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 asp... See more...

Aliases for CASP8 Gene

Aliases for CASP8 Gene

  • Caspase 8 2 3 5
  • Caspase 8, Apoptosis-Related Cysteine Peptidase 2 3
  • Caspase 8, Apoptosis-Related Cysteine Protease 2 3
  • MORT1-Associated Ced-3 Homolog 3 4
  • ICE-Like Apoptotic Protease 5 3 4
  • Apoptotic Cysteine Protease 3 4
  • Apoptotic Protease Mch-5 3 4
  • FADD-Like ICE 3 4
  • Caspase-8 3 4
  • FLICE 3 4
  • CAP4 3 4
  • MACH 3 4
  • MCH5 3 4
  • FADD-Homologous ICE/CED-3-Like Protease 3
  • FADD-Homologous ICE/Ced-3-Like Protease 4
  • MACH-Beta-1/2/3/4 Protein 3
  • MACH-Alpha-1/2/3 Protein 3
  • EC 3.4.22.61 4
  • ALPS2B 3
  • Casp-8 3
  • CASP-8 4

External Ids for CASP8 Gene

Previous GeneCards Identifiers for CASP8 Gene

  • GC02P200315
  • GC02P200822
  • GC02P202062
  • GC02P202300
  • GC02P201923
  • GC02P201807
  • GC02P193949

Summaries for CASP8 Gene

Entrez Gene Summary for CASP8 Gene

  • 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]

CIViC Summary for CASP8 Gene

GeneCards Summary for CASP8 Gene

CASP8 (Caspase 8) is a Protein Coding gene. Diseases associated with CASP8 include Caspase 8 Deficiency and Hepatocellular Carcinoma. Among its related pathways are Apoptosis and survival Caspase cascade and CDK-mediated phosphorylation and removal of Cdc6. Gene Ontology (GO) annotations related to this gene include protein heterodimerization activity. An important paralog of this gene is CASP10.

UniProtKB/Swiss-Prot Summary for CASP8 Gene

  • 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 (PubMed:23516580, PubMed:9006941). Cleaves RIPK1 at 'Asp-325' which is crucial for limiting apoptosis and necroptosis during embryonic development (By similarity).

Tocris Summary for CASP8 Gene

  • Caspases (cysteinyl aspartate proteases) are involved in the signaling pathways of apoptosis, necrosis and inflammation. These enzymes can be divided into initiators and effectors. The initiator isoforms are activated by, and interact with, upstream adaptor molecules.

Gene Wiki entry for CASP8 Gene

Additional gene information for CASP8 Gene

No data available for PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CASP8 Gene

Genomics for CASP8 Gene

GeneHancer (GH) Regulatory Elements for CASP8 Gene

Promoters and enhancers for CASP8 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J201251 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 556.2 +25.1 25059 13.4 ZBTB40 EP300 SIN3A TCF12 POLR2G SP1 JUND FOS CTCF ZNF10 CASP8 NONHSAG030244.2 FLACC1 STRADB PPIL3 CASP10 CLK1 CFLAR FAM126B piR-48300-061
GH02J201231 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 505.4 +0.9 935 5.4 RXRA FOXK2 ZBTB40 ZNF217 CTCF SIN3A USF1 POLR2G SP1 TEAD4 CASP8 lnc-CASP10-2 CASP10 PPIL3 NONHSAG030244.2
GH02J201450 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 24.4 +218.6 218602 3.7 EP300 FOXK2 ZBTB40 ZNF217 SIN3A TCF12 POLR2G SP1 NCOR1 PHF8 STRADB HSALNG0021558 TRAK2 lnc-C2CD6-2 CASP8 ORC2 CLK1 NOP58 ENSG00000213090 TMEM237
GH02J201356 Promoter/Enhancer 1.1 EPDnew Ensembl ENCODE 23 +124.1 124122 1.7 RFX1 NFYB SIN3A ESRRA NFYA PKNOX1 RFX5 NFYC SP1 FOXA2 FLACC1 lnc-TRAK2-2 piR-57134-074 CASP8 STRADB
GH02J201364 Enhancer 0.8 Ensembl ENCODE 33.5 +130.5 130516 0.7 CTCF REST RAD21 TRIM22 SMC3 ZNF316 MAFF MAFK SMARCA5 ZNF654 CASP8 STRADB TMEM237 RNU6-651P FLACC1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CASP8 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CASP8

Top Transcription factor binding sites by QIAGEN in the CASP8 gene promoter:
  • STAT3

Genomic Locations for CASP8 Gene

Genomic Locations for CASP8 Gene
chr2:201,233,443-201,287,711
(GRCh38/hg38)
Size:
54,269 bases
Orientation:
Plus strand
chr2:202,098,166-202,152,434
(GRCh37/hg19)
Size:
54,269 bases
Orientation:
Plus strand

Genomic View for CASP8 Gene

Genes around CASP8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CASP8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CASP8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CASP8 Gene

Proteins for CASP8 Gene

  • Protein details for CASP8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14790-CASP8_HUMAN
    Recommended name:
    Caspase-8
    Protein Accession:
    Q14790
    Secondary Accessions:
    • O14676
    • Q14791
    • Q14792
    • Q14793
    • Q14794
    • Q14795
    • Q14796
    • Q15780
    • Q15806
    • Q53TT5
    • Q8TDI1
    • Q8TDI2
    • Q8TDI3
    • Q8TDI4
    • Q8TDI5
    • Q96T22
    • Q9C0K4
    • Q9UQ81

