Casp1
entrez
12362
canonical
uniprot
P29452
canonical
ensembl
ENSMUSG00000025888
resolver
ensp
ENSMUSP00000027015
resolver
enst
ENSMUST00000027015
resolver
genesymbol
Casp1
resolver
genesymbol_syn
Il1bc
resolver
uniprot_entry
CASP1_MOUSE
resolver
amino_acid_sequence
MADKILRAKRKQFINSVSIGTINGLLDELLEKRVLNQEEMDKIKLANITAMDKARDLCDHVSKKGPQASQIFITYICNEDCYLAGILELQSAPSAETFVATEDSKGGHPSSSETKEEQNKEDGTFPGLTGTLKFCPLEKAQKLWKENPSEIYPIMNTTTRTRLALIICNTEFQHLSPRVGAQVDLREMKLLLEDLGYTVKVKENLTALEMVKEVKEFAACPEHKTSDSTFLVFMSHGIQEGICGTTYSNEVSDILKVDTIFQMMNTLKCPSLKDKPKVIIIQACRGEKQGVVLLKDSVRDSEEDFLTDAIFEDDGIKKAHIEKDFIAFCSSTPDNVSWRHPVRGSLFIESLIKHMKEYAWSCDLEDIFRKVRFSFEQPEFRLQMPTADRVTLTKRFYLFPGH
uniprot
proteins
ec_number
3.4.22.36
uniprot
proteins
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:21147462, PubMed:32109412). Plays a key role in cell immunity as an inflammatory response initiator: once activated through formation of an inflammasome complex, it initiates a pro-inflammatory 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:21147462). Cleaves a tetrapeptide after an Asp residue at position P1 (PubMed:21147462). Also initiates pyroptosis, a programmed lytic cell death pathway, through cleavage of GSDMD (PubMed:32109412). In contrast to cleavage of interleukin 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:32109412). Cleaves and activates CASP7 in response to bacterial infection, promoting plasma membrane repair (PubMed:18667412, PubMed:22464733, PubMed:35705808). 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 (By similarity). {ECO:0000250|UniProtKB:P29466, ECO:0000269|PubMed:21147462, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:35705808}.
uniprot
proteins
mass_dalton
45640
uniprot
proteins
mutagenesis
MUTAGEN 102..122; /note="EDSKGGHPSSSETKEEQNKED->AASKGGHPSSSATKAAQNKAA: Prevents autoprocessing."; /evidence="ECO:0000269|PubMed:32109412"; MUTAGEN 103; /note="D->N: In C71 mutant; abolished cleavage and ability to generate caspase-1 subunits; abolished ability to process inflammatory cytokine interleukin-1 beta (IL1B) and ability to induce programmed cell death; when associated with N-122 and 296-N--N-314."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 122; /note="D->N: In C71 mutant; abolished cleavage and ability to generate caspase-1 subunits; abolished ability to process inflammatory cytokine interleukin-1 beta (IL1B) and ability to induce programmed cell death; when associated with N-103 and 296-N--N-314."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 284; /note="C->A: Loss of protease activity."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 296..314; /note="DSVRDSEEDFLTDAIFEDD->NSVRDSEEDFLTNAIFENN: In C71 mutant; abolished cleavage and ability to generate caspase-1 subunits; abolished ability to process inflammatory cytokine interleukin-1 beta (IL1B) and ability to induce programmed cell death; when associated with N-103 and N-122."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 296..314; /note="DSVRDSEEDFLTDAIFEDD->NSVRNSEENFLTNAIFENN: In C60 mutant; impaired cleavage and ability to generate caspase-1 subunits p10 and p20; abolished ability to process inflammatory cytokine interleukin-1 beta (IL1B) without affecting ability to induce programmed cell death."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 296; /note="D->N: In C47 mutant; does not affect ability to mediate inflammatory response; when associated with 313-N-N-314."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 313..314; /note="DD->NN: In C47 mutant; does not affect ability to mediate inflammatory response and cell death; when associated with N-296."; /evidence="ECO:0000269|PubMed:21147462"; MUTAGEN 316; /note="I->N: Mediates autoprocessing but are unable to mediate cleavage of Gasdermin-D (GSDMD)."; /evidence="ECO:0000269|PubMed:32109412
uniprot
proteins
post_translational_modification
PTM: The two subunits are derived from the precursor sequence by an autocatalytic mechanism. {ECO:0000269|PubMed:21147462, ECO:0000269|PubMed:32109412}.; PTM: Ubiquitinated via 'Lys-11'-linked polyubiquitination. Deubiquitinated by USP8. {ECO:0000250|UniProtKB:P29466}.
uniprot
proteins
protein_family
Peptidase C14A family
uniprot
proteins
pubmed
1431103
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18667412
uniprot
proteins
pubmed
21147462
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22464733
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
28314590
uniprot
proteins
pubmed
30692621
uniprot
proteins
pubmed
32109412
uniprot
proteins
pubmed
34471287
uniprot
proteins
pubmed
35705808
uniprot
proteins
pubmed
8034321
uniprot
proteins
pubmed
8446594
uniprot
proteins
pubmed
9038361
uniprot
proteins
sequence_length
402
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21147462}. Cell membrane {ECO:0000250|UniProtKB:P29466}.
uniprot
proteins