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caspase-1; IL1 beta-converting enzyme [ICE] (CASP1, IL1BC, IL1BCE)
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
Note:
- 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
Interactions
molecular events
Specific
procaspase-1
General
caspase; cysteinyl aspartate-specific proteinase; ICE/CED3 family protease
multisubunit protein
Properties
SIZE: entity length = 404 aa
MW = 45 kD
COMPARTMENT: cytoplasm
MOTIF: CARD domain {1-91}
histidine residue {H237}
cysteine residue {C285}
Database Correlations
OMIM 147678
UniProt P29466
PFAM correlations
Entrez Gene 834
KEGG correlations
ENZYME 3.4.22.36
References
- 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: 8087842
- 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: 7535475
- Kumar S.
ICE-like proteases in apoptosis.
Trends Biochem Sci. 1995 May;20(5):198-202. Review.
PMID: 7610484
- Martin SJ, Green DR.
Protease activation during apoptosis: death by a thousand cuts?
Cell. 1995 Aug 11;82(3):349-52. Review. No abstract available.
PMID: 7634323
Component-of
inflammasome