InnateDB Protein
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IDBP-92274.4
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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CARD9
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Protein Name
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caspase recruitment domain family, member 9
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Synonyms
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000360797
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InnateDB Gene
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IDBG-92266 (CARD9)
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Protein Structure
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Function |
Adapter protein that plays a key role in innate immune response to a number of intracellular pathogens, such as C.albicans and L.monocytogenes. Is at the crossroads of ITAM- tyrosine kinase and the Toll-like receptors (TLR) and NOD2 signaling pathways. Probably controls various innate immune response pathways depending on the intracellular pathogen. In response to L.monocytogenes infection, acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B. 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). Controls CLEC7A (dectin-1)-mediated myeloid cell activation induced by the yeast cell wall component zymosan, leading to cytokine production and innate anti-fungal immunity: acts by regulating BCL10-MALT1-mediated NF-kappa-B activation pathway. Activates NF-kappa-B via BCL10. In response to the hyphal form of C.albicans, mediates CLEC6A (dectin-2)-induced I-kappa-B kinase ubiquitination, leading to NF-kappa-B activation via interaction with BCL10. In response to fungal infection, may be required for the development and subsequent differentiation of interleukin 17-producing T helper (TH-17) cells. {ECO:0000250, ECO:0000269PubMed:11053425}.
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Subcellular Localization |
Cytoplasm {ECO:0000269PubMed:11053425}.
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Disease Associations |
Candidiasis, familial, 2 (CANDF2) [MIM:212050]: 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. {ECO:0000269PubMed:19864672, ECO:0000269PubMed:23335372, ECO:0000269PubMed:24131138}. Note=The disease is caused by mutations 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. Neutrophils show a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae (PubMed:23335372). {ECO:0000269PubMed:23335372}.
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Tissue Specificity |
Highly expressed in spleen. Also detected in liver, placenta, lung, peripheral blood leukocytes and in brain.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 27 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.
Experimentally validated |
Total |
27
[view]
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Protein-Protein |
27
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
4 [view]
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Molecular Function |
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Biological Process |
GO:0009620
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response to fungus
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GO:0032494
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response to peptidoglycan
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GO:0032495
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response to muramyl dipeptide
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GO:0032755
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positive regulation of interleukin-6 production
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GO:0032760
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positive regulation of tumor necrosis factor production
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GO:0032874
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positive regulation of stress-activated MAPK cascade
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GO:0035872
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nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
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GO:0042493
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response to drug
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GO:0042534
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regulation of tumor necrosis factor biosynthetic process
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GO:0042981
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regulation of apoptotic process
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GO:0043123
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positive regulation of I-kappaB kinase/NF-kappaB signaling
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GO:0043330
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response to exogenous dsRNA
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GO:0045076
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regulation of interleukin-2 biosynthetic process
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GO:0045087
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innate immune response (InnateDB)
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GO:0045089
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positive regulation of innate immune response
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GO:0045408
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regulation of interleukin-6 biosynthetic process
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GO:0046330
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positive regulation of JNK cascade
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GO:0050830
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defense response to Gram-positive bacterium
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GO:0051607
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defense response to virus
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GO:0070423
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nucleotide-binding oligomerization domain containing signaling pathway
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Cellular Component |
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PDB ID |
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InterPro |
IPR001315
CARD domain
IPR011029
Death-like domain
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PFAM |
PF00619
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PRINTS |
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PIRSF |
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SMART |
SM00114
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TIGRFAMs |
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Modification |
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SwissProt |
Q9H257
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PhosphoSite |
PhosphoSite-Q9H257
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TrEMBL |
A0A024R8F1
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UniProt Splice Variant |
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Entrez Gene |
64170
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UniGene |
Hs.694071
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RefSeq |
NP_434700
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HUGO |
HGNC:16391
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OMIM |
607212
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CCDS |
CCDS6997
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HPRD |
06236
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IMGT |
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EMBL |
AF311287
AK024001
AK292081
AL592301
BC008877
CH471090
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GenPept |
AAG28790
AAH08877
BAB14766
BAF84770
CAI13931
CAI13932
EAW88220
EAW88222
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