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    CASP8 caspase 8 [ Homo sapiens (human) ]

    Gene ID: 841, updated on 9-Jul-2017
    Official Symbol
    CASP8provided by HGNC
    Official Full Name
    caspase 8provided by HGNC
    Primary source
    HGNC:HGNC:1509
    See related
    Ensembl:ENSG00000064012 MIM:601763; Vega:OTTHUMG00000132821
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CAP4; MACH; MCH5; FLICE; ALPS2B; Casp-8
    Summary
    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]
    Orthologs
    Location:
    2q33.1
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 2 NC_000002.12 (201233443..201287711)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (202098166..202152434)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene caspase 10 Neighboring gene mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 5 pseudogene 25 Neighboring gene mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 pseudogene 23 Neighboring gene amyotrophic lateral sclerosis 2 chromosome region 12 Neighboring gene trafficking kinesin protein 2 Neighboring gene SCY1 like pseudokinase 2 pseudogene

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Caspase-8 deficiency
    MedGen: C1846545 OMIM: 607271 GeneReviews: Not available
    Compare labs
    Familial cancer of breast Compare labs
    Hepatocellular carcinoma
    MedGen: C2239176 OMIM: 114550 GeneReviews: Not available
    Compare labs
    Lung cancer
    MedGen: C0684249 OMIM: 211980 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    NHGRI GWA Catalog
    Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
    NHGRI GWA Catalog
    Genome-wide association study identifies three new melanoma susceptibility loci.
    NHGRI GWA Catalog
    Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120-treated vaginal epithelial cells show downregulation of caspase 8 (CASP8, apoptosis-related cysteine peptidase) expression as compared to untreated control PubMed
    env Treatment of HIV-1 Env-pseudotyped virus-infected MDM cells with both soluble TRAIL and an agonistic anti-DR5 antibody AD5-10 induces activation of caspase-3, -8, and -9 PubMed
    env HIV-1 gp120-induced neuron apoptosis requires the upregulation of the death receptor Fas and its associated death proteins, FADD and CASP8 PubMed
    env Caspase 8 proteolytic target protein Bid is cleaved and undergoes mitochondrial translocation in gp120-treated p53 expression neurons PubMed
    env HIV-1 gp120-mediated activation of caspase 8 occurs in a p53 independent manner, while HIV-1 gp120-mediated activation of caspase 3 requires p53 PubMed
    env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    Envelope transmembrane glycoprotein gp41 env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    Nef nef Stable expression of HIV-1 Nef in Jurkat T cells confers resistance to Fas-mediated apoptosis through inactivation of caspase-3 and caspase-8 PubMed
    Tat tat FasL-induced activation of caspase-3 and -8 proteins is inhibited in HIV-1 Tat101-expressing Jurkat cells PubMed
    tat Both HIV-1 Tat 47-59 and FITC-labeled Tat 47-59 peptides upregulate gene expression of caspase 8, apoptosis-related cysteine protease (CASP8) in U-937 macrophages PubMed
    tat HIV-1 Tat induces apoptosis and increases sensitivity to apoptotic signals by upregulating FLICE/Caspase-8 PubMed
    Vpr vpr HIV-1 Vpr-induced caspase-8 activation causes cleavage of BID to tBID through ERK activation PubMed
    vpr HIV-1 Vpr induces apoptosis through caspase activation and caspase 8 has been specifically demonstrated in one study to be activated during this process, however in other studies it was not activated PubMed
    Vpu vpu Caspase-8 and caspase-3 activity are required for HIV-1 Vpu-induced cleavage of IRF3 and HIV-1 infection also induces caspase-mediated IRF3 cleavage PubMed
    retropepsin gag-pol HIV-1 Protease cleaves procaspase 8 between amino acids 355 and 356 and generates casp8p41 protein in cells. Casp8p41 is produced in HIV-1-infected cells and colocalizes with dying cells PubMed
    gag-pol HIV-1 protease directly cleaves and activates procaspase 8 in T cells, which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP PubMed

