InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CASP8

Summary

InnateDB Protein

IDBP-78536.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CASP8

Protein Name

caspase 8, apoptosis-related cysteine peptidase

Synonyms

ALPS2B; CAP4; Casp-8; FLICE; MACH; MCH5;

Species

Homo sapiens

Ensembl Protein

ENSP00000264275

InnateDB Gene

IDBG-78534 (CASP8)

Protein Structure

UniProt Annotation

Function

Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death- inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp--AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000269PubMed:9006941, ECO:0000269Ref.26}.

Subcellular Localization

Cytoplasm.

Disease Associations

Caspase-8 deficiency (CASP8D) [MIM:607271]: Disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization. {ECO:0000269PubMed:12353035}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform 1, isoform 5 and isoform 7 are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 219 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.

Experimentally validated
Total	219 [view]
Protein-Protein	208 [view]
Protein-DNA	6 [view]
Protein-RNA	0
DNA-DNA	5 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	17 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004197	cysteine-type endopeptidase activity
GO:0005515	protein binding
GO:0008233	peptidase activity
GO:0008234	cysteine-type peptidase activity
GO:0031625	ubiquitin protein ligase binding
GO:0035877	death effector domain binding
GO:0097110	scaffold protein binding
GO:0097153	cysteine-type endopeptidase activity involved in apoptotic process
GO:0097199	cysteine-type endopeptidase activity involved in apoptotic signaling pathway

Biological Process

GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006508	proteolysis
GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0016032	viral process
GO:0030101	natural killer cell activation
GO:0030225	macrophage differentiation
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034612	response to tumor necrosis factor
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0036462	TRAIL-activated apoptotic signaling pathway
GO:0042110	T cell activation
GO:0042113	B cell activation
GO:0042981	regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0045651	positive regulation of macrophage differentiation
GO:0045862	positive regulation of proteolysis
GO:0051603	proteolysis involved in cellular protein catabolic process
GO:0060715	syncytiotrophoblast cell differentiation involved in labyrinthine layer development
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway
GO:0071260	cellular response to mechanical stimulus
GO:0097190	apoptotic signaling pathway
GO:0097191	extrinsic apoptotic signaling pathway
GO:0097193	intrinsic apoptotic signaling pathway
GO:0097194	execution phase of apoptosis
GO:0097202	activation of cysteine-type endopeptidase activity
GO:1900740	positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:2001239	regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005815	microtubule organizing center
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0031264	death-inducing signaling complex
GO:0031265	CD95 death-inducing signaling complex
GO:0097342	ripoptosome

Protein Structure and Domains

PDB ID

InterPro

IPR001309 Peptidase C14, ICE, catalytic subunit p20
IPR001875 Death effector domain
IPR002138 Peptidase C14, caspase non-catalytic subunit p10
IPR011029 Death-like domain
IPR011600 Peptidase C14, caspase domain
IPR015917 Peptidase C14A, caspase precursor p45, core

PFAM

PF01335
PF00656

PRINTS

PR00376

PIRSF

SMART

SM00031
SM00115

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt