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Gene Review

FCGRT  -  Fc fragment of IgG, receptor, transporter,...

Homo sapiens

Synonyms: FCRN, FcRn, IgG Fc fragment receptor transporter alpha chain, IgG receptor FcRn large subunit p51, Neonatal Fc receptor, ...
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Disease relevance of FCGRT

  • Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene [1].
  • Here we expressed the human FcRn alpha-chain alone or in combination with beta(2)m in human melanoma FO-1 cells [2].
  • In the current study we have investigated FcRn expression in various histologic types of human breast carcinoma and lymph node metastases [3].
  • To determine directly whether this function contributes to humoral autoimmune disease, we examined whether a deficiency in the FcRn heavy chain influences autoimmune arthritis in the K/BxN mouse model [4].
  • These data demonstrate that the therapeutic efficacy of HDIG treatment in the pemphigus and pemphigoid models is dependent on FcRn [5].

High impact information on FCGRT

  • Multiple roles for the major histocompatibility complex class I- related receptor FcRn [6].
  • In addition, FcRn expression in tissues such as liver, mammary gland, and adult intestine suggests that it may modulate IgG transport at these sites [6].
  • Recent studies have shown that FcRn rescues IgG from intracellular lysosomal degradation by recycling it from the sorting endosome to the cell surface [7].
  • A passionate kiss, then run: exocytosis and recycling of IgG by FcRn [7].
  • The MHC-class-I-like Fcgamma receptor FcRn recycles immunoglobulin (Ig)G from most cells and transports it bi-directionally across epithelial barriers to affect systemic and mucosal immunity [7].

Biological context of FCGRT


Anatomical context of FCGRT


Associations of FCGRT with chemical compounds

  • Mutation of non-paired cysteine residues at positions 48 and 251 within the human FcRn cDNA failed to eliminate the oligomers [13].
  • Treatment of BeWo and BeWo/hFcRn cells with brefeldin A, an inhibitor of the secretory pathway, abrogated this effect, demonstrating that hFcRn alpha-chain expression retained otherwise secreted beta2m [14].
  • We find that alteration of a histidine pair within the alpha 3 domain of FcRn and of a nearby loop (the FcRn counterpart of the class I CD8-binding loop) affects the affinity for IgG [15].
  • Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells [16].
  • Sequences in the CH2 and CH3 region of IgG have been shown to regulate the rate of clearance through their interaction with FcRn [17].

Physical interactions of FCGRT


Co-localisations of FCGRT


Regulatory relationships of FCGRT


Other interactions of FCGRT

  • Many of these genes, including CD1, the neonatal Fc receptor for immunoglobulin G, HLA-G, the MHC class I chain-related gene A, and Hfe, are prominently displayed on epithelial cells, suggesting an important role in epithelial cell biology [22].
  • The 2.8 A complex structure demonstrates that FcRn uses its alpha2 and beta2-microglobulin domains and carbohydrate to interact with the Fc C(gamma)2-C(gamma)3 interface [23].
  • From sorting endosomes to exocytosis: association of Rab4 and Rab11 GTPases with the Fc receptor, FcRn, during recycling [24].
  • Of the 44 beta 2m-alpha-chain contacts defined for Class I HLA, 24 alpha-chain contact sites were conserved in CD1, 25 in FcRn and 17 in the H301-gene product [25].
  • In addition, the pathways taken by FcRn and the transferrin receptor overlap, despite distinct mechanisms of ligand uptake [11].

