PYCARD
entrez
29108
canonical
uniprot
Q9ULZ3
canonical
ensembl
ENSG00000103490
resolver
ensp
ENSP00000247470
resolver
ensp
ENSP00000340441
resolver
genesymbol
PYCARD
resolver
genesymbol_syn
ASC
resolver
genesymbol_syn
CARD5
resolver
genesymbol_syn
TMS1
resolver
hgnc
HGNC:16608
resolver
uniprot
Q96D12
resolver
uniprot
Q9BSZ5
resolver
uniprot
Q9HBD0
resolver
uniprot
Q9NXJ8
resolver
uniprot_entry
ASC_HUMAN
resolver
uniprot_sec
Q96D12
resolver
uniprot_sec
Q9BSZ5
resolver
uniprot_sec
Q9HBD0
resolver
uniprot_sec
Q9NXJ8
resolver
amino_acid_sequence
MGRARDAILDALENLTAEELKKFKLKLLSVPLREGYGRIPRGALLSMDALDLTDKLVSFYLETYGAELTANVLRDMGLQEMAGQLQAATHQGSGAAPAGIQAPPQSAAKPGLHFIDQHRAALIARVTNVEWLLDALYGKVLTDEQYQAVRAEPTNPSKMRKLFSFTPAWNWTCKDLLLQALRESQSYLVEDLERS
uniprot
proteins
function
FUNCTION: Functions as a key mediator in apoptosis and inflammation (PubMed:11103777, PubMed:12646168, PubMed:15030775, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMed:19494289, PubMed:21487011, PubMed:24630722, PubMed:25847972, PubMed:30674671, PubMed:34678144, PubMed:36050480). Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner (PubMed:11103777, PubMed:12646168). 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 (PubMed:14730312, PubMed:16964285). Involved in innate immune response by acting as an integral adapter in the assembly of various inflammasomes (NLRP1, NLRP2, NLRP3, NLRP6, AIM2 and probably IFI16) which recruit and activate caspase-1 leading to processing and secretion of pro-inflammatory cytokines (PubMed:15030775, PubMed:16982856, PubMed:17349957, PubMed:17599095, PubMed:19158675, PubMed:19158676, PubMed:19234215, PubMed:21487011, PubMed:23530044, PubMed:24630722, PubMed:25847972, PubMed:29440442, PubMed:30674671, PubMed:33980849, PubMed:34678144, PubMed:34706239). Caspase-1-dependent inflammation leads to macrophage pyroptosis, a form of cell death (PubMed:24630722). The function as activating adapter in different types of inflammasomes is mediated by the pyrin and CARD domains and their homotypic interactions (PubMed:14499617, PubMed:19234215, PubMed:24630722). Clustered PYCARD nucleates the formation of caspase-1 filaments through the interaction of their respective CARD domains, acting as a platform for of caspase-1 polymerization (PubMed:24630722). In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1 (PubMed:17349957). In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation (PubMed:16964285). May be involved in RIGI-triggered pro-inflammatory responses and inflammasome activation (PubMed:19915568). 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 (PubMed:19158675, PubMed:19158676). 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 (PubMed:22732093). 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 (PubMed:12486103, PubMed:16585594). For regulation of NF-kappa-B activating and inhibiting functions have been reported (PubMed:12486103). Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK (PubMed:12486103, PubMed:16585594). 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 (PubMed:16585594). Modulates host resistance to DNA virus infection, probably by inducing the cleavage of and inactivating CGAS in presence of cytoplasmic double-stranded DNA (PubMed:28314590). {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12486103, ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:14499617, ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:16585594, ECO:0000269|PubMed:16964285, ECO:0000269|PubMed:16982856, ECO:0000269|PubMed:17349957, ECO:0000269|PubMed:17599095, ECO:0000269|PubMed:19158675, ECO:0000269|PubMed:19158676, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:19494289, ECO:0000269|PubMed:19915568, ECO:0000269|PubMed:21487011, ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:23530044, ECO:0000269|PubMed:24630722, ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:29440442, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:33980849, ECO:0000269|PubMed:34678144, ECO:0000269|PubMed:34706239, ECO:0000269|PubMed:36050480}.; FUNCTION: [Isoform 2]: May have a regulating effect on the function as inflammasome adapter. {ECO:0000269|PubMed:19759850, ECO:0000269|PubMed:20482797}.; FUNCTION: [Isoform 3]: Seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. {ECO:0000269|PubMed:20482797}.
