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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 | 5 |
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 | |
Alphafold | Q8TDQ0 (Hs), Q8VIM0 (Mm), P0C0K5 (Rn) |
CATH/Gene3D | 2.60.40.10 |
ChEMBL Target | CHEMBL4630879 (Hs) |
Ensembl Gene | ENSG00000135077 (Hs), ENSMUSG00000020399 (Mm), ENSRNOG00000031443 (Rn) |
Entrez Gene | 84868 (Hs), 171285 (Mm), 363578 (Rn) |
Human Protein Atlas | ENSG00000135077 (Hs) |
KEGG Gene | hsa:84868 (Hs), mmu:171285 (Mm), rno:363578 (Rn) |
OMIM | 606652 (Hs) |
Pharos | Q8TDQ0 (Hs) |
RefSeq Nucleotide | NM_032782 (Hs), NM_134250 (Mm), NM_001100762 (Rn) |
RefSeq Protein | NP_116171 (Hs), NP_599011 (Mm), NP_001094232 (Rn) |
UniProtKB | Q8TDQ0 (Hs), Q8VIM0 (Mm), P0C0K5 (Rn) |
Wikipedia | HAVCR2 (Hs) |
Natural/Endogenous Ligands |
galectin 9 {Sp: Human} |
Download all structure-activity data for this target as a CSV file
Antibodies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [5]. 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 [1,7], and may provide an additional strategy for cancers that develop adaptive resistance to current PD-1/PD-L1 axis immune checkpoint inhibitor therapies [3]. 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 ± spartalizumab (PDR001, anti-PD-1) 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). |
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||
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General Comments |
This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590. The C-type lectin galectin-9 is a TIM3 ligand [1]. |
1. Anderson AC. (2014) Tim-3: an emerging target in the cancer immunotherapy landscape. Cancer Immunol Res, 2 (5): 393-8. [PMID:24795351]
2. da Silva IP, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, Osman I, Bhardwaj N. (2014) Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res, 2 (5): 410-22. [PMID:24795354]
3. 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]
4. Mariotti FR, Quatrini L, Munari E, Vacca P, Moretta L. (2019) Innate Lymphoid Cells: Expression of PD-1 and Other Checkpoints in Normal and Pathological Conditions. Front Immunol, 10: 910. [PMID:31105707]
5. 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]
6. Pernaa N, Vakkuri A, Arvonen M, Kuismin O, Santaniemi W, Glumoff V, Lappi-Blanco E, Lantto U, Okkonen M, Kaikkonen K et al.. (2024) Germline HAVCR2/TIM-3 Checkpoint Inhibitor Receptor Deficiency in Recurrent Autoinflammatory Myocarditis. J Clin Immunol, 44 (3): 81. [PMID:38485795]
7. Romero D. (2016) Immunotherapy: PD-1 says goodbye, TIM-3 says hello. Nat Rev Clin Oncol, 13 (4): 202-3. [PMID:26977783]
8. Schwartz S, Patel N, Longmire T, Jayaraman P, Jiang X, Lu H, Baker L, Velez J, Ramesh R, Wavreille AS et al.. (2022) Characterization of sabatolimab, a novel immunotherapy with immuno-myeloid activity directed against TIM-3 receptor. Immunother Adv, 2 (1): ltac019. [PMID:36196369]
9. Xu L, Huang Y, Tan L, Yu W, Chen D, Lu C, He J, Wu G, Liu X, Zhang Y. (2015) Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. Int Immunopharmacol, 29 (2): 635-641. [PMID:26428847]
Other immune checkpoint proteins: TIM3 (CD366). Last modified on 18/03/2024. Accessed on 09/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2940.