Casp8
entrez
12370
canonical
uniprot
O89110
canonical
ensembl
ENSMUSG00000026029
resolver
ensp
ENSMUSP00000027189
resolver
ensp
ENSMUSP00000127375
resolver
ensp
ENSMUSP00000140335
resolver
ensp
ENSMUSP00000140546
resolver
ensp
ENSMUSP00000245023
resolver
enst
ENSMUST00000027189
resolver
enst
ENSMUST00000165549
resolver
enst
ENSMUST00000190213
resolver
enst
ENSMUST00000191201
resolver
genesymbol
Casp8
resolver
uniprot
A0A087WQT6
resolver
uniprot
O35669
resolver
uniprot
Q3U607
resolver
uniprot_entry
A0A087WQT6_MOUSE
resolver
uniprot_entry
CASP8_MOUSE
resolver
uniprot_entry
Q3U607_MOUSE
resolver
uniprot_sec
O35669
resolver
activity_regulation
ACTIVITY REGULATION: CASP8 activity is restricted by RIPK1. {ECO:0000269|PubMed:24813849, ECO:0000269|PubMed:24813850}.; ACTIVITY REGULATION: (Microbial infection) Inhibited by baculovirus p35 protein P35. {ECO:0000269|PubMed:9837723}.
uniprot
proteins
amino_acid_sequence
MDFQSCLYAIAEELGSEDLAALKFLCLDYIPHKKQETIEDAQKLFLRLREKGMLEEGNLSFLKELLFHISRWDLLVNFLDCNREEMVRELRDPDNAQISPYRVMLFKLSEEVSELELRSFKFLLNNEIPKCKLEDDLSLLEIFVEMEKRTMLAENNLETLKSICDQVNKSLLGKIEDYERSSTERRMSLEGREELPPSVLDEMSLKMAELCDSPREQDSESRTSDKVYQMKNKPRGYCLIINNHDFSKAREDITQLRKMKDRKGTDCDKEALSKTFKELHFEIVSYDDCTANEIHEILEGYQSADHKNKDCFICCILSHGDKGVVYGTDGKEASIYDLTSYFTGSKCPSLSGKPKIFFIQACQGSNFQKGVPDEAGFEQQNHTLEVDSSSHKNYIPDEADFLLGMATVKNCVSYRDPVNGTWYIQSLCQSLRERCPQGDDILSILTGVNYDVSNKDDRRNKGKQMPQPTFTLRKKLFFPP
uniprot
proteins
ec_number
3.4.22.61
uniprot
proteins
function
FUNCTION: Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:12065591, PubMed:18455983, PubMed:30361383, PubMed:30381458, PubMed:31511692, PubMed:31748744, PubMed:33397971, PubMed:9727491, PubMed:9727492). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death (PubMed:24813849, PubMed:24813850, PubMed:9654089, PubMed:9837723). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (By similarity). Binding to the adapter molecule FADD recruits it to either receptor FAS/CD95 or TNFRSF1A (PubMed:29440439). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (By similarity). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (By similarity). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (By similarity). Also cleaves and activates BID, thereby promoting cytochrome C release from mitochrondria (PubMed:9727491, PubMed:9727492). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-325', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31511692). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:30361383, PubMed:30381458). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (PubMed:30361383, PubMed:30381458). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (PubMed:32971525). May participate in the Granzyme B (GZMB) cell death pathways (By similarity). Cleaves PARP1 and PARP2 (PubMed:12065591). {ECO:0000250|UniProtKB:Q14790, ECO:0000269|PubMed:12065591, ECO:0000269|PubMed:18455983, ECO:0000269|PubMed:24813849, ECO:0000269|PubMed:24813850, ECO:0000269|PubMed:29440439, ECO:0000269|PubMed:30361383, ECO:0000269|PubMed:30381458, ECO:0000269|PubMed:31511692, ECO:0000269|PubMed:31748744, ECO:0000269|PubMed:32971525, ECO:0000269|PubMed:33397971, ECO:0000269|PubMed:9654089, ECO:0000269|PubMed:9727491, ECO:0000269|PubMed:9727492, ECO:0000269|PubMed:9837723}.
uniprot
proteins
mass_dalton
55357
uniprot
proteins
mutagenesis
MUTAGEN 212; /note="D->A: Loss of autocatalytic cleavage; when associated with A-218; A-225 and A-387."; /evidence="ECO:0000269|PubMed:31511692"; MUTAGEN 218; /note="D->A: Loss of autocatalytic cleavage; when associated with A-212; A-225 and A-387."; /evidence="ECO:0000269|PubMed:31511692"; MUTAGEN 225; /note="D->A: Loss of autocatalytic cleavage; when associated with A-212; A-218 and A-387."; /evidence="ECO:0000269|PubMed:31511692"; MUTAGEN 362; /note="C->A: Loss of kinase activity. Knockin mice show embryonic lethality caused by endothelial cell necroptosis leading to cardiovascular defects. Mlkl deficiency rescues the cardiovascular phenotype of knockin mice, but causes perinatal lethality caused by induction of pyroptosis."; /evidence="ECO:0000269|PubMed:31511692, ECO:0000269|PubMed:31748744"; MUTAGEN 387; /note="D->A: Loss of autocatalytic cleavage; when associated with A-212; A-218 and A-225."; /evidence="ECO:0000269|PubMed:31511692
uniprot
proteins
post_translational_modification
PTM: Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease (PubMed:31511692). GZMB and CASP10 can be involved in these processing events (By similarity). {ECO:0000250|UniProtKB:Q14790, ECO:0000269|PubMed:31511692}.; PTM: (Microbial infection) Proteolytically cleaved by the cowpox virus CRMA death inhibitory protein. {ECO:0000269|PubMed:9837723}.; PTM: Phosphorylation on Ser-389 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (By similarity). {ECO:0000250|UniProtKB:Q14790}.
uniprot
proteins
protein_family
Peptidase C14A family
uniprot
proteins
pubmed
12065591
uniprot
proteins
pubmed
15383280
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17245429
uniprot
proteins
pubmed
18455983
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
24813849
uniprot
proteins
pubmed
24813850
uniprot
proteins
pubmed
29440439
uniprot
proteins
pubmed
30361383
uniprot
proteins
pubmed
30381458
uniprot
proteins
pubmed
31511692
uniprot
proteins
pubmed
31519887
uniprot
proteins
pubmed
31748744
uniprot
proteins
pubmed
32971525
uniprot
proteins
pubmed
33397971
uniprot
proteins
pubmed
34471287
uniprot
proteins
pubmed
9654089
uniprot
proteins
pubmed
9727491
uniprot
proteins
pubmed
9727492
uniprot
proteins
pubmed
9729047
uniprot
proteins
pubmed
9837723
uniprot
proteins
sequence_length
480
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12065591}. Nucleus {ECO:0000269|PubMed:12065591}. Note=Translocates into the nucleus during apoptosis. {ECO:0000269|PubMed:12065591}.
uniprot
proteins