Tchem CASP4 Caspase-4

Protein Summary

Description

Inflammatory caspase (PubMed:7797510, PubMed:23516580, PubMed:25119034). Essential effector of NLRP3 inflammasome-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 (PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:24879791, PubMed:25964352). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection (PubMed:25121752). In later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034). Does not directly process IL1B (PubMed:7743998, PubMed:7797592, PubMed:7797510). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590). 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]

Uniprot Accession IDs

• P49662
• A2NHL8
• A2NHL9
• A2NHM0
• B3KPZ9
• B4DJH5
• B4E2D2
• O95601
• Q7KYX7
• Q9UG96
• CASP-4

Gene Name

• CASP4

Ensembl ID

• ENST00000393150
• ENSP00000376857
• ENSG00000196954
• ENST00000444739
• ENSP00000388566

Symbol

• ICH2
• TX
• Mih1
• ICH-2
• Mih1/TX
• ICEREL-II
• ICE(rel)II

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	1
protein domain	0.99
disease perturbation	0.93
PubMedID	0.92
transcription factor perturbation	0.8

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Cysteine Protease / Caspase-4

Protein / Enzyme Modulator / Protease Inhibitor / Caspase-4

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Caspase-4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 244.46   (req: < 5)

Gene RIFs: 70   (req: <= 3)

Antibodies: 673   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 244.46   (req: >= 5)

Gene RIFs: 70   (req: > 3)

Antibodies: 673   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 21

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0