Recombinant Mouse TIM-3 Protein (C-Fc)

Name: Recombinant Mouse TIM-3 Protein (C-Fc)
Brand: Beta LifeScience
SKU: BL-0130NP
Availability: InStock

BL-0130NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Collections: Co-inhibitory receptors, Featured immune checkpoint protein molecules, Immune checkpoint proteins, Recombinant proteins

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Product Overview

Description	Recombinant Mouse T cell Immunoglobulin And Mucin Domain-3 is produced by our Mammalian expression system and the target gene encoding Arg20-Arg191 is expressed with a human IgG1 Fc tag at the C-terminus.
Accession	Q8VIM0
Synonym	Hepatitis A virus cellular receptor 2 homolog; HAVcr-2; T-cell immunoglobulin and mucin domain-containing protein 3; T-cell immunoglobulin mucin receptor 3; T-cell membrane protein 3; Tim3; Timd3
Gene Background	T cell immunoglobulin and mucin domain-3 (TIM3), also called hepatitis A virus cellular receptor 2 (HAVCR2), is a transmembrane glycoprotein of the TIM family of immune regulating molecules and plays an important role in the Th1-mediated immune response. TIM3 is expressed on the Th1 cells, CD8 T-cells, monocytes, and dendritic cells, but not on Th2 cells. TIM3 expressed by monocytes and dendritic cells facilitates phagocytosis of apoptotic cells and up-regulates cross-presentation of apoptotic cell-associated antigens through interaction with phosphatidylserine. Engagement of TIM3 by its ligand galectin-9 induces a range of immunosuppressive functions which enhance immune tolerance and inhibit anti-tumor immunity. Stimulation of TIM3 with an agonistic antibody promotes inflammation through the activation of innate immune cells. TIM3 is also regarded as a potential target molecule for immunotherapy. TIM3 and programmed cell death 1 (PD-1) as two important coinhibitory regulators of T cell responses, have been implicated with the T-cell dysfunction or exhaustion associated with chronic HBV infection including HBV-related HCC.
Molecular Mass	46.3 KDa
Apmol Mass	50-80 KDa, reducing conditions
Formulation	Lyophilized from a 0.2 μm filtered solution of PBS, pH 7.4.
Endotoxin	Less than 0.1 ng/µg (1 EU/µg) as determined by LAL test.
Purity	Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity	Not tested
Reconstitution	Always centrifuge tubes before opening. Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles.
Storage	Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.
Shipping	The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature listed below.
Usage	For Research Use Only

Target Details

Target Function	Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand. Regulates macrophage activation. Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits. In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN. Expressed on Treg cells can inhibit Th17 cell responses. Receptor for LGALS9. Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6. Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth. However, the function as receptor for LGALS9 has been challenged. Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes. Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent. May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells. Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha. In tumor-imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid-sensing and trafficking of nucleid acids to endosomes. Can enhance mast cell production of Th2 cytokines Il-4, IL-6 and IL-13. Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9. In contrast, shown to suppress NK cell-mediated cytotoxicity. Negatively regulates NK cell function in LPS-induced endotoxic shock.
Subcellular Location	[Isoform 1]: Membrane; Single-pass type I membrane protein. Cell junction.; [Isoform 2]: Secreted.
Protein Families	Immunoglobulin superfamily, TIM family
Database References	KEGG: mmu:171285 STRING: 10090.ENSMUSP00000020668 UniGene: Mm.72168
Tissue Specificity	Expressed in T-helper type 1 lymphocytes. Not expressed by naive T-cells but up-regulated as they differentiate into T-helper-1 cells. Also expressed by differentiated type 1 CD8+ cytotoxic T-cells. Expressed on peritoneal exudate macrophages, monocytes,

