HAVCR2 (TIM-3)

Hepatitis A virus cellular receptor 2 (HAVCR2), formerly known as T cell immunoglobulin and mucin domain-3 (HAVCR2), 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 HAVCR2 has established the HAVCR2-Galectin-9 pathway as an important regulator of Th1 immunity and tolerance induction. Engagement of HAVCR2 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 HAVCR2-galectin-9 pathway could underlie chronic autoimmune disease states, such as multiple sclerosis. Recent work has explored the role of HAVCR2 in systemic lupus erythematosus (SLE), and their results indicate that HAVCR2 may represent a novel target for the treatment of SLE. Numerous studies have demonstrated that HAVCR2 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 HAVCR2 (sHAVCR2) significantly impaired T cell antitumor immunity, evidenced by decreased antitumor CTL activity and reduced amount of tumor-infiltrating lymphocytes in tumor. sHAVCR2 as an immunoregulatory molecule that may be involved in the negative regulation of T cell-mediated immune response.

HAVCR2 (TIM-3) Related Areas

Immunology>>Adaptive Immunity>>T Cell>>Helper T Cell>>TIM-3/HAVCR2

HAVCR2 (TIM-3) Alternative Names

Tim-3, HAVCR2, TIM3, FLJ14428, KIM-3, TIMD3 [Homo sapiens]

TIM-3, HAVCR2, Tim3, RP23-248K2.7, MGC124149, MGC124150, Timd3 [Mus musculus]

Summaries for HAVCR2 (TIM-3)

Entrez Gene summary for HAVCR2 (TIM-3):

The protein encoded by HAVCR2 gene belongs to the immunoglobulin superfamily, and TIM family of proteins. CD4-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas, Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. This protein is a Th1-specific cell surface protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. [provided by RefSeq, Sep 2011]

OMIM - description for HAVCR2 (TIM-3):

CD4 (186940)-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells and their associated cytokines are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. The 2 types of cells also cross-regulate the functions of the other. TIM3 is a Th1-specific cell surface protein that regulates macrophage activation and enhances the severity of experimental autoimmune encephalomyelitis in mice.

Wikipedia summary for HAVCR2 (TIM-3):

Hepatitis A virus cellular receptor 2 is a protein that in humans is encoded by the HAVCR2 gene.
CD4 (MIM 186940)-positive T helper lymphocytes can be divided into types 1 (Th1) and 2 (Th2) on the basis of their cytokine secretion patterns. Th1 cells and their associated cytokines are involved in cell-mediated immunity to intracellular pathogens and delayed-type hypersensitivity reactions, whereas Th2 cells are involved in the control of extracellular helminthic infections and the promotion of atopic and allergic diseases. The 2 types of cells also cross-regulate the functions of the other. TIM3 is a Th1-specific cell surface protein that regulates macrophage activation and enhances the severity of experimental autoimmune encephalomyelitis in mice.[supplied by OMIM]

Human HAVCR2 (TIM-3) Protein General Information

 

• Protein names: Hepatitis A virus cellular receptor 2
  Short name=HAVCR2
• Sequence length: 301 AA.
• Domain: Immunoglobulin domain
  Signal
  Transmembrane
  Transmembrane helix
• Sequence similarities: Belongs to the immunoglobulin superfamily. TIM family.
  Contains 1 Ig-like V-type (immunoglobulin-like) domain.
• Post-translational modification: O-glycosylated with core 1 or possibly core 8 glycans.
• Subcellular location: Membrane; Single-pass type I membrane protein .
• Tissue specificity: T-helper type 1 lymphocyte (Th1)-specific.

General information above from UniProt

Function for HAVCR2 (TIM-3) Protein

UniProtKB:

HAVCR2 regulates macrophage activation. HAVCR2 inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance. HAVCR2 may be also involved in T-cell homing. HAVCR2 is receptor for LGALS9.

Genatlas:

• HAVCR2 roles in the induction of allergies and autoimmune diseases by regulating macrophage activation and/or functions
• HAVCR2 negatively regulates IFN-gamma secretion and influences the ability to induce T cell tolerance