    Go to the HIV-1, Human Interaction Database

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      Caspase cascade in apoptosis
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    • Coregulation of Androgen receptor activity, organism-specific biosystem (from Pathway Interaction Database)
      Coregulation of Androgen receptor activity, organism-specific biosystem
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    • DNA Damage Response, organism-specific biosystem (from WikiPathways)
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    • Death Receptor Signalling, organism-specific biosystem (from REACTOME)
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    • Dimerization of procaspase-8, organism-specific biosystem (from REACTOME)
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    • FAS (CD95) signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      FAS (CD95) signaling pathway, organism-specific biosystem
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    • FasL/ CD95L signaling, organism-specific biosystem (from REACTOME)
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    • HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem (from Pathway Interaction Database)
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    • Herpes simplex infection, organism-specific biosystem (from KEGG)
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    • Herpes simplex infection, conserved biosystem (from KEGG)
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    • Huntington's disease, organism-specific biosystem (from KEGG)
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    • Integrated Cancer Pathway, organism-specific biosystem (from WikiPathways)
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    • NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10, organism-specific biosystem (from REACTOME)
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    • Non-alcoholic fatty liver disease (NAFLD), organism-specific biosystem (from KEGG)
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    • Non-alcoholic fatty liver disease (NAFLD), conserved biosystem (from KEGG)
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    • Parkin-Ubiquitin Proteasomal System pathway, organism-specific biosystem (from WikiPathways)
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    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
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    • Programmed Cell Death, organism-specific biosystem (from REACTOME)
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    • RIG-I-like receptor signaling pathway, organism-specific biosystem (from KEGG)
      RIG-I-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
    • RIG-I-like receptor signaling pathway, conserved biosystem (from KEGG)
      RIG-I-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
    • RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystem (from REACTOME)
      RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways, organism-specific biosystemRIG-I-like helicases (RLHs) the retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5) are RNA helicases that recognize viral RNA present within the cytoplasm. F...
    • RIPK1-mediated regulated necrosis, organism-specific biosystem (from REACTOME)
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    • Regulated Necrosis, organism-specific biosystem (from REACTOME)
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    • Regulation by c-FLIP, organism-specific biosystem (from REACTOME)
      Regulation by c-FLIP, organism-specific biosystemc-FLIP proteins (CASP8 and FADD-like apoptosis regulators or c-FLICE inhibitory proteins) are death effector domain (DED)-containing proteins that are recruited to the death-inducing signaling comple...
    • Regulation of TNFR1 signaling, organism-specific biosystem (from REACTOME)
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    • Regulation of necroptotic cell death, organism-specific biosystem (from REACTOME)
      Regulation of necroptotic cell death, organism-specific biosystemA regulated balance between cell survival and cell death is essential for normal development and homeostasis of multicellular organisms. Defects in control of this balance may contribute to autoimmu...
    • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
      Regulation of toll-like receptor signaling pathway, organism-specific biosystem
      Regulation of toll-like receptor signaling pathway
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • TNF alpha Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TNF alpha Signaling Pathway, organism-specific biosystemTumor necrosis factor alpha (TNF?) is a proinflammatory cytokine involved in various biological processes including regulation of cell proliferation, differentiation, apoptosis and immune response. T...
    • TNF receptor signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      TNF receptor signaling pathway, organism-specific biosystem
      TNF receptor signaling pathway
    • TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TNF related weak inducer of apoptosis (TWEAK) Signaling Pathway, organism-specific biosystemTNF related weak inducer of apoptosis (TWEAK) is a small pleiotropic cytokine of the TNF super family and its gene is located at chromosome 17p13.1. TWEAK has been reported to be expressed in tissues...
    • TNF signaling, organism-specific biosystem (from REACTOME)
      TNF signaling, organism-specific biosystemThe inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) is expressed in immune and nonimmune cell types including macrophages, T cells, mast cells, granulocytes, natural killer (NK) cells, ...
    • TNF signaling pathway, organism-specific biosystem (from KEGG)
      TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
    • TNF signaling pathway, conserved biosystem (from KEGG)
      TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
    • TNFR1-induced proapoptotic signaling, organism-specific biosystem (from REACTOME)
      TNFR1-induced proapoptotic signaling, organism-specific biosystemActivation of tumor necrosis factor receptor 1 (TNFR1) can trigger multiple signal transduction pathways to induce cell survival or cell death (Ward C et al. 1999; Micheau O and Tschopp J 2003; Wider...
    • TRAIL signaling, organism-specific biosystem (from REACTOME)
      TRAIL signaling, organism-specific biosystemTumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family. This group of apoptosis induction pathways all work throug...
    • TRAIL signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      TRAIL signaling pathway, organism-specific biosystem
      TRAIL signaling pathway
    • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
      TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
    • TRIF-mediated programmed cell death, organism-specific biosystem (from REACTOME)
      TRIF-mediated programmed cell death, organism-specific biosystemTLR3 and -4 trigger TRIF-dependent programmed cell death in various human and mouse cells (Kalai M et al. 2002; Han KJ et al. 2004; Kaiser WJ and Offermann MK 2005; Estornes Y et al. 2012; He S et al...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
    • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
      Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
    • Toll-like Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Toll-like Receptor Signaling Pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
      Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
      Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
    • Toxoplasmosis, organism-specific biosystem (from KEGG)
      Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
    • Toxoplasmosis, conserved biosystem (from KEGG)
      Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
    • Tuberculosis, organism-specific biosystem (from KEGG)
      Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • Tuberculosis, conserved biosystem (from KEGG)
      Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • Viral carcinogenesis, organism-specific biosystem (from KEGG)
      Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
    • Viral carcinogenesis, conserved biosystem (from KEGG)
      Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
    • Viral myocarditis, organism-specific biosystem (from KEGG)
      Viral myocarditis, organism-specific biosystemMyocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is stil...
    • miRNA Regulation of DNA Damage Response, organism-specific biosystem (from WikiPathways)
      miRNA Regulation of DNA Damage Response, organism-specific biosystemThis is the first out of two pathways which deals with the DNA damage response. It is comprised of two central gene products (ATM and ATR) influenced by different sources of DNA damage (in blue). The...
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • FLJ17672, MGC78473

