Product Details

Target Names

TYROBP

Uniprot No.

Alternative Names

TYROBP; DAP12; KARAP; TYRO protein tyrosine kinase-binding protein; DNAX-activation protein 12; Killer-activating receptor-associated protein; KAR-associated protein

Species

Homo sapiens (Human)

Expression Region

22-113

Target Protein Sequence

LRPVQAQAQSDCSCSTVSPGVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEAATRKQRITETESPYQELQGQRSDVYSDLNTQRPYYK

Protein Length

Full Length of Mature Protein

Tag Info

Tag type will be determined during the manufacturing process.

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.

Form

Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer before Lyophilization

Tris/PBS-based buffer, 6% Trehalose, pH 8.0

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

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.

Lead Time

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet

Please contact us to get it.

Target Background

Function

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 KIR2DS2 and the KLRD1/KLRC2 heterodimer to mediate NK cell activation. Also enhances trafficking and cell surface expression of NK cell receptors KIR2DS1, KIR2DS2 and KIR2DS4 and ensures their stability at the cell surface. Associates with SIRPB1 to mediate activation of myeloid cells such as monocytes and dendritic cells. 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) produced by TREM2 ectodomain shedding which suppresses the release of pro-inflammatory cytokines. 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

Heterozygous carriership of the TYROBP deletion is not a major risk factor of cognitive impairment. PMID: 29336840
Mutations in TYROBP are not a common cause of dementia in this Turkish cohort. PMID: 28716534
Rare TYROBP variants might contribute to early-onset Alzheimer's disease risk by reduction of TREM2 expression, a well-established risk factor for AD. PMID: 27658901
TYROBP influences a batch of genes that are related to Alzheimer's disease; ZNF329 and RB1 significantly regulate those 'mesenchymal' gene expression signature genes for brain tumors. By merely leveraging gene expression data, Context Based Dependency Network (CBDN) can efficiently infer the existence of gene-gene interactions as well as their regulatory directions. PMID: 27556418
TYROBP/CSTA gene interaction might play pivotal roles in the occurrence and development of Postmenopausal Osteoporosis PMID: 26676054
The different expression of DAP12 compared to TREM2 represents the first description of such variable expressivity in Nasu-Hakola disease (NHD) microglia. PMID: 26001891
the microglial membrane adaptor protein DAP12 was required for both nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and the ensuing pain, but not for microglial proliferation PMID: 26642091
Impaired signaling by the TREM2-DAP12 pathway leads to altered immune responses in phagocytosis, cytokine production, and microglial proliferation and survival, thus contributing to disease pathogenesis. Review. PMID: 26337043
T cells modified to express a KIR-CAR and DAP12 exhibit superior antitumor activity compared with standard first- and second-generation CD3zeta-based CARs in a xenograft model of mesothelioma highly resistant to immunotherapy. PMID: 25941351
This study reveled that TYROBP having a central role in the bipolar disease and schizophrenia manifestation. PMID: 25487697
isolated PMNs have an increased proportion of both TREM1 and DAP12 compared to normal healthy control PMID: 25642940
results support a role of DAP12 in stabilizing TREM2-CTF, thereby protecting against excessive pro-inflammatory responses. PMID: 25957402
Its mutation is a known genetic cause of Nasu-Hakola disease. PMID: 24612676
Data indicate that NKG2 receptor NKG2E was capable of associating with CD94 and DAP12 but that the complex was retained intracellularly at the endoplasmic reticulum. PMID: 24935923
Macrophage traits in BRC cells facilitate the metastatic process and DAP12 expression might promote metastatic homing to bone and liver tissues. PMID: 23810293
DAP12 has a role in trafficking newly synthesized KIR to the cell surface. It interacts with an immature KIR2DS isoform likely initiating in the ER. DAP12also impacts KIR2DS surface stability. PMID: 23715743
dynamics and dimerization of the TM helix of DAP12 in the membrane bilayer PMID: 23561520
A molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in Nasu-Hakola disease. PMID: 22080356
