Alternative titles; symbols
HGNC Approved Gene Symbol: IL5RA
Cytogenetic location: 3p26.2 Genomic coordinates (GRCh38): 3:3,066,324-3,110,374 (from NCBI)
Tavernier et al. (1991) isolated cDNA clones encoding 2 receptor proteins involved in the binding of human interleukin-5 (IL5; 147850). The major transcript of this receptor gene, as analyzed in both eosinophilic sublines of human promyelocytic cells and in eosinophilic myelocytes grown from cord blood, encodes a secreted form of this receptor. A second component of the receptor was found to be identical to the beta chain of the human granulocyte-macrophage colony-stimulating factor high affinity receptor (CSF2RB; 138981). The finding that IL5 and CSF2 share a receptor subunit provides a molecular basis for the observation that these cytokines can partially interfere with each other's binding and have highly overlapping biologic activities on eosinophils. The common use of the same receptor component is reminiscent of the structural relatedness of IL3 (147740), IL5, and GM-CSF (CSF2; 138960). The homology at the C terminus may indicate a related binding domain. The common origin of all 3 cytokines is also suggested by their clustered chromosomal localization and by the structure of their genes.
The 60-kD alpha chain binds IL5; the 130-kD beta chain increases the binding affinity but cannot bind IL5 by itself. In addition, the beta chain is required for signal transduction, most likely by association with other receptor components. Tavernier et al. (1992) demonstrated that soluble isoforms of the alpha subunit result from a 'normal' splicing event or from the absence of splicing, whereas synthesis of membrane-anchored forms of the alpha subunit requires alternative splicing.
Using a yeast 2-hybrid screen of a granulocyte cDNA library with the cytoplasmic domain of IL5RA as bait, Geijsen et al. (2001) identified an interaction of IL5RA with syntenin (SDCBP; 602217). GST pull-down, BIAcore, coimmunoprecipitation, and deletion mutant analyses confirmed an association of syntenin with the last 15 C-terminal residues of IL5RA; syntenin did not interact with CFS2RB. Within this 15-residue stretch of IL5RA, the C-terminal phenylalanine is critical. Deletion of either of the 2 tandem PDZ domains of syntenin, which are known to interact with C-terminal peptide sequences, abrogated the IL5RA-syntenin interaction. A second 2-hybrid screen identified the mouse transcriptional factor Sox4 (184430) as a binding partner for syntenin but not for IL5RA. The syntenin-Sox4 interaction occurs outside of the PDZ domains of syntenin. Luciferase reporter analysis and fluorescence microscopy showed that IL5, but not IL3, induces cytoplasmic and nuclear expression of syntenin and, in a syntenin- and cytoplasmic IL5RA-dependent manner, of Sox4. Geijsen et al. (2001) concluded that syntenin acts as an adaptor molecule in the IL5RA-mediated activation of SOX4. They also noted that mice lacking either Il5ra or Sox4 have defects in B-cell development.
Sun et al. (1995) identified a promoter (P1) located 5-prime upstream of exon 1 of the IL5RA gene. Zhang et al. (1997) showed that an additional promoter (P2) was present in the 5-prime upstream region of exon 2 of the IL5RA gene.
By use of recombinant inbred strains of mice, Gough and Rakar (1992) localized the murine equivalent of the IL5R gene to the distal half of chromosome 6. The position lay between 2 regions of conserved synteny, one on human chromosome 2 and the second on human chromosome 3. The human IL5R gene presumably maps to one of these 2 chromosomes. Isobe et al. (1992) mapped the IL5RA gene to 3p26-p24 by Southern blot analysis of DNA from a panel of mouse-human hybrid somatic cell lines complemented by in situ hybridization. Jacob et al. (1993) assigned the IL5R gene to 3p26-p25 by study of human-rodent somatic cell hybrids containing various portions of human chromosome 3 and using a human-specific IL5R tandem repeat marker. Using the mouse-specific tandem repeat marker in recombinant inbred strains of mice, they assigned the Il5r gene to the distal part of mouse chromosome 6, close to the Raf1 locus.
Geijsen, N., Uings, I. J., Pals, C., Armstrong, J., McKinnon, M., Raaijmakers, J. A. M., Lammers, J.-W. J., Koenderman, L., Coffer, P. J. Cytokine-specific transcriptional regulation through an IL-5R-alpha interacting protein. Science 293: 1136-1138, 2001. [PubMed: 11498591] [Full Text: https://doi.org/10.1126/science.1059157]
Gough, N. M., Rakar, S. Localization of the IL-5 receptor gene to the distal half of murine chromosome 6 using recombinant inbred strains of mice. Genomics 12: 855-856, 1992. [PubMed: 1572667] [Full Text: https://doi.org/10.1016/0888-7543(92)90328-p]
Isobe, M., Kumura, Y., Murata, Y., Takaki, S., Tominaga, A., Takatsu, K., Ogita, Z. Localization of the gene encoding the alpha subunit of human interleukin-5 receptor (IL5RA) to chromosome region 3p24-3p26. Genomics 14: 755-758, 1992. [PubMed: 1427903] [Full Text: https://doi.org/10.1016/s0888-7543(05)80180-6]
Jacob, C. O., Mykytyn, K., Varcony, T., Drabkin, H. A. Mapping of the interleukin 5 receptor gene to human chromosome 3p25-p26 and to mouse chromosome 6 close to the Raf-1 locus with polymorphic tandem repeat sequences. Mammalian Genome 4: 435-439, 1993. [PubMed: 8104057] [Full Text: https://doi.org/10.1007/BF00296817]
Sun, Z., Yergeau, D. A., Tuypens, T., Tavernier, J., Paul, C. C., Baumann, M. A. Tenen, D. G.; Ackerman, S. J.: Identification and characterization of a functional promoter region in the human eosinophil IL-5 receptor alpha subunit gene. J. Biol. Chem. 270: 1462-1471, 1995. [PubMed: 7836416] [Full Text: https://doi.org/10.1074/jbc.270.3.1462]
Tavernier, J., Devos, R., Cornelis, S., Tuypens, T., Van der Heyden, J., Fiers, W., Plaetinck, G. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF. Cell 66: 1175-1184, 1991. [PubMed: 1833065] [Full Text: https://doi.org/10.1016/0092-8674(91)90040-6]
Tavernier, J., Tuypens, T., Plaetinck, G., Verhee, A., Fiers, W., Devos, R. Molecular basis of the membrane-anchored and two soluble isoforms of the human interleukin 5 receptor alpha subunit. Proc. Nat. Acad. Sci. 89: 7041-7045, 1992. [PubMed: 1495999] [Full Text: https://doi.org/10.1073/pnas.89.15.7041]
Zhang, J., Kuvelkar, R., Cheewatrakoolpong, B., Williams, S., Egan, R. W., Billah, M. M. Evidence for multiple promoters of the human IL-5 receptor alpha subunit gene: a novel 6-base pair element determines cell-specific promoter function. J. Immun. 15: 5412-5421, 1997.