IL4_13

Interleukins 4 and 13

• SMART accession number: SM00190
• Description: Interleukins-4 and -13 are cytokines involved in inflammatory and immune responses. IL-4 stimulates B and T cells.
• Interpro abstract (IPR001325): Interleukin-4 (IL-4) is a cytokine that plays a central role in the control and regulation of the immune and inflammatory system [(PUBMED:3284813), (PUBMED:1693082)]. IL-4 is a participant in several B-cell activation processes. It also stimulates other cell types such as T cells or mast cells. IL-4 is a glycoprotein that contains three disulphide bonds [(PUBMED:1993171)].

  Interleukin-13 (IL-13) is a pleiotropic cytokine which may be important in the regulation of the inflammatory and immune responses [(PUBMED:8096327)].

  The sequences of IL-4 and IL-13 are distantly related.

• GO process: immune response (GO:0006955)
• GO component: extracellular region (GO:0005576)
• GO function: cytokine receptor binding (GO:0005126)

There are 74 IL4_13 domains in 74 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Bamborough P, Duncan D, Richards WG
• Predictive modelling of the 3-D structure of interleukin-13.
• Protein Eng. 1994; 7: 1077-82

Several atomic structures are now available for the family of helical cytokines, which includes growth hormone as well as many of the interleukins. Using structural information from five members of this family, two alternative models of interleukin (IL)-13 are proposed. IL-13 has biological properties similar to those of IL-4 and, like the other interleukins, is a potentially important pharmaceutical target. The model of IL-13 is discussed and compared with the known interleukin structures.

• Minty A et al.
• Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses.
• Nature. 1993; 362: 248-50

The discovery of new cytokines normally relies on a prior knowledge of at least one of their biological effects, which is used as a criterion either for the purification of the protein or for the isolation of the complementary DNA by expression cloning. However, the redundancy of cytokine activities complicates the discovery of novel cytokines in this way, and the pleiotropic nature of many cytokines means that the principal activities of a new cytokine may bear little relation to that used for its isolation. We have adopted an alternative approach which relies on differential screening of an organized subtracted cDNA library from activated peripheral blood mononuclear cells, using the inducibility of lymphokine messenger RNAs by anti-CD28 as a primary screening criterion. The ligation of the CD28 antigen on the T lymphocyte by a surface antigen, B7/BB-1, expressed on activated B lymphocytes and monocytes is a key step in the activation of T lymphocytes and the accumulation of lymphokine mRNAs. Here we report the discovery by molecular cloning of a new interleukin (interleukin-13 or IL-13) expressed in activated human T lymphocytes. Recombinant IL-13 protein inhibits inflammatory cytokine production induced by lipopolysaccharide in human peripheral blood monocytes. Moreover, it synergizes with IL-2 in regulating interferon-gamma synthesis in large granular lymphocytes. Recent mapping of the IL-13 gene shows that it is closely linked to the IL-4 gene on chromosome 5q 23-31 (ref. 4). Interleukin-13 may be critical in regulating inflammatory and immune responses.

• Yokota T et al.
• Molecular biology of interleukin 4 and interleukin 5 genes and biology of their products that stimulate B cells, T cells and hemopoietic cells.
• Immunol Rev. 1988; 102: 137-87

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
33.33	map04664	Fc epsilon RI signaling pathway
33.33	map04060	Cytokine-cytokine receptor interaction
16.67	map04640	Hematopoietic cell lineage
16.67	map04660	T cell receptor signaling pathway

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with IL4_13 domain which could be assigned to a KEGG orthologous group, and not all proteins containing IL4_13 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of IL4_13 domains in PDB

PDB code	Title
1bbn	Three-dimensional solution structure of human interleukin-4 by multi-dimensional heteronuclear magnetic resonance spectroscopy
1bcn	Three-dimensional solution structure of human interleukin-4 by multi-dimensional heteronuclear magnetic resonance spectroscopy
1cyl	Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and nmr spectroscopy
1ga3	Nmr structure of interleukin-13
1hij	Interleukin-4 mutant with arg 88 replaced with gln (r88q)
1hik	Interleukin-4 (wild-type)
1hzi	Interleukin-4 mutant e9a
1iar	Interleukin-4 / receptor alpha chain complex
1ijz	Solution structure of human il-13
1ik0	Solution structure of human il-13
1iti	The high resolution three-dimensional solution structure of human interleukin-4 determined by multi-dimensional heteronuclear magnetic resonance spectroscopy
1itl	Human interleukin 4: the solution structure of a four-helix- bundle protein
1itm	Analysis of the solution structure of human interleukin 4 determined by heteronuclear three-dimensional nuclear magnetic resonance techniques
1rcb	Crystal structure of human recombinant interleukin-4 at 2.25 angstroms resolution
2b8u	Crystal structure of wildtype human interleukin-4
2b8x	Crystal stucture of the interleukin-4 variant f82d
2b8y	Crystal structure of the interleukin-4 variant t13df82d
2b8z	Crystal structure of the interleukin-4 variant r85a
2b90	Crystal structure of the interleukin-4 variant t13dr85a
2b91	Crystal structure of the interleukin-4 variant f82dr85a
2cyk	Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and nmr spectroscopy
2d48	Crystal structure of the interleukin-4 variant t13d
2int	Crystal structure of recombinant human interleukin-4
3bpl	Crystal structure of the il4-il4r-common gamma ternary complex
3bpn	Crystal structure of the il4-il4r-il13ra ternary complex
3bpo	Crystal structure of the il13-il4r-il13ra ternary complex
3g6d	Crystal structure of the complex between cnto607 fab and il-

Links (links to other resources describing this domain)

• BLOCKS: INTERLEUKIN_4_13
• PFAM: Interleukin4
• INTERPRO: IPR001325
• PROSITE: INTERLEUKIN_4_13