Seroatlas · Human Serome Atlas

CASP8

Caspase-8

Also known as: Casp-8, CASP8_HUMAN, FLICE, MACH, MCH5

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q14790
Gene
CASP8
Ensembl
ENSG00000064012
Chromosome
2
Canonical length
479 aa
Protein class
Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins
Subcellular location
Centriolar satellite,Mitochondria,Cytosol,Connecting piece,Mid piece,Principal piece

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

479 residues, UniProt reviewed canonical sequence.

>Q14790|CASP8
     1  MDFSRNLYDI GEQLDSEDLA SLKFLSLDYI PQRKQEPIKD ALMLFQRLQE KRMLEESNLS
    61  FLKELLFRIN RLDLLITYLN TRKEEMEREL QTPGRAQISA YRVMLYQISE EVSRSELRSF
   121  KFLLQEEISK CKLDDDMNLL DIFIEMEKRV ILGEGKLDIL KRVCAQINKS LLKIINDYEE
   181  FSKERSSSLE GSPDEFSNGE ELCGVMTISD SPREQDSESQ TLDKVYQMKS KPRGYCLIIN
   241  NHNFAKAREK VPKLHSIRDR NGTHLDAGAL TTTFEELHFE IKPHDDCTVE QIYEILKIYQ
   301  LMDHSNMDCF ICCILSHGDK GIIYGTDGQE APIYELTSQF TGLKCPSLAG KPKVFFIQAC
   361  QGDNYQKGIP VETDSEEQPY LEMDLSSPQT RYIPDEADFL LGMATVNNCV SYRNPAEGTW
   421  YIQSLCQSLR ERCPRGDDIL TILTEVNYEV SNKDDKKNMG KQMPQPTFTL RKKLVFPSD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CASP8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.31
Highest tissue expression
44 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 44 nTPM
  • spleen: 33 nTPM
  • lymph node: 26 nTPM
  • small intestine: 23 nTPM
  • tonsil: 23 nTPM
  • appendix: 21 nTPM

Single-cell type

  • cardiomyocytes: 382 nCPM
  • neutrophils: 238 nCPM
  • t-cells: 225 nCPM
  • nk-cells: 214 nCPM
  • thymocytes: 205 nCPM
  • innate lymphoid cells: 190 nCPM

Immune cell

  • neutrophil: 135 nTPM
  • basophil: 69 nTPM
  • eosinophil: 68 nTPM
  • memory CD8 T-cell: 64 nTPM
  • T-reg: 64 nTPM
  • gdT-cell: 60 nTPM

Brain region

  • white matter: 5.4 nTPM
  • choroid plexus: 5.2 nTPM
  • medulla oblongata: 4.8 nTPM
  • thalamus: 4.2 nTPM
  • spinal cord: 4.1 nTPM
  • midbrain: 3.8 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CASP8.

Disease | AllUniProt

Conditions CASP8 is implicated in, by any mechanism.

Disease | GeneticClinVar

24 pathogenic / likely-pathogenic of 406 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Disease | ImmuneIEDB

Conditions an epitope on CASP8 was assayed in.

Disease | AutoantibodyPubMed

Conditions in which antibodies against CASP8 are reported. Each links to that disease's full target list.

    Showing 0 of 1 — disease pages carrying at least 10 antigens.

    ReferencesPubMed · IEDB

    Publications for CASP8 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

    Reference: AutoantibodyPubMed

    6 publications

    Show 1 more

    Reference: B cellIEDB

    1 publication

    Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

    Genetic constraint and essentialitygnomAD · DepMap

    Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

    gnomAD LOEUF (loss-of-function intolerance)
    0.81
    gnomAD pLI
    0
    gnomAD missense Z
    1.01
    DepMap mean gene effect
    0.14
    DepMap dependency class
    selective

    Cancer expressionTCGA

    Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

    OntologyGO

    Biological processes

    Molecular functions

    Cellular components

    Protein domainsUniProt · Pfam · InterPro

    KeywordsUniProt

    InteractionsUniProt · HPA

    Protein binding partners of CASP8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

    Antibody and autoantibody relevanceSeroatlas analysis

    Seroatlas reads CASP8 as an antibody target. Whether an autoantibody or antibody against CASP8 could matter depends on whether native CASP8 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

    CASP8 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

    Annotation status

    The present source text does not explicitly label CASP8 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

    Canonical record: https://seroatlas.com/gene/CASP8. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

    Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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