CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases

Figure 1 CARD recruited membrane associated protein family members. A: The CARD recruited membrane associated (CARMA) protein family has three members: CARMA1, CARMA2 and CARMA3. Each member shares similar structures: an N-terminal caspase-recruitment domain (CARD), followed by a coiled-coil domain (CC), a linker region, a PDZ domain, an SH3 domain, and a GUK-like domain. Although all CARMA protein members share similar structures, they are transcribed by distinct genes, and expressed in different tissues. Specifically, CARMA1 is predominantly expressed in spleen, thymus, and peripheral blood leukocytes; CARMA2 is expressed only in placenta; and CARMA3 is expressed in a broad range of tissues, especially highly in liver, kidney, heart, and brain, but not in spleen, thymus, or peripheral blood lymphocytes; B: Upon activation, the linker region is phosphorylated. The CARD domain of CARMA protein interacts with Bcl10, which further binds MALT1, while PDZ and SH3 domains associate with the IκB kinase complex via NF-κB essential modulator (NEMO). Additionally, different CARMA proteins also interact with other unique signaling molecules. For example, CARMA3 interacts with β-arrestin 2, whereas CARMA1 associates with ADAP.