Tyrobp; Dap12; Karap; TYRO protein tyrosine kinase-binding protein; DNAX-activation protein 12; Killer-activating receptor-associated protein; KAR-associated protein
Species
Mus musculus (Mouse)
Source
in vitro E.coli expression system
Expression Region
22-114
Target Protein Sequence
LSPVQAQSDTFPRCDCSSVSPGVLAGIVLGDLVLTLLIALAVYSLGRLVSRGQGTAEGTRKQHIAETESPYQELQGQRPEVYSDLNTQRQYYR
Note: The complete
sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is
translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application,
please explicitly request the full and complete sequence of this protein before ordering.
Protein Length
Full Length of Mature Protein
Tag Info
N-terminal 10xHis-tagged
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.
Storage Condition
Store at -20°C, for extended storage, conserve at -20°C or -80°C.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
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. 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. Also has an inhibitory role in some cells. Non-covalently associates with activating receptors of the CD300 family to mediate cell activation. Also mediates cell activation through association with activating receptors of the CD200R family. Required for neutrophil activation mediated by integrin. Required for the activation of myeloid cells mediated by the CLEC5A/MDL1 receptor. Associates with natural killer (NK) cell receptors such as the KLRD1/KLRC2 heterodimer to mediate NK cell activation. Also associates non-covalently with the NK cell receptors KLRA4/LY49D and KLRA8/LY49H which leads to NK cell activation. Associates with TREM1 to mediate activation of neutrophils and monocytes. Associates with TREM2 on monocyte-derived dendritic cells to mediate up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival. Association with TREM2 mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages. Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) which is produced by TREM2 ectodomain shedding. In microglia, required with TREM2 for phagocytosis of apoptotic neurons. Required with ITGAM/CD11B in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development. Promotes proinflammatory responses in microglia following nerve injury which accelerates degeneration of injured neurons. Positively regulates the expression of the IRAK3/IRAK-M kinase and IL10 production by liver dendritic cells and inhibits their T cell allostimulatory ability. Negatively regulates B cell proliferation. Required for CSF1-mediated osteoclast cytoskeletal organization. Positively regulates multinucleation during osteoclast development.
Gene References into Functions
We identified modulatory effects of TYROBP deficiency on the level of phosphorylation of TAU that was accompanied by a reduction in the severity of neuritic dystrophy. TYROBP deficiency also altered the expression of several AD related genes, including Cd33. Electrophysiological abnormalities and learning behavior deficits associated with APP/PSEN1 transgenes were greatly attenuated on a Tyrobp-null background.PMID:28612290
These results demonstrate that PTX targets the innate immunity through DAP12, FcRgamma, and MyD88 providing new insights into the immunobiology of PTX.PMID:28089363
Recent studies have revealed that activated microglia in the spinal dorsal horn exacerbate neuropathic pain, which has suggested that suppression of microglial activity should be considered as a therapeutic target. However, only a few molecules have been identified as regulators of microglial activity. In this study, we focused on a receptor complex of TREM2 and DAP12, both of which are expressed by microglia and have beePMID:27798193
TNF/IL-6 generated osteoclasts in vitro that resorbed mineralized tissue through a pathway dependent on IL-6R, NFATc1, DNAX-activation protein 12, and cell proliferation.PMID:27563728
The findings suggest that DAP12 acts as a brake on the pulmonary immune response to C. neoformans by promoting pulmonary eosinophilia and by inhibiting the activation and antifungal activities of effector cells, including NK cells and macrophages.PMID:27068093
significant role of DAP12 in the initial inflammatory response, bone remodeling and regenerationPMID:26030755
DAP12-mediated microglial activation following axotomy promotes pro-inflammatory responses, and thereby accelerates nerve injury-induced neuron deathPMID:25690660
results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses.PMID:25957402
a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.PMID:25762783
DAP12 expression in liver grafts regulates donor mDC migration to host lymphoid tissue, alloreactive T cell responses and transplant tolerancePMID:24935196
Integrin alphav beta3/Dap12 double-deficient developed profound osteoporosis.PMID:25547154
Our study identifies the DAP12/IRAK-M/IL-10 to be a novel molecular pathway in APCs exploited by mycobacterial pathogens, allowing infection a foothold in the lung.PMID:24172845
We conclude that DAP12, partly through TREM1/3, is involved in renal inflammation during progression of unilateral ureter obstruction.PMID:24358193
Siglec-15 regulates osteoclast development and bone resorption by modulating receptor activator of nuclear factor kappaB ligand (RANKL) signaling in association with DAP12.PMID:23677868
Dap12- and FcRgamma-deficiency exacerbates Granulocyte-Macrophage Colony-Stimulating Factor-driven monocyte differentiation and production of inflammatory monocyte-derived dendritic cells.PMID:24155889
The effects of DAP12 deficiency on development of autoimmune uveitis are dramatically affected by environmental factors.PMID:23906311
