Domain: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. ,Domain:The box 1 motif is required for JAK interaction and/or activation. ,Domain:The extracellular domain represents the IL4 binding protein (IL4BP) . ,Domain:The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding. ,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 inflammmation. In certain cell types , can signal through activation of insulin receptor substrates , IRS1/IRS2. ,Function:Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells. ,online information:The Singapore human mutation and polymorphism database ,polymorphism:Allelic variants in IL4RA are associated with a susceptibility to atopy , an immunological condition that can lead to clinical symptoms such as allergic rhinitis , sinusitis , asthma and eczema. ,PTM: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. ,PTM:The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase. ,similarity:Belongs to the type I cytokine receptor family. Type 4 subfamily. ,similarity:Contains 1 fibronectin type-III domain. ,subunit: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. In Th1 cells , binds the N-terminal 50 amino acids of SOCS5 , which inhibits JAK1 interaction , STAT6 activation and Th2 cell differentiation. SOCS5 interaction is independent of tyrosine phosphorylation. ,tissue specificity:Both isoform 1 and isoform 2 are highly expressed in activated T-cells. ,
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