Caspase 1

From Anvita Health Wiki

Contents 1 Function 2 Structure 3 Compartment 4 Alternative-splicing 5 Expression 6 Notes 7 More General Terms 8 Internet Database 9 References

Function

• thiol protease that cleaves inactive IL-1 beta between an Asp & Ala, releasing mature proinflammatory cytokine IL-1 beta
• may also be involved in processing of other cytokines including IL-6 & TNF-alpha
• substrate specificity for Asp-X
• role in for defense against pathogens
• cleaves sterol regulatory element binding proteins ( SREBPs) & activates them.
• can promote apoptosis
• may be a component of the inflammasome
• interacts with INCA
• specifically inhibited by the cowpox virus Crma protein
• 2 subunits are derived from the precursor sequence by an autocatalytic mechanism
• strict requirement for an Asp residue at position P1 & has a preferred cleavage sequence of Tyr- Val- Ala- Asp-|-

Structure

• heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kD ( p20) & a 10 kD ( p10) subunit.
• p20 subunit can also form a heterodimer with the epsilon isoform which then has an inhibitory effect
• belongs to the peptidase C14 family
• contains 1 CARD domain

Compartment

• cytoplasm

Alternative-splicing

• named isoforms=6
• additional isoforms seem to exist

Expression

• synthesized principally in monocytes as an inactive proenzyme that autoprocesses to an active tetramer
• expressed in spleen & lung > liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney & testis
• no expression in the brain

Notes

• ICE is homologous to C. elegans ced-3 & represents a class of cysteine proteases important in apoptosis. Thymocytes from ICE -/- mice are sensitive to apoptosis induced by dexamethasone or ionizing radiation, but are resistant to apoptosis induced by Fas antibody [2]
• despite the defect in apoptosis, ICE -/- mice appear to develop normally

More General Terms

• caspase
• multisubunit protein

Internet Database

UniProt: [1]
Kegg: [2]
OMIM: 147678
Prosite: [3]
Prosite: [4]
Prosite: [5]
Prosite: [6]
Prosite: [7]
Entrez gene: 834

References

1. Wang L, Miura M, Bergeron L, Zhu H, Yuan J. Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death. Cell. 1994 Sep 9;78(5):739-50. PMID: [8]
2. Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS, Flavell RA. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science. 1995 Mar 31;267(5206):2000-3. PMID: [9]
3. Kumar S. ICE-like proteases in apoptosis. Trends Biochem Sci. 1995 May;20(5):198-202. Review. PMID: [10]

caspase-1; IL1 beta-converting enzyme [ICE] (CASP1, IL1BC, IL1BCE)