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Protein Page:
Casp8 (mouse)
p Phosphorylation
a Acetylation
m Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
u Ubiquitination
s Sumoylation
n Neddylation
gl O-GlcNAc
ga O-GalNAc
h Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage

Overview
Casp8 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. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. 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. Isoform 9 interacts at the endoplasmic reticulum with a complex containing BCAP31, BAP29, BCL2 and/or BCL2L1. Interacts with TNFAIP8L2. Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation. Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle. Belongs to the peptidase C14A family. 9 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; Protease; EC 3.4.22.61; EC 3.4.22.-
Cellular Component: centrosome; neuron projection; protein complex; mitochondrion; Noc1p-Noc2p complex; cytoplasm; CD95 death-inducing signaling complex; cytosol; nucleus; lipid raft
Molecular Function: peptidase activity; protein binding; protease binding; hydrolase activity; protein heterodimerization activity; cysteine-type endopeptidase activity; ubiquitin protein ligase binding; endopeptidase activity; tumor necrosis factor receptor binding; cysteine-type peptidase activity
Biological Process: caspase activation; cardiac muscle development; positive regulation of I-kappaB kinase/NF-kappaB cascade; macrophage differentiation; apoptosis; protein heterooligomerization; positive regulation of proteolysis; heart development; negative regulation of I-kappaB kinase/NF-kappaB cascade; proteolysis; regulation of apoptosis; response to ethanol; proteolysis involved in cellular protein catabolic process; induction of apoptosis via death domain receptors; angiogenesis; neural tube formation; positive regulation of macrophage differentiation
Reference #:  O89110 (UniProtKB)
Alt. Names/Synonyms: CASP-8; Casp8; caspase 8; Caspase-8; Caspase-8 subunit p10; Caspase-8 subunit p18; Fas-linked ICE-like protease; FLICE; MACH; Mch5
Gene Symbols: Casp8
Molecular weight: 55,357 Da
Basal Isoelectric point: 5.12  Predict pI for various phosphorylation states
CST Pathways:  Apoptosis Regulation  |  Death Receptor Signaling  |  ErbB/HER Signaling  |  Inhibition of Apoptosis  |  Mitochondrial Control of Apoptosis  |  Toll-Like Receptor Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

Casp8

Protein Structure Not Found.


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Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       mouse

 
0 9 - gap
0 2 K23 SEDLAALKFLCLDYI
0 9 K63 EGNLSFLKELLFHIS
0 1 K148 EIFVEMEKRTMLAEN
1 0 N156 RTMLAENNLETLKSI
0 14 S188-p SSTERRMsLEGREEL
0 2 S198-p GREELPPsVLDEMSL
0 5 S213-p KMAELCDsPREQDSE
0 1 S221 PREQDSESRTSDKVY
1 0 T265 KMKDRKGTDCDKEAL
1 0 K307 GYQSADHKNKDCFIC
0 12 Y336 DGKEASIYDLTSYFT
1 0 S349 FTGSKCPSLSGKPKI
0 3 F377 GVPDEAGFEQQNHTL
6 48 T383 GFEQQNHTLEVDSSS
3 0 S390 TLEVDSSSHKNYIPD
1 1 Y450 SILTGVNYDVSNKDD
0 1 K463 DDRRNKGKQMPQPTF
  human

► Hide Isoforms
 
- gap
K23-u SEDLASLkFLSLDYI
K63-u ESNLSFLkELLFRIN
K148-u DIFIEMEkRVILGEG
K156-a RVILGEGkLDILKRV
S188 FSKERSSSLEGSPDE
- gap
S211-p GVMTISDsPREQDSE
S219-p PREQDSEsQTLDKVY
T263-p SIRDRNGtHLDAGAL
S305-p IYQLMDHsNMDCFIC
Y334-p DGQEAPIyELTSQFT
S347-p FTGLKCPsLAGKPKV
S375-p GIPVETDsEEQPyLE
Y380-p TDsEEQPyLEMDLSs
S387-p yLEMDLSsPQTRYIP
Y448-p TILTEVNyEVSNKDD
K461-u DDKKNMGkQMPQPTF
  Casp8 iso9  
Y52-p PGKGGADyILLPFKK
K82 SEDLASLKFLSLDYI
K122 ESNLSFLKELLFRIN
K207 DIFIEMEKRVILGEG
K215 RVILGEGKLDILKRV
S247 FSKERSSSLEGSPDE
- gap
S270 GVMTISDSPREQDSE
S278 PREQDSESQTLDKVY
T322 SIRDRNGTHLDAGAL
S364 IYQLMDHSNMDCFIC
Y393 DGQEAPIYELTSQFT
S406 FTGLKCPSLAGKPKV
S434 GIPVETDSEEQPYLE
Y439 TDSEEQPYLEMDLSS
S446 YLEMDLSSPQTRYIP
Y507 TILTEVNYEVSNKDD
K520 DDKKNMGKQMPQPTF
  rat

 
- gap
K23 NEELAALKFLCLDHI
K63 EDNLSFLKELLFHIS
K148 DIFVEMEKRTILAEN
N156 RTILAENNLVTLKSI
S188-p SSTERRMsTEGGEEL
S198 GGEELPVSVLDEVTI
S213 KMQDMWDSPGEQESE
S221 PGEQESESLNSDNVY
T265 NMRDRKGTNYDEEAL
K307 SYQSKDHKGKDCFIC
Y336 DGKEASIYELTSYFT
S349 FTGSKCPSLAGKPKI
L379 PVPDETGLEQEHVLE
V384 TGLEQEHVLEEDSSS
S391 VLEEDSSSYKNYIPD
Y451 SILTGVNYDVSNKDN
K464 DNPRNMGKQMPQPIF
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