CASP4 protein expression summary - The Human Protein Atlas

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CASP4

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CASP4

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).	Cancer-related genes Enzymes
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	4
Protein interactions	Interacting with 1 protein

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.	Most tissues show cytoplasmic expression while gastro and lymphatic organs show high membranous expression.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	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.	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.	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.	Lymphoid tissue - 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.	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.	NK-cells - Adaptive immune response (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.	Cell type enriched (Colon - Endothelial cells, Skeletal muscle - Endothelial 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.	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 - Unknown function (mainly)

CANCER & CELL LINES
Prognostic summary	CASP4 is a prognostic marker in Glioblastoma multiforme, Kidney renal clear cell carcinoma, Pancreatic 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.	Lymphoma - Inflammatory response (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
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
Proximity extension assayⁱ Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years. Read more	Data available (Medium detectability)

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis 1, 2, 3, 4, 5, 6, 7. Also indirectly activates the NLRP3 and NLRP6 inflammasomes 8, 9, 10, 11. Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 12, 13, 14, 15, 16, 17, 18, 19. Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B 20, 21, 22, 23, 24, 25, 26. In the non-canonical inflammasome, CASP4 is activated by direct binding to the lipid A moiety of LPS without the need of an upstream sensor 27, 28, 29, 30, 31, 32. LPS-binding promotes CASP4 activation and CASP4-mediated cleavage of GSDMD and IL18, followed by IL18 secretion through the GSDMD pore, pyroptosis of infected cells and their extrusion into the gut lumen 33, 34, 35, 36. Also indirectly promotes secretion of mature cytokines (IL1A and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes 37, 38. Involved in NLRP3-dependent CASP1 activation and IL1B secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin 39, 40, 41, 42, 43, 44, 45. 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 secretion 46. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity 47. The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection 48, 49. Activation of the non-canonical inflammasome in brain endothelial cells can lead to excessive pyroptosis, leading to blood-brain barrier breakdown (By similarity). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation 50, 51, 52. May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC) (By similarity). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains 53, 54, 55. 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 56. Catalyzes cleavage and maturation of IL18; IL18 processing also depends of the exosite interface on CASP4 57, 58, 59. In contrast, it does not directly process IL1B 60, 61, 62. During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation 63.... 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
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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