Gene Summary: This IL4R 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 production. IL-4R, 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 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, sinusitus, asthma, or eczema. Polymorphisms in this gene are also associated with resistance to human immunodeficiency virus type-1 infection. Alternate splicing results in multiple transcript variants. General information above from NCBI
Subunit structure: The functional IL4 receptor is formed by initial binding of IL4 to IL4R. Subsequent recruitment to the complex of the common gamma chain, in immune cells, creates a type I receptor and, in non-immune cells, of IL13RA1 forms a type II receptor. IL4R can also interact with the IL13/IL13RA1 complex to form a similar type II receptor. Interacts with PIK3C3 (By similarity). Interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP (By similarity). Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5. Interacts with SOCS5; inhibits IL4 signaling (By similarity).
Domain: The extracellular domain represents the IL4 binding protein (IL4BP).
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell- surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2- containing phosphatases.
Subcellular location: Cell membrane; Single-pass type I membrane protein.
Isoform 2: Secreted.
Tissue specificity: Isoform 1 and isoform 2 are highly expressed in activated T-cells.
Post-translational: On IL4 binding, phosphorylated on C-terminal tyrosine residues. Phosphorylation on any one of tyrosine residues, Tyr- 575, Tyr-603 or Tyr-631, is required for STAT6-induced gene induction.
The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase.
Sequence similarities: Belongs to the type I cytokine receptor family. Type 4 subfamily.
Contains 1 fibronectin type-III domain.
General information above from UniProt