CASP8
entrez
841
canonical
uniprot
Q14790
canonical
ensembl
ENSG00000064012
resolver
ensp
ENSP00000264275
resolver
ensp
ENSP00000325722
resolver
ensp
ENSP00000351273
resolver
ensp
ENSP00000376087
resolver
ensp
ENSP00000376091
resolver
ensp
ENSP00000391709
resolver
ensp
ENSP00000394434
resolver
ensp
ENSP00000396869
resolver
ensp
ENSP00000397528
resolver
ensp
ENSP00000412523
resolver
ensp
ENSP00000501268
resolver
ensp
ENSP00000512369
resolver
ensp
ENSP00000512381
resolver
ensp
ENSP00000512382
resolver
ensp
ENSP00000627982
resolver
ensp
ENSP00000652420
resolver
ensp
ENSP00000652421
resolver
ensp
ENSP00000652424
resolver
ensp
ENSP00000688940
resolver
ensp
ENSP00000688941
resolver
ensp
ENSP00000688948
resolver
ensp
ENSP00000688949
resolver
ensp
ENSP00000688951
resolver
ensp
ENSP00000688954
resolver
enst
ENST00000696085
resolver
genesymbol
CASP8
resolver
genesymbol_syn
MCH5
resolver
hgnc
HGNC:1509
resolver
uniprot
A0A8Q3SID9
resolver
uniprot
O14676
resolver
uniprot
Q14791
resolver
uniprot
Q14792
resolver
uniprot
Q14793
resolver
uniprot
Q14794
resolver
uniprot
Q14795
resolver
uniprot
Q14796
resolver
uniprot
Q15780
resolver
uniprot
Q15806
resolver
uniprot
Q53TT5
resolver
uniprot
Q8TDI1
resolver
uniprot
Q8TDI2
resolver
uniprot
Q8TDI3
resolver
uniprot
Q8TDI4
resolver
uniprot
Q8TDI5
resolver
uniprot
Q96T22
resolver
uniprot
Q9C0K4
resolver
uniprot
Q9UQ81
resolver
uniprot_entry
A0A8Q3SID9_HUMAN
resolver
uniprot_entry
CASP8_HUMAN
resolver
uniprot_sec
O14676
resolver
uniprot_sec
Q14791
resolver
uniprot_sec
Q14792
resolver
uniprot_sec
Q14793
resolver
uniprot_sec
Q14794
resolver
uniprot_sec
Q14795
resolver
uniprot_sec
Q14796
resolver
uniprot_sec
Q15780
resolver
uniprot_sec
Q15806
resolver
uniprot_sec
Q53TT5
resolver
uniprot_sec
Q8TDI1
resolver
uniprot_sec
Q8TDI2
resolver
uniprot_sec
Q8TDI3
resolver
uniprot_sec
Q8TDI4
resolver
uniprot_sec
Q8TDI5
resolver
uniprot_sec
Q96T22
resolver
uniprot_sec
Q9C0K4
resolver
uniprot_sec
Q9UQ81
resolver
activity_regulation
ACTIVITY REGULATION: CASP8 activity is restricted by RIPK1 (By similarity). Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis (PubMed:23516580). {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:23516580}.
uniprot
proteins
amino_acid_sequence
MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSFLKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSFKFLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEEFSKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINNHNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQLMDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQACQGDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTWYIQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD
uniprot
proteins
disease_involvement
DISEASE: Caspase-8 deficiency (CASP8D) [MIM:607271]: Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization. {ECO:0000269|PubMed:12353035}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). 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:23516580, PubMed:35338844, PubMed:35446120, PubMed:8681376, PubMed:8681377, PubMed:8962078, PubMed:9006941, PubMed:9184224). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:16916640, PubMed:8962078, PubMed:9006941). Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). Also cleaves and activates BID, thereby promoting cytochrome C release from mitochrondria (By similarity). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). 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:32929201, PubMed:34012073). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376). Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380 (PubMed:18216014, PubMed:27109099). {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:18216014, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:27109099, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32929201, ECO:0000269|PubMed:34012073, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:8681376, ECO:0000269|PubMed:8681377, ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:8962078, ECO:0000269|PubMed:9006941, ECO:0000269|PubMed:9184224}.; FUNCTION: [Isoform 5]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 6]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 7]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade (PubMed:12010809). {ECO:0000269|PubMed:12010809, ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 8]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.
