| IED ID | IndEnz0002005843 |
| Enzyme Type ID | protease005843 |
| Protein Name |
Caspase-1 CASP-1 EC 3.4.22.36 Interleukin-1 beta convertase IL-1BC Interleukin-1 beta-converting enzyme ICE IL-1 beta-converting enzyme p45 Cleaved into: Caspase-1 subunit p20; Caspase-1 subunit p10 |
| Gene Name | CASP1 IL1BC IL1BCE |
| 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 | MADKVLKEKRKLFIRSMGEGTINGLLDELLQTRVLNKEEMEKVKRENATVMDKTRALIDSVIPKGAQACQICITYICEEDSYLAGTLGLSADQTSGNYLNMQDSQGVLSSFPAPQAVQDNPAMPTSSGSEGNVKLCSLEEAQRIWKQKSAEIYPIMDKSSRTRLALIICNEEFDSIPRRTGAEVDITGMTMLLQNLGYSVDVKKNLTASDMTTELEAFAHRPEHKTSDSTFLVFMSHGIREGICGKKHSEQVPDILQLNAIFNMLNTKNCPSLKDKPKVIIIQACRGDSPGVVWFKDSVGVSGNLSLPTTEEFEDDAIKKAHIEKDFIAFCSSTPDNVSWRHPTMGSVFIGRLIEHMQEYACSCDVEEIFRKVRFSFEQPDGRAQMPTTERVTLTRCFYLFPGH |
| Enzyme Length | 404 |
| Uniprot Accession Number | P29466 |
| Absorption | |
| Active Site | ACT_SITE 237; /evidence="ECO:0000269|PubMed:1574116"; ACT_SITE 285; /evidence="ECO:0000269|PubMed:1574116, ECO:0000305|PubMed:32051255" |
| Activity Regulation | ACTIVITY REGULATION: (Microbial infection) Specifically inhibited by the cowpox virus Crma protein. {ECO:0000269|PubMed:1339309}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp-|-.; EC=3.4.22.36; Evidence={ECO:0000269|PubMed:1574116}; |
| DNA Binding | |
| EC Number | 3.4.22.36 |
| Enzyme Function | FUNCTION: Thiol protease involved in a variety of inflammatory processes by proteolytically cleaving other proteins, such as the precursors of the inflammatory cytokines interleukin-1 beta (IL1B) and interleukin 18 (IL18) as well as the pyroptosis inducer Gasdermin-D (GSDMD), into active mature peptides (PubMed:15326478, PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:26375003, PubMed:32051255). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage of the two inflammatory cytokines IL1B and IL18, releasing the mature cytokines which are involved in a variety of inflammatory processes (PubMed:1574116, PubMed:7876192, PubMed:15498465, PubMed:15326478, PubMed:32051255). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:1574116, PubMed:7876192, PubMed:15498465). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:26375003). In contrast to cleavage of interleukins IL1B and IL1B, recognition and cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP1 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32051255, PubMed:32109412, PubMed:32553275). Upon inflammasome activation, during DNA virus infection but not RNA virus challenge, controls antiviral immunity through the cleavage of CGAS, rendering it inactive (PubMed:28314590). In apoptotic cells, cleaves SPHK2 which is released from cells and remains enzymatically active extracellularly (PubMed:20197547). {ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:15498465, ECO:0000269|PubMed:1574116, ECO:0000269|PubMed:20197547, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:32051255, ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32553275, ECO:0000269|PubMed:7876192}.; FUNCTION: [Isoform Delta]: Apoptosis inactive. {ECO:0000269|PubMed:7876192}.; FUNCTION: [Isoform Epsilon]: Apoptosis inactive. {ECO:0000269|PubMed:7876192}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (4); Beta strand (16); Chain (2); Cross-link (1); Domain (1); Erroneous initiation (1); Helix (9); Modified residue (1); Mutagenesis (6); Natural variant (1); Propeptide (2); Sequence caution (1); Sequence conflict (2); Turn (5) |
| Keywords | 3D-structure;Alternative splicing;Apoptosis;Cell membrane;Cytoplasm;Direct protein sequencing;Hydrolase;Isopeptide bond;Membrane;Phosphoprotein;Protease;Reference proteome;Thiol protease;Ubl conjugation;Zymogen |
| Interact With | Q5XLA6; P57730; Itself; P09038; P01583; O15553; O15553-2; Q9NPP4; Q9C000; Q9HC29; Q9ULZ3; P58753-2; Q08AM6; P05067; P54252; Q13867; P14136; P42858; Q13387-4; P27986-2; O14494; O60260-5; P49810; P84022; Q9BX74; O60784-2; Q08AM6; Q9UBQ0-2; O76024; P01583 |
