CARD9 is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a positive regulator of apoptosis and NF-κB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-κB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined.
It recently became clear that Card9 plays important roles as part of the innate immune response for the defense against pathogens such as yeasts. Card9 mediates signals from so called pattern recognition receptors (Dectin-1) to downstream signalling pathways such as NF-κB and by this activates pro-inflammatory cytokines (TNF, IL-23, IL-6, IL-2) and an anti-inflammatory cytokine (IL-10) and subsequently an appropriate innate and adaptive immune response for the efficient clearance of the infection. Importantly, it was reported that an autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9. Mutations in this gene have been associated to inflammatory diseases such as Ankylosing spondylitis and inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis).
^Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL et al. (Jan 2001). "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. Biol. Chem.275 (52): 41082–6. doi:10.1074/jbc.C000726200. PMID11053425.Check date values in: |year= / |date= mismatch (help)
^Gross O, Gewies A, Finger K, Schäfer M, Sparwasser T, Peschel C et al. (Aug 2006). "Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity". Nature442 (7103): 651–6. doi:10.1038/nature04926. PMID16862125.
^Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G et al. (August 2011). "Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility". Nat. Genet.43 (8): 761–7. doi:10.1038/ng.873. PMID21743469.
^Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL et al. (December 2000). "CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B". J. Biol. Chem.275 (52): 41082–6. doi:10.1074/jbc.C000726200. PMID11053425.
Hsu YM, Zhang Y, You Y, Wang D, Li H, Duramad O et al. (2007). "The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens". Nat. Immunol.8 (2): 198–205. doi:10.1038/ni1426. PMID17187069.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA et al. (2001). "Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B". J. Biol. Chem.276 (24): 21405–9. doi:10.1074/jbc.M102488200. PMID11259443.