uniprot
proteins
mass_dalton
55391
uniprot
proteins
mutagenesis
MUTAGEN 73; /note="D->A: Abolishes binding to FLASH. Induces NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:15592525"; MUTAGEN 360; /note="C->A: Does not affect localization to lamellipodia of migrating cells. Prevents DISC-mediated processing of CASP8."; /evidence="ECO:0000269|PubMed:18216014, ECO:0000269|PubMed:27109099"; MUTAGEN 360; /note="C->S: Abolishes interaction with UBR2."; /evidence="ECO:0000269|PubMed:28602583"; MUTAGEN 380; /note="Y->E: Phosphomimetic mutant which does not affect interaction with PIK3R1 or DISC-mediated processing."; /evidence="ECO:0000269|PubMed:27109099"; MUTAGEN 380; /note="Y->F: Abolishes phosphorylation at this site. Lack of efficient localization to lamellipodia and lack of promotion of cell migration. Lack of interaction with the SH2 domain of SRC. Lack of interaction with PIK3R1. Impaired DISC-mediated processing."; /evidence="ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18216014, ECO:0000269|PubMed:27109099"; MUTAGEN 387; /note="S->A: Impaired CDK1-mediated phosphorylation and enhanced apoptosis."; MUTAGEN 413; /note="R->A: Abolished ADP-riboxanation by C.violaceum CopC."; /evidence="ECO:0000269|PubMed:35446120
uniprot
proteins
post_translational_modification
PTM: Generation of the p10 and p18 subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease. GZMB and CASP10 can be involved in these processing events. {ECO:0000269|PubMed:8962078, ECO:0000269|PubMed:9184224}.; PTM: Phosphorylation on Ser-387 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis (PubMed:20937773). Phosphorylation on Tyr-380 by SRC is mediated by interaction with the SRC SH2 domain and does not affect dimerization or recruitment to the death-inducing signaling complex (DISC) but negatively regulates DISC-mediated processing and activation of CASP8, down-regulating its proapoptotic function (PubMed:16619028, PubMed:27109099). Phosphorylation on Tyr-380 also enhances localization to lamellipodia in migrating cells (PubMed:18216014). {ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18216014, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:27109099}.; PTM: (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks CASP8 processing, preventing CASP8 activation and ability to mediate extrinsic apoptosis. {ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120}.; PTM: (Microbial infection) Proteolytically cleaved by the cowpox virus CRMA death inhibitory protein. {ECO:0000269|PubMed:8962078}.
uniprot
proteins
protein_family
Peptidase C14A family
uniprot
proteins
pubmed
10442631
uniprot
proteins
pubmed
10508784
uniprot
proteins
pubmed
10508785
uniprot
proteins
pubmed
10860845
uniprot
proteins
pubmed
11161814
uniprot
proteins
pubmed
11427719
uniprot
proteins
pubmed
11917123
uniprot
proteins
pubmed
12010809
uniprot
proteins
pubmed
12353035
uniprot
proteins
pubmed
14759258
uniprot
proteins
pubmed
15069192
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15509781
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15592525
uniprot
proteins
pubmed
15601643
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16378960
uniprot
proteins
pubmed
16619028
uniprot
proteins
pubmed
16916640
uniprot
proteins
pubmed
17245429
uniprot
proteins
pubmed
17293864
uniprot
proteins
pubmed
17450141
uniprot
proteins
pubmed
18216014
uniprot
proteins
pubmed
18563783
uniprot
proteins
pubmed
18846110
uniprot
proteins
pubmed
20937773
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22858542
uniprot
proteins
pubmed
23516580
uniprot
proteins
pubmed
25674983
uniprot
proteins
pubmed
27109099
uniprot
proteins
pubmed
28602583
uniprot
proteins
pubmed
31827280
uniprot
proteins
pubmed
31827281
uniprot
proteins
pubmed
32929201
uniprot
proteins
pubmed
34012073
uniprot
proteins
pubmed
35338844
uniprot
proteins
pubmed
35446120
uniprot
proteins
pubmed
8681376
uniprot
proteins
pubmed
8681377
uniprot
proteins
pubmed
8755496
uniprot
proteins
pubmed
8962078
uniprot
proteins
pubmed
9006941
uniprot
proteins
pubmed
9184224
uniprot
proteins
pubmed
9228018
uniprot
proteins
pubmed
9334338
uniprot
proteins
pubmed
9931493
uniprot
proteins
sequence_length
479
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9JHX4}. Nucleus {ECO:0000250|UniProtKB:Q9JHX4}. Cell projection, lamellipodium {ECO:0000269|PubMed:18216014}. Note=Recruitment to lamellipodia of migrating cells is enhanced by phosphorylation at Tyr-380. {ECO:0000269|PubMed:18216014}.
uniprot
proteins