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Protein Page:
CASP8 (human)
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: EC 3.4.22.61; EC 3.4.22.-; Protease; Apoptosis
Cellular Component: mitochondrial outer membrane; neuron projection; cytoskeleton; mitochondrion; Noc1p-Noc2p complex; cytoplasm; nucleolus; microtubule organizing center; CD95 death-inducing signaling complex; nucleus; cytosol; lipid raft
Molecular Function: peptidase activity; protein binding; ubiquitin protein ligase binding; cysteine-type endopeptidase activity; tumor necrosis factor receptor binding; cysteine-type peptidase activity; receptor binding
Biological Process: macrophage differentiation; viral reproduction; T cell activation; positive regulation of proteolysis; apoptosis; protein heterooligomerization; heart development; natural killer cell activation; response to lipopolysaccharide; toll-like receptor 3 signaling pathway; proteolysis; response to estradiol stimulus; response to antibiotic; proteolysis involved in cellular protein catabolic process; angiogenesis; positive regulation of macrophage differentiation; toll-like receptor 4 signaling pathway; cell structure disassembly during apoptosis; caspase activation; positive regulation of I-kappaB kinase/NF-kappaB cascade; B cell activation; MyD88-independent toll-like receptor signaling pathway; negative regulation of I-kappaB kinase/NF-kappaB cascade; response to ethanol; induction of apoptosis via death domain receptors; toll-like receptor signaling pathway; response to cobalt ion; innate immune response; response to cold; neural tube formation
Reference #:  Q14790 (UniProtKB)
Alt. Names/Synonyms: ALPS2B; Apoptotic cysteine protease; Apoptotic protease Mch-5; CAP4; CASP-8; CASP8; caspase 8, apoptosis-related cysteine peptidase; caspase 8, apoptosis-related cysteine protease; Caspase-8; Caspase-8 subunit p10; Caspase-8 subunit p18; FADD-homologous ICE/ced-3-like protease; FADD-like ICE; FLICE; FLJ17672; ICE-like apoptotic protease 5; MACH; MACH-alpha-1/2/3 protein; MACH-beta-1/2/3/4 protein; MCH5; MGC78473; MORT1-associated ced-3 homolog
Gene Symbols: CASP8
Molecular weight: 55,391 Da
Basal Isoelectric point: 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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Sites Implicated In
apoptosis, altered: Y380‑p, S387‑p, Y448‑p
apoptosis, induced: Y380‑p
apoptosis, inhibited: S347‑p, Y380‑p, S387‑p
carcinogenesis, altered: S387‑p
cell adhesion, altered: Y380‑p
cell motility, altered: Y380‑p
activity, inhibited: S347‑p
enzymatic activity, inhibited: Y380‑p, S387‑p, Y448‑p
intracellular localization: S387‑p
molecular association, regulation: Y380‑p
phosphorylation: Y380‑p
protein processing: Y380‑p, S387‑p

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.


       human

► Hide Isoforms
 
0 9 - gap
0 2 K23-ub SEDLASLkFLSLDYI
0 9 K63-ub ESNLSFLkELLFRIN
0 1 K148-ub DIFIEMEkRVILGEG
1 0 K156-ac RVILGEGkLDILKRV
0 1 K173-ub QINKSLLkIINDYEE
0 15 S188 FSKERSSSLEGSPDE
0 2 - gap
0 1 S209-p LCGVMTIsDsPREQD
0 5 S211-p GVMTIsDsPREQDSE
0 1 S219-p PREQDSEsQTLDKVY
0 1 K224 SEsQTLDKVYQMKSK
0 1 Y235-p MKSKPRGyCLIINNH
1 0 T263-p SIRDRNGtHLDAGAL
1 0 S305-p IYQLMDHsNMDCFIC
0 12 Y334-p DGQEAPIyELTSQFT
1 0 S347-p FTGLKCPsLAGkPKV
0 1 K351-ub KCPsLAGkPKVFFIQ
0 1 T373-p QKGIPVEtDsEEQPy
0 3 S375-p GIPVEtDsEEQPyLE
6 32 Y380-p tDsEEQPyLEMDLSs
3 2 S387-p yLEMDLSsPQTRYIP
1 1 Y448-p TILTEVNyEVSNKDD
0 1 K461-ub DDKKNMGkQMPQPTF
  CASP8 iso9  
Y52-p PGKGGADyILLPFKK
K82 SEDLASLKFLSLDYI
K122 ESNLSFLKELLFRIN
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
  mouse

 
- gap
K23 SEDLAALKFLCLDYI
K63 EGNLSFLKELLFHIS
K148 EIFVEMEKRTMLAEN
N156 RTMLAENNLETLKSI
G173 QVNKSLLGKIEDYER
S188-p SSTERRMsLEGREEL
S198-p GREELPPsVLDEMSL
C211 SLKMAELCDsPREQD
S213-p KMAELCDsPREQDSE
S221 PREQDSESRTSDkVY
K226-ac SESRTSDkVYQMKNK
Y237 MKNKPRGYCLIINNH
T265 KMKDRKGTDCDKEAL
K307 GYQSADHKNKDCFIC
Y336 DGKEASIYDLTSYFT
S349 FTGSKCPSLSGKPKI
K353 KCPSLSGKPKIFFIQ
A375 QKGVPDEAGFEQQNH
F377 GVPDEAGFEQQNHTL
T383 GFEQQNHTLEVDSSS
S390 TLEVDSSSHKNYIPD
Y450 SILTGVNYDVSNKDD
K463 DDRRNKGKQMPQPTF
  rat

 
- gap
K23 NEELAALKFLCLDHI
K63 EDNLSFLKELLFHIS
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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