Interleukin-4 receptor

{{Redirect|Cd124|the isotope of cadmium (Cd-124 or ¹²⁴Cd)|Cadmium-124}}

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox protein family

| Symbol = IL4Ra_N

| Name = Interleukin-4 receptor alpha chain, N-terminal

| image = PDB 1iar EBI.jpg

| width =

| caption = interleukin-4 / receptor alpha chain complex

| Pfam = PF09238

| Pfam_clan =

| InterPro = IPR015319

| SMART =

| PROSITE =

| MEROPS =

| SCOP = 1iar

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain (γc, forming the type I IL4 receptor) or with IL-13Rα1 (forming the type II IL4 receptor).{{cite journal | vauthors = McCormick SM, Heller NM | title = Commentary: IL-4 and IL-13 receptors and signaling | journal = Cytokine | volume = 75 | issue = 1 | pages = 38–50 | date = September 2015 | pmid = 26187331 | pmc = 4546937 | doi = 10.1016/j.cyto.2015.05.023 }}

Function

This gene encodes the alpha chain of the interleukin-4 receptor, a type I transmembrane protein that can bind interleukin 4 and interleukin 13 to regulate IgE antibody production in B cells. Among T cells, the encoded protein also can bind interleukin 4 to promote differentiation of Th2 cells. A soluble form of the encoded protein can be produced by an alternate splice variant or by proteolysis of the membrane-bound protein, and this soluble form can inhibit IL4-mediated cell proliferation and IL5 upregulation by T-cells. Allelic variations in this gene have been associated with atopy, a condition that can manifest itself as allergic rhinitis, sinusitis, asthma, or eczema. Two transcript variants encoding different isoforms, a membrane-bound and a soluble form, have been found for this gene.{{cite web | title = Entrez Gene: IL4R interleukin 4 receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3566}} Interactions of IL-4 with TNFα promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation.{{cite journal | vauthors = Thornhill MH, Wellicome SM, Mahiouz DL, Lanchbury JS, Kyan-Aung U, Haskard DO | title = Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent binding mechanisms | journal = Journal of Immunology | volume = 146 | issue = 2 | pages = 592–598 | date = January 1991 | pmid = 1702807 | doi = 10.4049/jimmunol.146.2.592 | doi-access = free }}

The binding of IL-4 or IL-13 to the IL-4 receptor on the surface of macrophages results in the alternative activation of those macrophages. Alternatively activated macrophages (AAMΦ) downregulate inflammatory mediators such as IFNγ during immune responses, particularly with regards to helminth infections.{{cite journal | vauthors = Tundup S, Srivastava L, Harn DA | title = Polarization of host immune responses by helminth-expressed glycans | journal = Annals of the New York Academy of Sciences | volume = 1253 | issue = 1 | pages = E1–E13 | date = April 2012 | pmid = 22974465 | doi = 10.1111/j.1749-6632.2012.06618.x | s2cid = 43256244 | bibcode = 2012NYASA1253E...1T }}

Interactions

Interleukin-4 receptor has been shown to interact with SHC1.{{cite journal | vauthors = Ikizawa K, Yanagihara Y | title = Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line | journal = Biochemical and Biophysical Research Communications | volume = 268 | issue = 1 | pages = 54–59 | date = February 2000 | pmid = 10652211 | doi = 10.1006/bbrc.2000.2080 }}{{cite journal | vauthors = Kashiwada M, Giallourakis CC, Pan PY, Rothman PB | title = Immunoreceptor tyrosine-based inhibitory motif of the IL-4 receptor associates with SH2-containing phosphatases and regulates IL-4-induced proliferation | journal = Journal of Immunology | volume = 167 | issue = 11 | pages = 6382–6387 | date = December 2001 | pmid = 11714803 | doi = 10.4049/jimmunol.167.11.6382 | doi-access = free }}

Structure

The N-terminal (extracellular) portion of interleukin-4 receptor is related in overall topology to fibronectin type III modules and folds into a sandwich comprising seven antiparallel beta sheets arranged in a three-strand and a four-strand beta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of a Th2-dominated early immune response.{{cite journal | vauthors = Hage T, Sebald W, Reinemer P | title = Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface | journal = Cell | volume = 97 | issue = 2 | pages = 271–281 | date = April 1999 | pmid = 10219247 | doi = 10.1016/S0092-8674(00)80736-9 | s2cid = 18795930 | doi-access = free }}

References

External links

{{MeshName|CD124+Antigen}}
[https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P24394 PDBe-KB] provides an overview of all the structure information available in the PDB for Human Interleukin-4 receptor subunit alpha

Category:Type I cytokine receptors

Category:Clusters of differentiation

Category:Protein domains