CASP8 (Homo sapiens)
Description [+]
- Synonyms: CASP8, MCH5, MACH, FLICE
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-8 Precursor (CASP-8)(EC 3.4.22.61)(ICE-like apoptotic protease 5)(MORT1-associated CED-3 homolog)(MACH)(FADD-homologous ICE/CED-3-like protease)(FADD-like ICE)(FLICE)(Apoptotic cysteine protease)(Apoptotic protease Mch-5)(CAP4) [Contains Caspase-8 subunit p18;Caspase-8 subunit p10] [Source:UniProtKB/Swiss-Prot;Acc:Q14790]
- Family: CASPASE
- Process: apoptosis,
- Pathways: extrinsic pathway,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Casp8
- WIKI: CASP8-H_sapiens
References [+]
- Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death.
- Boldin MP, Goncharov TM, Goltsev YV, Wallach D
- Fas/APO-1 and p55 tumor necrosis factor (TNF) receptor (p55-R) activate cellular mechanisms that result in cell death. Upon activation of these receptors, Fas/APO-1 binds a protein called MORT1 (or FADD) and p55-R binds a protein called TRADD. MORT1 and TRADD can also bind to each other. We have cloned a novel protein, MACH, that binds to MORT1. This protein exists in multiple isoforms, some of which contain a region that has proteolytic activity and shows marked sequence homology to proteases of the ICE/CED-3 family. Cellular expression of the proteolytic MACH isoforms results in cell death. Expression of MACH isoforms that contain an incomplete ICE/CED-3 region provides effective protection against the cytotoxicity induced by Fas/APO-1 or p55-R triggering. These findings suggest that MACH is the most upstream enzymatic component in the Fas/APO-1- and p55-R-induced cell death signaling cascades. Cell. 1996 Jun 14;85(6):803-15.
- References from Mouse ortholog(s):
- Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally.
- Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D
- Homozygous targeted disruption of the mouse Caspase 8 (Casp8) gene was found to be lethal in utero. The Caspase 8 null embryos exhibited impaired heart muscle development and congested accumulation of erythrocytes. Recovery of hematopoietic colony-forming cells from the embryos was very low. In fibroblast strains derived from these embryos, the TNF receptors, Fas/Apo1, and DR3 were able to activate the Jun N-terminal kinase and to trigger IkappaB alpha phosphorylation and degradation. They failed, however, to induce cell death, while doing so effectively in wild-type fibroblasts. These findings indicate that Caspase 8 plays a necessary and nonredundant role in death induction by several receptors of the TNF/NGF family and serves a vital role in embryonal development. Immunity. 1998 Aug;9(2):267-76.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | DED | 62 | 145 |
| PFAM A | DED | 160 | 242 |
| PFAM A | Peptidase_C14 | 293 | 535 |
Protein sequence [+]
CASP8 | Homo sapiens | 9606 | length:538
MEGGRRARVVIESKRNFFLGAFPTPFPAEHVELGRLGDSETAMVPGKGGADYILLPFKKM
DFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSF
LKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSFK
FLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEEF
SKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINN
HNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQL
MDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQACQ
GDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTWY
IQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD
DFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSF
LKELLFRINRLDLLITYLNTRKEEMERELQTPGRAQISAYRVMLYQISEEVSRSELRSFK
FLLQEEISKCKLDDDMNLLDIFIEMEKRVILGEGKLDILKRVCAQINKSLLKIINDYEEF
SKERSSSLEGSPDEFSNGEELCGVMTISDSPREQDSESQTLDKVYQMKSKPRGYCLIINN
HNFAKAREKVPKLHSIRDRNGTHLDAGALTTTFEELHFEIKPHDDCTVEQIYEILKIYQL
MDHSNMDCFICCILSHGDKGIIYGTDGQEAPIYELTSQFTGLKCPSLAGKPKVFFIQACQ
GDNYQKGIPVETDSEEQPYLEMDLSSPQTRYIPDEADFLLGMATVNNCVSYRNPAEGTWY
IQSLCQSLRERCPRGDDILTILTEVNYEVSNKDDKKNMGKQMPQPTFTLRKKLVFPSD
Structure links:
- Smartdomain prediction information: SM00031
- Smartdomain prediction information: SM00115
- Prosite motif and domain information: PS01121
- Prosite motif and domain information: PS01122
- Profile motif and domain profile information: PS50168
- Profile motif and domain profile information: PS50207
- Profile motif and domain profile information: PS50208
- Interpro domain information: Q14790
- PFAM domain and domain family information: Q14790
- Protein 3D structures from PDB: 2C2Z 2FUN 1QDU 1QTN 1F9E 1I4E
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| NP_001038154.1 | orthology | Chicken |
| NP_989923.1 | orthology | Chicken |
| CASP8 | orthology | Chimpanzee |
| C_intestinalis_ENSCINP00000024485 | orthology | Ciona |
| NP_001039435.1 | orthology | Cow |
| Q38JA9_CANFA | orthology | Dog |
| T_rubripes_ENSTRUP00000024467 | orthology | Fugu |
| G_aculeatus_ENSGACP00000016969 | orthology | Gasterosteus |
| CASP8 | orthology | Gorilla |
| CASP8 | orthology | Horse |
| CASP8 | orthology | Macaca |
| Q56VC9_ORYLA | orthology | Medaka |
| CASP8 | orthology | Monodelphis |
| Casp8 | orthology | Mouse |
| Q5RCR7_PONPY | orthology | Orangutan |
| CASP8 | orthology | Ornithorhynchus |
| CASP8 | orthology | Rabbit |
| Casp8 | orthology | Rat |
| T_nigroviridis_ENSTNIP00000010722 | orthology | Tetraodon |
| CASP8 | orthology | Zebra finch |
| casp8l1 | orthology | Zebrafish |
| casp8 | orthology | Zebrafish |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| CASPS7 | paralogy | Anopheles |
| CASPS6 | paralogy | Anopheles |
| CASPS5 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| Q90WU0_CHICK | paralogy | Chicken |
