Entrez 64170 | Ensembl ENSG00000187796 | |
Aliases CARD9, CANDF2, hcaspase recruitment domain family member 9 External IDs MGI: 2685628 HomoloGene: 14150 GeneCards: CARD9 | ||
Caspase recruitment domain-containing protein 9 is an adaptor protein that in humans is encoded by the CARD9 gene.
Contents
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.
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. 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).
Interactions
CARD9 has been shown to interact with BCL10.
Model organisms
Model organisms have been used in the study of CARD9 function. A conditional knockout mouse line called Card9tm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping - in-depth bone and cartilage phenotyping