BinCARD

Bcl10-interacting CARD protein, also known as BinCARD, is a protein that in humans is encoded by the C9orf89 gene on chromosome 9. BinCARD is a member of the death-domain superfamily and contains a caspase recruitment domain (CARD). This protein regulates apoptosis and the immune response by inhibiting Bcl10, thus implicating it in diseases stemming from Bcl10 dysfunction.

Structure
BinCARD, as a CARD-containing protein, is a member of the death-domain superfamily, which shares a six—helix bundle. In humans, the protein has two alternatively spliced isoforms: BinCARD-1 and BinCARD-2. Both isoforms share identical sequences until residue 101, which include the CARD domain and exons 1 to 3. The longer isoform, BinCARD-1, has an extended exon 3, while the shorter BinCARD-2 has an extra transmembrane domain. The conserved CARD domain has three cysteines in its native form: Cys7, Cys77, and Cys63, of which Cys7 and Cys77 form a disulfide bond and Cys63 becomes a cysteine sulfenic acid when oxidized.

Function
The BinCARD protein is a member of the death-domain superfamily, which is known for regulating apoptosis and the immune response. BinCARD is a negative regulator that binds to, and thus blocks the phosphorylation of, Bcl10, effectively inhibiting Bcl10 from activating the nuclear factor-κB (NF-κB). In particular, the BinCARD-1 isoform contains an extended C-terminal that has been observed to bind Bcl10, though it mostly localizes to the nucleus. The second isoform, BinCARD-2, is more abundantly expressed and localizes to both the ER and the mitochondria. This isoform is expected to contribute to apoptosis via redox processes, as its three modifiable cysteines can be oxidized by reactive oxygen species (ROS) to stimulate an innate immune response.

Clinical significance
Mutations in BinCARD and other proteins containing CARD domains are linked to Bcl10-related diseases, including lymphoma of mucosa-associated lymphoid tissue.

Interactions
BinCARD has been shown to interact with:
 * Bcl10