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 Necroptosis and CLEC7A (Dectin-1) signaling. 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.

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
- 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

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).
    • (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.
    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

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.
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 IPI 9208847
GO:0008233 peptidase activity IDA,IMP 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:

Animal Model Products

CRISPR Products

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 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

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
.46
.42
.40
.35
2 Regulation by c-FLIP
3 Activated TLR4 signalling
4 Apoptosis Modulation and Signaling
.41
.31
5 Toll-like Receptor Signaling Pathway
genes like me logo Genes that share pathways with CASP8: view

Pathways by source for CASP8 Gene

SIGNOR curated interactions for CASP8 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CASP8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IDA 12888622
GO:0006915 apoptotic process IBA,IMP 22891283
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process TAS,IBA --
GO:0007166 cell surface receptor signaling pathway TAS --
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors IBA 21873635
genes like me logo Genes that share ontologies with CASP8: view

Drugs & Compounds for CASP8 Gene

(94) Drugs for CASP8 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cisplatin Approved Pharma Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum 3240
Bardoxolone Investigational Pharma Target Once-a-day treatment for CKD 0
PAC-1 Investigational Pharma Procaspase-3 activator 0
Tasisulam Investigational Pharma 0
Emricasan Investigational Pharma 0

(64) Additional Compounds for CASP8 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
PAC 1
315183-21-2

(4) Tocris Compounds for CASP8 Gene

Compound Action Cas Number
Apoptosis Activator 2 Promotes apoptosome formation and activates caspase-9/caspase-3 pathway. Selectively induces tumor cell apoptosis 79183-19-0
Cisplatin Potent pro-apoptotic anticancer agent; activates caspase-3 15663-27-1
PAC 1 Activator of procaspase-3; pro-apoptotic 315183-21-2
PETCM Activator of caspase-3 10129-56-3

(11) ApexBio Compounds for CASP8 Gene

Compound Action Cas Number
Apoptosis Activator 2 Indoledione caspase activator, cell-permeable 79183-19-0
Boc-D-FMK Pan-caspase inhibitor 187389-53-3, 634911-80-1
Caspase-8 Inhibitor Z-IETD-FMK Novel and selective caspase-8 inhibitor
Cisplatin Inhibits DNA synthesis,chemotherapy drug 15663-27-1
Gambogic Acid Caspase activator and apoptosis inducer 2752-65-0
PAC-1 Procaspase-3 activator 315183-21-2
Q-VD-OPh hydrate Cell-permeable, irreversible pan-caspase inhibitor 1135695-98-5
Tasisulam 519055-62-0
Z-DEVD-FMK Caspase-3 inhibitor 210344-95-9
Z-IETD-FMK Caspase-8 inhibitor 210344-98-2
Z-VAD-FMK Cell-permeable, irreversible pan-caspase inhibitor 187389-52-2
genes like me logo Genes that share compounds with CASP8: view

Transcripts for CASP8 Gene

CRISPR Products

Clone Products

  • Addgene plasmids for CASP8

Alternative Splicing Database (ASD) splice patterns (SP) for CASP8 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b · 10c ^ 11 ^ 12a · 12b ^ 13a · 13b · 13c ^ 14 ^ 15 ^
SP1: - - - - - - - - - -
SP2: - - - - - - - - - - - -
SP3: - - - - - - - - - - - -
SP4: - - - - - - - - - - -
SP5: -
SP6: - - - -
SP7: - - -
SP8: - -
SP9: - - - - - -
SP10: - - - - - - - - - - -
SP11: - - - - - - -
SP12: - - - - -
SP13: - - - - - - - -
SP14: -
SP15:
SP16: -

ExUns: 16a · 16b ^ 17 ^ 18a · 18b · 18c · 18d ^ 19a · 19b
SP1: - -
SP2: - -
SP3: - -
SP4: -
SP5: - -
SP6:
SP7: - -
SP8: - -
SP9:
SP10:
SP11:
SP12:
SP13: - - -
SP14:
SP15:
SP16:

Relevant External Links for CASP8 Gene

GeneLoc Exon Structure for
CASP8
ECgene alternative splicing isoforms for
CASP8

Expression for CASP8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS,