| SMART accession number: | SM00125
|
|---|
| Description: |
Cytokines with various biological functions. Interluekin 1 alpha and beta are also known as hematopoietin and catabolin. |
| Interpro abstract (IPR000975): |
Interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis (PUBMED:2969618). Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors (PUBMED:8702856). The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors. Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location (PUBMED:1833184). The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA). The crystal structures of IL1A and IL1B (PUBMED:2602367) have been solved, showing them to share the same 12-stranded beta-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors (PUBMED:1738162). The beta-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel beta-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding. The Vaccinia virus genes B15R and B18R each encode proteins with N-terminal hydrophobic sequences, possible sites for attachment of N-linked carbohydrate and a short C-terminal hydrophobic domain (PUBMED:1826022). These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons reveal that the gene products are related to each other (20% identity) and to the Ig superfamily. The highest degree of similarity is to the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. A novel method for virus immune evasion has been proposed in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6, preventing these cytokines reaching their natural receptors (PUBMED:1826022). A similar gene product from Cowpox virus (CPV) has also been shown to specifically bind murine IL-1 beta (PUBMED:1339315). This entry represents Interleukin-1.
|
| GO process: | immune response (GO:0006955) |
| GO component: | extracellular region (GO:0005576) |
| GO function: | interleukin-1 receptor binding (GO:0005149) |
| Family alignment: |
|
|---|
Click on the following links for more information.
- Evolution (species in which this domain is found)
-
- Literature (relevant references for this domain)
-
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Dinarello CA
- Interleukin-1.
- Cytokine Growth Factor Rev. 1997; 8: 253-65
- Display abstract
Interleukin-1 (IL-1) is the prototypic pro-inflammatory cytokine. There are two forms of IL-1, IL-1alpha and IL-1beta and in most studies, their biological activities are indistinguishable. IL-1 affects nearly every cell type, often in concert with another pro-inflammatory cytokine, tumor necrosis factor (TNF). Although IL-1 can upregulate host defenses and function as an immunoadjuvant, IL-1 is a highly inflammatory cytokine. The margin between clinical benefit and unacceptable toxicity in humans is exceedingly narrow. In contrast, agents that reduce the production and/or activity of IL-1 are likely to have an impact on clinical medicine. The synthesis, processing, secretion and activity of IL-1, particularly IL-1beta, are tightly regulated events. A unique aspect of cytokine biology is the naturally occurring IL-1 receptor antagonist (IL-1Ra). IL-1Ra is structurally similar to IL-1beta but lacking agonist activity is used in clinical trials to reduce disease severity. In addition, regulation of IL-1 activity extends to low numbers of surface receptors, circulating soluble receptors and a cell surface "decoy" receptor to down-regulate responses to IL-1beta. This review updates the current knowledge on IL-1.
- Patarca R, Fletcher MA
- Interleukin-1: basic science and clinical applications.
- Crit Rev Oncog. 1997; 8: 143-88
- Kurzrock R, Wetzler M, Estrov Z, Talpaz M
- Interleukin-1 and its inhibitors: a biologic and therapeutic model for the role of growth regulatory factors in leukemias.
- Cytokines Mol Ther. 1995; 1: 177-84
- Display abstract
Production of growth factors may provide a mechanism for disease evolution in some leukemias. Interleukin-1 is a plelotropic cytokine with the ability to synergize with other growth factors as well as to stimulate their production and release. Autocrine and/or paracrine secretion of interleukin-1 has been implicated in the pathogenesis of both chronic and acute myelogenous leukemia. Recently, a series of both specific and nonspecific IL-1 inhibitory molecules have been identified. These include IL-1 receptor antagonist, soluble IL-1 receptors, IL-1-converting enzyme inhibitor, IL-4, IL-10 and IL-1-antisense. Early experiments demonstrating the ability of some of these molecules to inhibit acute and chronic myelogenous leukemia growth suggest that clinical trials of these compounds may provide a novel management approach in these malignancies. Here we review the potential biologic and therapeutic role of IL-1 and its inhibitors in the myeloid leukemias.
