Tchem CASP4 Caspase-4

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

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

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: 167.02   (req: < 5)

Gene RIFs: 42   (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: 167.02   (req: >= 5)

Gene RIFs: 42   (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

Active Ligands (21)

Explore Active Ligands

1 – 10 of 21

CHEMBL366927

CASP4Tchem Enzyme

IC50: 9.52

CHEMBL3898379

CASP4Tchem Enzyme

Ki: 6.61

CHEMBL179503

CASP4Tchem Enzyme

IC50: 9.3

CHEMBL1412861

CASP4Tchem Enzyme

Ki: 6.47

CHEMBL3978901

CASP4Tchem Enzyme

Ki: 6.51

CHEMBL3939229

CASP4Tchem Enzyme

Ki: 6.56

CHEMBL3970645

CASP4Tchem Enzyme

Ki: 6.92

CHEMBL3941088

CASP4Tchem Enzyme

Ki: 6.83

CHEMBL3905486

CASP4Tchem Enzyme

Ki: 6.68

CHEMBL3904435

CASP4Tchem Enzyme

Ki: 6.57

Pathways (168)

Reactome (4)

KEGG (1)

PathwayCommons (1)

WikiPathways (162)

Immune System (R-HSA-168256)

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Items per page:

5

1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	NOD1/2 Signaling Pathway	31 targets	R-HSA-168638
Reactome	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	50 targets	R-HSA-168643

Name	Explore in Pharos	Explore in Source
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249
NOD1/2 Signaling Pathway	31 targets	R-HSA-168638
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	50 targets	R-HSA-168643

Gene Ontology Terms (21)

Functions (3)

Components (9)

Processes (9)

Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
cysteine-type endopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
CARD domain binding	Inferred from Physical Interaction (IPI)	UniProtKB
cysteine-type endopeptidase activity involved in apoptotic signaling pathway	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Protein-Protein Interactions (78)

Explore Interacting Targets

1 – 10 of 78

• See Interactions on String-DB

CASP5

Tchem

Family: Enzyme

Novelty: 0.00907686

p_int: 0.999999847

p_ni: 5e-9

p_wrong: 1.48e-7

Score: 0.893

Data Source: BioPlex,STRINGDB

CASP1

Tchem

Family: Enzyme

Novelty: 0.00043112

Score: 0.964

Data Source: STRINGDB

NOD1

Tchem

Novelty: 0.00337321

Score: 0.955

Data Source: STRINGDB

GSDMD

Tbio

Novelty: 0.01231428

Score: 0.944

Data Source: STRINGDB

CASP8

Tchem

Family: Enzyme

Novelty: 0.00026844

Score: 0.913

Data Source: STRINGDB

APAF1

Tbio

Family: Enzyme

Novelty: 0.00164778

Score: 0.904

Data Source: STRINGDB

EIF4A1

Tchem

Novelty: 0.0043238

Score: 0.904

Data Source: STRINGDB

EIF4E

Tchem

Novelty: 0.00088513

Score: 0.901

Data Source: STRINGDB

EIF4G3

Tbio

Novelty: 0.04202311

Score: 0.9

Data Source: STRINGDB

EIF4G1

Tbio

Novelty: 0.00219215

Score: 0.9

Data Source: STRINGDB

Publication Statistics

PubMed Score  167.02

PubMed score by year

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PubTator Score  204.17

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MAEGNHRKKPLKVLESLGKDFLTGVLDNLVEQNVLNWKEEEKKKYYDAKTEDKVRVMADSMQEKQRMAGQ

1-70

MLLQTFFNIDQISPNKKAHPNMEAGPPESGESTDALKLCPHEEFLRLCKERAEEIYPIKERNNRTRLALI

70-140

ICNTEFDHLPPRNGADFDITGMKELLEGLDYSVDVEENLTARDMESALRAFATRPEHKSSDSTFLVLMSH

140-210

GILEGICGTVHDEKKPDVLLYDTIFQIFNNRNCLSLKDKPKVIIVQACRGANRGELWVRDSPASLEVASS

210-280

QSSENLEEDAVYKTHVEKDFIAFCSSTPHNVSWRDSTMGSIFITQLITCFQKYSWCCHLEEVFRKVQQSF

280-350

ETPRAKAQMPTIERLSMTRYFYLFPGN

350-377

MAEGNHRKKPLKVLESLGKDFLTGVLDNLVEQNVLNWKEEEKKKYYDAKTEDKVRVMADSMQEKQRMAGQMLLQTFFNIDQISPNKKAHPNMEAGPPESGESTDALKLCPHEEFLRLCKERAEEIYPIKERNNRTRLALIICNTEFDHLPPRNGADFDITGMKELLEGLDYSVDVEENLTARDMESALRAFATRPEHKSSDSTFLVLMSHGILEGICGTVHDEKKPDVLLYDTIFQIFNNRNCLSLKDKPKVIIVQACRGANRGELWVRDSPASLEVASSQSSENLEEDAVYKTHVEKDFIAFCSSTPHNVSWRDSTMGSIFITQLITCFQKYSWCCHLEEVFRKVQQSFETPRAKAQMPTIERLSMTRYFYLFPGN

Find similar targets by:

Uniprot Keyword

Acetylation
Alternative splicing
Complete proteome
Cytoplasm
Endoplasmic reticulum
Hydrolase
Immunity
Inflammasome
Inflammatory response
Innate immunity