| IED ID | IndEnz0002014579 |
| Enzyme Type ID | protease014579 |
| Protein Name |
Apoptosis-associated speck-like protein containing a CARD hASC Caspase recruitment domain-containing protein 5 PYD and CARD domain-containing protein Target of methylation-induced silencing 1 |
| Gene Name | PYCARD ASC CARD5 TMS1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGRARDAILDALENLTAEELKKFKLKLLSVPLREGYGRIPRGALLSMDALDLTDKLVSFYLETYGAELTANVLRDMGLQEMAGQLQAATHQGSGAAPAGIQAPPQSAAKPGLHFIDQHRAALIARVTNVEWLLDALYGKVLTDEQYQAVRAEPTNPSKMRKLFSFTPAWNWTCKDLLLQALRESQSYLVEDLERS |
| Enzyme Length | 195 |
| Uniprot Accession Number | Q9ULZ3 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: 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 pyrin and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, NLRP6, AIM2 and probably IFI16 (PubMed:15030775, PubMed:17349957, PubMed:19158676, PubMed:19158675, PubMed:30674671, PubMed:34678144). 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. 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:21487011, ECO:0000269|PubMed:22732093, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:30674671, ECO:0000269|PubMed:34678144}.; 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}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (2); Beta strand (2); Chain (1); Domain (2); Frameshift (1); Helix (14); Modified residue (1); Mutagenesis (27); Turn (2) |
| Keywords | 3D-structure;Alternative splicing;Apoptosis;Cytoplasm;Endoplasmic reticulum;Golgi apparatus;Immunity;Inflammasome;Inflammatory response;Innate immunity;Membrane;Mitochondrion;Nucleus;Phosphoprotein;Reference proteome;Tumor suppressor |
| Interact With | O14862; Q07812; P29466; O00471; O15553; Q7RTR2; Q9C000; Q96P20; Itself; Q56P42; Q13546; P43405 |
| Induction | INDUCTION: In macrophages, up-regulated by endocannabinoid anandamide/AEA. {ECO:0000269|PubMed:23955712}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11103777, ECO:0000269|PubMed:15030775, ECO:0000269|PubMed:19234215}. 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}. 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}. |
| Modified Residue | MOD_RES 195; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9EPB4 |
| Post Translational Modification | PTM: Phosphorylated. {ECO:0000269|PubMed:12656673}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); Electron microscopy (4); X-ray crystallography (2) |
| Cross Reference PDB | 1UCP; 2KN6; 3J63; 5H8O; 6K99; 6KI0; 6N1H; 7KEU; |
| Mapped Pubmed ID | 12615073; 1574116; 16189514; 17418785; 19636848; 22267217; 22286270; 23650620; 24237704; 24407287; 24630722; 25266676; 25402006; 25416956; 25605870; 27069117; 27796369; 30279182; 31333677; 33431827; 8692836; |
| Motif | |
| Gene Encoded By | |
| Mass | 21,627 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |