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Protein Page:
CASP8 (mouse)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

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: Protease; EC 3.4.22.-; Apoptosis; EC 3.4.22.61
Cellular Component: neuron projection; protein complex; mitochondrion; Noc1p-Noc2p complex; cytoplasm; CD95 death-inducing signaling complex; microtubule organizing center; cytosol; nucleus; lipid raft
Molecular Function: peptidase activity; protein binding; hydrolase activity; protein heterodimerization activity; ubiquitin protein ligase binding; cysteine-type endopeptidase activity; endopeptidase activity; death receptor binding; protein complex binding; tumor necrosis factor receptor binding; cysteine-type peptidase activity
Biological Process: caspase activation; cardiac muscle development; macrophage differentiation; positive regulation of I-kappaB kinase/NF-kappaB cascade; 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; induction of apoptosis via death domain receptors; proteolysis involved in cellular protein catabolic process; 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 11 - gap
0 2 K23 SEDLAALKFLCLDYI
0 9 K63 EGNLSFLKELLFHIS
0 1 S113 FKLSEEVSELELRSF
0 1 K148 EIFVEMEKRTMLAEN
1 0 N156 RTMLAENNLETLKSI
0 1 G173 QVNKSLLGKIEDYER
0 15 S188-p SSTERRMsLEGREEL
0 2 S198-p GREELPPsVLDEMSL
0 1 C211 SLKMAELCDsPREQD
0 6 S213-p KMAELCDsPREQDSE
0 1 S221 PREQDSESRTSDkVY
0 1 K226-ac SESRTSDkVYQMKNK
0 1 Y237 MKNKPRGYCLIINNH
1 0 T265 KMKDRKGTDCDKEAL
1 0 K307 GYQSADHKNKDCFIC
0 12 Y336 DGKEASIYDLTSYFT
1 0 S349 FTGSKCPSLSGKPKI
0 1 K353 KCPSLSGKPKIFFIQ
0 1 A375 QKGVPDEAGFEQQNH
0 3 F377 GVPDEAGFEQQNHTL
6 35 T383 GFEQQNHTLEVDSSS
3 2 S390 TLEVDSSSHKNYIPD
1 1 Y450 SILTGVNYDVSNKDD
0 1 K463 DDRRNKGKQMPQPTF
  human

► Hide Isoforms
 
- gap
K23-ub SEDLASLkFLSLDYI
K63-ub ESNLSFLkELLFRIN
S113-p YQISEEVsRSELRSF
K148-ub DIFIEMEkRVILGEG
K156-ac RVILGEGkLDILKRV
K173-ub QINKSLLkIINDYEE
S188 FSKERSSSLEGSPDE
- gap
S209-p LCGVMTIsDsPREQD
S211-p GVMTIsDsPREQDSE
S219-p PREQDSEsQTLDKVY
K224 SEsQTLDKVYQMKSK
Y235-p MKSKPRGyCLIINNH
T263-p SIRDRNGtHLDAGAL
S305-p IYQLMDHsNMDCFIC
Y334-p DGQEAPIyELTSQFT
S347-p FTGLKCPsLAGkPKV
K351-ub KCPsLAGkPKVFFIQ
T373-p QKGIPVEtDsEEQPy
S375-p GIPVEtDsEEQPyLE
Y380-p tDsEEQPyLEMDLSs
S387-p yLEMDLSsPQTRYIP
Y448-p TILTEVNyEVSNKDD
K461-ub DDKKNMGkQMPQPTF
  CASP8 iso4  
- under review  
K23 SEDLASLKFLSLDYI
K63 ESNLSFLKELLFRIN
S145 YQISEEVSRSELRSF
K180 DIFIEMEKRVILGEG
K188 RVILGEGKLDILKRV
K205 QINKSLLKIINDYEE
- under review  
- under review  
S226 LCGVMTISDsPREQD
S228-p GVMTISDsPREQDSE
S236 PREQDSESQTLDKVY
K241 SESQTLDKVYQMKSK
Y252 MKSKPRGYCLIINNH
T280 SIRDRNGTHLDAGAL
S322 IYQLMDHSNMDCFIC
Y351 DGQEAPIYELTSQFT
S364 FTGLKCPSLAGKPKV
K368 KCPSLAGKPKVFFIQ
T390 QKGIPVETDSEEQPY
S392 GIPVETDSEEQPYLE
Y397 TDSEEQPYLEMDLSS
S404 YLEMDLSSPQTRYIP
Y465 TILTEVNYEVSNKDD
K478 DDKKNMGKQMPQPTF
  CASP8 iso9  
Y52-p PGKGGADyILLPFKK
K82 SEDLASLKFLSLDYI
K122 ESNLSFLKELLFRIN
S172 YQISEEVSRSELRSF
K207 DIFIEMEKRVILGEG
K215 RVILGEGKLDILKRV
K232 QINKSLLKIINDYEE
S247 FSKERSSSLEGSPDE
- gap
S268 LCGVMTISDSPREQD
S270 GVMTISDSPREQDSE
S278 PREQDSESQTLDKVY
K283 SESQTLDKVYQMKSK
Y294 MKSKPRGYCLIINNH
T322 SIRDRNGTHLDAGAL
S364 IYQLMDHSNMDCFIC
Y393 DGQEAPIYELTSQFT
S406 FTGLKCPSLAGKPKV
K410 KCPSLAGKPKVFFIQ
T432 QKGIPVETDSEEQPY
S434 GIPVETDSEEQPYLE
Y439 TDSEEQPYLEMDLSS
S446 YLEMDLSSPQTRYIP
Y507 TILTEVNYEVSNKDD
K520 DDKKNMGKQMPQPTF
  rat

 
- gap
K23 NEELAALKFLCLDHI
K63 EDNLSFLKELLFHIS
- under review  
K148 DIFVEMEKRTILAEN
N156 RTILAENNLVTLKSI
G173 RVNRSLLGRIDDYER
S188-p SSTERRMsTEGGEEL
S198 GGEELPVSVLDEVTI
W211 TIKMQDMWDSPGEQE
S213 KMQDMWDSPGEQESE
S221 PGEQESESLNSDNVY
N226 SESLNSDNVYQMKSK
Y237 MKSKPRGYCLIFNNN
T265 NMRDRKGTNYDEEAL
K307 SYQSKDHKGKDCFIC
Y336 DGKEASIYELTSYFT
S349 FTGSKCPSLAGKPKI
K353 KCPSLAGKPKIFFIQ
T377 AVPVPDETGLEQEHV
L379 PVPDETGLEQEHVLE
V384 TGLEQEHVLEEDSSS
S391 VLEEDSSSYKNYIPD
Y451 SILTGVNYDVSNKDN
K464 DNPRNMGKQMPQPIF
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