Interleukin-4 receptor

IL4R
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IAR, 1IRS, 3BPL, 3BPN, 3BPO, 5E4E
Identifiers
Aliases	IL4R, CD124, IL-4RA, IL4RA, Interleukin-4 receptor, interleukin 4 receptor
External IDs	MGI: 105367 HomoloGene: 7784 GeneCards: IL4R
Gene ontology Molecular function • signal transducer activity, downstream of receptor • protein binding • cytokine receptor activity • interleukin-4 receptor activity Cellular component • integral component of membrane • membrane • receptor complex • plasma membrane • integral component of plasma membrane • extracellular space • extracellular region Biological process • cytokine-mediated signaling pathway • immune system process • positive regulation of chemokine secretion • positive regulation of immunoglobulin production • positive regulation of macrophage activation • positive regulation of mast cell degranulation • response to estrogen • production of molecular mediator involved in inflammatory response • positive regulation of myoblast fusion • negative regulation of T-helper 1 cell differentiation • regulation of cell proliferation • immunoglobulin mediated immune response • immune response • positive regulation of T-helper 2 cell differentiation • ovulation • signal transduction • defense response to protozoan • interleukin-4-mediated signaling pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3566	16190
Ensembl	ENSG00000077238	ENSMUSG00000030748
UniProt	P24394	P16382
RefSeq (mRNA)	NM_000418 NM_001008699 NM_001257406 NM_001257407 NM_001257997	NM_001008700 NM_010557
RefSeq (protein)	NP_000409.1 NP_001244335.1 NP_001244336.1	NP_001008700.1
Location (UCSC)	Chr 16: 27.31 – 27.36 Mb	Chr 7: 125.55 – 125.58 Mb
PubMed search	[1]	[2]
Wikidata

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Interleukin-4 receptor alpha chain, N-terminal
interleukin-4 / receptor alpha chain complex
Identifiers
Symbol	IL4Ra_N
Pfam	PF09238
InterPro	IPR015319
SCOP	1iar
SUPERFAMILY	1iar
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The interleukin 4 receptor is a type I cytokine receptor. IL4R is its human gene.

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.^[3]

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.^[4]

Interactions

Interleukin-4 receptor has been shown to interact with SHC1.^[5][6]

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.^[7]

See also

• Cluster of differentiation

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. "Entrez Gene: IL4R interleukin 4 receptor".
4. Tundup S, Srivastava L, Harn DA (April 2012). "Polarization of host immune responses by helminth-expressed glycans". Ann. N. Y. Acad. Sci. 1253: E1–E13. doi:10.1111/j.1749-6632.2012.06618.x. PMID 22974465.
5. Ikizawa K, Yanagihara Y (February 2000). "Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line". Biochem. Biophys. Res. Commun. 268 (1): 54–9. doi:10.1006/bbrc.2000.2080. PMID 10652211.
6. Kashiwada M, Giallourakis CC, Pan PY, Rothman PB (December 2001). "Immunoreceptor tyrosine-based inhibitory motif of the IL-4 receptor associates with SH2-containing phosphatases and regulates IL-4-induced proliferation". J. Immunol. 167 (11): 6382–7. doi:10.4049/jimmunol.167.11.6382. PMID 11714803.
7. Hage T, Sebald W, Reinemer P (April 1999). "Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface". Cell. 97 (2): 271–81. doi:10.1016/S0092-8674(00)80736-9. PMID 10219247.

Further reading

• Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999). "The IL-4 receptor: signaling mechanisms and biologic functions.". Annu. Rev. Immunol. 17 (1): 701–38. doi:10.1146/annurev.immunol.17.1.701. PMID 10358772.
• Jiang H, Harris MB, Rothman P (2000). "IL-4/IL-13 signaling beyond JAK/STAT.". J. Allergy Clin. Immunol. 105 (6 Pt 1): 1063–70. doi:10.1067/mai.2000.107604. PMID 10856136.

External links

• CD124 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)

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