DOK3 physically associated with the ITAM of DAP12 through its phosphotyrosine-binding domain. In response to LPS, DOK3 was phosphorylated in a DAP12- and Src-dependent manner, which led to translocation of phosphorylated DOK3 to the plasma membrane.PMID:23962980
DAP12 is involved in microglia-induced dopaminergic neuron cell death in an in vitro model of Parkinson's disease.PMID:23844828
the Siglec-15-DAP12-Syk-signaling cascade plays a critical role in functional osteoclast formation.PMID:22451653
Because mouse and rat NKG2C and -E transmembrane regions contain a positively charged arginine residue located close to the extracellular surface, these receptors may not associate with DAP12.PMID:22084441
we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection.PMID:21908731
Data suggest that OSCAR is a collagen receptor that binds to specific collagen motifs and costimulates osteoclastogenesis in DAP12-deficient humans and mice.PMID:21841309
DAP12-coupled MAIR-II negatively regulates B cell-mediated adaptive immune responses.PMID:21727189
A regulatory role is highlighted for DAP12 in hepatic dendritic cell maturation; a mechanism via interleukin-1 receptor-associated kinase 3 (IRAK-M) is auggested whereby this function may be induced and maintained.PMID:21257958
Cytoskeletal dysfunction, and not arrested differentiation, is the dominant consequence of DAP12 deficiency in osteoclasts.PMID:20720152
demonstrate a previously uncharacterized interaction of SHIP1 with DAP12 that limits TREM2- and DAP12-dependent signaling and identify a mechanism through which SHIP1 regulates key ITAM-containing receptors by blocking the binding and activation of PI3KPMID:20484116
These findings indicate that DAP12, possibly through association with TREM2, contributes to alveolar macrophage chemotaxis and recruitment to the lung and may mediate macrophage accumulation in lung diseases such as emphysema.PMID:20421649
DAP12-associating lectin (MDL)-1 receptor is a key regulator of synovial injury and bone erosion in autoimmune joint inflammation.PMID:20212065
DAP12 and mature lymphocytes act synergistically to maintain normal bone mass, while playing similar but not synergistic roles in protecting bone loss after gonadal failure.PMID:17611620
a crucial role for a particular activating signaling pathway, in this case the one induced through KARAP/DAP12, in the NK cell-mediated resistance to an infectionPMID:11927627
Aberrant DAP12 signaling in the 129 strain of mice: implications for the analysis of gene-targeted mice.PMID:12165492
selective associations with DAP12 determine stimulatory versus costimulatory activity of NKG2DPMID:12426565
DAP12 has a role in signal transduction, bone modeling, and brain myelination [review]PMID:12569153
DAP12 has roles in preventing synaptic degeneration, impaired prepulse inhibition, and aberrant electrophysiological profiles in the thalamiPMID:12569157
stimulation of the DAP12 adapter protein plays a significant role in formation of multinuclear osteoclasts and that DAP12 and DARs likely participate in the regulation of bony remodelingPMID:14969392
DAP12 and FcRgamma have overlapping roles in supporting osteoclast development in osteoblast-osteoclast cocultures, which mirrors their overlapping functions in vivoPMID:15073337
DAP12 and its associating molecules are differentially regulated by mycobacterial infection and type 1 cytokinesPMID:15102754
IL-4-mediated dendritic cell (DC)-activated natural killer (NK) signaling is suppressed in vitro by KARAP/DAP12.PMID:15128777
KARAP/DAP12 may alter microglial physiology and subsequently synaptic function and plasticity through a novel microglia-neuron interaction.PMID:15601948
KARAP/DAP12-mediated signals play an important role in the regulation of both brain and bone homeostasis as seen in loss-of function mice.PMID:15632019
The importance of Fcgr3/Cd3z, Hcst, and Tyrobp in the activation of NK cells in the uterus of pregnant mice is reported.PMID:15878887
one or more DAP12-pairing receptors negatively regulate signaling through TLRsPMID:15895090
DAP12 has a role in mediating effector function in an NKG2D-dependent and major histocompatibility complex-independent mannerPMID:16169855
Consistent and selective association of the IDO-competent phenotype with down-modulation of the Tyrobp gene.PMID:16339401
plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12PMID:16715077
DAP12 must associate with a receptor present in the macrophage to inhibit Toll-like receptor- and Fc receptor-induced tumor necrosis factor (TNF) production.PMID:16887962
DAP12 signaling in plasmacytoid dendritic cells (pDC) can mediate different regulatory effects on their functions, depending on the mechanisms of pDC activationPMID:16920926
Ly49H signaling through DAP12 appears to directly augment NK cell sensitivity to low concentrations of proproliferative cytokines such as IL-15.PMID:17015680
This review discusses the dual functionality of DAP12 and presents evidence that DAP12 can suppress as well as activate natural killer (NK) cells.PMID:17100880
FcRgamma chain may provide cooperation with and/or compensation for DAP12 in MAIR-II-mediated inflammatory responses by peritoneal macrophagesPMID:17202337
Show
More
Hide
All
Subcellular Location
Cell membrane; Single-pass type I membrane protein.
Protein Families
TYROBP family
Tissue Specificity
Expressed on microglia (at protein level). Expressed on oligodendrocytes (at protein level). Expressed on macrophages and osteoclasts. Expressed on dendritic cells in liver, spleen, kidney and lung with highest levels in liver dendritic cells.