Summary: Interleukin 4
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Interleukin 4 Edit Wikipedia article
Crystal structure of human IL-4 (2INT)
|Symbols||; BCGF-1; BCGF1; BSF-1; BSF1; IL-4|
|RNA expression pattern|
analysis of the solution structure of human interleukin 4 determined by heteronuclear three-dimensional nuclear magnetic resonance techniques
The interleukin 4 (IL4) is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell. It is closely related and has functions similar to Interleukin 13.
It has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity. IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12.
Inflammation and wound repair
Tissue macrophages play an important role in chronic inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and fibrosis.
The receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to either another IL-4Rα, or a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions.
IL-4 has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds. One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist. The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet.
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- Interleukin-4 at the US National Library of Medicine Medical Subject Headings (MeSH)
- Interleukin-4 from Gentaur at Gentaur
- Recombinant Human Interleukin-4 from Cornell University
- Interleukin-4 from Allergy Glossary at Health On the Net Foundation
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This tab holds annotation information from the InterPro database.
InterPro entry IPR002354Cytokines are protein messengers that carry information from cell to cell [PUBMED:8151703]. Interleukin is one such molecule, and participates in several B-cell activation processes: e.g., it enhances production and secretion of IgG1 and IgE [PUBMED:3083412]; it induces expression of class II major histocompatability complex (MHC) molecules on resting B-cells; and it regulates expression of the low affinity Fc receptor for IgE on lymphocytes and monocytes. Interleukin-4 (IL4) has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds [PUBMED:1993171]. One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist [PUBMED:1400355]. The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet [PUBMED:1400355].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extracellular region (GO:0005576)|
|Molecular function||growth factor activity (GO:0008083)|
|interleukin-4 receptor binding (GO:0005136)|
|Biological process||immune response (GO:0006955)|
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Cytokines are regulatory peptides that can be produced by various cells for communicating and orchestrating the large multicellular system. Cytokines are key mediators of hematopoiesis, immunity, allergy, inflammation, tissue remodeling, angiogenesis, and embryonic development . This superfamily includes both the long and short chain helical cytokines.
The clan contains the following 22 members:CNTF EPO_TPO Flt3_lig GM_CSF Hormone_1 IFN-gamma IL10 IL11 IL12 IL13 IL2 IL22 IL3 IL34 IL4 IL5 IL6 Interferon Leptin LIF_OSM PRF SCF
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Curation and family details
|Seed source:||Pfam-B_833 (release 2.1)|
|Number in seed:||8|
|Number in full:||198|
|Average length of the domain:||84.40 aa|
|Average identity of full alignment:||48 %|
|Average coverage of the sequence by the domain:||78.13 %|
|HMM build commands:||
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IL4 domain has been found. There are 24 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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