| CFLAR | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| NP_990057.1 | paralogy | Chicken |
| CASP9 | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| CASP6 | paralogy | Chimpanzee |
| XR_025516.1 | paralogy | Chimpanzee |
| CFLAR | paralogy | Chimpanzee |
| CASP3_PANTR | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000011493 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000011503 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| IPI00704513.4 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| NP_001012281.1 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| CASP7 | paralogy | Dog |
| CASP6 | paralogy | Dog |
| CFLAR | paralogy | Dog |
| CASP10 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| decay | paralogy | Fly |
| Ice | paralogy | Fly |
| CASP6 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP9 | paralogy | Fugu |
| CASP6 | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016983 | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP7 | paralogy | Gorilla |
| CASP6 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP9 | paralogy | Horse |
| CFLAR | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP10 | paralogy | Horse |
| CASP6 | paralogy | Human |
| CASP10 | paralogy | Human |
| CASP3 | paralogy | Human |
| CFLAR | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP9 | paralogy | Human |
| CASP10 | paralogy | Lyzard |
| CASP3 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP6 | paralogy | Lyzard |
| CASP7 | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| CASP10 | paralogy | Macaca |
| Q8MJ18_MACMU | paralogy | Macaca |
| CASP9 | paralogy | Macaca |
| Q8JIS9_ORYLA | paralogy | Medaka |
| Q8JIS8_ORYLA | paralogy | Medaka |
| CASP9 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP10 | paralogy | Monodelphis |
| CFLAR | paralogy | Monodelphis |
| Casp7 | paralogy | Mouse |
| Casp6 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| CASP9 | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| CFLAR_PONPY | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP6 | paralogy | Orangutan |
| CASP3 | paralogy | Orangutan |
| CASP3 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000001054 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Ornithorhynchus |
| CASP6 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP10 | paralogy | Rabbit |
| CASP7 | paralogy | Rabbit |
| CFLAR | paralogy | Rabbit |
| Casp6 | paralogy | Rat |
| Casp3 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| CASP6 | paralogy | Tetraodon |
| CASP7 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| CASP3 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| casp6 | paralogy | Xenopus |
| T_guttata_ENSTGUP00000004278 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| CASP10 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| casp3a | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp6 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| LOC795066 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0034612 | response to tumor necrosis factor | biological_proccess | IMP |
| GO:0051603 | proteolysis involved in cellular protein catabolic process | biological_proccess | IMP |
| GO:0008624 | induction of apoptosis by extracellular signals | biological_proccess | IMP |
| GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
| GO:0008633 | activation of pro-apoptotic gene products | biological_proccess | EXP |
| GO:0043123 | positive regulation of I-kappaB kinase/NF-kappaB cascade | biological_proccess | IEP |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0007507 | heart development | biological_proccess | IEA |
| GO:0001525 | angiogenesis | biological_proccess | IEA |
| GO:0001841 | neural tube formation | biological_proccess | IEA |
| GO:0030225 | macrophage differentiation | biological_proccess | IEA |
| GO:0051291 | protein heterooligomerization | biological_proccess | IEA |
| GO:0042802 | identical protein binding | mollecular_function | IPI |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | TAS |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0005515 | protein binding | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | IEA |
| GO:0031264 | death-inducing signaling complex | cell_component | IDA |
| GO:0005856 | cytoskeleton | cell_component | TAS |
| GO:0005739 | mitochondrion | cell_component | TAS |
| GO:0005829 | cytosol | cell_component | EXP |
| GO:0005737 | cytoplasm | cell_component | IEA |
| GO:0005634 | nucleus | cell_component | IDA |
| GO:0005634 | nucleus | cell_component | IEA |
| GO:0030690 | Noc1p-Noc2p complex | cell_component | IEA |
| GO:0043234 | protein complex | cell_component | IEA |
| GO:0045121 | membrane raft | cell_component | IEA |
Check GO Evidence Codes here
Curated Isoforms [+]
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :1509
- Gene related info from GeneCards [?] : CASP8
- Ensembl genome browser [?] : ENSG00000064012
- Expression info from Arrayexpress [?] : ENSG00000064012
- Protein expression from Protein Atlas: [?] ENSG00000064012
- Community gene edition from Wikigenes: [?] 841
- entrezgene: 841
- refseq_dna: NM_001080125
- refseq_dna: NM_001228
- refseq_dna: NM_001080124
- refseq_dna: NM_033356
- refseq_dna: NM_033355
- refseq_dna: NM_033358
- refseq_peptide: NP_001073594
- refseq_peptide: NP_203519
- refseq_peptide: NP_001219
- refseq_peptide: NP_001073593
- refseq_peptide: NP_203520
- refseq_peptide: NP_203522
Click on [?] for more information.