the putative periodontal pathogen P. gingivalis can positively regulate the expression of the TREM-1/DAP12 pathway in monocytic cells. PMID: 21967868
DAP12 gene levels were not increased in the monocytes of schizophrenic, bioplar or major depressive disorder patients. PMID: 21421043
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
A transgenic mouse model demonstrates that induction of tolerance in Ly49H-positive natural killer (NK) cells by chronic exposure to virus-encoded ligand m157 requires signaling through the Ly49H adaptor protein DAP12, not the DAP10 adaptor protein. PMID: 21263069
Meta-analysis of gene-disease association. (HuGE Navigator) PMID: 20628624
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
Mutations in two genes encoding different subunits of a receptor signaling complex (TYROBP and TREM2) result in an identical disease phenotype PMID: 12080485
Myeloid abnormalities seen in KARAP/DAP12-transgenic mice indicate that KARAP/DAP12-driven signals are involved in inflammation & constitute an essential target to control resolution of inflammatory disorders based on monocytes/macrophages & neutrophils. PMID: 12207350
DAP12 has a role in signal transduction, bone modeling, and brain myelination [review] PMID: 12569153
CD158j in T cells functions as a costimulatory molecule through the JNK pathway independent of KARAP/DAP12 and DAP10. PMID: 12591902
These results indicate an important role for DAP12-TREM2 signaling complex in the differentiation and function of osteoclasts. PMID: 12925681
DAP12 association with natural cytotoxicity receptor NKp44 is required for activating properties and surface expression of NKp44 in natural killer (NK) cells. PMID: 14707061
In clones that lack expression of KARAP/DAP12, stimulation of killer Ig-receptor KIR2DS2 does not induce cytotoxicity, whereas expression of KARAP/DAP12 is sufficient to convert a costimulatory KIR receptor into a stimulatory molecule. PMID: 15356118
Splenic mature dendritic cells from transgenic mice with DAP12 overexpression are characterized by an impaired tolerogenic potential PMID: 16206234
requirement by activated and expanded CD8+ T cells for DAP12 for direct killing PMID: 16339517
Nasu-Hakola disease due to a DAP12 mutation 4. PMID: 16505336
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
This is the first case of Nasu-Hakola disease caused by compound heterozygosity for loss-of-function mutations in DAP12. PMID: 17125796
KIR3DS1 associates with the ITAM-bearing adaptor, DAP12 PMID: 17202323
activation signals delivered via DAP12 can be counterbalanced by the adaptor NTAL PMID: 17277102
Transcript analysis of DCs of PLOSL patients show that DAP12 deficient cells differentiated into DCs and responded to pathogenic stimuli. However, the DCs showed morphological differences due to defects in the actin filaments. PMID: 17530208
the DAP12-TREM2 complex unlikely has a role in genetic susceptibility of multiple sclerosis PMID: 19019460
Downstream targets of DAP10 and DAP12 are constitutively activated in large granular lymphocyte leukemia cells, and expression of dominant-negative DAP10 and DAP12 dramatically reduces their lytic capacity. PMID: 19075187
loss of function mutation results in recessive genetic disorder, Nasu-Hakola disease (bone development abnormalities and dementia at adolescence) PMID: 19120482
describe the generation and the characterization of an anti-DAP12 monoclonal antibody. Using this novel reagent, we show that DAP12 expression is restricted to innate immune cells in basal condition PMID: 19606219

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Involvement in disease

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)

Subcellular Location

Cell membrane; Single-pass type I membrane protein.

Protein Families

TYROBP family

Tissue Specificity

Expressed at low levels in the early development of the hematopoietic system and in the promonocytic stage and at high levels in mature monocytes. Expressed in hematological cells and tissues such as peripheral blood leukocytes and spleen. Also found in b

Database Links

HGNC: 12449

OMIM: 221770

KEGG: hsa:7305

STRING: 9606.ENSP00000262629

UniGene: Hs.515369

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Code	CSB-CF025398HU
MSDS	MSDS
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Source	in vitro E.coli expression system
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Recombinant Human TYRO protein tyrosine kinase-binding protein (TYROBP)

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