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Gene Review

PIGR  -  polymeric immunoglobulin receptor

Homo sapiens

Synonyms: Hepatocellular carcinoma-associated protein TB6, PIgR, Poly-Ig receptor, Polymeric immunoglobulin receptor
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The human polymeric immunoglobulin receptor (PIGR) is expressed by mucosal epithelial cells, and is, as the name states, a receptor for polymeric immunoglobulins. Specifically, it binds polymeric IgM and dimeric IgA and transports these across the mucosal epithelial barrier and releases them as secretory antibodies in the mucosal secretions [1].


Disease relevance of PIGR


High impact information on PIGR


Chemical compound and disease context of PIGR

  • The cDNA encoding the NH2-terminal 589 amino acids of the extracellular domain of the human polymeric immunoglobulin receptor was inserted into transfer vectors to generate recombinant baculo- and vaccinia viruses [8].
  • Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis [9].

Biological context of PIGR

  • An E-Box motif, which binds transcription factors of the basic helix-loop-helix/leucine zipper (bHLH/zip) family, was identified as a major regulatory element in the PIGR gene promoter [3].
  • Haplotype of the two missense PIGR SNPs, 1093G-->A and 1739C-->T, and sequence analyses have confirmed the role of the nucleotide PIGR1739 and excluded possibility of an additional significant nonsynonymous NPC susceptibility SNP [4].
  • To prove the hypothesis, we evaluated two candidate genes, complement receptor 2 (CR2) and polymeric immunoglobulin receptor (PIGR) by using 4 SNPs, CR2IVS2-848C-->T, PIGRIVS3-156G-->T, PIGR1093G-->A and PIGR1739C-->T, to genotype 175 cases and 317 controls, divided into Thai, Chinese and Thai-Chinese based on their respective ethnic origins [4].
  • Here we present a detailed analysis of the promoter of the PIGR gene by transient transfection of luciferase reporter plasmids into cultured cell lines [10].
  • The gene encoding human transmembrane secretory component (locus PIGR) is linked to D1S58 on chromosome 1 [11].

Anatomical context of PIGR


Associations of PIGR with chemical compounds


Physical interactions of PIGR


Regulatory relationships of PIGR

  • Expression of pIgR is regulated by microbial products through Toll-like receptor signaling and by host factors such as cytokines and hormones [13].
  • Transcription of pIgR is regulated both by promoter elements [19] as well as an intronic enhancer that is responsive to the cytokines IL4 [20] [21] and TNF [22][23]
  • We studied the mechanism by which interferon-gamma (IFN-gamma) induces pIgR expression in HT-29.74 cells, a subclone of the HT-29 cell line selected for high concns of pIgR [24].
  • Depletion of endogenous MAL2 drastically blocked transcytotic transport of exogenous polymeric immunoglobulin receptor and endogenous glycosylphosphatidylinositol-anchored protein CD59 to the apical membrane [25].
  • Transcytosis experiments performed using human polymeric immunoglobulin receptor (pIgR) expressing Madine-Darby canine kidney (MDCK) cells showed that one of the recombinants showed a high degree of colocalization with PDC-E2 [26].

Other interactions of PIGR

  • Multivariate regression analysis demonstrated that reduced USF2 mRNA and increased AP2-alpha mRNA levels were predictive of down-regulated PIGR mRNA expression in the majority of adenocarcinomas and in moderately differentiated squamous cell carcinomas [2].
  • The structure of pIgR domain 1 reveals a folding topology similar to immunoglobulin variable domains, but with differences in the counterparts of the complementarity determining regions (CDRs), including a helical turn in CDR1 and a CDR3 loop that points away from the other CDRs [27].
  • Here we present the first genetic linkage study of PIGR versus syntenic markers, including D1S58 and F13B, which have been previously regionalized to 1q31-q32 and 1q31-q32.1, respectively [11].
  • We found that PIGR is closely linked to D1S58 (lods + 5.06 at theta max = 0.06, without sex difference) [11].
  • In contrast, pIgR/SC production by cultured epithelial cells (quantified by enzyme-linked immunosorbent assay) was significantly increased by supernatants from interleukin-8/formylmethionylleucylphenylalanine-activated PMN (122.6 +/- 17.3 versus 70.9 +/- 9 ng/mg protein, P < 0.01) [15].

