CARD9
Caspase recruitment domain-containing protein 9 is an adaptor protein that in humans is encoded by the CARD9 gene.[1][2]
Function
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.[2]
Clinical significance
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.[3] Importantly, it was reported that an autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9.[4] Mutations in this gene have been associated to inflammatory diseases such as Ankylosing spondylitis and inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis).[5][6]
Interactions
CARD9 has been shown to interact with BCL10.[7]
References
- ↑ 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. PMID 11053425. Check date values in:
|year= / |date= mismatch(help) - ↑ 2.0 2.1 "Entrez Gene: CARD9 caspase recruitment domain family, member 9".
- ↑ 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". Nature 442 (7103): 651–6. doi:10.1038/nature04926. PMID 16862125. Vancouver style error (help)
- ↑ Glocker EO, Hennigs A, Nabavi M, Schäffer AA, Woellner C, Salzer U et al. (Oct 2009). "A homozygous CARD9 mutation in a family with susceptibility to fungal infections". N. Engl. J. Med. 361 (18): 1727–35. doi:10.1056/NEJMoa0810719. PMC 2793117. PMID 19864672. Vancouver style error (help)
- ↑ 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. PMID 21743469.
- ↑ Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK et al. (November 2011). "Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease". Nat. Genet. 43 (11): 1066–73. doi:10.1038/ng.952. PMC 3378381. PMID 21983784.
- ↑ 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. PMID 11053425.
Further reading
- Yang H, Minamishima YA, Yan Q, Schlisio S, Ebert BL, Zhang X et al. (2007). "pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappaB agonist Card9 by CK2". Mol. Cell 28 (1): 15–27. doi:10.1016/j.molcel.2007.09.010. PMC 2128776. PMID 17936701.
- 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. PMID 17187069.
- 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". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- 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. PMID 11259443.