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CASP8
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  • CASP8
PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
Hippocampal formation Amygdala Basal ganglia Midbrain Spinal cord Cerebral cortex Cerebellum Hypothalamus Choroid plexus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Colon Duodenum Rectum Small intestine Liver Gallbladder Pancreas Kidney Urinary bladder Testis Epididymis Prostate Seminal vesicle Vagina Breast Cervix Endometrium Fallopian tube Ovary Placenta Heart muscle Skeletal muscle Smooth muscle Adipose tissue Skin Bone marrow Thymus Appendix Tonsil Lymph node Spleen
CASP8 INFORMATION
Proteini

Full gene name according to HGNC.

Caspase 8
Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

CASP8 (Casp-8, FLICE, MACH, MCH5)
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

Cancer-related genes
Disease related genes
Enzymes
Human disease related genes
Potential drug targets
Protein evidence Evidence at protein level (all genes)
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

17
Protein interactions Interacting with 13 proteins
PROTEIN EXPRESSION AND LOCALIZATION
Tissue profilei

A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource.

"Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.
Cytoplasmic expression of varying intensity in most tissues.
Subcellular locationi

Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.

Localized to the Mitochondria, Cytosol In addition localized to the Centriolar satellite, Connecting piece, Mid piece, Principal piece
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

Intracellular
TISSUE RNA EXPRESSION
Tissue specificityi

The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.

Tissue enhanced (Bone marrow)
Tissue expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Lymphoid tissue & Bone marrow - Innate immune response (mainly)
Brain specificityi

The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category

Low human brain regional specificity
Brain expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Macrophages & Microglia - Immune response (mainly)
CELL TYPE RNA EXPRESSION
Single cell type specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Cell type enhanced (NK-cells, T-cells)
Single cell type
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

NK-cells & T-cells - Immune system & Transcription (mainly)
Tissue cell type classificationi

Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.

No predicted cell type specificity
Immune cell specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Low immune cell specificity
Immune cell
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Neutrophils - Protein binding (mainly)
CANCER & CELL LINES
Prognostic summary CASP8 is a prognostic marker in Bladder urothelial carcinoma, Cervical squamous cell carcinoma and endocervical adenocarcinoma
Cancer specificityi

Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.

Low cancer specificity
Cell line
expression clusteri

The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Myeloma - Immunoglobulins (mainly)
Cell line specificityi

RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.

Low cancer specificity
PROTEINS IN BLOOD
Upregulated in diseasei

A gene is classified as upregulated in a disease if the average concentration of all samples of that disease is significantly higher (adj P-value<0.005 and NPX difference>=1) than the average concentration of samples of all diseases as measured by PEA . For gender specific diseases the analysis includes only samples corresponding to the same gender from the other diseases.

Pediatric long COVID, Dengue fever, Influenza, Pediatric CNS tumor, Pediatric lymphoma, Staphylococcus aureus bacteremia, Pediatric kidney tumor, Bacterial gastroenteritis, Pediatric neuroblastoma, Malaria, Myositis, Systemic lupus erythematosus, Pediatric diffuse astrocytic and oligodendro. tumor, Pneumococcal pneumonia, Rheumatoid arthritis, Chronic liver disease, Sjögrens syndrome, Mycoplasma pneumonia, Pediatric retinoblastoma, Alcohol-related liver disease, Colorectal cancer, Chronic lymphocytic leukemia, Hepatocellular cancer, Systemic sclerosis, E.coli pyelonephritis, Pancreatic cancer, Viral hepatitis related cirrhosis, Lung cancer, Acute myeloid leukemia, Prostate cancer, Myeloma, Diffuse large B-cell lymphoma
Disease prediction modeli

The disease(s) the gene is associated with and able to predict according to glmnet prediction models. To be included the gene has to be upregulated according to differential expression analysis and have more than 50% overall importance as indicated by the prediction models.

No
Detected in blood by
immunoassayi

The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.

No (not applicable)
Detected in blood by
mass spectrometryi

Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.

No
Detected in blood by
proximity extension assayi

Detection or not of the gene in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with three visits during two years.

Yes
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood 1, 2, 3, 4, 5, 6, 7, 8. Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for FAS/CD95-mediated and TNFRSF1A-induced cell death 9, 10, 11, 12, 13, 14, 15, 16. Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 17, 18, 19. Binding to the adapter molecule FADD recruits it to either receptor FAS/TNFRSF6 or TNFRSF1A 20, 21. The resulting aggregate called the death-inducing signaling complex (DISC) performs CASP8 proteolytic activation 22. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases 23. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC 24. In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response 25, 26. Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis 27, 28. Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways 29. Cleaves PARP1 and PARP2 30. Independent of its protease activity, promotes cell migration following phosphorylation at Tyr-380 31, 32.... show less
Molecular function (UniProt)i

Keywords assigned by UniProt to proteins due to their particular molecular function.

Hydrolase, Protease, Thiol protease
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Apoptosis, Host-virus interaction
Gene summary (Entrez)i

Useful information about the gene from Entrez

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]... show less

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