TIM-3: TIM-3 Protein | TIM-3 Antibody

TIM-3 Gene family

TIM-3 Background

Hepatitis A virus cellular receptor 2 (HAVCR2), formerly known as T cell immunoglobulin and mucin domain-3 (TIM-3), is a transmembrane glycoprotein expressed on the surface of terminally differentiated Th1 cells but not on Th2 cells. It was the first surface molecule that specifically identifies Th1 cells in both mice and human. Recently, identification of Galectin-9 as a ligand for TIM-3 has established the TIM-3-Galectin-9 pathway as an important regulator of Th1 immunity and tolerance induction. Engagement of Tim-3 by its ligand galectin-9 negatively regulates IFN-gamma secretion and influences the ability to induce T cell tolerance in both mice and man. It suggests a novel paradigm in which dysregulation of the TIM-3-galectin-9 pathway could underlie chronic autoimmune disease states, such as multiple sclerosis. Recent work has explored the role of TIM-3 in systemic lupus erythematosus (SLE), and their results indicate that TIM-3 may represent a novel target for the treatment of SLE. Numerous studies have demonstrated that Tim-3 influences autoimmune diseases, including diabetes and multiple sclerosis, and its role in other inflammatory diseases including allergies and cancer is beginning to become clear. In tumor rejection model, soluble form of Tim-3 (sTim-3) significantly impaired T cell antitumor immunity, evidenced by decreased antitumor CTL activity and reduced amount of tumor-infiltrating lymphocytes in tumor. sTim-3 as an immunoregulatory molecule that may be involved in the negative regulation of T cell-mediated immune response.

Reference for TIM-3

  • Geng H, et al. (2006) Soluble form of T cell Ig mucin 3 is an inhibitory molecule in T cell-mediated immune response. J Immunol. 176(3): 1411-20.
  • Anderson AC, et al. (2006) TIM-3 in autoimmunity. Curr Opin Immunol. 18(6): 665-9.
  • Anderson DE. (2007) TIM-3 as a therapeutic target in human inflammatory diseases. Expert Opin Ther Targets. 11(8): 1005-9.
  • Pan HF, et al. (2010) TIM-3 as a new therapeutic target in systemic lupus erythematosus. Mol Biol Rep. 37(1): 395-8.

TIM-3 Protein

TIM-3 protein 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 (PubMed:24825777). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556005). 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, and/or LGALS9-dependent recruitment of PTPRC to the immunological synapse (PubMed:24337741, PubMed:26492563). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (By similarity). Expressed on Treg cells can inhibit Th17 cell responses (PubMed:24838857). Receptor for LGALS9 (PubMed:16286920, PubMed:24337741). 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 (By similarity). However, the function as receptor for LGALS9 has been challenged (PubMed:23555261). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (By similarity). 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 (By similarity). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9 (PubMed:22323453). In contrast, shown to suppress NK cell-mediated cytotoxicity (PubMed:22383801). Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity). {ECO:0000250|UniProtKB:Q8VIM0, ECO:0000269|PubMed:11823861, ECO:0000269|PubMed:14556005, ECO:0000269|PubMed:16286920, ECO:0000269|PubMed:22323453, ECO:0000269|PubMed:23555261, ECO:0000269|PubMed:24838857, ECO:0000269|PubMed:26492563, ECO:0000305|PubMed:24825777}.

TIM-3 protein expression

Tissue specificity

Expressed in T-helper type 1 (Th1) lymphocytes. Expressed on regulatory T (Treg) cells after TCR stimulation. Expressed in dendritic cells and natural killer (NK) cells. Expressed in epithelial tissues. Expression is increased on CD4+ and CD8+ T-cells in chronic hepatitis C virus (HCV) infection. In progressive HIV-1 infection, expression is up-regulated on HIV-1-specific CD8 T-cells.

TIM-3 protein sequence

This sequence information is just for reference only.From Uniport

  • Length
    301.00
  • Mass (Da)
    33.00

TIM-3 Antibody

There are 11 TIM-3 antibodies which are validated in multiple tissues with various applications, including ELISA, ELISA(Det), ELISA(Cap), WB. There are 11 TIM-3 antibody for ELISA, 1 TIM-3 antibody for ELISA(Det), 1 TIM-3 antibody for ELISA(Cap), 2 TIM-3 antibody for WB. Among all these TIM-3 antibodies, there are 1 anti-TIM-3 mouse monoclonal antibodies , 3 anti-TIM-3 rabbit monoclonal antibodies , 7 anti-TIM-3 rabbit polyclonal antibodies . All the TIM-3 anbodies are produced in house and all are in stock. TIM-3 antibody customerized service is available.

TIM-3 Gene

HAVCR2 gene / cDNA is a protein-coding gene which located on 5q33.3. The HAVCR2 gene is conserved in chimpanzee, dog, cow, mouse, and rat.128 organisms have orthologs with human gene HAVCR2.