Mouse Anti-CARD9 Recombinant Antibody (CBXC-2668) (CBMAB-C5736-CQ)

Caspase Recruitment Domain Family Member 9

The protein encoded by this gene 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 postive regulator of apoptosis and NF-kappaB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined.

Caspase Recruitment Domain Family Member 9; HCARD9; Caspase Recruitment Domain-Containing Protein 9; Caspase Recruitment Domain Family, Member 9; CANDF2;

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).

Defense response to Gram-positive bacterium Source: Ensembl
Defense response to virus Source: Ensembl
I-kappaB kinase/NF-kappaB signaling Source: Ensembl
Innate immune response Source: UniProtKB-KW
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: ARUK-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of interleukin-6 production Source: Ensembl
Positive regulation of JNK cascade Source: MGI
Positive regulation of stress-activated MAPK cascade Source: MGI
Positive regulation of tumor necrosis factor production Source: Ensembl
Regulation of apoptotic process Source: InterPro
Regulation of interleukin-2 production Source: Ensembl
Response to drug Source: Ensembl
Response to exogenous dsRNA Source: Ensembl
Response to fungus Source: Ensembl
Response to muramyl dipeptide Source: Ensembl
Response to peptidoglycan Source: Ensembl
Stimulatory C-type lectin receptor signaling pathway Source: Reactome

Cytoplasm

Candidiasis, familial, 2 (CANDF2): 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). A primary immunodeficiency disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.

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).