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CASP4
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  • CASP4
PROTEIN SUMMARY SECTION OVERVIEW RNA DATA ANTIBODY DATA
Amygdala Basal ganglia Thalamus Midbrain Pons Medulla oblongata Hippocampal formation Spinal cord White matter Cerebral cortex Cerebellum Choroid plexus Hypothalamus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Colon Rectum Small intestine Duodenum 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 Spleen Lymph node Tonsil
CASP4 INFORMATION
Proteini

Full gene name according to HGNC.

Caspase 4
Gene namei

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

CASP4 (ICE(rel)II, ICH-2, TX)
Protein classi

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

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Cancer-related genes
Enzymes
Number of transcriptsi

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

4
Protein evidence Evidence at protein level (all genes)
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 section.

"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.
Most tissues show cytoplasmic expression while gastro and lymphatic organs show high membranous expression.
Subcellular location Localized to the Cytosol In addition localized to the Plasma membrane
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.

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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.

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Low tissue specificity
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.

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Macrophages - 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

Read more
Low human brain regional specificity
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.

Read more
Low cell type specificity
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.

Read more
NK-cells - Immune response regulation (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.

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Cell type enriched (Colon - Endothelial cells, Skeletal muscle - Endothelial cells)
IMMUNE CELLS
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.

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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.

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Neutrophils - Inflammatory response (mainly)
CANCER & CELL LINES
Prognostic summary Prognostic marker in renal cancer (unfavorable) Renal cancer p<0.001
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.

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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.

Read more
Lymphoma - Cytokine signaling (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.

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Low cancer specificity
PROTEINS IN BLOOD
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.

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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.

Read more
No
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

Inflammatory caspase that acts as an essential effector of the NLRP3 and NLRP6 inflammasomes by mediating lipopolysaccharide (LPS)-induced pyroptosis 1, 2, 3, 4. Thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 5, 6, 7, 8, 9, 10. Required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a key role in NLRP3-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS 11, 12, 13, 14, 15, 16, 17, 18. Activated by direct binding to LPS without the need of an upstream sensor 19. Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B and IL18 secretion 20. Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, followed by IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators 21, 22. Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection: in later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which catalyzes cleavage of GSDMD, resulting in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion 23, 24, 25, 26, 27. Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part 28. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation 29, 30, 31. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity 32. Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains 33, 34, 35. Catalyzes cleavage and maturation of IL18 36. In contrast, it does not directly process IL1B 37, 38, 39. During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation 40.... 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.

Immunity, Inflammatory response, Innate immunity, Necrosis
Disease involvementi

Disease related keywords assigned by UniProt combined with Cancer-related genes and FDA approved drug targets

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Cancer-related genes
Gene summary (Entrez)i

Useful information about the gene from Entrez

This gene encodes a protein that is 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 and a large and 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 caspase is able to cleave and activate its own precursor protein, as well as caspase 1 precursor. When overexpressed, this gene induces cell apoptosis. Alternative splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]... show less

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