1. Gene Aliases

PVR Cell Adhesion Molecule, Poliovirus Receptor, CD155, NECL5, HVED, PVS, Nectin-Like Protein 5, Necl-5, NECL-5, TAGE4, Nectin-Like 5, CD155 Antigen, Tage4

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=PVR&keywords=Pvr]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

The interactions list has been truncated to include only interactions with the strongest support from the literature.

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

Adherens junctions interactions: The adherens junctions (AJ) are multiprotein complexes that promote homotypic cell adhesion in nearly all types of tissue by linking membrane and cytoskeletal components at discrete contact regions (reviewed in Hartsock & Nelson 2008; Gumbiner 2005; Ebnet, 2008). The molecular constituents of adherens junctions form adhesive units which are organized into higher order junctional adhesions that create a zipper-like seal between adjacent cells. Junctional adhesions function in epithelial cell polarization and in the coupling of cytoskeletons in adjacent cells that allow coordinated movements. During embryonic development, AJs function in specifying adhesion between cells and contribute in the sorting of different cell types. AJs also regulate cell polarity and shape, promote cell-cell communication and help mediate contact inhibition of cell growth. This module covers transdimerization events involving AJ transmembrane proteins (cadherins and nectins) (Gumbiner 2005; Ebnet 2008; Hartsock & Nelson 2008).[https://reactome.org/PathwayBrowser/#/R-HSA-418990].

Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell: A number of receptors and cell adhesion molecules play a key role in modifying the response of cells of lymphoid origin (such as B-, T- and NK cells) to self and tumor antigens, as well as to pathogenic organisms.

Molecules such as KIRs and LILRs form part of a crucial surveillance system that looks out for any derangement, usually caused by cancer or viral infection, in MHC Class I presentation. Somatic cells are also able to report internal functional impairment by displaying surface stress markers such as MICA. The presence of these molecules on somatic cells is picked up by C-lectin NK immune receptors.

Lymphoid cells are able to regulate their location and movement in accordance to their state of activation, and home in on tissues expressing the appropriate complementary ligands. For example, lymphoid cells may fine tune the presence and concentration of adhesion molecules belonging to the IgSF, Selectin and Integrin class that interact with a number of vascular markers of inflammation.

Furthermore, there are a number of avenues through which lymphoid cells may interact with antigen. This may be presented directly to a specific T-cell receptor in the context of an MHC molecule. Antigen-antibody complexes may anchor to the cell via a small number of lymphoid-specific Fc receptors that may, in turn, influence cell function further. Activated complement factor C3d binds to both antigen and to cell surface receptor CD21. In such cases, the far-reaching influence of CD19 on B-lymphocyte function is tempered by its interaction with CD21 [https://reactome.org/PathwayBrowser/#/R-HSA-198933].

Nectin/Necl trans heterodimerization: Nectins and Nectin-like molecules (Necls) also undergo trans-heterophilic interactions to interact with other nectin or Necl family members. Besides these trans interactions among nectins and nectin-like family members, trans-homophilic interactions have also been described between nectins or Necls with other immunoglobulin-superfamily members like CD96, CD226 and CRTAM (Sakisaka et al., 2007; Takai et al., 2008). It should be noted that some of these interactions might not exist in epithelial cell-cell contacts but may occur in other cell-cell adhesion systems.[https://reactome.org/PathwayBrowser/#/R-HSA-420597].

GO terms:

acrosome assembly [The formation of the acrosome from the spermatid Golgi. GO:0001675]

cell migration [The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. GO:0016477]

cell-cell adhesion [The attachment of one cell to another cell via adhesion molecules. GO:0098609]

coreceptor-mediated virion attachment to host cell [The process by which a virion attaches to a host cell by binding to a co-receptor on the host cell surface. GO:0046814]

cytoskeleton organization [A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures. GO:0007010]

establishment of mitochondrion localization [The directed movement of the mitochondrion to a specific location. GO:0051654]

fusion of virus membrane with host plasma membrane [Fusion of a viral membrane with the host cell membrane during viral entry. Results in release of the virion contents into the cytoplasm. GO:0019064]

heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules [The attachment of an adhesion molecule in one cell to a nonidentical adhesion molecule in an adjacent cell. GO:0007157]

homophilic cell adhesion via plasma membrane adhesion molecules [The attachment of a plasma membrane adhesion molecule in one cell to an identical molecule in an adjacent cell. GO:0007156]

positive regulation of T cell receptor signaling pathway [Any process that activates or increases the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell. GO:0050862]

positive regulation of immunoglobulin mediated immune response [Any process that activates or increases the frequency, rate, or extent of an immunoglobulin mediated immune response. GO:0002891]