    Protein attributes for CASP8 Gene

    Size:
    479 amino acids
    Molecular mass:
    55391 Da
    Quaternary structure:
    • Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 10 kDa (p10) subunit (PubMed:10508784). Interacts with FADD, CFLAR and PEA15 (PubMed:10442631). Isoform 9 interacts at the endoplasmic reticulum with a complex containing BCAP31, BAP29, BCL2 and/or BCL2L1 (PubMed:11917123, PubMed:9334338). Interacts with TNFAIP8L2 (By similarity). Interacts with CASP8AP2 (PubMed:16378960). Interacts with RFFL and RNF34; negatively regulate CASP8 through proteasomal degradation (PubMed:15069192). Interacts with NOL3; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium (PubMed:15509781). Interacts with UBR2 (PubMed:28602583). Interacts with RIPK1 (By similarity). Interacts with stimulated TNFRSF10B; this interaction is followed by CASP8 proteolytic cleavage and activation (PubMed:18846110).
    • (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein vICA/UL36; this interaction inhibits CASP8 activation.
    • (Microbial infection) Interacts with NleF from pathogenic E.coli.
    • (Microbial infection) Interacts with molluscum contagiosum virus protein MC160.
    Miscellaneous:
    • [Isoform 7]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
    SequenceCaution:
    • Sequence=CAA66858.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305}; Sequence=CAA66859.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CASP8 Gene

    Alternative splice isoforms for CASP8 Gene

neXtProt entry for CASP8 Gene

Post-translational modifications for CASP8 Gene

  • Generation of the subunits requires association with the death-inducing signaling complex (DISC), whereas additional processing is likely due to the autocatalytic activity of the activated protease. GZMB and CASP10 can be involved in these processing events.
  • Phosphorylation on Ser-387 during mitosis by CDK1 inhibits activation by proteolysis and prevents apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes.
  • Ubiquitination at Lys148 and Lys169
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for CASP8 Gene

Domains & Families for CASP8 Gene

Gene Families for CASP8 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for CASP8 Gene

Blocks:
  • Caspase-1, p20
  • Interleukin-1B converting enzyme signature
  • Death effector protein
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CASP8 Gene

GenScript: Design optimal peptide antigens:
  • Caspase 8 isoform C (B5BU46_HUMAN)
  • Caspase 8 splice variant (B6CGU5_HUMAN)
  • MORT1-associated ced-3 homolog (CASP8_HUMAN)
  • CASP8 protein (Q6NVI2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14790

UniProtKB/Swiss-Prot:

CASP8_HUMAN :
  • Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex.
  • Belongs to the peptidase C14A family.
Domain:
  • Isoform 9 contains a N-terminal extension that is required for interaction with the BCAP31 complex.
Family:
  • Belongs to the peptidase C14A family.
genes like me logo Genes that share domains with CASP8: view

Function for CASP8 Gene

Molecular function for CASP8 Gene

UniProtKB/Swiss-Prot 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 (PubMed:23516580, PubMed:9006941). Cleaves RIPK1 at 'Asp-325' which is crucial for limiting apoptosis and necroptosis during embryonic development (By similarity).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Strict requirement for Asp at position P1 and has a preferred cleavage sequence of (Leu/Asp/Val)-Glu-Thr-Asp- -(Gly/Ser/Ala).; EC=3.4.22.61; Evidence=. ;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by the effector protein NleF that is produced by pathogenic E.coli; this inhibits apoptosis.
GENATLAS Biochemistry:
caspase 8,initiator,cysteine containing aspartate-specific protease,CASP3 subfamily,stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli,promoting CD95/APO1/Fas apoptosis,through the cleavage of BID,C elegans CED1 homolog

Enzyme Numbers (IUBMB) for CASP8 Gene

Phenotypes From GWAS Catalog for CASP8 Gene

Gene Ontology (GO) - Molecular Function for CASP8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity TAS --
GO:0005123 death receptor binding IEA --
GO:0005164 tumor necrosis factor receptor binding IEA --
GO:0005515 protein binding IEA,IPI 9208847
GO:0008233 peptidase activity IMP,IDA 17047155
genes like me logo Genes that share ontologies with CASP8: view
genes like me logo Genes that share phenotypes with CASP8: view

Human Phenotype Ontology for CASP8 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CASP8 Gene

MGI Knock Outs for CASP8:

Clone Products

  • Addgene plasmids for CASP8

No data available for Transcription Factor Targets and HOMER Transcription for CASP8 Gene

Localization for CASP8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CASP8 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CASP8 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 5
mitochondrion 5
nucleus 5
cytosol 5
extracellular 3
endoplasmic reticulum 3
lysosome 3
peroxisome 2
endosome 2
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (4)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CASP8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IBA 21873635
GO:0005739 mitochondrion TAS 10891503
GO:0005741 mitochondrial outer membrane TAS --
genes like me logo Genes that share ontologies with CASP8: view

Pathways & Interactions for CASP8 Gene

PathCards logo

SuperPathways for CASP8 Gene

SuperPathway Contained pathways
1 TNFR1 Pathway
.87
.87
.56
.55
.52
.46
.42
.40
.35
2 Dimerization of procaspase-8