Caspase Recruitment Domain Family, Member 18 (CARD18)

ICEBERG inhibits generation of interleukin-1-beta (IL1B) by interacting with caspase-1 and preventing its association with RIP2. ICEBERG is induced by proinflammatory stimuli, suggesting that it may be part of a negative feedback loop. Consistent with this, enforced retroviral expression of ICEBERG inhibits lipopolysaccharide-induced IL1B generation.

The structure of ICEBERG reveals it to be a member of the death-domain-fold superfamily. The distribution of surface charge is complementary to the homologous prodomain of caspase-1, suggesting that charge-charge interactions mediate binding of ICEBERG to the prodomain of caspase-1. Analysis of multiple tissue cDNA panels and Northern blots revealed that ICEBERG is primarily expressed in the heart and placenta.