Caspase 8 | C14: Caspase | IUPHAR Guide to IMMUNOPHARMACOLOGY

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Caspase 8

Target id: 1624

Nomenclature: Caspase 8

Family: C14: Caspase

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: ON :     Caspase 8 has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 479 2q33-q34 CASP8 caspase 8
Mouse - 480 1 B Casp8 caspase 8
Rat - 482 9q31 Casp8 caspase 8
Previous and Unofficial Names
apoptotic protease Mch-5 | CAP4 | CE-like apoptotic protease 5 | FADD-homologous ICE/CED-3-like protease | FADD-like ICE | FLICE | MACH | MCH5 | caspase 8, apoptosis-related cysteine peptidase
Database Links
Specialist databases
MEROPS C14.009 (Hs)
Other databases
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.4.22.61
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
BH3 interacting-domain death agonist Hs - -
FLICE-like inhibitory protein Hs - -
caspase 8 Hs - -
pro-caspase 3 Hs - -
pro-caspase 6 Hs - -
pro-caspase 7 Hs - -
Endogenous activators (Human)
DISC

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 Affinity Units Reference
emricasan Hs Inhibition 8.3 pKi 5
pKi 8.3 (Ki 5x10-9 M) [5]
compound 4 [PMID: 12408711] Hs Inhibition 6.1 pKi 1
pKi 6.1 (Ki 8.8x10-7 M) [1]
Z-IETD-FMK Hs Inhibition - - 4
[4]
Clinically-Relevant Mutations and Pathophysiology
Disease:  Autoimmune lymphoproliferative syndrome with recurrent viral infections
Synonyms: Autoimmune lymphoproliferative syndrome [Disease Ontology: DOID:6688]
Autoimmune lymphoproliferative syndrome, type IIB; ALPS2B [OMIM: 607271]
Caspase 8 deficiency [OMIM: 607271]
Disease Ontology: DOID:6688
OMIM: 607271
Orphanet: ORPHA275517
Disease:  Breast cancer
Disease Ontology: DOID:1612
OMIM: 114480
Role: 
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human D302H rs1045485 2-3,6
Disease:  Hepatocellular carcinoma
Disease Ontology: DOID:684
OMIM: 114550
Disease:  Lung cancer
Disease Ontology: DOID:1324
OMIM: 211980
Role: 
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human -652 6Ndel 6 nucleotide deletion variant in the promotor region of CASP8 was found to be associated with reduced risk of lung cancer in a Han Chinese population. 9

References

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1. Choong IC, Lew W, Lee D, Pham P, Burdett MT, Lam JW, Wiesmann C, Luong TN, Fahr B, DeLano WL et al.. (2002) Identification of potent and selective small-molecule inhibitors of caspase-3 through the use of extended tethering and structure-based drug design. J. Med. Chem., 45 (23): 5005-22. [PMID:12408711]

2. Cox A, Dunning AM, Garcia-Closas M, Balasubramanian S, Reed MW, Pooley KA, Scollen S, Baynes C, Ponder BA, Chanock S et al.. (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nat. Genet., 39 (3): 352-8. [PMID:17293864]

3. Frank B, Bermejo JL, Hemminki K, Klaes R, Bugert P, Wappenschmidt B, Schmutzler RK, Burwinkel B. (2005) Re: Association of a common variant of the CASP8 gene with reduced risk of breast cancer. J. Natl. Cancer Inst., 97 (13): 1012; author reply 1012-3. [PMID:15998955]

4. Gregoli PA, Bondurant MC. (1999) Function of caspases in regulating apoptosis caused by erythropoietin deprivation in erythroid progenitors. J. Cell. Physiol., 178 (2): 133-43. [PMID:10048577]

5. Linton SD, Aja T, Armstrong RA, Bai X, Chen LS, Chen N, Ching B, Contreras P, Diaz JL, Fisher CD et al.. (2005) First-in-class pan caspase inhibitor developed for the treatment of liver disease. J. Med. Chem., 48 (22): 6779-82. [PMID:16250635]

6. MacPherson G, Healey CS, Teare MD, Balasubramanian SP, Reed MW, Pharoah PD, Ponder BA, Meuth M, Bhattacharyya NP, Cox A. (2004) Association of a common variant of the CASP8 gene with reduced risk of breast cancer. J. Natl. Cancer Inst., 96 (24): 1866-9. [PMID:15601643]

7. Man SM, Kanneganti TD. (2016) Converging roles of caspases in inflammasome activation, cell death and innate immunity. Nat. Rev. Immunol., 16 (1): 7-21. [PMID:26655628]

8. Rodrigue-Gervais IG, Saleh M. (2013) Caspases and immunity in a deadly grip. Trends Immunol., 34 (2): 41-9. [PMID:23069594]

9. Sun T, Gao Y, Tan W, Ma S, Shi Y, Yao J, Guo Y, Yang M, Zhang X, Zhang Q et al.. (2007) A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat. Genet., 39 (5): 605-13. [PMID:17450141]

How to cite this page

C14: Caspase: Caspase 8. Last modified on 10/02/2017. Accessed on 20/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1624.