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
     
    cysteine-type endopeptidase activity involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cysteine-type endopeptidase activity involved in apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cysteine-type endopeptidase activity involved in execution phase of apoptosis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    cysteine-type peptidase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    death effector domain binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    death receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    peptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    peptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein complex binding IEA
    Inferred from Electronic Annotation
    more info
     
    scaffold protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    tumor necrosis factor receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    B cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    T cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    TRAIL-activated apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    TRIF-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    activation of cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    activation of cysteine-type endopeptidase activity involved in apoptotic process TAS
    Traceable Author Statement
    more info
     
    activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
     
    apoptotic process IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
     
    cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    cellular response to organic cyclic compound IEA
    Inferred from Electronic Annotation
    more info
     
    death-inducing signaling complex assembly TAS
    Traceable Author Statement
    more info
     
    execution phase of apoptosis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    execution phase of apoptosis TAS
    Traceable Author Statement
    more info
     
    extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    macrophage differentiation TAS
    Traceable Author Statement
    more info
    PubMed 
    natural killer cell activation TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of I-kappaB kinase/NF-kappaB signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
    Traceable Author Statement
    more info
     
    nucleotide-binding oligomerization domain containing signaling pathway TAS
    Traceable Author Statement
    more info
     
    positive regulation of I-kappaB kinase/NF-kappaB signaling IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    positive regulation of I-kappaB kinase/NF-kappaB signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of macrophage differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
     
    positive regulation of proteolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    proteolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    proteolysis involved in cellular protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of extrinsic apoptotic signaling pathway via death domain receptors TAS
    Traceable Author Statement
    more info
     
    regulation of necroptotic process TAS
    Traceable Author Statement
    more info
     
    regulation of tumor necrosis factor-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    response to antibiotic IEA
    Inferred from Electronic Annotation
    more info
     
    response to cobalt ion IEA
    Inferred from Electronic Annotation
    more info
     
    response to cold IEA
    Inferred from Electronic Annotation
    more info
     
    response to estradiol IEA
    Inferred from Electronic Annotation
    more info
     
    response to ethanol IEA
    Inferred from Electronic Annotation
    more info
     
    response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    response to tumor necrosis factor IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process TAS
    Traceable Author Statement
    more info
     
    syncytiotrophoblast cell differentiation involved in labyrinthine layer development TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    CD95 death-inducing signaling complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell body IEA
    Inferred from Electronic Annotation
    more info
     
    cytoskeleton TAS
    Traceable Author Statement
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    death-inducing signaling complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane raft IEA
    Inferred from Electronic Annotation
    more info
     
