InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CARD9

Summary

InnateDB Protein

IDBP-589217.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CARD9

Protein Name

caspase recruitment domain family, member 9

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000451368

InnateDB Gene

IDBG-92266 (CARD9)

Protein Structure

UniProt Annotation

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}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:11053425}.

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}.

Tissue Specificity

Highly expressed in spleen. Also detected in liver, placenta, lung, peripheral blood leukocytes and in brain.

Comments

Interactions

Number of Interactions

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]
Protein-Protein	27 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0042803	protein homodimerization activity
GO:0050700	CARD domain binding

Biological Process

GO:0032874	positive regulation of stress-activated MAPK cascade
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0042981	regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0046330	positive regulation of JNK cascade
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway