Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (PubMed:26961233, PubMed:33558980). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (PubMed:24231284, PubMed:25702837, PubMed:25057046, PubMed:26679537, PubMed:26961233, PubMed:26521038, PubMed:27777981, PubMed:29080677, PubMed:33558980). 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 (By similarity). 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:11053425, PubMed:26488816, PubMed:31296852, PubMed:26961233, PubMed:33558980). 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:24231284). 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 (By similarity). 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 (By similarity). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (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 (By similarity). 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 (By similarity). Maintained in an autoinhibited state via homodimerization in which the CARD domain forms an extensive interaction with the adjacent linker and coiled-coil regions (PubMed:31296852). Activation downstream of C-type lectin receptors, by phosphorylation by PRKCD and/or ubiquitination by TRIM62, triggers disruption of the CARD domain-coiled coil interface, CARD9 homooligomerization and BCL10 recruitment, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:26488816, PubMed:31296852). Zinc-binding inhibits activation by stabilizing the CARD ground-state conformation and restricting its capacity to form BCL10-nucleating filaments (PubMed:30206119). Monomer (PubMed:30206119). Homodimer; homodimerization is mediated by the CARD domain which forms an extensive interaction with the adjacent linker and coiled-coil regions; leads to an autoinhibited state (PubMed:30206119, PubMed:31296852). Homomultimer; polymerizes following activation, forming a nucleating helical template that seeds BCL10-filament formation via a CARD-CARD interaction (PubMed:31296852). Interacts (via CARD domain) with BCL10 (via CARD domain); interaction takes place following CARD9 activation and polymerization, leading to the formation of a filamentous CBM complex assembly (PubMed:11053425, PubMed:26488816, PubMed:31296852, PubMed:26521038). Component of a CBM complex (CARD9-BCL10, MALT1), composed of CARD9, BCL10 and MALT1 (PubMed:26521038). Interacts with RASGRF1 (PubMed:26521038). Interacts with NOD2 (via NACHT domain); interaction is direct (PubMed:24960071). Interacts with RIPK2 (By similarity). Interacts with VHL; without leading to protein degradation (By similarity). Expression is restricted to several populations of phagocytes, such as macrophages, monocytes, and dendritic cells (PubMed:33548172). Highly expressed in spleen (PubMed:11053425). Also detected in liver, placenta, lung, peripheral blood leukocytes and in brain (PubMed:11053425). The linker region, also named autoinhibitory interface, is required to prevent constitutive activation and maintain CARD9 in an autoinhibitory state (PubMed:31296852). Disruption of this region triggers polymerization and activation, leading to formation of BCL10-nucleating filaments (PubMed:31296852). Phosphorylated at Thr-231 by PRKCD downstream of C-type lectin receptors activation: phosphorylation promotes interaction with BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Phosphorylated at Thr-531 and Thr-533 by CK2 following interaction with VHL, leading to inhibit the ability to activate NF-kappa-B (By similarity). Ubiquitinated at Lys-125 via 'Lys-27'-linked ubiquitin by TRIM62 downstream of C-type lectin receptors activation; leading to CARD9 activation, followed by activation of NF-kappa-B and MAP kinase p38 pathways (PubMed:26488816, PubMed:31296852). Deubiquitinated at Lys-125 by USP15, inhibiting CARD9 (PubMed:33093067). The disease is caused by variants affecting the gene represented in this entry. Defects induce reduced numbers of CD4(+) Th17 lymphocytes as well as a lack of monocyte-derived cytokines in response to Candida strains (PubMed:23335372). Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (PubMed:23335372). May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.