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caspase-2; ich-1 protein; Nedd-2, neural precursor cell expressed developmentally down-regulated 2 protein (CASP2)

Function: - role in the activation cascade of caspases responsible for apoptosis execution - required for translocation of bax to mitochondria, mitochondrial permeabilization as well as release of cytochrome c, smac/diablo & AIF, directly or through cleavage of bid - might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival - interacts with LRDD - the mature protease can process its own propeptide, but not that of other caspases - strict requirement for an Asp residue at P1, with 316-Asp being essential for proteolytic activity - preferred cleavage sequence of Val-Asp-Val-Ala-Asp-|- Structure: - heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit & a p12 subunit - belongs to the peptidase C14 family - contains 1 CARD domain Alternative splicing: - named isoforms=2 - two isoforms Ich-1L & ich-1S derived from alternative splicing of the same gene transcript have opposing effects on apoptosis - Ich-1L apparently promotes apoptosis - ich-1S inhibits it Expression: expressed - expressed in embryonic lung, liver & kidney > heart & brain - in adults, expressed in placenta, lung, kidney, pancreas > heart, brain, liver & skeletal muscle Note: - Ich-1 is the protein product of a gene related to the C elegans cell death gene ced-3 & to the mammalian gene ICE encoding the interleukin-1 beta converting enzyme

Related

neural precursor cell expressed developmentally downregulated (NEDD) protein

Specific

Ich-1 protease (caspase-2), stimulatory or long isoform Ich-1 protease (caspase-2), suppressive or short isoform

General

caspase; cysteinyl aspartate-specific proteinase; ICE/CED3 family protease

Properties

SIZE: entity length = 452 aa MW = 51 kD MOTIF: CARD domain {32-120} histidine residue {H277} cysteine residue {C320}

Database Correlations

OMIM 600639 UniProt P42575 PFAM correlations Entrez Gene 835 KEGG correlations ENZYME 3.4.22.55

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: 8087842
  2. UniProt :accession P42575