Analytical, diagnostic and therapeutic context of PIGR


  1. Regulation of the formation and external transport of secretory immunoglobulins. Norderhaug, I.N., Johansen, F.E., Schjerven, H., Brandtzaeg, P. Crit. Rev. Immunol. (1999) [Pubmed]
  2. Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2. Khattar, N.H., Lele, S.M., Kaetzel, C.S. J. Biomed. Sci. (2005) [Pubmed]
  3. Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene. Bruno, M.E., West, R.B., Schneeman, T.A., Bresnick, E.H., Kaetzel, C.S. Mol. Immunol. (2004) [Pubmed]
  4. Polymeric immunoglobulin receptor polymorphisms and risk of nasopharyngeal cancer. Hirunsatit, R., Kongruttanachok, N., Shotelersuk, K., Supiyaphun, P., Voravud, N., Sakuntabhai, A., Mutirangura, A. BMC Genet. (2003) [Pubmed]
  5. Transepithelial transport of immunoglobulins. Mostov, K.E. Annu. Rev. Immunol. (1994) [Pubmed]
  6. The polymeric immunoglobulin receptor translocates pneumococci across human nasopharyngeal epithelial cells. Zhang, J.R., Mostov, K.E., Lamm, M.E., Nanno, M., Shimida, S., Ohwaki, M., Tuomanen, E. Cell (2000) [Pubmed]
  7. Deletion of the cytoplasmic domain of the polymeric immunoglobulin receptor prevents basolateral localization and endocytosis. Mostov, K.E., de Bruyn Kops, A., Deitcher, D.L. Cell (1986) [Pubmed]
  8. Production of human secretory component with dimeric IgA binding capacity using viral expression systems. Rindisbacher, L., Cottet, S., Wittek, R., Kraehenbuhl, J.P., Corthésy, B. J. Biol. Chem. (1995) [Pubmed]
  9. Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis. Murthy, A.K., Dubose, C.N., Banas, J.A., Coalson, J.J., Arulanandam, B.P. J. Gastroenterol. Hepatol. (2006) [Pubmed]
  10. Transcriptional regulation of the human polymeric Ig receptor gene: analysis of basal promoter elements. Hempen, P.M., Phillips, K.M., Conway, P.S., Sandoval, K.H., Schneeman, T.A., Wu, H.J., Kaetzel, C.S. J. Immunol. (2002) [Pubmed]
  11. The gene encoding human transmembrane secretory component (locus PIGR) is linked to D1S58 on chromosome 1. Krajci, P., Gedde-Dahl, T., Høyheim, B., Rogde, S., Olaisen, B., Brandtzaeg, P. Hum. Genet. (1992) [Pubmed]
  12. Genetic mapping of the human polymeric immunoglobulin receptor gene to chromosome region 1q31----q41. Davidson, M.K., Le Beau, M.M., Eddy, R.L., Shows, T.B., DiPietro, L.A., Kingzette, M., Hanly, W.C. Cytogenet. Cell Genet. (1988) [Pubmed]
  13. The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Kaetzel, C.S. Immunol. Rev. (2005) [Pubmed]
  14. Interactions between the exocytic and endocytic pathways in polarized Madin-Darby canine kidney cells. Orzech, E., Cohen, S., Weiss, A., Aroeti, B. J. Biol. Chem. (2000) [Pubmed]
  15. Secretory component is cleaved by neutrophil serine proteinases but its epithelial production is increased by neutrophils through NF-kappa B- and p38 mitogen-activated protein kinase-dependent mechanisms. Pilette, C., Ouadrhiri, Y., Dimanche, F., Vaerman, J.P., Sibille, Y. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  16. Insights into IgA-mediated immune responses from the crystal structures of human FcalphaRI and its complex with IgA1-Fc. Herr, A.B., Ballister, E.R., Bjorkman, P.J. Nature (2003) [Pubmed]
