CARD family

The CARMA/CARD protein family consists of CARD9, CARD10 (or CARMA3), CARD11 (or CARMA1) and CARD14 (or CARMA2) (Blonska M et al. 2011). These scaffold proteins are evolutionarily conserved, structurally homologous, mostly membrane-associated (with the exception of CARD9) and have different expression patterns in the body. Mutations in this protein family have been associated with various pathological conditions, including CARD9 deficiency, which increases susceptibility to fungal infections, and CARD14 mutations, which are associated with increased susceptibility to psoriasis (Jordan CT et al.2012). and pityriasis rubra pilaris (Fuchs-Telem D et al. 2012).

Each CARD protein is involved in its own "CBM" complex with BCL10 and MALT1 in different cell types to facilitate downstream signaling events leading to NF-κB activation.

• CARD11 mediates lymphocyte activation through the antigen receptors BCR and TCR and facilitates natural killer (NK) cell activation.
• CARD14 is expressed in placenta and skin tissue and can mediate NF-κB activation in keratinocytes.
• CARD10 is widely expressed in non-hematopoietic cells and serves as a link between G protein-coupled receptors (GPCRs) and NF-κB.
• CARD9 is mainly expressed by myeloid cells (macrophages, dendritic cells, neutrophils) and transmits signals that originate from C-type lectin receptors (Dectin-1, Dectin-2, Mincle) and ITAM-associated receptors (FcRγ, DAP12). CARD9 deficiency also leads to immunodeficiency.

1. Blonska M et al. (2011) NF-kappaB signaling pathways regulated by CARMA family of scaffold proteins. Cell Res 21:55-70.
2. Fuchs-Telem D et al. (2012) Familial pityriasis rubra pilaris is caused by mutations in CARD14. Am J Hum Genet 91:163-170.