Gene Functions References

TIM-3 expression was predominantly localized to myeloid cells in both human and murine tumors PMID: 29316433
Here, the authors demonstrate that Tim-3 inhibits macrophage phagocytosis of Listeria monocytogenes by inhibiting the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway and increases bacterial burden. PMID: 28205579
Studied role of Tim-3 role's in T cell activation using a chronic disease model. Results showed a major function of Tim-3 is to enhance T cell activation during either acute or chronic viral infection, and that Tim-3 is not required for the development of T cell exhaustion. PMID: 29463725
the data suggested that Tim-3 played a crucial role in the macrophage polarization and brain inflammation following intracerebral hemorrhage PMID: 29107214
Tim-3 might contribute to successful pregnancy by restraining Th1 bias PMID: 29083087
synergism in cell death by Caspase-1- and RipK3 resulted in restriction of PD-1 and TIM3 expression on primed CD8(+) T cells, which promoted the survival of activated CD8(+) T cells. PMID: 28686578
these findings reveal a critical role for Tim-3-Gal-9 signaling-mediated immunoregulation by pNK cells in maternal-fetal immune tolerance and suggest that Tim-3 abundance on pNK cells is a potential biomarker for recurrent miscarriage diagnosis. PMID: 28951537
Tim-3 and PD-1 pathways play critical roles in regulating CD8(+) T cell function and maintaining normal pregnancy. PMID: 28331165
CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1alpha/TIM-3 signalling pathway in microglia PMID: 28253997
Our results show that Tim-3 is a critical negative regulator of NLRP3 inflammasome and provides a potential target for intervention of diseases with uncontrolled inflammasome activation. PMID: 28799242
demonstrated that both IL-10 and TGF-beta upregulated TIM-3 surface expression on dendritic cells via a common signaling pathway that involved sequential activation of c-Src and Bruton's tyrosine kinase PMID: 27439518
Methylation level of the TIM-3 promoter gradually decreased after each round of T-cell polarization, and this decrease was inversely correlated with TIM-3 expression. PMID: 26890332
in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation. PMID: 27209052
Authors found that a CD8(+) T-cell population with age-associated exhaustion was distinguishable by its expression of Tim-3. PMID: 26750587
TIM4 binds TIM3 on the surface of polarized Th1 cells to induce Th1 cell apoptosis, which may contribute to the development of Th2-dominant immune disorders. PMID: 26403707
decreases immunological rejection during composite tissue allotransplantation PMID: 26561949
The Gal-9/Tim-3 signal is important for the regulation of decidua NK cells function, which is beneficial for the maintenance of a normal pregnancy. PMID: 25578313
TIM-3 expression by NK cells and gamma/delta T cells is similar in the peripheral and decidual immune cells from pregnant mice. PMID: 26278059
Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcepsilonRI ligation. PMID: 26598760
Our data indicate that Tim-3 expression on NK cells is regulated by T-bet, and that Tim-3 levels correlate with advanced stages of gastric cancer PMID: 26214042
TIM-3 plays a role in regulating the uterine natural killer cells and contributes to the maintenance of tolerance at the feto-maternal interface. PMID: 25897749
TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes in a HIF-1-dependent manner. PMID: 25790768
These data identify an IL-27/NFIL3 signalling axis as a key regulator of effector T-cell responses via induction of Tim-3, IL-10 and T-cell dysfunction. PMID: 25614966
CD4+ T cell-dependent "negative" TIM-3 costimulation is essential for hepatic homeostasis and resistance against IR stress in OLTs PMID: 25676534
In DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Tim-3 effect on macrophage response may be TLR4 dependent. PMID: 26208474
These data suggest that Tim-3 and IFN-gamma may play a regulatory role in T. gondii-infected pregnant mouse model. PMID: 25270237
Gal-9, a natural TIM-3 ligand, was produced primarily by and released from ischemia-reperfusion-stressed hepatocytes, both in vivo and in vitro. PMID: 25450716
HCC conditioned medium or transforming growth factor-beta fostered Tim-3 expression and the alternative activation of macrophages. PMID: 25608525
Tim-3 induces Th2-biased immunity and macrophage activation during Schistosoma japonicum infection. PMID: 25987707
The Tim-3 pathway plays an inhibitory role in natural killer cell function. PMID: 25337993
Specific antigen-presenting cell subsets and the inhibitory receptor Tim-3 may contribute to CD8+ T cell impairment in metapneumovirus pathogenesis. PMID: 25653440
Tim-3 modulates microglia activity and regulates the interaction of microglia-neural cells. PMID: 25557503
The TIM-3 pathway ameliorates Theiler's murine encephalomyelitis virus-induced demyelinating disease. PMID: 24486565
CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity PMID: 25363763
Tim-3 is widely involved in the physiopathology of sepsis by regulating innate and adaptive immune responses. Blockade of the Tim-3 pathway or decreased Tim-3 expression may exacerbate sepsis by increasing immune deviation and immunosuppression in vivo. PMID: 24945079
Tim-3 signaling pathway acts as a novel negative mediator in LPS-induced endotoxic shock and could be a potential therapeutic target for the treatment of sepsis. PMID: 24561184
These results demonstrate an essential role for Btk-c-Src signaling in TIM-3-induced DC suppression. PMID: 25172495
The increased expression of IL-17 and Tim-3 in BALF. PMID: 23904364
Tim-3/galectin-9 pathway plays a critical role in the homeostasis of hepatic Tregs through the elimination induction in Teffs and the inhibition of IFN-gamma release. PMID: 24333756
Our findings demonstrate that Tim-3 plays an important role in brain inflammation after intracerebral hemorrhage PMID: 24289479
Data indicate that the absence of T cell Ig and mucin domain (Tim) 3 (Tim-3) expression impairs CD8 T cell responses to Listeria monocytogenes infection. monocytogenes PMID: 24567532
results indicate that the Tim-3 pathway is highly involved in the regulation of asthma; targeting Tim-3 by siRNA may hold therapeutic potential in preventing the development of allergic asthma PMID: 23232962
These data indicate that Tim-3 may be involved in the process of toxoplasmic encephalitis in mice infected with the Toxoplasma gondii Pru strain. PMID: 23595213
Anti-Tim-3 treatment augments atherosclerosis lesion development, accompanied by an increase in the number of monocytes/macrophages and CD4(+) T cells and by decreased regulatory T cells and regulatory B cells. PMID: 23990206
These results indicate that the therapeutic efficacy of targeting Tim-3 in experimental autoimmune encephalomyelitis is dependent on the nature of the effector T cells contributing to the disease. PMID: 23562810
Up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression. PMID: 22038354
In the liver Tim-3+ natural killer {NK)T cells are in an activated state, and Gal-9 directly induces Tim-3+ NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. PMID: 23296703
T-cell Ig mucin-3 (Tim-3) and its ligand, galectin 9 (Gal-9), were significantly decreased in dextran sodium sulfate-induced colitis PMID: 23117395
Deletion of the terminal cytoplasmic domain of Tim3 potentiates its ability to downregulate cytotoxic lymphocytes (Tc1) inflammation; this enhanced Tim3 activity is associated with decreased phosphorylation of the T cell receptor-CD3zeta-chain. PMID: 22875804
TIM-3 circumvents the stimulatory effects of nucleic acids in tumor immunity by interactding with HMGB1 to interfere with the recruitment of nucleic acids into dendritic cell endosomes PMID: 22842346

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

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