Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  Caspase-8  

UniProtKB / Swiss-Prot ID :  CASP8_HUMAN

Gene Name (Synonyms) : 
CASP8, MCH5  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Cytoplasm. 

Protein 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. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. 

Protein Sequence MDFSRNLYDIGEQLDSEDLASLKFLSLDYIPQRKQEPIKDALMLFQRLQEKRMLEESNLSFLKELLFRIN...
Predicted Secondary Structure CCHHHHHHHHHHCCCHHHHHHHHHHHHHHHHHCCCCCCCCHHHHHHHHHHHCCCCCCCHHHHHHHHHHHH...
Protein Variant
LocationDescription
219S -> T (in dbSNP:rs35976359). VAR_025816
248R -> W (in CASP8D; dbSNP:rs17860424). VAR_014204
285D -> H (associated with protectionagainst breast cancer; also associated
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
63Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)LSFLKELLF
HHHHHHHHH
44.28Phosphositeplus
Link-
148Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)IEMEKRVIL
HHHHHHHHC
51.13Phosphositeplus
Link-
156N6-acetyllysineLGEGKLDIL
CCCCCHHHH
38.39Phosphositeplus
Link-
210noneMTISDSPRE
CCHHHHHHH
59.83HPRD
Link-
216nonePREQDSESQ
HHHHCCCCC
50.01HPRD
Link-
217PhosphoserineREQDSESQT
HHHCCCCCC
38.55HPRD
Link-
219PhosphoserineQDSESQTLD
HCCCCCCHH
32.20HPRD
Link-
219PhosphoserineQDSESQTLD
HCCCCCCHH
32.20PhosphoELM
Link-
219PhosphoserineQDSESQTLD
HCCCCCCHH
32.20Phosphositeplus
Link-
219Phosphoserine.QDSESQTLD
HCCCCCCHH
32.20UniProtKB
Link-
230PhosphoserineYQMKSKPRG
HCCCCCCCC
42.42HPRD
Link-
263PhosphothreonineDRNGTHLDA
CCCCHHHHH
23.86Phosphositeplus
Link-
334PhosphotyrosineEAPIYELTS
ECCHHHHHH
12.11PhosphoELM
Link-
334PhosphotyrosineEAPIYELTS
ECCHHHHHH
12.11Phosphositeplus
Link-
334Phosphotyrosine.EAPIYELTS
ECCHHHHHH
12.11UniProtKB
Link-
347PhosphoserineLKCPSLAGK
CCCCCCCCC
40.08Phosphositeplus
Link-
347Phosphoserine (MAPK14)LKCPSLAGK
CCCCCCCCC
40.08PhosphoELM
Link-
374nonePVETDSEEQ
EECCCCCCC
40.31HPRD
Link-
380PhosphotyrosineEEQPYLEMD
CCCCCCCCC
18.26Phosphositeplus
Link-
384noneYLEMDLSSP
CCCCCCCCC
33.74HPRD
Link-
387PhosphoserineMDLSSPQTR
CCCCCCCCC
28.46Phosphositeplus
Link-
387Phosphoserine; by CDK1.MDLSSPQTR
CCCCCCCCC
28.46UniProtKB
Link-
448PhosphotyrosineTEVNYEVSN
HHHHHHHCC
23.92Phosphositeplus
Link
461Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)KNMGKQMPQ
CCCEEECCC
32.43Phosphositeplus
Link
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
NOL3_HUMANphysical interactionMINT-16248MINT9560245
ANDR_HUMANdirect interactionMINT-4051509MINT17170703
TNR6_HUMANcolocalizationMINT-4055373MINT17159907
TNR6_HUMANcolocalizationMINT-1956415MINT16498403
MK01_HUMANphysical interactionMINT-4329848MINT17290218
TNFL6_HUMANphysical interactionMINT-1956272MINT16498403
TFCP2_HUMANphysical interactionMINT-64085MINT16169070
CHD3_HUMANphysical interactionMINT-64186MINT16169070
CASP8_HUMANphysical interactionMINT-64184MINT16169070
Q8N9S6_HUMANphysical interactionMINT-64185MINT16169070
TOPRS_HUMANphysical interactionMINT-4329782MINT17290218
C8AP2_HUMANphysical interactionMINT-4298767MINT17245429
C8AP2_HUMANphysical interactionMINT-4298744MINT17245429
C8AP2_HUMANphysical interactionMINT-18006MINT10235259
C8AP2_HUMANphysical interactionMINT-18007MINT10235259
C8AP2_HUMANcolocalizationMINT-4298716MINT17245429
BAP31_HUMANphysical interactionEBI-78059
intact9334338
FADD_HUMANphysical interaction
direct interaction
physical interaction
physical interaction
physical interaction
EBI-1561717
EBI-495215
EBI-51
intact14612908
11717445
12887920
12887920
12887920
RIPK1_HUMANphysical interaction
physical interaction
physical interaction
EBI-515198
EBI-514887
EBI-514
intact12887920
12887920
12887920
CFLAR_HUMANphysical interaction
physical interaction
physical interaction
EBI-515081
EBI-514887
EBI-514
intact12887920
12887920
12887920
TRADD_HUMANphysical interaction
physical interaction
EBI-514887
EBI-514691
intact12887920
12887920
TRAF2_HUMANphysical interaction
physical interaction
EBI-514887
EBI-514691
intact12887920
12887920
BIRC2_HUMANphysical interaction
physical interaction
EBI-514691
EBI-514691
intact12887920
12887920
TRAF1_HUMANphysical interactionEBI-514691
intact12887920
