| IED ID | IndEnz0002005847 |
| Enzyme Type ID | protease005847 |
| Protein Name |
Caspase recruitment domain-containing protein 8 EC 3.4.-.- Cleaved into: Caspase recruitment domain-containing protein 8, C-terminus CARD8-CT ; Caspase recruitment domain-containing protein 8, N-terminus CARD8-NT |
| Gene Name | CARD8 |
| Organism | Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) |
| 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) Ponginae Pongo Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) |
| Enzyme Sequence | MGIPTSSVSEEQESSEGQDSGDICSEENQIVSSYASKVCFEIEQDYKNRQFLGPEGNVDVELIDKSTNTYSVRFPTAGWYLWPATGLGFLVRDVVTLTIGFGSWNQHLALDLQHHEQWLVGGPLFDITAEPEEAVAEIHLPHFISLQAGEVDVSWFLIAHFKNEGMVLEHPARVEPFYAVLEKPSFSLMGILLRIASGTRLSIPITSNTLIYYHPHPEDIKFHLYLVPSDALLTKMIDDEEDRFCGVRLQTSPPVEPLNFGARYIVSNSAHLEIIPTELKLSYRSPGEIQHFSKFYAGQMKEPIQLEITEKRHETLVWKTVVKPVDIQLGAASAPPAFSGAAFVKENHRQLQARMGDLKGVLDDLQDNEVLTENEKELVEQAKTRQSKNDTLLTMVEKKGDRALELLFRSISERDPYLVSYLRQQSL |
| Enzyme Length | 427 |
| Uniprot Accession Number | Q5RAV7 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: CARD8 inflammasome is inhibited by DPP8 and DPP9, which sequester the C-terminal fragment of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus) in a ternary complex, thereby preventing CARD8 oligomerization and activation. CARD8 inflammasome is activated by Val-boroPro (Talabostat, PT-100), an inhibitor of dipeptidyl peptidases DPP8 and DPP9. Val-boroPro relieves inhibition of DPP8 and/or DPP9 by inducing the proteasome-mediated destruction of the N-terminal part of CARD8, releasing its C-terminal part from autoinhibition. {ECO:0000250|UniProtKB:Q9Y2G2}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.-.- |
| Enzyme Function | FUNCTION: Inflammasome sensor, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis of CD4(+) T-cells and macrophages. Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation. Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as Val-boroPro inhibitor, and mediates CARD8 inflammasome activation. In response to pathogen-associated signals, the N-terminal part of CARD8 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes to initiate the formation of the inflammasome complex: the CARD8 inflammasome directly recruits pro-caspase-1 (proCASP1) independently of PYCARD/ASC and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis. Also acts as a negative regulator of the NLRP3 inflammasome. May also act as an inhibitor of NF-kappa-B activation. {ECO:0000250|UniProtKB:Q9Y2G2}.; FUNCTION: [Caspase recruitment domain-containing protein 8]: Constitutes the precursor of the CARD8 inflammasome, which mediates autoproteolytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals. {ECO:0000250|UniProtKB:Q9Y2G2}.; FUNCTION: [Caspase recruitment domain-containing protein 8, N-terminus]: Regulatory part that prevents formation of the CARD8 inflammasome: in absence of pathogens and other damage-associated signals, interacts with the C-terminal part of CARD8 (Caspase recruitment domain-containing protein 8, C-terminus), preventing activation of the CARD8 inflammasome. In response to pathogen-associated signals, this part is ubiquitinated by the N-end rule pathway and degraded by the proteasome, releasing the cleaved C-terminal part of the protein, which polymerizes and forms the CARD8 inflammasome. {ECO:0000250|UniProtKB:Q9Y2G2}.; FUNCTION: [Caspase recruitment domain-containing protein 8, C-terminus]: Constitutes the active part of the CARD8 inflammasome. In absence of pathogens and other damage-associated signals, interacts with the N-terminal part of CARD8 (Caspase recruitment domain-containing protein 8, N-terminus), preventing activation of the CARD8 inflammasome. In response to pathogen-associated signals, the N-terminal part of CARD8 is degraded by the proteasome, releasing this form, which polymerizes to form the CARD8 inflammasome complex: the CARD8 inflammasome complex then directly recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, leading to gasdermin-D (GSDMD) cleavage and subsequent pyroptosis. {ECO:0000250|UniProtKB:Q9Y2G2}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Chain (3); Domain (2); Region (3); Site (1) |
| Keywords | Apoptosis;Cytoplasm;Hydrolase;Immunity;Inflammasome;Inflammatory response;Innate immunity;Necrosis;Nucleus;Protease;Reference proteome;Ubl conjugation |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2G2}. Nucleus {ECO:0000250|UniProtKB:Q9Y2G2}.; SUBCELLULAR LOCATION: [Caspase recruitment domain-containing protein 8, C-terminus]: Inflammasome {ECO:0000250|UniProtKB:Q9Y2G2}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Caspase recruitment domain-containing protein 8]: Undergoes autocatalytic processing within the FIIND domain to generate the N-terminal and C-terminal parts, which are associated non-covalently in absence of pathogens and other damage-associated signals. {ECO:0000250|UniProtKB:Q9Y2G2}.; PTM: [Caspase recruitment domain-containing protein 8, N-terminus]: Ubiquitinated by the N-end rule pathway in response to pathogens and other damage-associated signals, leading to its degradation by the proteasome and subsequent release of the cleaved C-terminal part of the protein (Caspase recruitment domain-containing protein 8, C-terminus), which polymerizes and forms the CARD8 inflammasome. {ECO:0000250|UniProtKB:Q9Y2G2}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 48,186 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |