NECTIN3 (CD155/PVR): A Multifaceted Regulator of Cell Adhesion, Immunity, and Cancer
Comprehensive biomedical reference for NECTIN3, covering genomic architecture, expression profiles, disease associations, and functional implications.
Gene Information Card
| Symbol | NECTIN3 |
|---|---|
| Full Name | nectin cell adhesion molecule 3 |
| Gene Type | protein coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 25945 ncbi.nlm.nih.gov/gene/25945 |
| Ensembl ID | ENSG00000167772 |
| UniProt ID | Q15116 |
| OMIM ID | 600054 |
| HGNC ID | 17669 |
| Aliases | CD155, PVR, PVS, HVED, NECL5, Tage4 |
Description
NECTIN3, also known as CD155 or PVR (poliovirus receptor), is a type I transmembrane glycoprotein belonging to the nectin family of cell adhesion molecules. It functions as a Ca2+-independent immunoglobulin-like cell adhesion molecule involved in the formation of adherens junctions and the organization of epithelial and endothelial cell layers. Beyond its role in cell adhesion, NECTIN3 is a critical regulator of immune responses. It serves as a ligand for the activating receptor CD226 (DNAM-1) and the inhibitory receptors TIGIT and CD96, thereby modulating natural killer (NK) cell and T cell functions. NECTIN3 is also the primary receptor for poliovirus and is involved in tumor immune evasion, making it a significant target for cancer immunotherapy research.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Cancer (various types) | Overexpression of NECTIN3 on tumor cells promotes immune evasion by engaging inhibitory receptors (TIGIT, CD96) on immune cells, suppressing anti-tumor immunity. It also contributes to tumor cell proliferation, migration, and invasion. | ClinVar, COSMIC, PubMed (multiple studies) |
| Poliomyelitis | NECTIN3 (PVR) is the cellular receptor for poliovirus. Viral entry is mediated by the interaction of the viral capsid with the extracellular domain of NECTIN3. | UniProt, OMIM, PubMed |
| Inflammatory and Autoimmune Diseases | Altered NECTIN3 expression or function can dysregulate immune cell activation and tolerance, potentially contributing to chronic inflammation and autoimmunity. | PubMed (emerging evidence) |
| Viral Infections (other) | Acts as a receptor for other viruses, including coxsackievirus B and certain echoviruses, facilitating viral entry and infection. | UniProt, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Lymphoid tissues (spleen, lymph nodes) | High | High |
| Bone marrow | High | High |
| Lung | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Brain | Low | Low |
| Muscle | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HeLa (cervical cancer) | High | Classical cell line used for poliovirus receptor studies. |
| A549 (lung cancer) | High | High expression associated with tumor immune evasion. |
| HCT116 (colorectal cancer) | High | Expression correlates with invasive potential. |
| Jurkat (T cell leukemia) | Low | Low expression on T cells; expression is upregulated upon activation. |
| THP-1 (monocytic leukemia) | Medium | Expressed on myeloid cells, involved in immune regulation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| Missense mutations (various) | Single nucleotide variants | Low (<1%) | May alter protein structure, affecting ligand binding or cell adhesion properties. Clinical significance is often uncertain. |
| Copy number alterations (amplification) | Genomic amplification | Variable (tumor-specific) | Amplification of the NECTIN3 locus leads to protein overexpression, enhancing immune evasion and tumor progression. |
| Splice-site variants | Splice site mutation | Rare | Can lead to aberrant splicing, potentially producing truncated or non-functional proteins. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in NECTIN3 are rare and not well-characterized. They could potentially impair cell adhesion, disrupt tissue integrity, or alter immune cell regulation, but specific disease associations are not firmly established.
Gain of Function (GOF)
Gain-of-function is primarily achieved through gene amplification or transcriptional upregulation, leading to protein overexpression. This is a common oncogenic event that enhances tumor cell survival, invasion, and immune evasion by engaging inhibitory receptors on immune cells.
Dominant Negative (DN)
No clear evidence for dominant-negative mutations in NECTIN3 has been reported. The protein functions as a monomer or homodimer, and mutant forms that could interfere with wild-type function have not been identified.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion | • cell-cell adhesion |
| • heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules | • homophilic cell adhesion via plasma membrane adhesion molecules |
| • immune response | • innate immune response |
| • adaptive immune response | • negative regulation of natural killer cell mediated cytotoxicity |
| • positive regulation of T cell activation | • viral entry into host cell |
| • receptor-mediated virion attachment to host cell | • signal transduction |
| • plasma membrane | • integral component of plasma membrane |
| • extracellular region | • protein binding |
Pathways
• Cell adhesion molecules (CAMs)
• Natural killer cell mediated cytotoxicity
• T cell receptor signaling pathway
• PD-1 signaling
• TIGIT signaling in cancer
Protein Summary
The NECTIN3 protein is a type I membrane glycoprotein with an extracellular region containing three immunoglobulin-like domains (one V-type and two C2-type), a transmembrane domain, and a cytoplasmic tail. The cytoplasmic domain interacts with afadin, linking NECTIN3 to the actin cytoskeleton and facilitating cell-cell junction formation. As a ligand for CD226, TIGIT, and CD96, NECTIN3 plays a central role in the immune synapse, balancing activating and inhibitory signals in NK cells and T cells. It is also the primary receptor for poliovirus, mediating viral attachment and entry. The protein is heavily glycosylated and can undergo proteolytic cleavage, releasing a soluble form that may modulate immune responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NECTIN3 Knockout HEK293 Cell Line | EDJ-KQ8316 | Human | 25945 | Details Get a Quote |
| NECTIN3 Knockout A-549 Cell Line | EDJ-KQ34299 | Human | 25945 | Details Get a Quote |
| NECTIN3 Knockout HCT 116 Cell Line | EDJ-KQ34300 | Human | 25945 | Details Get a Quote |
| NECTIN3 Knockout HeLa Cell Line | EDJ-KQ34301 | Human | 25945 | Details Get a Quote |
