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
GenitoUrinary Development Molecular Anatomy Project
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).
Immuno 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
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  macrophage activation involved in immune response (GO:0002281) IEA
negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002859) IEA
inflammatory response (GO:0006954) IEA
negative regulation of myeloid dendritic cell activation (GO:0030886) IMP
toll-like receptor 3 signaling pathway (GO:0034138) IEA
toll-like receptor 7 signaling pathway (GO:0034154) IEA
toll-like receptor 9 signaling pathway (GO:0034162) IEA
positive regulation of macrophage activation (GO:0043032) IEA
innate immune response (GO:0045087) IEA
negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
References: 
Immuno Process:  T cell (activation)
Immuno Process ID:  4
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  adaptive immune response (GO:0002250) IEA
regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
negative regulation of T-helper 1 type immune response (GO:0002826) IEA
positive regulation of T cell proliferation (GO:0042102) IEA
negative regulation of T cell proliferation (GO:0042130) IEA
negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
negative regulation of T-helper 1 type immune response (GO:0002826) IEA
negative regulation of natural killer cell mediated cytotoxicity directed against tumor cell target (GO:0002859) IEA
negative regulation of myeloid dendritic cell activation (GO:0030886) IMP
negative regulation of natural killer cell activation (GO:0032815) IEA
toll-like receptor 3 signaling pathway (GO:0034138) IEA
toll-like receptor 7 signaling pathway (GO:0034154) IEA
toll-like receptor 9 signaling pathway (GO:0034162) IEA
positive regulation of T cell proliferation (GO:0042102) IEA
negative regulation of T cell proliferation (GO:0042130) IEA
positive regulation of macrophage activation (GO:0043032) IEA
negative regulation of immunological synapse formation (GO:2000521) IEA
negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
References: 
Immuno Process:  Immune system development
Immuno Process ID:  8
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  natural killer cell tolerance induction (GO:0002519) IMP
regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  negative regulation of interferon-alpha production (GO:0032687) IDA
negative regulation of interferon-gamma production (GO:0032689) IDA
negative regulation of interleukin-2 production (GO:0032703) IDA
negative regulation of interleukin-3 production (GO:0032712) IDA
negative regulation of interleukin-6 production (GO:0032715) IEA
negative regulation of tumor necrosis factor production (GO:0032720) IMP
positive regulation of chemokine production (GO:0032722) IEA
positive regulation of interferon-gamma production (GO:0032729) IEA
positive regulation of interleukin-1 production (GO:0032732) IEA
positive regulation of interleukin-4 production (GO:0032753) IMP
negative regulation of granulocyte colony-stimulating factor production (GO:0071656) IDA
positive regulation of tumor necrosis factor secretion (GO:1904469) IMP
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of chemokine production (GO:0032722) IEA
positive regulation of T cell proliferation (GO:0042102) IEA
negative regulation of T cell proliferation (GO:0042130) IEA
negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  macrophage activation involved in immune response (GO:0002281) IEA
negative regulation of myeloid dendritic cell activation (GO:0030886) IMP
negative regulation of natural killer cell activation (GO:0032815) IEA
toll-like receptor 3 signaling pathway (GO:0034138) IEA
toll-like receptor 7 signaling pathway (GO:0034154) IEA
toll-like receptor 9 signaling pathway (GO:0034162) IEA
positive regulation of T cell proliferation (GO:0042102) IEA
negative regulation of T cell proliferation (GO:0042130) IEA
positive regulation of macrophage activation (GO:0043032) IEA
negative regulation of immunological synapse formation (GO:2000521) IEA
negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell (GO:2001189) IDA
References: 
Immuno Process:  B cell (activation)
Immuno Process ID:  5
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  adaptive immune response (GO:0002250) IEA
regulation of tolerance induction dependent upon immune response (GO:0002652) IEA
negative regulation of T-helper 1 type immune response (GO:0002826) IEA
References: 
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 Res2 (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 Commun7: 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. Nature415 (6871): 536-41. [PMID:11823861]

4. Romero D. (2016) Immunotherapy: PD-1 says goodbye, TIM-3 says hello. Nat Rev Clin Oncol13 (4): 202-3. [PMID:26977783]

How to cite this page

CD molecules: TIM3 (CD366). Last modified on 07/06/2017. Accessed on 24/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2940.