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Caspase 4

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1620

Nomenclature: Caspase 4

Family: C14: Caspase

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 377 11q22.3 CASP4 caspase 4
Mouse - 373 9 2.46 cM Casp4 caspase 4, apoptosis-related cysteine peptidase
Rat - 373 8q11 Casp4 caspase 4
Previous and Unofficial Names Click here for help
TX protease | Casp11 | caspase 11 | ich-3 | ICE(rel)II | ICH-2 | caspase 4, apoptosis-related cysteine peptidase
Database Links Click here for help
Specialist databases
MEROPS C14.007 (Hs)
Other databases
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.4.22.57
Substrates and Reaction Kinetics Click here for help
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
pro-caspase 1 Substrate is endogenous in the given species Hs - -

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VRT-043198 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.4 pKi 5
pKi 9.4 (Ki 4x10-10 M) [5]
casp 4 inhib Small molecule or natural product Hs Inhibition 5.4 pKi 2
pKi 5.4 (Ki 4x10-6 M) [2]
M826 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 1
pIC50 6.5 (IC50 3x10-7 M) [1]
Immunopharmacology Comments
Recognition of cytoplasmic lipopolysaccharide (LPS) by Inflammatory caspases including caspases-4 and -5 leads to pyroptosis and secretion of inflammatory mediators [3-4]. The caspase activation and recruitment domain (CARD) of caspase-4 recognises the lipid A moiety of LPS. Activation of caspase-4 results in pyroptosis, and induction of NLRP3 inflammasome activation which promotes IL-1β and IL-18 maturation and secretion.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0050727 regulation of inflammatory response IBA
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
GO:0045087 innate immune response IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0050727 regulation of inflammatory response IBA

References

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1. Han Y, Giroux A, Colucci J, Bayly CI, Mckay DJ, Roy S, Xanthoudakis S, Vaillancourt J, Rasper DM, Tam J et al.. (2005) Novel pyrazinone mono-amides as potent and reversible caspase-3 inhibitors. Bioorg Med Chem Lett, 15 (4): 1173-80. [PMID:15686936]

2. Lee D, Long SA, Murray JH, Adams JL, Nuttall ME, Nadeau DP, Kikly K, Winkler JD, Sung CM, Ryan MD et al.. (2001) Potent and selective nonpeptide inhibitors of caspases 3 and 7. J Med Chem, 44 (12): 2015-26. [PMID:11384246]

3. Shi J, Gao W, Shao F. (2017) Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem Sci, 42 (4): 245-254. [PMID:27932073]

4. Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L, Shao F. (2014) Inflammatory caspases are innate immune receptors for intracellular LPS. Nature, 514 (7521): 187-92. [PMID:25119034]

5. Wannamaker W, Davies R, Namchuk M, Pollard J, Ford P, Ku G, Decker C, Charifson P, Weber P, Germann UA et al.. (2007) (S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylic acid ((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide (VX-765), an orally available selective interleukin (IL)-converting enzyme/caspase-1 inhibitor, exhibits potent anti-inflammatory activities by inhibiting the release of IL-1beta and IL-18. J Pharmacol Exp Ther, 321 (2): 509-16. [PMID:17289835]

How to cite this page

C14: Caspase: Caspase 4. Last modified on 11/02/2019. Accessed on 13/04/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1620.