VIME_HUMANphysical interactionEBI-729696
intact16169070
CHD3_HUMANphysical interactionEBI-731509
intact16169070
CASP8_HUMANdirect interaction
direct interaction
physical interaction
EBI-495149
EBI-495175
EBI-731
intact11717445
11717445
16169070
PSN1_HUMANin vitro
in vivo
HPRD:03459HPRD10069390
A4_HUMANin vitroHPRD:03459HPRD10911620
CTNB1_HUMANin vivoHPRD:03459HPRD12189238
PCY1A_HUMANin vitro
in vivo
HPRD:03459HPRD12052891
TNR6_HUMANin vivoHPRD:03459HPRD11101867
17159907
BCL2_HUMANin vivoHPRD:03459HPRD11406564
E2AK2_HUMANin vitro
in vivo
HPRD:03459HPRD11555640
USO1_HUMANin vitro
in vivo
HPRD:03459HPRD12438416
TAU_HUMANin vitro
in vivo
HPRD:03459HPRD12888622
BCLX_HUMANin vitroHPRD:03459HPRD11733517
TNR27_HUMANin vitroHPRD:03459HPRD15280356
CADH1_HUMANin vivoHPRD:03459HPRD12189238
VIME_HUMANin vivoHPRD:03459HPRD11423904
10469173
BAP31_HUMANin vivoHPRD:03459HPRD9334338
12668660
PLEC1_HUMANin vivoHPRD:03459HPRD10891503
BID_HUMANin vitro
in vivo
HPRD:03459HPRD9727491
11085743
12196516
12097160
9727492
RIPK1_HUMANin vitro
in vivo
HPRD:03459HPRD11002417
10521396
12215447
KPCZ_HUMANin vitroHPRD:03459HPRD11016947
CFLAR_HUMANin vitro
in vivo
HPRD:03459HPRD9289491
9208847
12215447
9380701
12097160
17159907
GRIA1_HUMANin vivoHPRD:03459HPRD11751897
CDN1B_HUMANin vitroHPRD:03459HPRD11420686
PARP2_HUMANin vitro
in vivo
HPRD:03459HPRD12065591
CASP3_HUMANin vitro
in vivo
HPRD:03459HPRD11437602
CASP6_HUMANin vitro
in vivo
HPRD:03459HPRD12232792
IKKA_HUMANin vivoHPRD:03459HPRD11002417
PSN2_HUMANin vivoHPRD:03459HPRD9990034
9219695
10069390
TRAF1_HUMANin vitro
in vivo
HPRD:03459HPRD11098060
11181075
PIAS1_HUMANyeast 2-hybridHPRD:03459HPRD15782135
HIP1_HUMANin vivoHPRD:03459HPRD11788820
RB_HUMANin vitroHPRD:03459HPRD15735701
SUMO1_HUMANin vivo
yeast 2-hybrid
HPRD:03459HPRD15782135
TRAF2_HUMANin vitro
in vivo
HPRD:03459HPRD16227629
11340079
PRKN2_HUMANin vitroHPRD:03459HPRD12692130
CD2L1_HUMANin vitroHPRD:03459HPRD9632733
RBP1_HUMANin vitro
in vivo
HPRD:03459HPRD16227629
STK24_HUMANin vitro
in vivo
HPRD:03459HPRD12107159
CASP8_HUMANin vitro
in vivo
yeast 2-hybrid
HPRD:03459HPRD8681376
TFCP2_HUMANyeast 2-hybridHPRD:03459HPRD16169070
CHD3_HUMANyeast 2-hybridHPRD:03459HPRD16169070
RBP1_HUMANENSP00000351273STRING
TNR1A_HUMANENSP00000351273STRING
TR10A_HUMANENSP00000351273STRING
AATF_HUMANENSP00000351273STRING
BIRC2_HUMANENSP00000351273STRING
IFNG_HUMANENSP00000351273STRING
E2AK2_HUMANENSP00000351273STRING
E2AK2_HUMANENSP00000351273STRING
C8AP2_HUMANENSP00000351273STRING
TNF10_HUMANENSP00000351273STRING
IRF1_HUMANENSP00000351273STRING
RIPK1_HUMANENSP00000351273STRING
MK03_HUMANENSP00000351273STRING
BIRC3_HUMANENSP00000351273STRING
P53_HUMANENSP00000351273STRING
TR10B_HUMANENSP00000351273STRING
AIFM1_HUMANENSP00000351273STRING
FCN2_HUMANENSP00000351273STRING
FCN2_HUMANENSP00000351273STRING
CASP7_HUMANENSP00000351273STRING
FADD_HUMANENSP00000351273STRING
BCLX_HUMANENSP00000351273STRING
CYC_HUMANENSP00000351273STRING
CYC_HUMANENSP00000351273STRING
CASP3_HUMANENSP00000351273STRING
CFLAR_HUMANENSP00000351273STRING
TRAF6_HUMANENSP00000351273STRING
BID_HUMANENSP00000351273STRING
HIP1_HUMANENSP00000351273STRING
TRADD_HUMANENSP00000351273STRING
BAP31_HUMANENSP00000351273STRING
E2F1_HUMANENSP00000351273STRING
TNR6_HUMANENSP00000351273STRING
PTN13_HUMANENSP00000351273STRING
APAF_HUMANENSP00000351273STRING
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Disease Reference
Kegg disease
OMIM disease
607271Caspase-8 deficiency (CASP8D)
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.;
Nat. Biotechnol. 23:94-101(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-334, AND MASSSPECTROMETRY.
"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage.";
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
Science 316:1160-1166(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219, AND MASSSPECTROMETRY.
"Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity.";
Matthess Y., Raab M., Sanhaji M., Lavrik I.N., Strebhardt K.;
Mol. Cell. Biol. 30:5726-5740(2010).
Cited for: PHOSPHORYLATION AT SER-387 BY CDK1.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures