TIM-3 Extracellular Domain (human, recombinant)

TIM-3 is a member of the T-cell immunoglobulin and mucin-domain containing (TIM) protein family of immunoregulatory proteins and is encoded by the HAVCR2 gene in humans. It is a transmembrane protein composed of an N-terminal immunoglobulin variable (IgV) domain, as well as mucin stalk, transmembrane, and C-terminal cytoplasmic tail domains. The IgV domain contains cysteine residues that form non-canonical intramolecular disulfide bonds resulting in a cleft and channel not found in non-TIM immunoglobulin domains that is important for non-canonical ligand binding. TIM-3 is expressed primarily on T cells but is also expressed on other immune cells such as natural killer and dendritic cells. The TIM-3 ligand galectin 9 (Cay-32012), located on immune or tumor cells, binds to glycosylated sites of the IgV and mucin stalk domains and induces TIM-3 oligomerization to activate downstream signaling that impairs immune synapse formation and leads to T cell anergy or apoptosis. The TIM-3 IgV cleft domain binds non-canonical ligands, such as phosphatidylserine on apoptotic cells or CEACAM1 on antigen-presenting or tumor cells. TIM-3 is an inhibitory co-receptor that helps maintain immune tolerance but, when expressed on certain cells during chronic infection or cancer, can lead to immune exacerbation. Inhibition of the TIM-3 pathway by Tim-3 fusion or extracellular domain-only proteins prevents the induction of immune tolerance in a mouse islet allograft model or increases weight loss and tissue injury in a mouse model of TNBS-induced colitis, respectively. Expression of TIM-3 is decreased in patients with autoimmune diseases, including ulcerative colitis. TIM-3 is expressed on tumor-infiltrating T cells and expressed on a higher proportion of regulatory T cells from cancer patients. Its overexpression on T cells increases tumor progression in an EL4 mouse model of lymphoma, while TIM-3 inhibition decreases tumor growth in a mouse model of head and neck cancer. SNPs in HAVCR2 are associated with allergic diseases, immunity, and cancer. Cayman's TIM-3 Extracellular Domain (human, recombinant) protein is a disulfide-linked homodimer. The reduced monomer, comprised of TIM-3 (amino acids 22-200) fused to mouse IgG1 Fc at its C-terminus, consists of 412 amino acids, has a calculated molecular weight of 46.2 kDa, and a predicted N-terminus of Ser22 after signal peptide cleavage. As a result of glycosylation, the monomer migrates at approximately 50-55 kDa by SDS-PAGE under reducing conditions.Synonyms: CD366, Hepatitis A Virus Cellular Receptor 2 Precursor, KIM-3, T Cell Immunoglobulin and Mucin Domain-containing Protein 3, T Cell Immunoglobulin Mucin Receptor 3, T Cell Membrane Protein 3, TIMD-3. Purity: >90% estimated by SDS-PAGE. Source: Recombinant C-terminal mouse IgG2a Fc-tagged TIM-3 expressed in HEK293 cells. Amino Acids: 22-200. MW: 46.2 kDa. Formulation: (Request formulation change), Lyophilized from sterile 20 mM Tris, 150 mM sodium chloride, pH 8.5.