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HGNC Approved Gene Symbol: IGHE
Cytogenetic location: 14q32.33 Genomic coordinates (GRCh38): 14:105,600,066-105,601,727 (from NCBI)
This locus determines the heavy chain of IgE. No idiotypic variation is known. Nishida et al. (1982) identified at least 3 germline epsilon-constant genes in human DNA. Immunoglobulins of the IgE isotype are responsible for the immediate hypersensitivity reactions that occur in diseases such as hay fever, allergic asthma, and anaphalaxis (Ishizaka and Ishizaka, 1967).
By RT-PCR, Zhang et al. (1992) identified 2 forms of human IgE RNA that were produced by alternative splicing. One form presumably encodes the IgE that is expressed on the membrane of IgE-producing lymphocytes, and the other encodes IgE that is secreted.
Wan et al. (2002) reported the crystal structure of the complete IgE constant fragment (Fc) at 2.6-angstrom resolution. The structure revealed that the disulfide-linked C-epsilon-2 domain pair, which replace the hinge region found in IgG (see FCGR3A, 146740), are folded back asymmetrically onto the C-epsilon-3 and C-epsilon-4 domains. This fold causes an acute bend in the IgE molecule. Wan et al. (2002) inferred that a substantial conformational change involving C-epsilon-2 accompanies binding to the mast cell receptor FC-epsilon-RI (see 147140), and may explain the exceptionally slow dissociation rate of the IgE-FC-epsilon-RI complex and the ability of IgE to cause persistent allergic sensitization of mast cells.
PSEUDOGENES
Processed genes, i.e., genes that resemble processed RNA transcripts rather than interrupted genomic sequences, have been identified as dispersed members of several gene families. Battey et al. (1982) identified a 'processed' epsilon gene that had moved to chromosome 9. The processed IgE gene has precisely lost its 3 introns, thereby fusing its 4 coding domains. Location on chromosome 9 was demonstrated by somatic cell hybridization. Another epsilon pseudogene has lost the first 2 coding domains and the 5-prime-flanking sequences found adjacent to the functional gene (Max et al., 1982) on chromosome 14. The latter was referred to as pseudo-epsilon-1 (IGHEP1), and the processed gene on chromosome 9 as pseudo-epsilon-2 (IGHEP2). A pseudo-gamma-immunoglobulin gene (Hollis et al., 1982) and a pseudo-beta-tubulin gene (see 191130), both of the processed type, have been shown to have a chromosomal location different from that of the functional gene. All humans show these processed pseudogenes, as does the chimpanzee. Processed pseudogenes accumulate at a slow rate over tens of millions of years. Lotscher et al. (1986) mapped 2 solitary V(k) genes and a cluster of 3 V(k) genes to chromosomes 1, 15, and 22, respectively. The 3 genes that they had sequenced were nonprocessed pseudogenes, and the same may be true of the other 2 genes. This was the first demonstration of V-gene segments separated from the C-gene-containing chromosomes. The pseudogene on chromosome 1 was located in the 1p13-q12 segment.
Battey, J., Max, E. E., McBride, O. W., Swan, D., Leder, P. A processed human immunoglobulin epsilon gene has moved to chromosome 9. Proc. Nat. Acad. Sci. 79: 5956-5960, 1982. [PubMed: 6964396] [Full Text: https://doi.org/10.1073/pnas.79.19.5956]
Hisajima, H., Nishida, Y., Nakai, S., Takahashi, N., Ueda, S., Honjo, T. Structure of the human immunoglobulin C-epsilon-2 gene, a truncated pseudogene: implications for its evolutionary origin. Proc. Nat. Acad. Sci. 80: 2995-2999, 1983. [PubMed: 6407005] [Full Text: https://doi.org/10.1073/pnas.80.10.2995]
Hollis, G. F., Hieter, P. A., McBride, O. W., Swan, D., Leder, P. Processed genes: a dispersed human immunoglobulin gene bearing evidence of RNA-type processing. Nature 296: 321-325, 1982. [PubMed: 6801526] [Full Text: https://doi.org/10.1038/296321a0]
Ishizaka, K., Ishizaka, T. Identification of gamma-E-antibodies as a carrier of reaginic activity. J. Immun. 99: 1187-1198, 1967. [PubMed: 4168663]
Kenten, J. H., Molgaard, H. V., Houghton, M., Derbyshire, R. B., Viney, J., Bell, L. O., Gould, H. J. Cloning and sequence determination of the gene for the human immunoglobulin epsilon chain expressed in a myeloma cell line. Proc. Nat. Acad. Sci. 79: 6661-6665, 1982. [PubMed: 6815656] [Full Text: https://doi.org/10.1073/pnas.79.21.6661]
Lotscher, E., Grzeschik, K.-H., Bauer, H. G., Pohlenz, H.-D., Straubinger, B., Zachau, H. G. Dispersed human immunoglobulin kappa light-chain genes. Nature 320: 456-458, 1986. [PubMed: 3083265] [Full Text: https://doi.org/10.1038/320456a0]
Max, E. E., Battey, J., Ney, R., Kirsch, I. R., Leder, P. Duplication and deletion in the human immunoglobulin epsilon genes. Cell 29: 691-699, 1982. [PubMed: 6288268] [Full Text: https://doi.org/10.1016/0092-8674(82)90185-4]
Nishida, Y., Miki, T., Hisajima, H., Honjo, T. Cloning of human immunoglobulin epsilon chain genes: evidence for multiple C-epsilon genes. Proc. Nat. Acad. Sci. 79: 3833-3837, 1982. [PubMed: 6808515] [Full Text: https://doi.org/10.1073/pnas.79.12.3833]
van Loghem, E., Aalberse, R. C., Matsumoto, H. A genetic marker of human IgE heavy chains, Em(1). Vox Sang. 46: 195-206, 1984. [PubMed: 6201004] [Full Text: https://doi.org/10.1111/j.1423-0410.1984.tb00075.x]
Wan, T., Beavil, R. L., Fabiane, S. M., Beavil, A. J., Sohi, M. K., Keown, M., Young, R. J., Henry, A. J., Owens, R. J., Gould, H. J., Sutton, B. J. The crystal structure of IgE Fc reveals an asymmetrically bent conformation. Nature Immun. 3: 681-686, 2002. [PubMed: 12068291] [Full Text: https://doi.org/10.1038/ni811]
Zhang, K., Saxon, A., Max, E. E. Two unusual forms of human immunoglobulin E encoded by alternative RNA splicing of the epsilon heavy chain membrane exons. J. Exp. Med. 176: 233-243, 1992. [PubMed: 1613458] [Full Text: https://doi.org/10.1084/jem.176.1.233]