    mitochondrial outer membrane TAS
    Traceable Author Statement
    more info
     
    mitochondrion TAS
    Traceable Author Statement
    more info
    PubMed 
    neuron projection IEA
    Inferred from Electronic Annotation
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    ripoptosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    caspase-8
    Names
    FADD-homologous ICE/CED-3-like protease
    FADD-like ICE
    ICE-like apoptotic protease 5
    MACH-alpha-1/2/3 protein
    MACH-beta-1/2/3/4 protein
    MORT1-associated ced-3 homolog
    apoptotic cysteine protease
    apoptotic protease Mch-5
    caspase 8, apoptosis-related cysteine peptidase
    caspase 8, apoptosis-related cysteine protease
    NP_001073593.1
    NP_001073594.1
    NP_001219.2
    NP_203519.1
    NP_203520.1
    NP_203522.1
    XP_005246942.1
    XP_005246943.1
    XP_005246944.1
    XP_005246945.1
    XP_005246946.1
    XP_005246947.1
    XP_005246948.1
    XP_005246949.1
    XP_005246950.1
    XP_005246951.1
    XP_005246952.1
    XP_006712852.1
    XP_006712853.1
    XP_006712856.1
    XP_011510271.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007497.1 RefSeqGene

      Range
      4986..59254
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_34

    mRNA and Protein(s)

    1. NM_001080124.1NP_001073593.1  caspase-8 isoform C precursor

      See identical proteins and their annotated locations for NP_001073593.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (F) includes different segments in the 5' UTR and lacks an alternate in-frame segment in the coding region, compared to variant G. Variants C and F both encode isoform C, which is shorter than isoform G. Isoform C has also been labelled as Alpha-2 or MCH5-beta.
      Source sequence(s)
      AC007256, AF422927, AI351872, DA420056
      Consensus CDS
      CCDS2343.1
      UniProtKB/Swiss-Prot
      Q14790
      UniProtKB/TrEMBL
      A0A024R3Z8
      Related
      ENSP00000376091.2, OTTHUMP00000165063, ENST00000392263.6, OTTHUMT00000257909
      Conserved Domains (3) summary
      cd00032
      Location:210462
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    2. NM_001080125.1NP_001073594.1  caspase-8 isoform G precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (G), also known as procaspase-8L or 8L, encodes the longest protein (isoform G).
      Source sequence(s)
      AC007256, AF422927, AI351872, X98172
      Consensus CDS
      CCDS42798.1
      UniProtKB/Swiss-Prot
      Q14790
      Related
      ENSP00000351273.4, OTTHUMP00000163717, ENST00000358485.8, OTTHUMT00000256278
      Conserved Domains (3) summary
      cd00032
      Location:284536
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:62143
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:157239
      DD; Death Domain Superfamily of protein-protein interaction domains
    3. NM_001228.4NP_001219.2  caspase-8 isoform A precursor

      See identical proteins and their annotated locations for NP_001219.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (A), also known as Alpha-4, has multiple differences in the 5' UTR and coding region, compared to variant G. It encodes isoform A which is shorter than isoform G.
      Source sequence(s)
      AC007256, AI351872, BC028223, DA420056, U60520
      Consensus CDS
      CCDS42799.1
      UniProtKB/Swiss-Prot
      Q14790
      Related
      ENSP00000264275.5, OTTHUMP00000165062, ENST00000264275.9, OTTHUMT00000257907
      Conserved Domains (3) summary
      cd00032
      Location:242494
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:134212
      DD; Death Domain Superfamily of protein-protein interaction domains
    4. NM_033355.3NP_203519.1  caspase-8 isoform B precursor

      See identical proteins and their annotated locations for NP_203519.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (B) includes different segments in its 5' UTR and lacks a 5' coding region segment, compared to variant G. This results in translation at a downstream start codon, and the encoded protein (isoform B) has a shorter N-terminus when it is compared to isoform G.
      Source sequence(s)
      AC007256, AF422928, AI351872, DA420056
      Consensus CDS
      CCDS2342.1
      UniProtKB/Swiss-Prot
      Q14790
      Related
      ENSP00000412523.2, OTTHUMP00000206552, ENST00000432109.6, OTTHUMT00000336853
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    5. NM_033356.3NP_203520.1  caspase-8 isoform C precursor

