Reviewed,
UniProtKB/Swiss-Prot O89110 (CASP8_MOUSE)
Last modified
November 3, 2009.
Version 91.
History...
Clusters with 100%,
90%,
50% identity |
Documents (3) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Caspase-8 Short name=CASP-8 EC=3.4.22.61 Cleaved into the following 2 chains: 1- Recommended name: Caspase-8 subunit p18 2- Recommended name: Caspase-8 subunit p10 | ||
| Gene names |
| ||
| Organism | Mus musculus (Mouse) | ||
| Taxonomic identifier | 10090 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 480 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. |
| Catalytic activity | Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp-|-(Gly/Ser/Ala). |
| Enzyme regulation | Inhibited by Z-VAD-FK, Crma and P35. |
| Subunit structure | Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit. Interacts with FADD, CFLAR and PEA15 By similarity. Interacts with TNFAIP8L2. |
| Tissue specificity | Expressed in a wide variety of tissues. Highest expression in spleen, thymus, lung, liver and kidney. Lower expression in heart, brain, testis and skeletal muscle. |
| Developmental stage | In the embryo, highest expression occurs at day 7. |
| Post-translational modification | 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. GZMB and CASP10 can be involved in these processing events By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR By similarity. |
| Sequence similarities | Belongs to the peptidase C14A family. Contains 2 DED (death effector) domains. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Apoptosis |
| Domain | Repeat |
| Molecular function | Hydrolase Protease Thiol protease |
| PTM | Phosphoprotein Zymogen |
| Gene Ontology (GO) | |
| Biological process | angiogenesis Inferred from mutant phenotype. Source: MGI apoptosisInferred from direct assay. Source: MGI heart developmentInferred from mutant phenotype. Source: MGI macrophage differentiationInferred from mutant phenotype. Source: MGI neural tube formationInferred from mutant phenotype. Source: MGI proteolysisInferred from electronic annotation. Source: InterPro regulation of apoptosisInferred from electronic annotation. Source: InterPro |
| Cellular component | Noc1p-Noc2p complex Inferred from mutant phenotype. Source: MGI mitochondrionInferred from direct assay. Source: MGI |
| Molecular function | cysteine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro protein binding Ref.5Inferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Fadd | Q61160 | 1 | EBI-851690,EBI-524415 | |
| Tnfaip8l2 | Q9D8Y7 | 2 | EBI-851690,EBI-1781612 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Propeptide | 1 – 218 | 218 | By similarity | PRO_0000004632 | |||||
| Chain | 219 – 376 | 158 | Caspase-8 subunit p18 | PRO_0000004633 | |||||
| Propeptide | 377 – 387 | 11 | By similarity | PRO_0000004634 | |||||
| Chain | 388 – 480 | 93 | Caspase-8 subunit p10 | PRO_0000004635 | |||||
Regions | |||||||||
| Domain | 3 – 80 | 78 | DED 1 | ||||||
| Domain | 101 – 177 | 77 | DED 2 | ||||||
Sites | |||||||||
| Active site | 319 | 1 | By similarity | ||||||
| Active site | 362 | 1 | By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 188 | 1 | Phosphoserine Ref.6 Ref.7 Ref.8 | ||||||
| Modified residue | 221 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 336 | 1 | Phosphotyrosine By similarity | ||||||
Experimental info | |||||||||
| Sequence conflict | 68 – 71 | 4 | HISR → PHPVG in CAA04196. Ref.4 | ||||||
| Sequence conflict | 94 – 99 | 6 | DNAQIS → RQCPRFL in CAA04196. Ref.4 | ||||||
| Sequence conflict | 96 | 1 | A → V in CAA07677. Ref.2 | ||||||
| Sequence conflict | 103 – 107 | 5 | VMLFK → SCSFR in CAA04196. Ref.4 | ||||||