| Induction | INDUCTION: Transcription and translation induced by M.tuberculosis and a number of different M.tuberculosis components; EsxA is the most potent activator tested (at protein level) (PubMed:20148899). {ECO:0000269|PubMed:20148899}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20197547}. Cell membrane {ECO:0000269|PubMed:20197547}. |
| Modified Residue | MOD_RES 302; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P29452 |
| Post Translational Modification | PTM: The two subunits are derived from the precursor sequence by an autocatalytic mechanism. {ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:8044845}.; PTM: Ubiquitinated via 'Lys-11'-linked polyubiquitination. Deubiquitinated by USP8. {ECO:0000269|PubMed:30065070}.; PTM: Cleavage in the interdomain linker region is required to induce pyroptosis. {ECO:0000269|PubMed:32051255}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (2); X-ray crystallography (36) |
| Cross Reference PDB | 1BMQ; 1IBC; 1ICE; 1RWK; 1RWM; 1RWN; 1RWO; 1RWP; 1RWV; 1RWW; 1RWX; 1SC1; 1SC3; 1SC4; 2FQQ; 2H48; 2H4W; 2H4Y; 2H51; 2H54; 2HBQ; 2HBR; 2HBY; 2HBZ; 3D6F; 3D6H; 3D6M; 3E4C; 3NS7; 5FNA; 5MMV; 5MTK; 6BZ9; 6F6R; 6KN0; 6PZP; 6VIE; 7KEU; |
| Mapped Pubmed ID | 10329646; 11145836; 11226410; 11278253; 11374873; 11390368; 11821383; 11967258; 12019269; 12096920; 12170183; 12191486; 12215842; 12387869; 12459463; 12628757; 12692130; 14584052; 14669344; 15039421; 15471361; 15561713; 15809717; 16037825; 16087165; 16123779; 16135520; 16260731; 16274992; 16405550; 16428475; 16511067; 16621994; 16682620; 16780720; 16817903; 16903774; 16920334; 17036048; 17173859; 17284521; 17303764; 17360653; 17418785; 17477815; 17597823; 17623017; 17703412; 17959595; 18209072; 18263705; 18263805; 18304957; 18329368; 18390730; 18523309; 18550243; 18577712; 18590738; 18799371; 18981155; 19074885; 19117953; 19141860; 19158675; 19158676; 19258923; 19269008; 19382257; 19414860; 19439663; 19573080; 19648107; 19737897; 19773279; 19779610; 19825518; 19833722; 19913121; 20038581; 20048342; 20060974; 20170165; 20184726; 20402676; 20485444; 20503287; 20628086; 20656488; 20711500; 20808838; 20855536; 20959405; 21037509; 21052690; 21311905; 21320026; 21463955; 21757759; 21792841; 21832064; 21862576; 21862623; 22046441; 22227487; 22491736; 22537218; 22833538; 22837397; 23021143; 23190696; 23209292; 23226468; 23236067; 23278288; 23386603; 23508996; 23637985; 23703390; 23793845; 23839215; 23884363; 24022484; 24130483; 24158569; 24275551; 24356306; 24453977; 24481253; 24553140; 24630722; 24699513; 24701032; 24947802; 24954757; 25061439; 25174821; 25284686; 25330190; 25372293; 25403406; 25416956; 25562666; 25567507; 25589411; 25658455; 25684031; 25759090; 25806508; 25938942; 26146985; 26168332; 26218605; 26240347; 26324708; 26324711; 26453510; 26457439; 26466953; 26492464; 26496436; 26510601; 26599267; 27043298; 27045344; 27146654; 27148834; 27174093; 27482083; 27626170; 27669650; 27965258; 28000894; 28011505; 28052562; 28153878; 28244850; 28272793; 28383547; 28388569; 28407357; 28456882; 28584053; 28726636; 29113699; 29177860; 29365280; 29438387; 29483915; 29485395; 29545514; 29592872; 29648825; 29653983; 29672590; 29724886; 29891674; 29895691; 29957081; 30100068; 30279182; 30393369; 30584943; 30596757; 30987692; 31252176; 31429707; 31877317; 32122970; 32129540; 32176433; 32258157; 32397236; 32420343; 32613271; 32907600; 32996055; 33383234; 33385378; 33430857; 33559194; 33571624; 33741902; 33886057; 33968032; 33971110; 33999861; 34087627; 34270981; 34335569; 34598017; 34635624; 34769294; 7721861; 7797510; 8035875; 8242741; 8978814; 8999548; 9027312; 9070648; 9121587; 9435230; 9705938; |
| Motif | |
| Gene Encoded By | |
| Mass | 45,159 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.36; |