Caspase 4 | C14: Caspase | IUPHAR/BPS Guide to PHARMACOLOGY

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Caspase 4

target has curated data in GtoImmuPdb

Target id: 1620

Nomenclature: Caspase 4

Family: C14: Caspase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 377 11q22.2-q22.3 CASP4 caspase 4
Mouse - 373 9 A1 Casp4 caspase 4, apoptosis-related cysteine peptidase
Rat - 373 8q11 Casp4 caspase 4
Previous and Unofficial Names
TX protease | Casp11 | caspase 11 | ich-3 | ICE(rel)II | ICH-2 | caspase 4, apoptosis-related cysteine peptidase
Database Links
Specialist databases
MEROPS C14.007 (Hs)
Other databases
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.22.57
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
pro-caspase 1 Hs - -

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VRT-043198 Hs Inhibition 9.4 pKi 5
pKi 9.4 (Ki 4x10-10 M) [5]
casp 4 inhib Hs Inhibition 5.4 pKi 2
pKi 5.4 (Ki 4x10-6 M) [2]
M826 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 2 GO processes
GO:0050718 positive regulation of interleukin-1 beta secretion IGI
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 19/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1620.