PVR cell adhesion molecule | Immunoglobulin like domain containing proteins | IUPHAR Guide to IMMUNOPHARMACOLOGY

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PVR cell adhesion molecule

  Target has curated data in GtoImmuPdb

Target id: 3095

Nomenclature: PVR cell adhesion molecule

Abbreviated Name: CD155

Family: Immunoglobulin like domain containing proteins

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 417 19q13.31 PVR PVR cell adhesion molecule
Gene and Protein Information Comments
Multiple transcript variants encoding different isoforms have been found for this gene.
Previous and Unofficial Names
CD155 | NECL5 | nectin-like 5 | poliovirus receptor | Tage4
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Immunopharmacology Comments
The PVR protein (a.k.a. CD155) is a single-pass immunoglobulin-like adhesion molecule. It plays a role in modulating natural killer and T cell-mediated immunity. PVR expression is upregulated in response to exposure to different stimuli, such as Toll-like receptor activation or T cell receptor stimulation [5,9]. It is a ligand for three receptors that are commonly found on NK cells: CD96 [2], TIGIT (which are both co-inhibitory receptors) and DNAM-1 (CD226; a co-stimulatory receptor) [10]. It exhibits the highest binding affinity for CD96 [3]. Interactions with these receptors culminate in the formation of a mature immunological synapse which promotes NK cell activation and cytoxicity.

PVR is frequently overexpressed in human malignant tumours as a mechanism of immunoevasion and contributes to tumour progression and metastasis [7]. Subsequently, PVR is being explored as a novel immuno-oncology therapeutic target [1,4,6,8,11-12].
Immuno Process Associations
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001618 virus receptor activity IEA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0060370 susceptibility to T cell mediated cytotoxicity IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 5 GO processes
GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target IMP
GO:0042271 susceptibility to natural killer cell mediated cytotoxicity IMP
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity IMP
GO:0050776 regulation of immune response TAS
GO:0060370 susceptibility to T cell mediated cytotoxicity IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0002860 positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target IMP
GO:0042271 susceptibility to natural killer cell mediated cytotoxicity IMP
GO:0045954 positive regulation of natural killer cell mediated cytotoxicity IMP
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0060370 susceptibility to T cell mediated cytotoxicity IDA
General Comments
PVR was originally identified as the host cell receptor used by the poliovirus to facilitate viral entry. Poliovirus binds to one of the protein's extracellular domains. The PVR protein normally functions as an immunoglobulin-like adhesion molecule that is involved in cell motility, and natural killer and T cell-mediated immunity. It can be produced as a membrane anchored protein or in a soluble form that lacks the transmembrane domain, and is generally expressed at low levels in healthy tissues.
The PVR 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.

References

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1. Basile MS, Mazzon E, Russo A, Mammana S, Longo A, Bonfiglio V, Fallico M, Caltabiano R, Fagone P, Nicoletti F et al.. (2019) Differential modulation and prognostic values of immune-escape genes in uveal melanoma. PLoS ONE, 14 (1): e0210276. [PMID:30653520]

2. Deuss FA, Watson GM, Fu Z, Rossjohn J, Berry R. (2019) Structural Basis for CD96 Immune Receptor Recognition of Nectin-like Protein-5, CD155. Structure, 27 (2): 219-228.e3. DOI: 10.1016/j.str.2018.10.023 [PMID:30528596]

3. Dougall WC, Kurtulus S, Smyth MJ, Anderson AC. (2017) TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol. Rev., 276 (1): 112-120. [PMID:28258695]

4. Gao J, Zheng Q, Xin N, Wang W, Zhao C. (2017) CD155, an onco-immunologic molecule in human tumors. Cancer Sci., 108 (10): 1934-1938. [PMID:28730595]

5. Kamran N, Takai Y, Miyoshi J, Biswas SK, Wong JS, Gasser S. (2013) Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells. PLoS ONE, 8 (1): e54406. [PMID:23349877]

6. Kučan Brlić P, Lenac Roviš T, Cinamon G, Tsukerman P, Mandelboim O, Jonjić S. (2019) Targeting PVR (CD155) and its receptors in anti-tumor therapy. Cell. Mol. Immunol., 16 (1): 40-52. [PMID:30275538]

7. Li XY, Das I, Lepletier A, Addala V, Bald T, Stannard K, Barkauskas D, Liu J, Aguilera AR, Takeda K et al.. (2018) CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. J. Clin. Invest., 128 (6): 2613-2625. [PMID:29757192]

8. Sanchez-Correa B, Valhondo I, Hassouneh F, Lopez-Sejas N, Pera A, Bergua JM, Arcos MJ, Bañas H, Casas-Avilés I, Durán E et al.. (2019) DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers (Basel), 11 (6). DOI: 10.3390/cancers11060877 [PMID:31234588]

9. Yamashita-Kanemaru Y, Takahashi Y, Wang Y, Tahara-Hanaoka S, Honda S, Bernhardt G, Shibuya A, Shibuya K. (2015) CD155 (PVR/Necl5) mediates a costimulatory signal in CD4+ T cells and regulates allergic inflammation. J. Immunol., 194 (12): 5644-53. [PMID:25972481]

10. Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, Tom I, Ivelja S, Refino CJ, Clark H et al.. (2009) The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol., 10 (1): 48-57. [PMID:19011627]

11. Zhand S, Hosseini SM, Tabarraei A, Saeidi M, Jazi MS, Kalani MR, Moradi A. (2018) Oral poliovirus vaccine-induced programmed cell death involves both intrinsic and extrinsic pathways in human colorectal cancer cells. Oncolytic Virother, 7: 95-105. [PMID:30464928]

12. Zhao H, Ma J, Lei T, Ma W, Zhang M. (2019) The bispecific anti-CD3 × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer. Invest New Drugs, 37 (5): 810-817. [PMID:30374653]

How to cite this page

Immunoglobulin like domain containing proteins: PVR cell adhesion molecule. Last modified on 07/08/2019. Accessed on 04/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3095.