Alternative titles; symbols
HGNC Approved Gene Symbol: PCDH1
Cytogenetic location: 5q31.3 Genomic coordinates (GRCh38): 5:141,853,090-141,878,410 (from NCBI)
Cadherins are a group of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. See 601120. By PCR of rat, mouse, and human neural cell cDNA with degenerate primers based on conserved regions of the cadherin extracellular domain, Sano et al. (1993) isolated partial cDNAs encoding pc42 and pc43 (PCDH2; 603627). They used the partial cDNAs to screen a human brain library and recovered cDNAs corresponding to the entire coding sequence of both genes. Like typical cadherins, both pc42 and pc43 contain an N-terminal extracellular domain, a transmembrane domain, and a C-terminal cytoplasmic region. The extracellular domains of pc42 and pc43 contain 7 and 6 repeats, respectively, of a subdomain that is very similar to those of cadherins, but with characteristic properties. The cytoplasmic domains of pc42 and pc43 share no homology with those of cadherins. The authors isolated partial cDNAs encoding proteins with the protocadherin repeats from Xenopus, Drosophila, and C. elegans. Since pc42 and pc43 are more closely related to one another than to classic cadherins, and because of the existence of similar proteins in distantly related organisms, Sano et al. (1993) suggested the name 'protocadherins' for this family of proteins.
Sano et al. (1993) reported that pc42 migrated at 170 kD on Western blots of extracts of mammalian cells expressing the protein. Immunofluorescence microscopy localized pc42 to the periphery of cells, primarily in cell-cell contact sites. Cells expressing pc42 showed cell aggregation activity.
Jangra et al. (2018) identified the PCDH1 gene as an essential determinant of entry and infection in pulmonary endothelial cells by 2 hantaviruses that cause hantavirus pulmonary syndrome, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, Jangra et al. (2018) showed that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1, a member of the cadherin superfamily, to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 rendered Syrian golden hamsters highly resistant to a usually lethal ANDV challenge.
By analysis of somatic cell hybrids, Del Mastro et al. (1995) mapped the pc42 gene to 5q32-q33. Sago et al. (1995) noted that the mouse Pcdh1, Pcdh2, and Pcdh3 genes form a cluster on chromosome 18.
Del Mastro, R. G., Wang, L., Simmons, A. D., Gallardo, T. D., Clines, G. A., Ashley, J. A., Hilliard, C. J., Wasmuth, J. J., McPherson, J. D., Lovett, M. Human chromosome-specific cDNA libraries: new tools for gene identification and genome annotation. Genome Res. 5: 185-194, 1995. [PubMed: 9132272] [Full Text: https://doi.org/10.1101/gr.5.2.185]
Jangra, R. K., Herbert, A. S., Li, R., Jae, L. T., Kleinfelter, L. M., Slough, M. M., Barker, S. L., Guardado-Calvo, P., Roman-Sosa, G., Dieterle, M. E., Kuehne, A. I., Muena, N. A., and 17 others. Protocadherin-1 is essential for cell entry by New World hantaviruses. Nature 563: 559-563, 2018. [PubMed: 30464266] [Full Text: https://doi.org/10.1038/s41586-018-0702-1]
Sago, H., Kitagawa, M., Obata, S., Mori, N., Taketani, S., Rochelle, J. M., Seldin, M. F., Davidson, M., St. John, T., Suzuki, S. T. Cloning, expression, and chromosomal localization of a novel cadherin-related protein, protocadherin-3. Genomics 29: 631-640, 1995. [PubMed: 8575755] [Full Text: https://doi.org/10.1006/geno.1995.9956]
Sano, K., Tanihara, H., Heimark, R. L., Obata, S., Davidson, M., St. John, T., Taketani, S., Suzuki, S. Protocadherins: a large family of cadherin-related molecules in central nervous system. EMBO J. 12: 2249-2256, 1993. [PubMed: 8508762] [Full Text: https://doi.org/10.1002/j.1460-2075.1993.tb05878.x]