| Interleukin-4 receptor alpha chain, N-terminal | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 interleukin-4 / receptor alpha chain complex | |||||||||
| Identifiers | |||||||||
| Symbol | IL4Ra_N | ||||||||
| Pfam | PF09238 | ||||||||
| InterPro | IPR015319 | ||||||||
| SCOP2 | 1iar /SCOPe /SUPFAM | ||||||||
| |||||||||
Theinterleukin 4 receptor is atype I cytokine receptor. It is aheterodimer, that is, composed of two subunits.IL4R is the humangene coding for IL-4Rα, the subunit which combines with eithercommon gamma chain (γc, forming the type IIL4 receptor) or withIL-13Rα1 (forming the type II IL4 receptor).[5]
This gene encodes the alpha chain of the interleukin-4 receptor, atype I transmembrane protein that can bindinterleukin 4 andinterleukin 13 to regulateIgEantibody production inB cells. AmongT cells, the encoded protein also can bind interleukin 4 to promote differentiation ofTh2 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.[6] Interactions of IL-4 withTNFα promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation.[7]
The binding of IL-4 or IL-13 to the IL-4 receptor on the surface ofmacrophages results in the alternative activation of those macrophages. Alternatively activated macrophages (AAMΦ) downregulate inflammatory mediators such asIFNγ during immune responses, particularly with regards tohelminth infections.[8]
Interleukin-4 receptor has been shown tointeract withSHC1.[9][10]
TheN-terminal (extracellular) portion of interleukin-4 receptor is related in overall topology tofibronectin type III modules andfolds into a sandwich comprising sevenantiparallelbeta sheets arranged in a three-strand and a four-strandbeta-pleated sheet. They are required for binding of interleukin-4 to the receptor alpha chain, which is a crucial event for the generation of aTh2-dominated earlyimmune response.[11]