  17. Solution structure of choline binding protein A, the major adhesin of Streptococcus pneumoniae. Luo, R., Mann, B., Lewis, W.S., Rowe, A., Heath, R., Stewart, M.L., Hamburger, A.E., Sivakolundu, S., Lacy, E.R., Bjorkman, P.J., Tuomanen, E., Kriwacki, R.W. EMBO J. (2005) [Pubmed]
  18. Single chain Fv: a ligand in receptor-mediated gene delivery. Gupta, S., Eastman, J., Silski, C., Ferkol, T., Davis, P.B. Gene Ther. (2001) [Pubmed]
  19. A composite DNA element in the promoter of the polymeric immunoglobulin receptor regulates its constitutive expression. Johansen, F.E., Bosløven, B.A., Krajci, P., Brandtzaeg, P. Eur. J. Immunol. (1998) [Pubmed]
  20. Mechanism of IL-4-mediated up-regulation of the polymeric Ig receptor: role of STAT6 in cell type-specific delayed transcriptional response. Schjerven, H., Brandtzaeg, P., Johansen, F.E. J. Immunol. (2000) [Pubmed]
  21. Hepatocyte NF-1 and STAT6 cooperate with additional DNA-binding factors to activate transcription of the human polymeric Ig receptor gene in response to IL-4. Schjerven, H., Brandtzaeg, P., Johansen, F.E. J. Immunol. (2003) [Pubmed]
  22. A novel NF-kappa B/Rel site in intron 1 cooperates with proximal promoter elements to mediate TNF-alpha-induced transcription of the human polymeric Ig receptor. Schjerven, H., Brandtzaeg, P., Johansen, F.E. J. Immunol. (2001) [Pubmed]
  23. De novo synthesized RelB mediates TNF-induced up-regulation of the human polymeric Ig receptor. Schjerven, H., Tran, T.N., Brandtzaeg, P., Johansen, F.E. J. Immunol. (2004) [Pubmed]
  24. Interferon-gamma induces polymeric immunoglobulin receptor mRNA in human intestinal epithelial cells by a protein synthesis dependent mechanism. Piskurich, J.F., France, J.A., Tamer, C.M., Willmer, C.A., Kaetzel, C.S., Kaetzel, D.M. Mol. Immunol. (1993) [Pubmed]
  25. MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells. de Marco, M.C., Martín-Belmonte, F., Kremer, L., Albar, J.P., Correas, I., Vaerman, J.P., Marazuela, M., Byrne, J.A., Alonso, M.A. J. Cell Biol. (2002) [Pubmed]
  26. Characterization of recombinant monoclonal IgA anti-PDC-E2 autoantibodies derived from patients with PBC. Fukushima, N., Nalbandian, G., Van De Water, J., White, K., Ansari, A.A., Leung, P., Kenny, T., Kamita, S.G., Hammock, B.D., Coppel, R.L., Stevenson, F., Ishibashi, H., Gershwin, M.E. Hepatology (2002) [Pubmed]
  27. Crystal structure of a polymeric immunoglobulin binding fragment of the human polymeric immunoglobulin receptor. Hamburger, A.E., West, A.P., Bjorkman, P.J. Structure (Camb.) (2004) [Pubmed]
  28. Secretory component mRNA and protein expression in colorectal adenomas and carcinomas. Krajci, P., Meling, G.I., Andersen, S.N., Hofstad, B., Vatn, M.H., Rognum, T.O., Brandtzaeg, P. Br. J. Cancer (1996) [Pubmed]
  29. Molecular cloning and exon-intron mapping of the gene encoding human transmembrane secretory component (the poly-Ig receptor). Krajci, P., Kvale, D., Taskén, K., Brandtzaeg, P. Eur. J. Immunol. (1992) [Pubmed]
  30. Gene transfer into respiratory epithelial cells by targeting the polymeric immunoglobulin receptor. Ferkol, T., Kaetzel, C.S., Davis, P.B. J. Clin. Invest. (1993) [Pubmed]
  31. A composite DNA element in the promoter of the polymeric immunoglobulin receptor regulates its constitutive expression. Johansen, F.E., Bosløven, B.A., Krajci, P., Brandtzaeg, P. Eur. J. Immunol. (1998) [Pubmed]
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