Alternative titles; symbols
HGNC Approved Gene Symbol: NECTIN2
Cytogenetic location: 19q13.32 Genomic coordinates (GRCh38) : 19:44,846,297-44,889,223 (from NCBI)
NECTIN2, or PVRL2, belongs to the nectin subfamily of immunoglobulin-like adhesion molecules that participate in Ca(2+)-independent cell-cell adhesion. Nectins bind to the actin cytoskeleton through the adaptor protein afadin (AFDN; 159559) and are key components of adherens junctions (summary by Barron et al. (2008)).
Entry of the poliovirus into permissive cells is dependent on the expression of a specific receptor, the poliovirus receptor (PVR; 173850), which is an integral membrane glycoprotein. Its extracellular region exhibits 3 immunoglobulin-like domains. Two integral forms, PVR-alpha and PVR-delta, and 2 soluble forms, PVR-beta and PVR-gamma, are lacking a transmembrane region generated by alternative splicing of mRNA. The normal cellular function of PVR is unknown. The identification of human PVR prompted study of its counterpart in other species. In the monkey, 2 genes located at 2 separate genetic loci, AGM1 and AGM2, have been cloned. AGM1 encodes 2 membrane-bound splice variant forms homologous to PVR-alpha and PVR-delta. AGM2 encodes a membrane-bound form, PVR-alpha-2. Morrison and Racaniello (1992) described a murine gene, Mph, as a structural homolog of human PVR. Two Mph molecules, Mph-alpha and Mph-beta, are thought to be generated by alternative splicing from a primary transcript.
Following the discovery of the human PVR-related gene (PVRR1; 600644), other PVR-related molecules were sought. Using degenerate oligonucleotides in a PCR-based methodology, Eberle et al. (1995) identified a second PVR-related cDNA, which they called PRR2. Furthermore, they presented evidence that PRR2, and not PVR, is the homolog of Mph, and questioned the existence of a true murine homolog of PVR. The PRR2 gene encodes 2 glycoproteins, PRR2-alpha (short form) and PRR2-delta (long form), which have 69% and 73% identity within Mph-alpha and Mph-beta, respectively. In contrast, the human PVR protein exhibits only 51% identity which is, moreover, restricted to the 3 immunoglobulin domains of the murine protein. Northern blot analysis showed that 2 mRNA isoforms of 3.0 kb (PRR2-alpha) and 4.4 kb (PRR2-delta) are ubiquitously found in various normal human tissues.
Bottino et al. (2003) immunized mice with natural killer (NK)-susceptible human target cells and obtained antibodies to PVR and PVRL2. Binding analysis and flow cytometry demonstrated that both molecules bound strongly with DNAM1 (CD226; 605397), but not with other activating NK receptors, including NKp46 (NCR1; 604530) and NKp30 (NCR3; 611550). Expression of PVR or PVRL2 rendered cells susceptible to enhanced lysis in a DNAM1-dependent manner that was nearly abrogated in the presence of antibody to PVR, PVRL2, or DNAM1.
Liu et al. (2012) generated the crystal structure of the nectin-2 Ig-like V-set domain at 1.85-angstrom resolution. The structure bound to both the soluble ectodomain of DNAM1 and cell surface-expressed full-length DNAM1. Mutational analysis revealed that disruption of the homodimeric interface of nectin-2 led to failure of homodimer formation and loss of binding to DNAM1.
By isotopic hybridization, Eberle et al. (1995) mapped the PRR2 gene to 19q13.2-q13.4 in the same chromosomal region as PVR. By genomic sequence analysis, Freitas et al. (1998) mapped the PRR2 gene to chromosome 19q13.2, where it lies centromeric to the TOMM40 gene (608061) and the APOE (107741)-APOC2 (608083) gene cluster.
Barron, M. J., Brookes, S. J., Draper, C. E., Garrod, D., Kirkham, J., Shore, R. C., Dixon, M. J. The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice. Hum. Molec. Genet. 17: 3509-3520, 2008. [PubMed: 18703497] [Full Text: https://doi.org/10.1093/hmg/ddn243]
Bottino, C., Castriconi, R., Pende, D., Rivera, P., Nanni, M., Carnemolla, B., Cantoni, C., Grassi, J., Marcenaro, S., Reymond, N., Vitale, M., Moretta, L., Lopez, M., Moretta, A. Identification of PVR (CD155) and nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198: 557-567, 2003. [PubMed: 12913096] [Full Text: https://doi.org/10.1084/jem.20030788]
Eberle, F., Dubreuil, P., Mattei, M.-G., Devilard, E., Lopez, M. The human PRR2 gene, related to the human poliovirus receptor gene (PVR), is the true homolog of the murine Mph gene. Gene 159: 267-272, 1995. [PubMed: 7622062] [Full Text: https://doi.org/10.1016/0378-1119(95)00180-e]
Freitas, E. M., Zhang, W. J., Lalonde, J.-P., Tay, G. K., Gaudieri, S., Ashworth, L. K., van Bockxmeer, F. M., Dawkins, R. L. Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1. DNA Seq. 9: 89-101, 1998. [PubMed: 10520737] [Full Text: https://doi.org/10.3109/10425179809086433]
Liu, J., Qian, X., Chen, Z., Xu, X., Gao, F., Zhang, S., Zhang, R., Qi, J., Gao, G. F., Yan, J. Crystal structure of cell adhesion molecule nectin-2/CD112 and its binding to immune receptor DNAM-1/CD226. J Immun. 188: 5511-5520, 2012. [PubMed: 22547693] [Full Text: https://doi.org/10.4049/jimmunol.1200324]
Morrison, M. E., Racaniello, V. R. Molecular cloning and expression of a murine homolog of the human poliovirus receptor gene. J. Virol. 66: 2807-2813, 1992. [PubMed: 1560525] [Full Text: https://doi.org/10.1128/JVI.66.5.2807-2813.1992]