uniprot
proteins
mass_dalton
21627
uniprot
proteins
mutagenesis
MUTAGEN 8; /note="I->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 12; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:15641782"; MUTAGEN 12; /note="L->Q: Abolishes promotion of apoptosis and NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:12646168, ECO:0000269|PubMed:15641782"; MUTAGEN 13; /note="E->A: Abolishes interaction with PYDC1."; /evidence="ECO:0000269|PubMed:15456791, ECO:0000269|PubMed:15641782, ECO:0000269|PubMed:18362139"; MUTAGEN 13; /note="E->W: Abolishes interaction with NLRP2."; /evidence="ECO:0000269|PubMed:15456791, ECO:0000269|PubMed:15641782, ECO:0000269|PubMed:18362139"; MUTAGEN 15; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 19; /note="E->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 20; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 21; /note="K->A,E,Q: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 23; /note="F->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 25; /note="L->A,E,G,K,N,Q: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 26; /note="K->A,Q: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 27; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 36; /note="Y->A: Abolishes interaction with PYDC1."; /evidence="ECO:0000269|PubMed:18362139"; MUTAGEN 40; /note="P->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 41; /note="R->A,Q,W: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 45; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 47; /note="M->A,N,Q: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 48; /note="D->A,K: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782, ECO:0000269|PubMed:18362139"; MUTAGEN 48; /note="D->A: Abolishes interaction with PYDC1."; /evidence="ECO:0000269|PubMed:15641782, ECO:0000269|PubMed:18362139"; MUTAGEN 52; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 55; /note="K->R: Strongly reduced PELI1-mediated ubiquitination."; /evidence="ECO:0000269|PubMed:34706239"; MUTAGEN 56; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 62; /note="E->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 67; /note="E->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 68; /note="L->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 72; /note="V->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 76; /note="M->A: Abolishes homooligomerization."; /evidence="ECO:0000269|PubMed:15641782"; MUTAGEN 174; /note="K->R: Loss of inflammasome activation activity."; /evidence="ECO:0000269|PubMed:25847972
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. {ECO:0000269|PubMed:12656673}.; PTM: 'Lys-63'-linked polyubiquitination by TRAF3 is critical for speck formation and inflammasome activation (PubMed:25847972). 'Lys-63'-linked deubiquitinated by USP50; a crucial step for NLRP3-mediated inflammasome activation (PubMed:28094437). 'Lys-63'-linked polyubiquitination by PELI1 is also critical for speck formation and inflammasome activation (PubMed:34706239). Deubiquitinated by USP3 that cleaves 'Lys-48'-linked ubiquitin chains and strengthens its stability by blocking proteasomal degradation (PubMed:36050480). {ECO:0000269|PubMed:25847972, ECO:0000269|PubMed:28094437, ECO:0000269|PubMed:36050480}.
uniprot
proteins
pubmed
10567338
uniprot
proteins
pubmed
11103776
uniprot
proteins
pubmed
11103777
uniprot
proteins
pubmed
11374873
uniprot
proteins
pubmed
11498534
uniprot
proteins
pubmed
11786556
uniprot
proteins
pubmed
11967258
uniprot
proteins
pubmed
12191486
uniprot
proteins
pubmed
12486103
uniprot
proteins
pubmed
12646168
uniprot
proteins
pubmed
12656673
uniprot
proteins
pubmed
14499617
uniprot
proteins
pubmed
14634131
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14730312
uniprot
proteins
pubmed
15020601
uniprot
proteins
pubmed
15030775
uniprot
proteins
pubmed
15096476
uniprot
proteins
pubmed
15456791
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15641782
uniprot
proteins
pubmed
16037825
uniprot
proteins
pubmed
16585594
uniprot
proteins
pubmed
16964285
uniprot
proteins
pubmed
16982856
uniprot
proteins
pubmed
17178784
uniprot
proteins
pubmed
17339483
uniprot
proteins
pubmed
17349957
uniprot
proteins
pubmed
17599095
uniprot
proteins
pubmed
18362139
uniprot
proteins
pubmed
19158675
uniprot
proteins
pubmed
19158676
uniprot
proteins
pubmed
19234215
uniprot
proteins
pubmed
19494289
uniprot
proteins
pubmed
19759015
uniprot
proteins
pubmed
19759850
uniprot
proteins
pubmed
19915568
uniprot
proteins
pubmed
20482797
uniprot
proteins
pubmed
21124315
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21487011
uniprot
proteins
pubmed
21575908
uniprot
proteins
pubmed
22732093
uniprot
proteins
pubmed
23229815
uniprot
proteins
pubmed
23530044
uniprot
proteins
pubmed
23955712
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24630722
uniprot
proteins
pubmed
25847972
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27432880
uniprot
proteins
pubmed
28094437
uniprot
proteins
pubmed
28314590
uniprot
proteins
pubmed
29440442
uniprot
proteins
pubmed
30674671
uniprot
proteins
pubmed
33420028
uniprot
proteins
pubmed
33420033
uniprot
proteins
pubmed
33980849
uniprot
proteins
pubmed
34341353
uniprot
proteins
pubmed
34678144
uniprot
proteins
pubmed
34706239
uniprot
proteins
pubmed
35559676
uniprot
proteins
pubmed
36050480
uniprot
proteins
pubmed
40250624
uniprot
proteins
sequence_length
195
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:25847972}. Inflammasome {ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:34678144}. Endoplasmic reticulum {ECO:0000269|PubMed:21124315}. Mitochondrion {ECO:0000269|PubMed:14730312, ECO:0000269|PubMed:21124315}. Nucleus {ECO:0000269|PubMed:19234215, ECO:0000269|PubMed:25847972}. Note=Upstream of caspase activation, a redistribution from the cytoplasm to the aggregates occurs. These appear as hollow, perinuclear spherical, ball-like structures (PubMed:11103777, PubMed:12191486, PubMed:15030775). Upon NLRP3 inflammasome activation redistributes to the perinuclear space localizing to endoplasmic reticulum and mitochondria (PubMed:12191486, PubMed:15030775). Localized primarily to the nucleus in resting monocytes/macrophages and rapidly redistributed to the cytoplasm upon pathogen infection (PubMed:19234215). Localized to large cytoplasmic aggregate appearing as a speck containing AIM2, PYCARD, CASP8 and bacterial DNA after infection with Francisella tularensis (By similarity). {ECO:0000250|UniProtKB:Q9EPB4, ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:12191486, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:19234215}.; SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:23229815}. Note=(Microbial infection) Upon HRSV infection, the protein is mainly located in lipid rafts in the Golgi membrane. {ECO:0000269|PubMed:23229815}.
uniprot
proteins