Protein: Caspase recruitment domain-containing protein 9 (rCARD9) (Q9EPY0)
Organism: Rattus norvegicus (Rat)
Function: Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (By similarity). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (By similarity). 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. 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. 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 (By similarity). 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 (By similarity). 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 (By similarity). 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).
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q9H257}.
Sequence: MSDYENDDECWSALESFRVKLISVIDPSRITPYLRQCKVLNPDDEEQVLSDPNLVIRKRKVGVLLDILQRTGHKGYVAFLESLELYYPQLYRKVTGKEPARVFSMIIDASGESGLTQLLMTEVMKLQKKVQDLTALLSSKDDFIKELRVKDSLLRKHQERVQRLKEECELSSAELKRCKDENYDLAMRLAHLSEEKGAALMRNRDLQLEVDQLRHSLMKAEDDCKVERKHTLKLRHAMEQRPSQELLWDLQQERDLLQARVQELEVSVQEGKLHRNSPYIQVLEEDWRQALQEHQEQASTIFSLRKDLRQAEALRTRCMEEKEMFELQCLALRKDAKMYKDRIEAILQQMEEVSIERDQAMTSREELHAQCAQSFQDKDKLRKQVRELDEKADELQLQLFQTESRLLAAEGRLKQQQLDMLILSSDLEDSSPRNSQELSLPQDLEEDAQLSDKGVLADRESPEQPFVVLNKKHLSQTHDTVPSSSEPPEKERRRLKESFENYRRKRALRKMQNSWRQGEGDHGNTTGSDNTDTEGS
InterPro domains: - IPR042142: CARD9, CARD domain (domain) [10-95]
- IPR011029: Death-like domain superfamily (homologous_superfamily) [6-105]
- IPR001315: CARD domain (domain) [6-98]
Interaction partners: - B-cell lymphoma/leukemia 10
- Paracaspase
- Caspase-8
- Receptor-interacting serine/threonine-protein kinase 2
- Protein kinase C delta type
- Mitogen-activated protein kinase 14
- Nucleotide-binding oligomerization domain-containing protein 2
- Interferon regulatory factor 3
- mitogen-activated protein kinase
- Tyrosine-protein kinase SYK
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0044877 (protein-containing complex binding), GO:0005515 (protein binding), GO:0019904 (protein domain specific binding), GO:0046983 (protein dimerization activity), GO:0042803 (protein homodimerization activity)
Biological Process (BP): GO:0008150 (biological process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009605 (response to external stimulus), GO:0009628 (response to abiotic stimulus), GO:0023056 (positive regulation of signaling), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0051240 (positive regulation of multicellular organismal process), GO:0032879 (regulation of localization), GO:0051241 (negative regulation of multicellular organismal process), GO:0051239 (regulation of multicellular organismal process), GO:0051050 (positive regulation of transport), GO:0009892 (negative regulation of metabolic process), GO:0065008 (regulation of biological quality), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0065009 (regulation of molecular function), GO:0006950 (response to stress), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0050790 (regulation of catalytic activity), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:1903530 (regulation of secretion by cell), GO:1903829 (positive regulation of protein localization), GO:0051049 (regulation of transport), GO:0044093 (positive regulation of molecular function), GO:0051047 (positive regulation of secretion), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046887 (positive regulation of hormone secretion), GO:0006979 (response to oxidative stress), GO:0044092 (negative regulation of molecular function), GO:0060341 (regulation of cellular localization), GO:0044057 (regulation of system process), GO:0009966 (regulation of signal transduction), GO:0060255 (regulation of macromolecule metabolic process), GO:1901700 (response to oxygen-containing compound), GO:0043502 (regulation of muscle adaptation), GO:0010817 (regulation of hormone levels), GO:0031324 (negative regulation of cellular metabolic process), GO:0010033 (response to organic substance), GO:0046883 (regulation of hormone secretion), GO:0009991 (response to extracellular stimulus), GO:0009894 (regulation of catabolic process), GO:0042594 (response to starvation), GO:0010646 (regulation of cell communication), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0010647 (positive regulation of cell communication), GO:0031323 (regulation of cellular metabolic process), GO:0009895 (negative regulation of catabolic process), GO:0080090 (regulation of primary metabolic process), GO:0051222 (positive regulation of protein transport), GO:0009612 (response to mechanical stimulus), GO:1903532 (positive regulation of secretion by cell), GO:0043086 (negative regulation of catalytic activity), GO:0034097 (response to cytokine), GO:0042177 (negative regulation of protein catabolic process), GO:0042176 (regulation of protein catabolic process), GO:0051246 (regulation of protein metabolic process), GO:1904951 (positive regulation of establishment of protein localization), GO:0070201 (regulation of establishment of protein localization), GO:0062197 (cellular response to chemical stress), GO:0051248 (negative regulation of protein metabolic process), GO:0002793 (positive regulation of peptide secretion), GO:0010506 (regulation of autophagy), GO:0032880 (regulation of protein localization), GO:0050714 (positive regulation of protein secretion), GO:0051223 (regulation of protein transport), GO:0090276 (regulation of peptide hormone secretion), GO:0090087 (regulation of peptide transport), GO:0031667 (response to nutrient levels), GO:0072359 (circulatory system development), GO:0010563 (negative regulation of phosphorus metabolic process), GO:0051046 (regulation of secretion), GO:0090277 (positive regulation of peptide hormone secretion), GO:0071260 (cellular response to mechanical stimulus), GO:0034341 (response to type II interferon), GO:0014070 (response to organic cyclic compound), GO:0050708 (regulation of protein secretion), GO:0031669 (cellular response to nutrient levels), GO:0051174 (regulation of phosphorus metabolic process), GO:1902531 (regulation of intracellular signal transduction), GO:0007507 (heart development), GO:0043408 (regulation of MAPK cascade), GO:0032024 (positive regulation of insulin secretion), GO:0030162 (regulation of proteolysis), GO:0031399 (regulation of protein modification process), GO:0050796 (regulation of insulin secretion), GO:0031400 (negative regulation of protein modification process), GO:1901799 (negative regulation of proteasomal protein catabolic process), GO:0019220 (regulation of phosphate metabolic process), GO:0002791 (regulation of peptide secretion), GO:0034612 (response to tumor necrosis factor), GO:2000059 (negative regulation of ubiquitin-dependent protein catabolic process), GO:0061136 (regulation of proteasomal protein catabolic process), GO:0045861 (negative regulation of proteolysis), GO:2000058 (regulation of ubiquitin-dependent protein catabolic process), GO:0045936 (negative regulation of phosphate metabolic process), GO:0042325 (regulation of phosphorylation), GO:0001933 (negative regulation of protein phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0070374 (positive regulation of ERK1 and ERK2 cascade), GO:0042326 (negative regulation of phosphorylation), GO:0045859 (regulation of protein kinase activity), GO:1903050 (regulation of proteolysis involved in protein catabolic process), GO:0071356 (cellular response to tumor necrosis factor), GO:0070372 (regulation of ERK1 and ERK2 cascade), GO:0001933 (negative regulation of protein phosphorylation), GO:0033673 (negative regulation of kinase activity), GO:0043407 (negative regulation of MAP kinase activity), GO:0034644 (cellular response to UV), GO:0071900 (regulation of protein serine/threonine kinase activity), GO:0006469 (negative regulation of protein kinase activity), GO:0071901 (negative regulation of protein serine/threonine kinase activity), GO:0043405 (regulation of MAP kinase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure), GO:0005737 (cytoplasm), GO:0140535 (intracellular protein-containing complex)