J Biol Chem. 2004 Dec 10;279(50):51729-38. Epub 2004 Sep 21.

INCA, a novel human caspase recruitment domain protein that inhibits interleukin-1beta generation.External

Lamkanfi, M., Denecker, G., Kalai, M., D'hondt, K., Meeus, A., Declercq, W., Saelens, X., Vandenabeele, P.,
--- - Unit of Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, VIB-Ghent University, Technologiepark 927, Zwijnaarde B-9052, Belgium.
Using in silico methods for screening the human genome for new caspase recruitment domain (CARD) proteins, we have identified INCA (Inhibitory CARD) as a protein that shares 81% identity with the prodomain of caspase-1. The INCA gene is located on chromosome 11q22 between the genes of COP/Pseudo-ICE and ICEBERG, two other CARD proteins that arose from caspase-1 gene duplications. We show that INCA mRNA is expressed in many tissues. INCA is specifically upregulated by interferon-gamma in the monocytic cell lines THP-1 and U937. INCA physically interacts with procaspase-1 and blocks the release of mature IL-1beta from LPS-stimulated macrophages. Unlike COP/Pseudo-ICE and procaspase-1, INCA does not interact with RIP2 and does not induce NF-kappaB activation. Our data show that INCA is a novel intracellular regulator of procaspase-1 activation, involved in the regulation of pro-IL-1beta processing and its release during inflammation.
PMID: 15383541External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD CARD16 Link CARD17 Co-immunoprecipitation HEK293 Human 1-106 Human Not specified 15383541
CARD CARD17 Link CARD17 Co-immunoprecipitation HEK293 Human Not specified Human Not specified 15383541
CARD CARD17 Link CARD18 Co-immunoprecipitation HEK293 Human Not specified Human Full length 15383541
CARD CARD17 Link Caspase1 Co-immunoprecipitation HEK293 Human Not specified Not specified Not specified 15383541
(Link: click this icon to show interactions only between the two corresponding DDs)