Function: Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.
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. 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. Ref.6 Ref.7
Subcellular location: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted.
Tissue specificity: Expressed in both Th1 and Th2 cells.
Domain: The extracellular domain represents the IL4 binding protein (IL4BP)
By similarity.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.
Post-translational modification: On IL4 binding, phosphorylated on C-terminal tyrosine residues. Ref.7Soluble IL4R can also be produced by proteolytic cleavage at the cell surface (shedding).
Miscellaneous: The sequences from strains C3H, CBA, DBA/2 and FVB/N are all identical to the one displayed.
Sequence similarities: Belongs to the type I cytokine receptor family. Type 4 subfamily.Contains 1 fibronectin type-III domain.
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