Tchem CASP8 Caspase-8

Protein Summary

Description

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. This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q14790
• O14676
• Q14791
• Q14792
• Q14793
• Q14794
• Q14795
• Q14796
• Q15780
• Q15806
• Q53TT5
• Q8TDI1
• Q8TDI2
• Q8TDI3
• Q8TDI4
• Q8TDI5
• Q96T22
• Q9C0K4
• Q9UQ81
• CASP-8

Gene Name

• CASP8

Ensembl ID

• ENST00000264274
• ENSP00000264274
• ENSG00000064012
• ENST00000264275
• ENSP00000264275
• ENST00000323492
• ENSP00000325722
• ENST00000358485
• ENSP00000351273
• ENST00000392258
• ENSP00000376087
• ENST00000392263
• ENSP00000376091
• ENST00000432109
• ENSP00000412523

Symbol

• MCH5
• CAP4
• MACH
• MCH5
• FLICE
• ALPS2B
• Casp-8

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
chemical	1
hub protein	1
protein domain	0.97
protein complex	0.94

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Cysteine Protease / Caspase-8

Protein / Enzyme Modulator / Protease Inhibitor / Caspase-8

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Caspase-8

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3925.21   (req: < 5)

Gene RIFs: 519   (req: <= 3)

Antibodies: 1364   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 3925.21   (req: >= 5)

Gene RIFs: 519   (req: > 3)

Antibodies: 1364   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 52

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 198

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (198)

Explore Active Ligands

1 – 10 of 198

M826

CASP8Tchem Enzyme

pKi : 8.3

SID24788424

CASP8Tchem Enzyme

pIC50 : 7.1

CHEMBL179503

CASP8Tchem Enzyme

pIC50 : 10.05

CHEMBL23226

CASP8Tchem Enzyme

pIC50 : 8.3

CHEMBL237310

CASP8Tchem Enzyme

pIC50 : 8.22

CHEMBL180263

CASP8Tchem Enzyme

pIC50 : 7.96

SID24809205

CASP8Tchem Enzyme

pAC50 : 7.2

CHEMBL2324339

CASP8Tchem Enzyme

pIC50 : 6.89

CHEMBL430648

CASP8Tchem Enzyme

pIC50 : 8.92

CHEMBL328412

CASP8Tchem Enzyme

pIC50 : 8.46

Protein-Protein Interactions (418)

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1 – 10 of 418

• See Interactions on String-DB

FAS

Tbio

Novelty:  0.00043286

p_int:  0.999999548

p_ni:  4.5e-7

p_wrong:  2e-9

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

TNFRSF10A

Tchem

Novelty:  0.0003383

p_int:  0.999999361

p_ni:  6.25e-7

p_wrong:  1.4e-8

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

TNFRSF10B

Tbio

Novelty:  0.00054433

p_int:  0.999999353

p_ni:  6.45e-7

p_wrong:  2e-9

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

CFLAR

Tbio

Novelty:  0.00108805

p_int:  0.999978129

p_ni:  0.000021731

p_wrong:  1.41e-7

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

CASP7

Tchem

Family:  Enzyme

Novelty:  0.00126224

Score:  0.999

Data Source:  STRINGDB

CASP6

Tchem

Family:  Enzyme

Novelty:  0.00234346

Score:  0.999

Data Source:  STRINGDB

BCL2L1

Tchem

Novelty:  0.00018414

Score:  0.999

Data Source:  STRINGDB

CASP3

Tchem

Family:  Enzyme

Novelty:  0.00003555

Score:  0.999

Data Source:  STRINGDB

FADD

Tbio

Novelty:  0.00137968

Score:  0.999

Data Source:  Reactome,STRINGDB

XIAP

Tchem

Family:  Enzyme

Novelty:  0.00062268

Score:  0.999

Data Source:  STRINGDB

Nearest Tclin Targets (3)

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Upstream (3)

1 – 3 of 3

CD3E

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  4

1: Chagas disease (American trypanosomiasis)

2: Measles

3: Human immunodeficiency virus 1 infection

4: Epstein-Barr virus infection

CD3G

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  4

1: Chagas disease (American trypanosomiasis)

2: Measles

3: Human immunodeficiency virus 1 infection

4: Epstein-Barr virus infection

CD3D

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  4

1: Chagas disease (American trypanosomiasis)

2: Measles

3: Human immunodeficiency virus 1 infection

4: Epstein-Barr virus infection

Pathways (117)

Reactome (38)

KEGG (31)

PathwayCommons (21)

WikiPathways (27)

Activation, myristolyation of BID and translocation to mitochondria (R-HSA-75108)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation, myristolyation of BID and translocation to mitochondria	4 targets	R-HSA-75108
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Apoptotic cleavage of cellular proteins	38 targets	R-HSA-111465
Reactome	Apoptotic execution phase	52 targets	R-HSA-75153
Reactome	C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481

Name	Explore in Pharos	Explore in Source
Activation, myristolyation of BID and translocation to mitochondria	4 targets	R-HSA-75108
Apoptosis	177 targets	R-HSA-109581
Apoptotic cleavage of cellular proteins	38 targets	R-HSA-111465
Apoptotic execution phase	52 targets	R-HSA-75153
C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (64)

Functions (12)

Components (12)

Processes (40)

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GO Term	Evidence	Assigned by
cysteine-type endopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
peptidase activity	Inferred from Direct Assay (IDA)	BHF-UCL
death effector domain binding	Inferred from Physical Interaction (IPI)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
scaffold protein binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
cysteine-type endopeptidase activity involved in apoptotic process	Inferred from Mutant Phenotype (IMP)	UniProtKB
cysteine-type endopeptidase activity involved in apoptotic signaling pathway	Inferred from Mutant Phenotype (IMP)	UniProtKB
cysteine-type peptidase activity	Traceable Author Statement (TAS)	ProtInc
death receptor binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations (null)

No disease associations found

GWAS Traits (33)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
basal cell carcinoma	EFO_0004193	5	5	1	1.1	99.3
lymphocyte count	EFO_0004587	4	4	4		88.5
keratinocyte carcinoma	EFO_0010176	1	1	0	1.1	84.7
chronic lymphocytic leukemia	EFO_0000095	3	3	0	1.2	83.6
triglyceride measurement	EFO_0004530	2	2	2		81.9

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
basal cell carcinoma	EFO_0004193	1	1.1	99.3
lymphocyte count	EFO_0004587	4		88.5
keratinocyte carcinoma	EFO_0010176	0	1.1	84.7
chronic lymphocytic leukemia	EFO_0000095	0	1.2	83.6
triglyceride measurement	EFO_0004530	2		81.9

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Apoptosis
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Host-virus interaction
Hydrolase

GWAS Trait Find Similar Targets

No Header	No Header
basal cell carcinoma
breast carcinoma
cancer
caspase-8 measurement
chronic lymphocytic leukemia
cutaneous melanoma
cutaneous squamous cell carcinoma
erythrocyte count
esophageal carcinoma
esophageal squamous cell carcinoma

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	caspase 8	VGNC:119	746477
Macaque	caspase 8		702781
Mouse	caspase 8	MGI:1261423	12370
Rat	caspase 8	RGD:620945	64044
Dog	caspase 8	VGNC:38736	488473

Species	Name	OMA	EggNOG	Inparanoid
Chimp	caspase 8
Macaque	caspase 8
Mouse	caspase 8
Rat	caspase 8
Dog	caspase 8

Publication Statistics

PubMed Score 3925.21

PubMed score by year

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PubTator Score 3511.69

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Related Publications

Text Mined References (727)

GeneRif Annotations (519)

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PMID	Year	Title