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Target id: 2956
Nomenclature: V-set immunoregulatory receptor
Abbreviated Name: VISTA
Family: Other immune checkpoint proteins
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 1 | 311 | 10q22.1 | VSIR | V-set immunoregulatory receptor | |
Mouse | 1 | 308 | 10 B4 | Vsir | V-set immunoregulatory receptor | |
Rat | 1 | 309 | 20q11 | Vsir | V-set immunoregulatory receptor |
Previous and Unofficial Names |
B7-H5 | B7H5 | PD-1H | programmed death-1 homologue-1 | V-domain Ig suppressor of T cell activation | VISTA |
Database Links | |
Alphafold | Q9H7M9 (Hs), Q9D659 (Mm) |
ChEMBL Target | CHEMBL4523457 (Hs) |
Ensembl Gene | ENSG00000107738 (Hs), ENSMUSG00000020101 (Mm), ENSRNOG00000000569 (Rn) |
Entrez Gene | 64115 (Hs), 74048 (Mm), 690899 (Rn) |
Human Protein Atlas | ENSG00000107738 (Hs) |
KEGG Gene | hsa:64115 (Hs), mmu:74048 (Mm), rno:690899 (Rn) |
OMIM | 615608 (Hs) |
Pharos | Q9H7M9 (Hs) |
RefSeq Nucleotide | NM_022153 (Hs), NM_028732 (Mm), NM_001044300 (Rn) |
RefSeq Protein | NP_071436 (Hs), NP_083008 (Mm), NP_001037765 (Rn) |
UniProtKB | Q9H7M9 (Hs), Q9D659 (Mm) |
Wikipedia | VSIR (Hs) |
Antibody Comments | ||
An experimental anti-Vsir monoclonal antibody has shown preventative action in graft-versus-host disease in semi- and fully allogeneic murine models [4]. |
Immunopharmacology Comments |
V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA in the literature corpus. This is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule. In common with other T cell co-inhibitory receptors (e.g. CTLA-4, PD-1, TIM3, and LAG3) it is involved in maintaining peripheral tolerance [6] and controlling immune responses against self [8], infectious agents [1], and cancer [2,5]. Experimental pharmacological interventions that enhance VISTA regulatory activity are being explored as a novel mechanism for the treatment of autoimmune disease, as cancer immunotherapy [7], and for graft-versus-host disease [4]. |
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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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. |
1. Bharaj P, Chahar HS, Alozie OK, Rodarte L, Bansal A, Goepfert PA, Dwivedi A, Manjunath N, Shankar P. (2014) Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals. PLoS ONE, 9 (10): e109103. [PMID:25279955]
2. Böger C, Behrens HM, Krüger S, Röcken C. (2017) The novel negative checkpoint regulator VISTA is expressed in gastric carcinoma and associated with PD-L1/PD-1: A future perspective for a combined gastric cancer therapy?. Oncoimmunology, 6 (4): e1293215. [PMID:28507801]
3. Flies DB, Han X, Higuchi T, Zheng L, Sun J, Ye JJ, Chen L. (2014) Coinhibitory receptor PD-1H preferentially suppresses CD4⁺ T cell-mediated immunity. J Clin Invest, 124 (5): 1966-75. [PMID:24743150]
4. Flies DB, Wang S, Xu H, Chen L. (2011) Cutting edge: A monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models. J Immunol, 187 (4): 1537-41. [PMID:21768399]
5. Kakavand H, Jackett LA, Menzies AM, Gide TN, Carlino MS, Saw RPM, Thompson JF, Wilmott JS. (2017) Negative immune checkpoint regulation by VISTA: a mechanism of acquired resistance to anti-PD-1 therapy in metastatic melanoma patients. Mod Pathol, 30 (12): 1666-1676. [PMID:28776578]
6. Li N, Xu W, Yuan Y, Ayithan N, Imai Y, Wu X, Miller H, Olson M, Feng Y, Huang YH et al.. (2017) Immune-checkpoint protein VISTA critically regulates the IL-23/IL-17 inflammatory axis. Sci Rep, 7 (1): 1485. [PMID:28469254]
7. Lines JL, Sempere LF, Broughton T, Wang L, Noelle R. (2014) VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy. Cancer Immunol Res, 2 (6): 510-7. [PMID:24894088]
8. Sergent PA, Plummer SF, Pettus J, Mabaera R, DeLong JK, Pechenick DA, Burns CM, Noelle RJ, Ceeraz S. (2018) Blocking the VISTA pathway enhances disease progression in (NZB × NZW) F1 female mice. Lupus, 27 (2): 210-216. [PMID:28659048]
9. Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, Lu LF, Gondek D, Wang Y, Fava RA et al.. (2011) VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med, 208 (3): 577-92. [PMID:21383057]
Other immune checkpoint proteins: V-set immunoregulatory receptor. Last modified on 07/08/2019. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2956.