CARD9 protein expression summary - The Human Protein Atlas

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CARD9

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STRUCT & INT

CARD9

CARD9 INFORMATION
Proteinⁱ Full gene name according to HGNC.	Caspase recruitment domain family member 9
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	CARD9
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s).	Disease related genes Human disease related genes
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	2
Protein interactions	Interacting with 3 proteins

PROTEIN EXPRESSION AND LOCALIZATION
Tissue profileⁱ A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource. "Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.	Cytoplasmic expression in several tissues, including immune cells.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Not available
Predicted locationⁱ All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions. Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached. Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s). The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.	Intracellular

TISSUE RNA EXPRESSION
Tissue specificityⁱ The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.	Tissue enhanced (Bone marrow, Lymphoid tissue)
Tissue expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Lymphoid tissue & Bone marrow - Innate immune response (mainly)
Brain specificityⁱ The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category	Low human brain regional specificity
Brain expression clusterⁱ The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Hindbrain - Mixed function (mainly)

CELL TYPE RNA EXPRESSION
Single cell type specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Cell type enhanced (monocytes, Hofbauer cells, Macrophages, Kupffer cells, Langerhans cells, Endometrial stromal cells)
Single cell type expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Monocytes - Innate immune response (mainly)
Tissue cell type classificationⁱ Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.	Cell type enriched in 10 tissues
Immune cell specificityⁱ The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.	Immune cell enhanced (intermediate monocyte, non-classical monocyte)
Immune cell expression clusterⁱ The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Monocytes - Innate immune response (mainly)

CANCER & CELL LINES
Prognostic summary	CARD9 is not prognostic
Cancer specificityⁱ Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.	Low cancer specificity
Cell line expression clusterⁱ The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.	Myeloid leukemia - Innate immune response (mainly)
Cell line specificityⁱ RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.	Cancer enriched (Leukemia)

PROTEINS IN BLOOD
Detected in blood by immunoassayⁱ The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.	No (not applicable)
Detected in blood by mass spectrometryⁱ Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.	No
Proximity extension assayⁱ Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years. Read more	Not available

PROTEIN FUNCTION
Protein function (UniProt)ⁱ Useful information about the protein provided by UniProt.	Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors 1, 2. CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota 3, 4, 5, 6, 7, 8, 9, 10, 11. 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 12, 13, 14, 15, 16. 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 17. 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 18. 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 19. 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).... show less
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Adaptive immunity, Immunity, Innate immunity
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	Metal-binding, Zinc
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	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. [provided by RefSeq, Jul 2008]... show less

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