Analytical, diagnostic and therapeutic context of FCGRT


  1. Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene. Wani, M.A., Haynes, L.D., Kim, J., Bronson, C.L., Chaudhury, C., Mohanty, S., Waldmann, T.A., Robinson, J.M., Anderson, C.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. beta(2)-Microglobulin is important for cell surface expression and pH-dependent IgG binding of human FcRn. Praetor, A., Hunziker, W. J. Cell. Sci. (2002) [Pubmed]
  3. The MHC class I related Fc receptor, FcRn, is expressed in the epithelial cells of the human mammary gland. Cianga, P., Cianga, C., Cozma, L., Ward, E.S., Carasevici, E. Hum. Immunol. (2003) [Pubmed]
  4. The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease. Akilesh, S., Petkova, S., Sproule, T.J., Shaffer, D.J., Christianson, G.J., Roopenian, D. J. Clin. Invest. (2004) [Pubmed]
  5. Complete FcRn dependence for intravenous Ig therapy in autoimmune skin blistering diseases. Li, N., Zhao, M., Hilario-Vargas, J., Prisayanh, P., Warren, S., Diaz, L.A., Roopenian, D.C., Liu, Z. J. Clin. Invest. (2005) [Pubmed]
  6. Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Ghetie, V., Ward, E.S. Annu. Rev. Immunol. (2000) [Pubmed]
  7. A passionate kiss, then run: exocytosis and recycling of IgG by FcRn. Lencer, W.I., Blumberg, R.S. Trends Cell Biol. (2005) [Pubmed]
  8. The human gene encoding the heavy chain of the major histocompatibility complex class I-like Fc receptor (FCGRT) maps to 19q13.3. Kandil, E., Egashira, M., Miyoshi, O., Niikawa, N., Ishibashi, T., Kasahara, M., Miyosi, O. Cytogenet. Cell Genet. (1996) [Pubmed]
  9. Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport. Leach, J.L., Sedmak, D.D., Osborne, J.M., Rahill, B., Lairmore, M.D., Anderson, C.L. J. Immunol. (1996) [Pubmed]
  10. Exocytosis of IgG as mediated by the receptor, FcRn: an analysis at the single-molecule level. Ober, R.J., Martinez, C., Lai, X., Zhou, J., Ward, E.S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn. Ober, R.J., Martinez, C., Vaccaro, C., Zhou, J., Ward, E.S. J. Immunol. (2004) [Pubmed]
  12. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. Zhu, X., Meng, G., Dickinson, B.L., Li, X., Mizoguchi, E., Miao, L., Wang, Y., Robert, C., Wu, B., Smith, P.D., Lencer, W.I., Blumberg, R.S. J. Immunol. (2001) [Pubmed]
  13. The heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic reticulum by forming oligomers in the absence of beta2-microglobulin association. Zhu, X., Peng, J., Raychowdhury, R., Nakajima, A., Lencer, W.I., Blumberg, R.S. Biochem. J. (2002) [Pubmed]
  14. Overexpression of the human neonatal Fc-receptor alpha-chain in trophoblast-derived BeWo cells increases cellular retention of beta2-microglobulin. Ellinger, I., Reischer, H., Lehner, C., Leitner, K., Hunziker, W., Fuchs, R. Placenta (2005) [Pubmed]
  15. Investigation of the interaction between the class I MHC-related Fc receptor and its immunoglobulin G ligand. Raghavan, M., Chen, M.Y., Gastinel, L.N., Bjorkman, P.J. Immunity (1994) [Pubmed]
  16. Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Yoshida, M., Claypool, S.M., Wagner, J.S., Mizoguchi, E., Mizoguchi, A., Roopenian, D.C., Lencer, W.I., Blumberg, R.S. Immunity (2004) [Pubmed]
  17. Chimeric human-mouse IgG antibodies with shuffled constant region exons demonstrate that multiple domains contribute to in vivo half-life. Zuckier, L.S., Chang, C.J., Scharff, M.D., Morrison, S.L. Cancer Res. (1998) [Pubmed]
  18. Membrane-anchored human FcRn can oligomerize in the absence of IgG. Praetor, A., Jones, R.M., Wong, W.L., Hunziker, W. J. Mol. Biol. (2002) [Pubmed]
  19. Co-localization of the neonatal Fc gamma receptor and IgG in human placental term syncytiotrophoblasts. Kristoffersen, E.K., Matre, R. Eur. J. Immunol. (1996) [Pubmed]
  20. Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin. Claypool, S.M., Dickinson, B.L., Yoshida, M., Lencer, W.I., Blumberg, R.S. J. Biol. Chem. (2002) [Pubmed]
  21. Activation of the JAK/STAT-1 signaling pathway by IFN-gamma can down-regulate functional expression of the MHC class I-related neonatal Fc receptor for IgG. Liu, X., Ye, L., Bai, Y., Mojidi, H., Simister, N.E., Zhu, X. J. Immunol. (2008) [Pubmed]
  22. Current concepts in mucosal immunity. II. One size fits all: nonclassical MHC molecules fulfill multiple roles in epithelial cell function. Blumberg, R.S. Am. J. Physiol. (1998) [Pubmed]
  23. Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Martin, W.L., West, A.P., Gan, L., Bjorkman, P.J. Mol. Cell (2001) [Pubmed]
  24. From sorting endosomes to exocytosis: association of Rab4 and Rab11 GTPases with the Fc receptor, FcRn, during recycling. Ward, E.S., Martinez, C., Vaccaro, C., Zhou, J., Tang, Q., Ober, R.J. Mol. Biol. Cell (2005) [Pubmed]
  25. Molecular comparisons of the beta 2-microglobulin-binding site in class I major-histocompatibility-complex alpha-chains and proteins of related sequences. Tysoe-Calnon, V.A., Grundy, J.E., Perkins, S.J. Biochem. J. (1991) [Pubmed]
  26. Calnexin and ERp57 facilitate the assembly of the neonatal Fc receptor for IgG with beta 2-microglobulin in the endoplasmic reticulum. Zhu, X., Peng, J., Chen, D., Liu, X., Ye, L., Iijima, H., Kadavil, K., Lencer, W.I., Blumberg, R.S. J. Immunol. (2005) [Pubmed]
  27. Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions. Schilling, R., Ijaz, S., Davidoff, M., Lee, J.Y., Locarnini, S., Williams, R., Naoumov, N.V. J. Virol. (2003) [Pubmed]
  28. Conferring the binding properties of the mouse MHC class I-related receptor, FcRn, onto the human ortholog by sequential rounds of site-directed mutagenesis. Zhou, J., Mateos, F., Ober, R.J., Ward, E.S. J. Mol. Biol. (2005) [Pubmed]
  29. Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor(,). West, A.P., Bjorkman, P.J. Biochemistry (2000) [Pubmed]
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