      See identical proteins and their annotated locations for NP_203520.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (C) includes a different segment in the 5' UTR and lacks an alternate in-frame segment in the coding region, compared to variant G. Variants C and F both encode isoform C, which is shorter than isoform G. Isoform C has also been labelled as Alpha-2 or MCH5-beta.
      Source sequence(s)
      AC007256, AI351872, AL601594, BC028223, X98173
      Consensus CDS
      CCDS2343.1
      UniProtKB/Swiss-Prot
      Q14790
      UniProtKB/TrEMBL
      A0A024R3Z8
      Related
      ENSP00000325722.7, OTTHUMP00000165064, ENST00000323492.11, OTTHUMT00000257912
      Conserved Domains (3) summary
      cd00032
      Location:210462
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    6. NM_033358.3NP_203522.1  caspase-8 isoform E

      See identical proteins and their annotated locations for NP_203522.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (E), also known as Beta-1, has multiple differences, one of which causes a frameshift, compared to variant G. It encodes isoform E, which is shorter than isoform G.
      Source sequence(s)
      DA420056, DB157537, X98176
      Consensus CDS
      CCDS2345.1
      UniProtKB/Swiss-Prot
      Q14790
      Related
      ENSP00000376087.3, OTTHUMP00000163720, ENST00000392258.7, OTTHUMT00000256281
      Conserved Domains (2) summary
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains

    RNA

    1. NR_111983.1 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (H) has an alternate splice site in the central region, compared to variant G. This variant is represented as non-coding because use of the 5'-most expected translation start codon, as used in variant G, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC007256, AF380342, BG236020, U60520

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p7 Primary Assembly

      Range
      201233443..201287711
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712789.1XP_006712852.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_006712852.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    2. XM_005246887.1XP_005246944.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_005246944.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    3. XM_006712793.2XP_006712856.1  caspase-8 isoform X8

      See identical proteins and their annotated locations for XP_006712856.1

      UniProtKB/Swiss-Prot
      Q14790
      Related
      ENSP00000397528.1, OTTHUMP00000206557, ENST00000413726.5, OTTHUMT00000336861
      Conserved Domains (2) summary
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    4. XM_005246894.3XP_005246951.1  caspase-8 isoform X6

      Conserved Domains (1) summary
      cd00032
      Location:26278
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
    5. XM_005246888.1XP_005246945.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_005246945.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    6. XM_005246891.4XP_005246948.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_005246948.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    7. XM_006712790.3XP_006712853.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_006712853.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    8. XM_005246889.1XP_005246946.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_005246946.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    9. XM_005246892.1XP_005246949.1  caspase-8 isoform X3

      See identical proteins and their annotated locations for XP_005246949.1

      UniProtKB/Swiss-Prot
      Q14790
      UniProtKB/TrEMBL
      A0A024R3Z8
      Conserved Domains (3) summary
      cd00032
      Location:210462
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    10. XM_005246885.1XP_005246942.1  caspase-8 isoform X1

      Conserved Domains (3) summary
      cd00032
      Location:269521
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:62143
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:157239
      DD; Death Domain Superfamily of protein-protein interaction domains
    11. XM_005246893.2XP_005246950.1  caspase-8 isoform X5

      See identical proteins and their annotated locations for XP_005246950.1

      Conserved Domains (2) summary
      cd08333
      Location:62143
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:157239
      DD; Death Domain Superfamily of protein-protein interaction domains
    12. XM_005246895.2XP_005246952.1  caspase-8 isoform X7

      Conserved Domains (2) summary
      cd08333
      Location:62143
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:157239
      DD; Death Domain Superfamily of protein-protein interaction domains
    13. XM_005246890.3XP_005246947.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_005246947.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    14. XM_005246886.1XP_005246943.1  caspase-8 isoform X2

      See identical proteins and their annotated locations for XP_005246943.1

      UniProtKB/Swiss-Prot
      Q14790
      Conserved Domains (3) summary
      cd00032
      Location:225477
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cd08333
      Location:384
      DED_Caspase_8_r1; Death effector domain, repeat 1, of Caspase-8
      cl14633
      Location:98180
      DD; Death Domain Superfamily of protein-protein interaction domains
    15. XM_011511969.1XP_011510271.1  caspase-8 isoform X4

      Conserved Domains (2) summary
      cd00032
      Location:80332
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
      cl14633
      Location:135
      DD; Death Domain Superfamily of protein-protein interaction domains

    RNA

    1. XR_001738971.1 RNA Sequence

    2. XR_923035.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018913.2 Alternate CHM1_1.1

      Range
      202104145..202158454
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_033357.2: Suppressed sequence

      Description
      NM_033357.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
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