Biology:Interleukin-4 receptor

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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).

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. Interactions of IL-4 with TNFα promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation.

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.

Interactions

Interleukin-4 receptor has been shown to interact with SHC1.

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.

See also

• Macrophage-activating factor
• Macrophage polarization
• Cluster of differentiation
• Fibronectin type III domain

Further reading

• "The IL-4 receptor: signaling mechanisms and biologic functions.". Annu. Rev. Immunol. 17 (1): 701–38. 1999. doi:10.1146/annurev.immunol.17.1.701. PMID 10358772. https://zenodo.org/record/1234989. 
• "IL-4/IL-13 signaling beyond JAK/STAT.". J. Allergy Clin. Immunol. 105 (6 Pt 1): 1063–70. 2000. doi:10.1067/mai.2000.107604. PMID 10856136. 

External links

• CD124+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Interleukin-4 receptor subunit alpha

This article incorporates text from the public domain Pfam and InterPro: IPR015319