TYROBP protein expression summary - The Human Protein Atlas

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TYROBP

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STRUCT & INT

TYROBP

TYROBP INFORMATION
Proteinⁱ Full gene name according to HGNC.	Transmembrane immune signaling adaptor TYROBP
Gene nameⁱ Official gene symbol, which is typically a short form of the gene name, according to HGNC.	TYROBP (DAP12, KARAP, PLO-SL, PLOSL)
Protein classⁱ Assigned HPA protein class(es) for the encoded protein(s).	Disease related genes Human disease related genes Potential drug targets Transporters
Protein evidence	Evidence at protein level (all genes)
Number of transcriptsⁱ Number of protein-coding transcripts from the gene as defined by Ensembl.	5
Protein interactions	Interacting with 1 protein

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 different tissue types, including immune cells.
Subcellular locationⁱ Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.	Localized to the Plasma membrane
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.	Membrane

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.	Macrophages & Microglia - Immune response (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 (Hofbauer cells, monocytes, Kupffer cells, Langerhans cells, Macrophages, NK-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.	Core cell type enriched (Macrophages)
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 (neutrophil)
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 & Neutrophils - Degranulation (mainly)

CANCER & CELL LINES
Prognostic summary	TYROBP is a prognostic marker in Skin cuteneous melanoma
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.	HMC-1 - 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 which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors 1, 2, 3. TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation 4. Also has an inhibitory role in some cells 5. Non-covalently associates with activating receptors of the CD300 family to mediate cell activation 6, 7, 8, 9. Also mediates cell activation through association with activating receptors of the CD200R family (By similarity). Required for neutrophil activation mediated by integrin (By similarity). Required for the activation of myeloid cells mediated by the CLEC5A/MDL1 receptor 10. Associates with natural killer (NK) cell receptors such as KIR2DS2 and the KLRD1/KLRC2 heterodimer to mediate NK cell activation 11, 12, 13. Also enhances trafficking and cell surface expression of NK cell receptors KIR2DS1, KIR2DS2 and KIR2DS4 and ensures their stability at the cell surface 14. Associates with SIRPB1 to mediate activation of myeloid cells such as monocytes and dendritic cells 15. Associates with TREM1 to mediate activation of neutrophils and monocytes 16. Associates with TREM2 on monocyte-derived dendritic cells to mediate up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival 17. Association with TREM2 mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages 18. Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) produced by TREM2 ectodomain shedding which suppresses the release of pro-inflammatory cytokines 19. In microglia, required with TREM2 for phagocytosis of apoptotic neurons (By similarity). Required with ITGAM/CD11B in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (By similarity). Promotes pro-inflammatory responses in microglia following nerve injury which accelerates degeneration of injured neurons (By similarity). Positively regulates the expression of the IRAK3/IRAK-M kinase and IL10 production by liver dendritic cells and inhibits their T cell allostimulatory ability (By similarity). Negatively regulates B cell proliferation 20. Required for CSF1-mediated osteoclast cytoskeletal organization (By similarity). Positively regulates multinucleation during osteoclast development (By similarity).... show less
Biological process (UniProt)ⁱ Keywords assigned by UniProt to proteins because they are involved in a particular biological process.	Immunity
Ligand (UniProt)ⁱ Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.	Calcium, Metal-binding
Gene summary (Entrez)ⁱ Useful information about the gene from Entrez	This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. This protein may bind zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. Mutations within this gene have been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Multiple alternative transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Mar 2010]... show less

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