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Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 513 | 6p22.2 | BTN3A1 | butyrophilin subfamily 3 member A1 | |
Gene and Protein Information Comments | ||||||
Several transcript variants and protein isoforms are predicted from the human gene. We provide details for the longest form (variant 1, isoform a) here. |
Previous and Unofficial Names |
BT3.1 | BTN3.1 | CD277 |
Database Links | |
Alphafold | O00481 (Hs) |
CATH/Gene3D | 2.60.40.10 |
ChEMBL Target | CHEMBL4105758 (Hs) |
Ensembl Gene | ENSG00000026950 (Hs) |
Entrez Gene | 11119 (Hs) |
Human Protein Atlas | ENSG00000026950 (Hs) |
KEGG Gene | hsa:11119 (Hs) |
OMIM | 613593 (Hs) |
Pharos | O00481 (Hs) |
RefSeq Nucleotide | NM_007048 (Hs) |
RefSeq Protein | NP_008979 (Hs) |
UniProtKB | O00481 (Hs) |
Wikipedia | BTN3A1 (Hs) |
Other Binding Ligands | |||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | Click column headers to sort | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
Vγ2Vδ2 (a.k.a. Vγ9Vδ2) T cells bridge the gap between innate and adaptive immunity and play roles in microbial immunity and tumour immunity [2]. Evidence supports a role for BTN3A1 in mediating activation of Vγ2Vδ2 T cells by detecting both self and non-self isoprenoid metabolites [4]. Vγ2Vδ2 T cells activated by this mechanism proliferate and can traffic to peripheral sites where they secrete Th1 cytokines, such as IFN-β and TNF-α, inflammatory chemokines, and growth factors while killing infected cells, and can use their TCR and NK receptors to recognize and kill a variety of tumour cells, in a tissue origin, MHC expression, or MHC haplotype independent manner [2]. Aminobisphosphonates (e.g. zoledronic acid, or zoledronate) and alkylamines expand Vγ2Vδ2 T cells via inhibition of farnesyl diphosphate synthase (one of the steps of the lanosterol biosynthesis pathway), which results in the accumulation of the upstream isopentenyl pyrophosphate (IPP) metabolite that stimulates the Vγ2Vδ2 T cells. Druggability: A synthetic, cell-permeable prodrug analogue of the Vγ2Vδ2 T cell activator (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP), POM2-C-HMBP, acts intracellularly to mediate BTN3A1-dependent lysis of malignant cells by Vγ2Vδ2 effector T cells. Zoledronate has been shown to enhance BTN3A1 expression by epithelial cells and tumour-associated fibroblasts in colorectal cancer (CRC), and to activate Vγ2Vδ2-mediated killing of ex-vivo CRC cells [5]. See also [3] which describes BTN3A1-binding agonistic nucleotidic phosphoantigens. 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. |
Immuno Process Associations | ||
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Physiological Functions | ||||||||
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1. Kilcollins AM, Li J, Hsiao CH, Wiemer AJ. (2016) HMBPP Analog Prodrugs Bypass Energy-Dependent Uptake To Promote Efficient BTN3A1-Mediated Malignant Cell Lysis by Vγ9Vδ2 T Lymphocyte Effectors. J Immunol, 197 (2): 419-28. [PMID:27271567]
2. Morita CT, Jin C, Sarikonda G, Wang H. (2007) Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev, 215: 59-76. [PMID:17291279]
3. Moulin M, Alguacil J, Gu S, Mehtougui A, Adams EJ, Peyrottes S, Champagne E. (2017) Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens. Cell Mol Life Sci, 74 (23): 4353-4367. [PMID:28669030]
4. Wang H, Morita CT. (2015) Sensor Function for Butyrophilin 3A1 in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells. J Immunol, 195 (10): 4583-94. [PMID:26475929]
5. Zocchi MR, Costa D, Venè R, Tosetti F, Ferrari N, Minghelli S, Benelli R, Scabini S, Romairone E, Catellani S et al.. (2017) Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity. Oncoimmunology, 6 (3): e1278099. [PMID:28405500]
Butyrophilin and butyrophilin-like proteins: butyrophilin subfamily 3 member A1. Last modified on 07/08/2019. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2948.