| Sequence conflict | 475 | 1 | K → N in CAA04196. Ref.4 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning and characterization of mouse caspase-8." Sakamaki K., Tsukumo S., Yonehara S. Eur. J. Biochem. 253:399-405(1998) [PubMed: 9654089] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], CHARACTERIZATION. Strain: 129/SvJ. |
| [2] | "Molecular cloning and identification of murine caspase-8." Van de Craen M., Van Loo G., Declercq W., Schotte P., van den Brande I., Mandruzzato S., van der Bruggen P., Fiers W., Vandenabeele P. J. Mol. Biol. 284:1017-1026(1998) [PubMed: 9837723] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Colon and Mammary gland. |
| [4] | Kioschis P., Kischkel F., Poustka A., Krammer P. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 57-476. |
| [5] | "TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis." Sun H., Gong S., Carmody R.J., Hilliard A., Li L., Sun J., Kong L., Xu L., Hilliard B., Hu S., Shen H., Yang X., Chen Y.H. Cell 133:415-426(2008) [PubMed: 18455983] [Abstract] Cited for: INTERACTION WITH TNFAIP8L2. |
| [6] | "Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, MASS SPECTROMETRY. Tissue: Liver. |
| [7] | "Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed: 18630941] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, MASS SPECTROMETRY. Tissue: Liver. |
| [8] | "Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed: 19131326] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, MASS SPECTROMETRY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
AF067841 AF067840 Genomic DNA. Translation: AAC40132.1. AF067834 mRNA. Translation: AAC40131.1. AJ007749 mRNA. Translation: CAA07677.1. BC006737 mRNA. Translation: AAH06737.1. BC049955 mRNA. Translation: AAH49955.1. AJ000641 mRNA. Translation: CAA04196.1. | |
| IPI | IPI00131533. |
| RefSeq | NP_001073595.1. NP_033942.1. |
| UniGene | Mm.336851 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1QTN based on UniProtKB Q9C0K4. |
| SMR | O89110. Positions 225-479. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O89110. 3 interactions. |
| STRING | O89110. |
Protein family/group databases | |
| MEROPS | C14.009. |
PTM databases | |
| PhosphoSite | O89110. |
Proteomic databases | |
| PRIDE | O89110. |
Genome annotation databases | |
| Ensembl | ENSMUST00000027189; ENSMUSP00000027189; ENSMUSG00000026029; Mus musculus. [Genome view] |
| GeneID | 12370. |
| KEGG | mmu:12370. |
| UCSC | uc007bcs.1. mouse. |
Organism-specific databases | |
| CTD | 12370. |
| MGI | MGI:1261423. Casp8. |
Phylogenomic databases | |
| HOGENOM | O89110. |
| HOVERGEN | O89110. |
| OMA | MGKQMPQ. |
Enzyme and pathway databases | |
| BRENDA | 3.4.22.61. 244. |
Gene expression databases | |
| ArrayExpress | O89110. |
| Bgee | O89110. |
| CleanEx | MM_CASP8. |
| Genevestigator | O89110. |
| GermOnline | ENSMUSG00000026029. Mus musculus. |
Family and domain databases | |
| InterPro | IPR011029. DEATH-like. IPR001875. DED. IPR011600. Pept_C14_cat. IPR001309. Pept_C14_ICE_p20. IPR016129. Pept_C14_ICE_p20_AS. IPR002138. Pept_C14_p10. IPR002398. Pept_C14_p45. IPR015917. Pept_C14_p45_core. [Graphical view] |
| Gene3D | G3DSA:1.10.533.10. DEATH_like. 2 hits. |
| PANTHER | PTHR10454. Pept_C14_p45. 1 hit. |
| Pfam | PF01335. DED. 2 hits. PF00656. Peptidase_C14. 1 hit. [Graphical view] |
| PRINTS | PR00376. IL1BCENZYME. |
| SMART | SM00115. CASc. 1 hit. SM00031. DED. 2 hits. [Graphical view] |
| PROSITE | PS01122. CASPASE_CYS. 1 hit. PS01121. CASPASE_HIS. 1 hit. PS50207. CASPASE_P10. 1 hit. PS50208. CASPASE_P20. 1 hit. PS50168. DED. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 281064. |
| SOURCE | Search... |
Entry information
| Entry name | CASP8_MOUSE | ||||||||
| Accession | Primary (citable) accession number: O89110 Secondary accession number(s): O35669 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


