TIM3 (CD366)

Target id: 2940

Nomenclature: TIM3 (CD366)

Family: Other immune checkpoint proteins, CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     TIM3 (CD366) has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 301 5q33.3 HAVCR2 hepatitis A virus cellular receptor 2 3
Mouse 1 281 11 B1.1 Havcr2 hepatitis A virus cellular receptor 2
Rat 1 282 10q21 Havcr2 hepatitis A virus cellular receptor 2
Previous and Unofficial Names
T-cell immunoglobulin mucin family member 3 | TIM-3 | TIMD-3
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
galectin 9 {Sp: Human}
Immunopharmacology Comments
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [3]. It is a co-inhibitory receptor immune checkpoint protein that regulates macrophage activation, and inhibits Th1-mediated auto- and alloimmune responses, and promotes immunological tolerance. TIM3 is an immuno-oncology drug target [1,4], and may provide an additional strategy for cancers that develop adaptive resistance to current PD-1/PD-L1 axis immune checkpoint inhibitor therapies [2]. LY3321367 and MBG453 are anti-TIM3 monoclonals in early stage clinical trial: LY3321367 in Phase 1 trial NCT03099109 with LY3300054 (a novel anti-PD-L1 checkpoint inhibitor), and MBG453 ± PDR001 (a novel anti-PD-1 mAb) vs. both advanced solid tumours (NCT02608268, Phase 1/2) and hematological malignancies (NCT03066648, Phase 1). Symphogen have the anti-TIM3 mAb Sym023 in their immuno-oncology pipeline (see Phase 1 trial NCT03489343). Tesaro's anti-TIM3 mAb TSR-022 is also in Phase 1 development (NCT02817633).
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   T-helper 1 cell (CL:0000545)
Comment:  TIM3 is a selective marker of differentiated Th1 cells. Upregulation of TIM3 expression is reported as a biomarker associated with adaptive resistance to PD-1 blockade.
References:  2
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 10 GO processes
GO:0030886 negative regulation of myeloid dendritic cell activation IMP
GO:2001189 negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell IDA
click arrow to show/hide IEA associations
GO:0002281 macrophage activation involved in immune response IEA
GO:0002859 negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target IEA
GO:0006954 inflammatory response IEA
GO:0034138 toll-like receptor 3 signaling pathway IEA
GO:0034154 toll-like receptor 7 signaling pathway IEA
GO:0034162 toll-like receptor 9 signaling pathway IEA
GO:0043032 positive regulation of macrophage activation IEA
GO:0045087 innate immune response IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 6 GO processes
GO:2001189 negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell IDA
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
GO:0002652 regulation of tolerance induction dependent upon immune response IEA
GO:0002826 negative regulation of T-helper 1 type immune response IEA
GO:0042102 positive regulation of T cell proliferation IEA
GO:0042130 negative regulation of T cell proliferation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 13 GO processes
GO:0030886 negative regulation of myeloid dendritic cell activation IMP
GO:2001189 negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell IDA
click arrow to show/hide IEA associations
GO:0002652 regulation of tolerance induction dependent upon immune response IEA
GO:0002826 negative regulation of T-helper 1 type immune response IEA
GO:0002859 negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target IEA
GO:0032815 negative regulation of natural killer cell activation IEA
GO:0034138 toll-like receptor 3 signaling pathway IEA
GO:0034154 toll-like receptor 7 signaling pathway IEA
GO:0034162 toll-like receptor 9 signaling pathway IEA
GO:0042102 positive regulation of T cell proliferation IEA
GO:0042130 negative regulation of T cell proliferation IEA
GO:0043032 positive regulation of macrophage activation IEA
GO:2000521 negative regulation of immunological synapse formation IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 2 GO processes
GO:0002519 natural killer cell tolerance induction IMP
click arrow to show/hide IEA associations
GO:0002652 regulation of tolerance induction dependent upon immune response IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 12 GO processes
GO:0032687 negative regulation of interferon-alpha production IDA
GO:0032689 negative regulation of interferon-gamma production IDA
GO:0032703 negative regulation of interleukin-2 production IDA
GO:0032712 negative regulation of interleukin-3 production IDA
GO:0032720 negative regulation of tumor necrosis factor production IMP
GO:0032753 positive regulation of interleukin-4 production IMP
GO:0071656 negative regulation of granulocyte colony-stimulating factor production IDA
GO:1904469 positive regulation of tumor necrosis factor secretion IMP
click arrow to show/hide IEA associations
GO:0032715 negative regulation of interleukin-6 production IEA
GO:0032722 positive regulation of chemokine production IEA
GO:0032729 positive regulation of interferon-gamma production IEA
GO:0032732 positive regulation of interleukin-1 production IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 4 GO processes
GO:2001189 negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell IDA
click arrow to show/hide IEA associations
GO:0032722 positive regulation of chemokine production IEA
GO:0042102 positive regulation of T cell proliferation IEA
GO:0042130 negative regulation of T cell proliferation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 11 GO processes
GO:0030886 negative regulation of myeloid dendritic cell activation IMP
GO:2001189 negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell IDA
click arrow to show/hide IEA associations
GO:0002281 macrophage activation involved in immune response IEA
GO:0032815 negative regulation of natural killer cell activation IEA
GO:0034138 toll-like receptor 3 signaling pathway IEA
GO:0034154 toll-like receptor 7 signaling pathway IEA
GO:0034162 toll-like receptor 9 signaling pathway IEA
GO:0042102 positive regulation of T cell proliferation IEA
GO:0042130 negative regulation of T cell proliferation IEA
GO:0043032 positive regulation of macrophage activation IEA
GO:2000521 negative regulation of immunological synapse formation IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
GO:0002652 regulation of tolerance induction dependent upon immune response IEA
GO:0002826 negative regulation of T-helper 1 type immune response IEA
General Comments
The C-type lectin galectin-9 is a TIM3 ligand [1].

References

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1. Anderson AC. (2014) Tim-3: an emerging target in the cancer immunotherapy landscape. Cancer Immunol Res, 2 (5): 393-8. [PMID:24795351]

2. Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H et al.. (2016) Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun, 7: 10501. [PMID:26883990]

3. Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, Manning S, Greenfield EA, Coyle AJ, Sobel RA et al.. (2002) Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature, 415 (6871): 536-41. [PMID:11823861]

4. Romero D. (2016) Immunotherapy: PD-1 says goodbye, TIM-3 says hello. Nat Rev Clin Oncol, 13 (4): 202-3. [PMID:26977783]

How to cite this page

Other immune checkpoint proteins: TIM3 (CD366). Last modified on 08/06/2018. Accessed on 19/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2940.