positive regulation of mast cell activation [Any process that activates or increases the frequency, rate, or extent of mast cell activation. GO:0033005]

positive regulation of natural killer cell mediated cytotoxicity [Any process that activates or increases the frequency, rate or extent of natural killer cell mediated cytotoxicity. GO:0045954]

positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target [Any process that activates or increases the frequency, rate, or extent of natural killer cell mediated cytotoxicity directed against tumor cell target. GO:0002860]

regulation of viral entry into host cell [Any process that modulates the frequency, rate or extent of the viral entry into the host cell. GO:0046596]

susceptibility to T cell mediated cytotoxicity [The process of causing a cell to become susceptible to T cell mediated cytotoxicity. GO:0060370]

susceptibility to natural killer cell mediated cytotoxicity [The process of causing a cell to become susceptible to natural killer cell mediated cytotoxicity.|Note that this term is intended for cell-surface molecules on a target cell which interact with activating receptors on a natural killer cell to promote natural killer cell mediated cytotoxicity. GO:0042271]

symbiont entry into host cell [The process that occurs after viral attachment by which a virus, or viral nucleic acid, breaches the plasma membrane or cell envelope and enters the host cell. The process ends when the viral nucleic acid is released into the host cell cytoplasm.|Viral attachment to the host cell is not part of viral entry in GO because virus attachment does not always lead to viral entry: attachment can also result in the virion being carried by the host cell to another location. GO:0046718]

MSigDB Signatures:

REACTOME_ADAPTIVE_IMMUNE_SYSTEM: Adaptive Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ADAPTIVE_IMMUNE_SYSTEM.html]

REACTOME_CELL_CELL_COMMUNICATION: Cell-Cell communication [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_CELL_COMMUNICATION.html]

KEGG_CELL_ADHESION_MOLECULES_CAMS: Cell adhesion molecules (CAMs) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_CELL_ADHESION_MOLECULES_CAMS.html]

AMIT_SERUM_RESPONSE_40_MCF10A: Genes whose expression peaked at 40 min after stimulation of MCF10A cells with serum. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/AMIT_SERUM_RESPONSE_40_MCF10A.html]

REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS: Adherens junctions interactions [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS.html]

AMIT_SERUM_RESPONSE_480_MCF10A: Genes whose expression peaked at 480 min after stimulation of MCF10A cells with serum. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/AMIT_SERUM_RESPONSE_480_MCF10A.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

GeneCards Summary: PVR (PVR Cell Adhesion Molecule) is a Protein Coding gene. Diseases associated with PVR include Poliomyelitis and Paralytic Poliomyelitis. Among its related pathways are Regulation of CDH11 Expression and Function and Innate Immune System. Gene Ontology (GO) annotations related to this gene include signaling receptor activity and virus receptor activity. An important paralog of this gene is NECTIN2.

UniProtKB/Swiss-Prot Summary: Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration. Acts as a receptor for poliovirus. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport. Acts as a receptor for Pseudorabies virus. Is prevented to reach cell surface upon infection by Human cytomegalovirus /HHV-5, presumably to escape immune recognition of infected cell by NK cells.

8. Cellular Location of Gene Product

Membrane and cytoplasmic expression in several tissues. Positivity in plasma. Localized to the nucleoplasm, plasma membrane & vesicles. Predicted location: Secreted, Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000073008/subcellular]

9. Mechanistic Information

Summary

PVR (CD155) encodes for a transmembrane glycoprotein involved in cell adhesion, immune response modulation, and serves as a receptor for various pathogens [CS: 9]. By mediating both cell attachment to the extracellular matrix and interactions with cytoskeletal components, PVR contributes to processes such as cell motility [CS: 9]. At the immune level, PVR binds immune receptors like CD226 on NK cells, enhancing their lytic activity against target cells [CS: 9].

In the context of kidney diseases and associated toxicities, increased PVR expression at the mRNA and protein levels is noted in renal tubular cells during acute allograft rejection and in certain renal tumors [CS: 8]. During kidney injuries or toxic stress, the upregulation of PVR facilitates the adhesion and transendothelial migration of immune cells, which may enhance the inflammatory response as a form of tissue defense against injury [CS: 7]. This increase also reflects the cell's response to regain homeostasis by promoting tissue repair and regeneration [CS: 7]. However, despite PVR's potential benefits in supporting immune surveillance, its prolonged expression may contribute to pathology if the control mechanisms are dysregulated, potentially leading to exacerbated inflammation, tissue damage or facilitating tumor cell evasion of immune detection [CS: 6].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: low tissue specificity [https://www.proteinatlas.org/ENSG00000073008/tissue]

Cell type enchanced: alveolar cells type 1 (cell type enhanced) [https://www.proteinatlas.org/ENSG00000073008/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: