Alternative titles; symbols
HGNC Approved Gene Symbol: PIGR
Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:206,928,522-206,946,466 (from NCBI)
The poly-Ig receptor is expressed on several glandular epithelia including those of liver and breast. It mediates transcellular transport of polymeric immunoglobulin molecules. It is a member of the immunoglobulin superfamily (Hood et al., 1985). The receptor has 5 units with homology to the variable (V) units of immunoglobulins and a transmembrane region, which also has some homology to certain immunoglobulin variable regions.
Davidson et al. (1988) cloned the human PIGR gene.
Krajci et al. (1992) identified 11 exons covering the entire PIGR coding region.
Zhang et al. (2000) reported that human PIGR can bind to a major pneumococcal adhesin, CbpA. Expression of PIGR in human nasopharyngeal cells and MDCK cells greatly enhanced pneumococcal adherence and invasion. The PIGR-mediated bacterial adherence and invasion were abolished by either insertional knockout of CbpA or antibodies against either PIGR or CbpA. These results suggested that pneumococci are a novel example of a pathogen coopting the PIG transcytosis machinery to promote translocation across a mucosal barrier.
PIGR binds its ligand, dimeric IgA (dIgA; see 146900), at the basolateral surface of epithelial cells. After endocytosis, the PIGR-dIgA complex traverses several endosomal compartments and is exocytosed at the apical plasma membrane. Van IJzendoorn et al. (2002) found that Rab3b (179510) localized to vesicular structures containing Pigr in canine kidney cells and that GTP-bound Rab3b interacted directly with the cytoplasmic domain of Pigr. Binding of dIgA to Pigr dissociated Rab3b, but a constitutively active Rab3b mutant maintained its interaction with Pigr in dIgA-treated cells. Furthermore, GTP-locked Rab3b inhibited dIgA-stimulated transcytosis.
Davidson et al. (1988) localized the PIGR gene to 1q31-q41 by a combination of somatic cell hybridization and in situ hybridization. By Southern blot analysis of human/rodent somatic hybrid panels, including hybrids with translocation chromosomes carrying different parts of chromosome 1, Krajci et al. (1991) confirmed the assignment of PIGR to 1q31-q42. Krajci et al. (1992) found linkage evidence supporting the location of PIGR in this region.
Obara et al. (2003) performed a case-control association study involving 389 Japanese patients with immunoglobulin A nephropathy (IgAN; 161950) and 465 controls. A significant association was found between IgAN and 6 SNPs in the PIGR gene. One of the SNPs, PIGR17, caused an amino acid substitution from alanine to valine at codon 580. Another SNP, PIGR2, may affect promoter activity. Pairwise analyses demonstrated that all 6 SNPs were in almost complete linkage disequilibrium. Biopsy specimens from IgAN patients were positively stained by antibody against the secretory component of PIGR, but corresponding tissues from non-IgAN patients were not.
This variant, formerly titled IgA NEPHROPATHY, SUSCEPTIBILITY TO, has been reclassified based on the findings of Maxwell and Wang (2006).
In a case-control association study involving 389 Japanese patients with immunoglobulin A nephropathy (IGAN; 161950) and 465 controls, Obara et al. (2003) found an association between an SNP, designated PIGR17, and IGAN. The PIGR17 SNP consists of a C-to-T transition at nucleotide 1740 in exon 7, which results in an ala-to-val amino acid substitution at codon 580 (A580V). The odds ratio of homozygotes for the minor allele (T) compared to CC or CT genotypes was 2.71.
Maxwell and Wang (2006) included the PIGR variant reported by Obara et al. (2003) in a table of genetic associations with IgA nephropathy, noting that although plausible, these genetic associations had not generally been observed in more than 1 study and could not be proved to contribute to IgA nephropathy causation or progression.
Davidson, M. K., Le Beau, M. M., Eddy, R. L., Shows, T. B., DiPietro, L. A., Kingzette, M., Hanly, W. C. Genetic mapping of the human polymeric immunoglobulin receptor gene to chromosome region 1q31-q41. Cytogenet. Cell Genet. 48: 107-111, 1988. [PubMed: 3197448] [Full Text: https://doi.org/10.1159/000132601]
Hood, L., Kronenberg, M., Hunkapiller, T. T cell antigen receptors and the immunoglobulin supergene family. Cell 40: 225-229, 1985. [PubMed: 3917857] [Full Text: https://doi.org/10.1016/0092-8674(85)90133-3]
Krajci, P., Gedde-Dahl, T., Jr., Hoyheim, B., Rogde, S., Olaisen, B., Brandtzaeg, P. The gene encoding human transmembrane secretory component (locus PIGR) is linked to D1S58 on chromosome 1. Hum. Genet. 90: 215-219, 1992. [PubMed: 1487233] [Full Text: https://doi.org/10.1007/BF00220065]
Krajci, P., Grzeschik, K. H., Geurts van Kessel, A. H. M., Olaisen, B., Brandtzaeg, P. The human transmembrane secretory component (poly-Ig receptor): molecular cloning, restriction fragment length polymorphism and chromosomal sublocalization. Hum. Genet. 87: 642-648, 1991. [PubMed: 1682231] [Full Text: https://doi.org/10.1007/BF00201717]
Krajci, P., Kvale, D., Tasken, K., Brandtzaeg, P. Molecular cloning and exon-intron mapping of the gene encoding human transmembrane secretory component (the poly-Ig receptor). Europ. J. Immun. 22: 2309-2315, 1992. Note: Erratum: Europ. J. Immun. 23: 311 only, 1993. [PubMed: 1355431] [Full Text: https://doi.org/10.1002/eji.1830220920]
Maxwell, P. H., Wang, Y. Genetic studies of IgA nephropathy. Nephron Exp. Nephrol. 102: e76-e80, 2006. Note: Electronic Article. [PubMed: 16282702] [Full Text: https://doi.org/10.1159/000089685]
Obara, W., Iida, A., Suzuki, Y., Tanaka, T., Akiyama, F., Maeda, S., Ohnishi, Y., Yamada, R., Tsunoda, T., Takei, T., Ito, K., Honda, K., and 12 others. Association of single-nucleotide polymorphisms in the polymeric immunoglobulin receptor gene with immunoglobulin A nephropathy (IgAN) in Japanese patients. J. Hum. Genet. 48: 293-299, 2003. [PubMed: 12740691] [Full Text: https://doi.org/10.1007/s10038-003-0027-1]
van IJzendoorn, S. C. D., Tuvim, M. J., Weimbs, T., Dickey, B. F., Mostov, K. E. Direct interaction between Rab3b and the polymeric immunoglobulin receptor controls ligand-stimulated transcytosis in epithelial cells. Dev. Cell 2: 219-228, 2002. [PubMed: 11832247] [Full Text: https://doi.org/10.1016/s1534-5807(02)00115-6]
Zhang, J.-R., Mostov, K. E., Lamm, M. E., Nanno, M., Shimida, S., Ohwaki, M., Tuomanen, E. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Cell 102: 827-837, 2000. [PubMed: 11030626] [Full Text: https://doi.org/10.1016/s0092-8674(00)00071-4]