Interleukin-4 receptor

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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	OMIM: 147781; MGI: 105367; HomoloGene: 7784; GeneCards: IL4R; OMA:IL4R - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p12.1 Start 27,313,668 bp[1] End 27,364,778 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 F3|7 68.94 cM Start 125,151,292 bp[2] End 125,178,646 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte right lung gastric mucosa upper lobe of left lung muscle layer of sigmoid colon appendix spleen transverse colon right lobe of liver lymph node Top expressed in lumbar spinal ganglion stroma of bone marrow granulocyte mesenteric lymph nodes thymus ankle joint uterus right lung lobe spleen ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding cytokine receptor activity interleukin-4 receptor activity Cellular component integral component of membrane membrane receptor complex integral component of plasma membrane extracellular region extracellular space plasma membrane Biological process immune system process 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 population 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 response to odorant cytokine-mediated signaling pathway positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
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_001363983 RefSeq (protein) NP_000409 NP_001244335 NP_001244336 NP_001244926 NP_001008700 NP_001350912 Location (UCSC) Chr 16: 27.31 – 27.36 Mb Chr 7: 125.15 – 125.18 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Interleukin-4 receptor alpha chain, N-terminal
interleukin-4 / receptor alpha chain complex
Identifiers
Symbol	IL4Ra_N
Pfam	PF09238
InterPro	IPR015319
SCOP2	1iar / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain (γc, forming the type I IL4 receptor) or with IL-13Rα1 (forming the type II IL4 receptor).^[5]

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.^[6] Interactions of IL-4 with TNFα promote structural changes to vascular endothelial cells, thus playing an important role in tissue inflammation.^[7]

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.^[8]

Interactions

Interleukin-4 receptor has been shown to interact with SHC1.^[9][10]

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.^[11]

See also

• Macrophage-activating factor
• Macrophage polarization
• Cluster of differentiation
• Fibronectin type III domain

References

1. GRCh38: Ensembl release 89: ENSG00000077238 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030748 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. McCormick SM, Heller NM (September 2015). "Commentary: IL-4 and IL-13 receptors and signaling". Cytokine. 75 (1): 38–50. doi:10.1016/j.cyto.2015.05.023. PMC 4546937. PMID 26187331.
6. "Entrez Gene: IL4R interleukin 4 receptor".
7. Thornhill MH, Wellicome SM, Mahiouz DL, Lanchbury JS, Kyan-Aung U, Haskard DO (January 1991). "Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent binding mechanisms". Journal of Immunology. 146 (2): 592–598. doi:10.4049/jimmunol.146.2.592. PMID 1702807.
8. Tundup S, Srivastava L, Harn DA (April 2012). "Polarization of host immune responses by helminth-expressed glycans". Annals of the New York Academy of Sciences. 1253 (1): E1–E13. Bibcode:2012NYASA1253E...1T. doi:10.1111/j.1749-6632.2012.06618.x. PMID 22974465. S2CID 43256244.
9. Ikizawa K, Yanagihara Y (February 2000). "Possible involvement of Shc in IL-4-induced germline epsilon transcription in a human B cell line". Biochemical and Biophysical Research Communications. 268 (1): 54–59. doi:10.1006/bbrc.2000.2080. PMID 10652211.
10. 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". Journal of Immunology. 167 (11): 6382–6387. doi:10.4049/jimmunol.167.11.6382. PMID 11714803.
11. 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): 271–281. doi:10.1016/S0092-8674(00)80736-9. PMID 10219247. S2CID 18795930.

Further reading

• Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999). "The IL-4 receptor: signaling mechanisms and biologic functions". Annual Review of Immunology. 17 (1): 701–738. doi:10.1146/annurev.immunol.17.1.701. PMID 10358772.
• Jiang H, Harris MB, Rothman P (June 2000). "IL-4/IL-13 signaling beyond JAK/STAT". The Journal of Allergy and Clinical Immunology. 105 (6 Pt 1): 1063–1070. doi:10.1067/mai.2000.107604. PMID 10856136.

External links

• CD124+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Interleukin-4 receptor subunit alpha

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