UniProt functional annotation for P24394



	UniProt functional annotation for P24394

UniProt code: P24394.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:8124718}.

Function: Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells. {ECO:0000269|PubMed:8124718}.

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 (PubMed:7775445, PubMed:8804422). Interacts with PIK3C3 (By similarity). Interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP (PubMed:11714803). Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5. Interacts with SOCS5; inhibits IL4 signaling (By similarity). Interacts with JAK3 (PubMed:7538655). Interacts with CLM1 (By similarity). {ECO:0000250|UniProtKB:P16382, ECO:0000269|PubMed:11714803, ECO:0000269|PubMed:7538655, ECO:0000269|PubMed:7775445, ECO:0000269|PubMed:8804422}.

Subcellular location: Cell membrane; Single-pass type I membrane protein.

Subcellular location: [Isoform 2]: Secreted.

Tissue specificity: Isoform 1 and isoform 2 are highly expressed in activated T-cells.

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.

Domain: The box 1 motif is required for JAK interaction and/or activation.

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.

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. {ECO:0000269|PubMed:8624803}.

Ptm: The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase. {ECO:0000269|PubMed:10341317}.

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.

Polymorphism: Allelic variants in IL4RA are associated with cedar pollen sensitization. Individuals develop Japanese cedar pollinosis with increased exposure to cedar pollen. Japanese cedar pollinosis is a type I allergic disease with ocular and nasal symptoms that develop paroxysmally on contact with Japanese cedar pollen. These symptoms, which occur seasonally each year, are typical features of allergic rhinitis, such as sneezing, excessive nasal secretion, nasal congestion, and conjunctival itching.

Similarity: Belongs to the type I cytokine receptor family. Type 4 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:8124718}.



Function:		Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells. {ECO:0000269\|PubMed:8124718}.


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 (PubMed:7775445, PubMed:8804422). Interacts with PIK3C3 (By similarity). Interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP (PubMed:11714803). Interacts with JAK1 through a Box 1-containing region; inhibited by SOCS5. Interacts with SOCS5; inhibits IL4 signaling (By similarity). Interacts with JAK3 (PubMed:7538655). Interacts with CLM1 (By similarity). {ECO:0000250\|UniProtKB:P16382, ECO:0000269\|PubMed:11714803, ECO:0000269\|PubMed:7538655, ECO:0000269\|PubMed:7775445, ECO:0000269\|PubMed:8804422}.
Subcellular location:		Cell membrane; Single-pass type I membrane protein.
Subcellular location:		[Isoform 2]: Secreted.
Tissue specificity:		Isoform 1 and isoform 2 are highly expressed in activated T-cells.
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.
Domain:		The box 1 motif is required for JAK interaction and/or activation.
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.
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. {ECO:0000269\|PubMed:8624803}.
Ptm:		The soluble form (sIL4R/IL4BP) can also be produced by proteolytic cleavage at the cell surface (shedding) by a metalloproteinase. {ECO:0000269\|PubMed:10341317}.
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.
Polymorphism:		Allelic variants in IL4RA are associated with cedar pollen sensitization. Individuals develop Japanese cedar pollinosis with increased exposure to cedar pollen. Japanese cedar pollinosis is a type I allergic disease with ocular and nasal symptoms that develop paroxysmally on contact with Japanese cedar pollen. These symptoms, which occur seasonally each year, are typical features of allergic rhinitis, such as sneezing, excessive nasal secretion, nasal congestion, and conjunctival itching.
Similarity:		Belongs to the type I cytokine receptor family. Type 4 subfamily. {ECO:0000305}.