Gene information
Function: Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (PubMed:16862125, PubMed:20538615, PubMed:26679537, PubMed:29080677). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (PubMed:16862125, PubMed:20538615, PubMed:24470469, PubMed:25621893, PubMed:26679537, PubMed:29080677, PubMed:32548948). Transduces signals in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated molecular pattern metabolites (PAMPs), such as fungal carbohydrates, and trigger CARD9 activation (PubMed:16862125, PubMed:20538615). Upon activation, CARD9 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:16862125, PubMed:20538615, PubMed:22265677, PubMed:29080677). CARD9 signaling in antigen-presenting cells links innate sensing of fungi to the activation of adaptive immunity and provides a cytokine milieu that induces the development and subsequent of interleukin 17-producing T helper (Th17) cells (PubMed:17450144, PubMed:24470469, PubMed:32358020). Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (PubMed:17486093). CARD9 can also be engaged independently of BCL10: forms a complex with RASGRF1 downstream of C-type lectin receptors, which recruits and activates HRAS, leading to ERK activation and the production of cytokines (PubMed:25267792). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (PubMed:27158904, PubMed:33548172). Plays an essential role in antifungal immunity against dissemination of gut fungi: acts by promoting induction of antifungal IgG antibodies response in CX3CR1(+) macrophages to confer protection against disseminated C.albicans or C.auris infection (PubMed:33548172). Also mediates immunity against other pathogens, such as certain bacteria, viruses and parasites; CARD9 signaling is however redundant with other innate immune responses (PubMed:17187069, PubMed:26679537, PubMed:29080677). In response to L.monocytogenes infection, required for the production of inflammatory cytokines activated by intracellular peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B (PubMed:17187069). {ECO:0000269|PubMed:16862125, ECO:0000269|PubMed:17187069, ECO:0000269|PubMed:17450144, ECO:0000269|PubMed:17486093, ECO:0000269|PubMed:20538615, ECO:0000269|PubMed:22265677, ECO:0000269|PubMed:24470469, ECO:0000269|PubMed:25267792, ECO:0000269|PubMed:25621893, ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:27158904, ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:32358020, ECO:0000269|PubMed:32548948, ECO:0000269|PubMed:33548172}. | Subcellular Location: Cytoplasm {ECO:0000250|UniProtKB:Q9H257}. |
Expression of "Card9"gene in different tissues
OCR associated with "Card9" gene
