 and
CC pycard is required for the sequential recruitment of caspa and then
CC caspb (PubMed:30150286). Within the complex caspa is preferentially
CC recruited first and this causes the cleavage of pro-il1b into the
CC midformed il1b (PubMed:30150286). This is followed by the recruitment
CC of caspb, which is activated and cleaves the midformed il1b resulting
CC in il1b maturation (PubMed:30150286). Interacts (via pyrin domain) with
CC NLP3X1 (via pyrin domain) (PubMed:29791979).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:29791979,
CC ECO:0000269|PubMed:30150286}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12464617,
CC ECO:0000269|PubMed:30150286}. Inflammasome
CC {ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30150286}. Note=Co-
CC localizes with nlrp1, caspa and caspb in the cytoplasm
CC (PubMed:30150286). Co-localizes with caspa and caspb independently at
CC large cytoplasmic aggregates, known as specks (PubMed:12464617,
CC PubMed:30150286, PubMed:29791979). {ECO:0000269|PubMed:12464617,
CC ECO:0000269|PubMed:29791979, ECO:0000269|PubMed:30150286}.
CC -!- TISSUE SPECIFICITY: Expressed in the kidney, intestine and gill
CC (PubMed:29791979). Expressed at low levels in the heart
CC (PubMed:29791979). {ECO:0000269|PubMed:29791979}.
CC -!- DEVELOPMENTAL STAGE: First expressed during embryonic development at 1
CC somite at 10 hours post-fertilization (hpf) (PubMed:29791979). During
CC embryonic development, expressed in the epidermis, mouth and pharyngeal
CC arches at 48 and 72 hpf (PubMed:12464617).
CC {ECO:0000269|PubMed:12464617, ECO:0000269|PubMed:29791979}.
CC -!- INDUCTION: Up-regulated in response to infection with the bacteria
CC E.tarda. {ECO:0000269|PubMed:30150286}.
CC -!- DOMAIN: The pyrin domain mediates homotypic interactions with pyrin
CC domain of other proteins. {ECO:0000250|UniProtKB:Q9ULZ3}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown in one-cell embryos results
CC in reduced caspa activity and impairs caspa activity in response to
CC infection with the bacterium S.typhimurium (PubMed:29123523). In
CC addition, there is increased susceptibility to the bacterium
CC S.typhimurium (PubMed:29123523). {ECO:0000269|PubMed:29123523}.
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DR EMBL; AF231013; AAF66956.1; -; mRNA.
DR PDB; 5GPP; X-ray; 2.00 A; A/B=3-88.
DR PDB; 5GPQ; X-ray; 2.10 A; A=119-201.
DR PDBsum; 5GPP; -.
DR PDBsum; 5GPQ; -.
DR AlphaFoldDB; Q9I9N6; -.
DR SMR; Q9I9N6; -.
DR ComplexPortal; CPX-4947; NLRP1 inflammasome, variant 1.
DR ComplexPortal; CPX-4948; NLRP1 inflammasome, variant 2.
DR IntAct; Q9I9N6; 1.
DR STRING; 7955.ENSDARP00000055920; -.
DR PRIDE; Q9I9N6; -.
DR ZFIN; ZDB-GENE-000511-2; pycard.
DR eggNOG; ENOG502S3G5; Eukaryota.
DR InParanoid; Q9I9N6; -.
DR PhylomeDB; Q9I9N6; -.
DR PRO; PR:Q9I9N6; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072558; C:NLRP1 inflammasome complex; IDA:ComplexPortal.
DR GO; GO:0140738; C:NLRP6 inflammasome complex; ISS:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0032090; F:Pyrin domain binding; IPI:ZFIN.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; IGI:ZFIN.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IGI:ZFIN.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IPI:ZFIN.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:ComplexPortal.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IC:ComplexPortal.
DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro.
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 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 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasm; Immunity; Inflammasome;
KW Inflammatory response; Innate immunity; Reference proteome;
KW Tumor suppressor.
FT CHAIN 1..203
FT /note="Apoptosis-associated speck-like protein containing a
FT CARD"
FT /id="PRO_0000064691"
FT DOMAIN 1..91
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 112..203
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT MUTAGEN 10
FT /note="Q->A: Impairs inflammasome activity, but does not
FT impair speck formation."
FT /evidence="ECO:0000269|PubMed:29791979"
FT MUTAGEN 14
FT /note="E->R: Defective speck formation and impairs
FT inflammasome activity."
FT /evidence="ECO:0000269|PubMed:29791979"
FT MUTAGEN 19
FT /note="D->A: Impairs inflammasome activity, but does not
FT impair speck formation."
FT /evidence="ECO:0000269|PubMed:29791979"
FT MUTAGEN 22
FT /note="R->E: Abolishes speck formation and impairs
FT inflammasome activity."
FT /evidence="ECO:0000269|PubMed:29791979"
FT MUTAGEN 47
FT /note="D->R: Abolishes speck formation and impairs
FT inflammasome activity."
FT /evidence="ECO:0000269|PubMed:29791979"
FT MUTAGEN 50
FT /note="D->R: Abolishes speck formation and impairs
FT inflammasome activity."
FT /evidence="ECO:0000269|PubMed:29791979"
FT HELIX 3..16
FT /evidence="ECO:0007829|PDB:5GPP"
FT HELIX 18..30
FT /evidence="ECO:0007829|PDB:5GPP"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:5GPP"
FT HELIX 39..43
FT /evidence="ECO:0007829|PDB:5GPP"
FT HELIX 48..59
FT /evidence="ECO:0007829|PDB:5GPP"
FT HELIX 61..74
FT /evidence="ECO:0007829|PDB:5GPP"
FT HELIX 78..86
FT /evidence="ECO:0007829|PDB:5GPP"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:5GPQ"
FT HELIX 135..143
FT /evidence="ECO:0007829|PDB:5GPQ"
FT HELIX 149..156
FT /evidence="ECO:0007829|PDB:5GPQ"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:5GPQ"
FT HELIX 161..170
FT /evidence="ECO:0007829|PDB:5GPQ"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:5GPQ"
FT HELIX 177..191
FT /evidence="ECO:0007829|PDB:5GPQ"
FT HELIX 193..199
FT /evidence="ECO:0007829|PDB:5GPQ"
SQ SEQUENCE 203 AA; 22867 MW; EF457179EB7A78A7 CRC64;
MAESFKEHLQ EAFEDLGADN LRKFKSKLGD RRQEPRVTKS AIEKLKDEID LADLMVGVFT
SKDAVSVTVE ILRAIKCNAV ADDLLRNTGQ SESKGALSDE SKCASSKAVS KVAFSKVNFI
DEHWKELIDR VNNVDPILDI LRQKKVITNE DYCTIRNKET PQKKMRELLT GPITCAGNKG
KEVLYDALRE SNKFLMDDLE DAE