- Metabolism (metabolic pathways involving proteins which contain this domain)
-
 Click the image to view the interactive version of the map in iPath | | % proteins involved | KEGG pathway ID | Description |
|---|
| 19.19 | map04060 | Cytokine-cytokine receptor interaction | | 15.15 | map04640 | Hematopoietic cell lineage | | 15.15 | map04010 | MAPK signaling pathway | | 15.15 | map04210 | Apoptosis | | 15.15 | map04940 | Type I diabetes mellitus | | 9.09 | map04620 | Toll-like receptor signaling pathway | | 9.09 | map05010 | Alzheimer's disease | | 1.01 | map00970 | Aminoacyl-tRNA biosynthesis | | 1.01 | map00290 | Valine, leucine and isoleucine biosynthesis |
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 IL1 domain which could be assigned to a KEGG orthologous group, and not all proteins containing IL1 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 IL1 domains in PDB
| PDB code | Main view | Title | | 1hib |  | The structure of an interleukin-1 beta mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition |
| 1i1b |  | Crystal structure of recombinant human interleukin-1beta at 2.0 angstroms resolution |
| 1ilr |  | Crystal structure of the interleukin-1 receptor antagonist |
| 1ilt |  | X-ray structure of interleukin-1 receptor antagonist at 2.0 angstroms resolution |
| 1iob |  | Interleukin-1 beta from joint x-ray and nmr refinement |
| 1ira |  | Complex of the interleukin-1 receptor with the interleukin- receptor antagonist (il1ra) |
| 1irp |  | Solution structure of human interleukin-1 receptor antagonist protein |
| 1itb |  | Type-1 interleukin-1 receptor complexed with interleukin-1 beta |
| 1j0s |  | Solution structure of the human interleukin-18 |
| 1l2h |  | Crystal structure of interleukin 1-beta f42w/w120f mutant |
| 1md6 |  | High resolution crystal structure of murine il-1f5 reveals unique loop conformation for specificity |
| 1s0l |  | Interleukin 1 beta mutant f42w |
| 1t4q |  | Interleukin 1 beta f101w |
| 1too |  | Interleukin 1b mutant f146w |
| 1tp0 |  | Triple mutation in interleukin 1 beta cavity:replacement of phenylalanines with tryptophan. |
| 1twe |  | Interleukin 1 beta mutant f101y |
| 1twm |  | Interleukin-1 beta mutant f146y |
| 21bi |  | Interleukin-1 beta (il-1 beta) (mutant with cys 71 replaced by ala) (c71a) |
| 2i1b |  | Crystallographic refinement of interleukin-1 beta at 2.0 angstroms resolution |
| 2ila |  | Structure of interleukin 1alpha at 2.7-angstroms resolution |
| 2irt |  | Initial crystallographic analyses of a recombinant interleukin-1 receptor antagonist protein |
| 2kh2 |  | |
| 2mib |  | The structure of murine interleukin-1 beta at 2.8 angstroms resolution |
| 2nvh |  | Determination of solvent content in cavities in interleukin- using experimentally-phased electron density |
| 2vxt |  | |
| 31bi |  | Interleukin-1 beta (il-1 beta) (mutant with cys 71 replaced by ser) (c71s) |
| 3f62 |  | |
| 41bi |  | Interleukin-1 beta (il-1 beta) (mutant with cys 8 replaced by ala (c8a) |
| 4i1b |  | Functional implications of interleukin-1beta based on the three-dimensional structure |
| 5i1b |  | A comparison of the high resolution structures of human and murine interleukin-1b |
| 6i1b |  | High-resolution three-dimensional structure of interleukin- beta in solution by three-and four-dimensional nuclear magnetic resonance spectroscopy |
| 7i1b |  | High-resolution three-dimensional structure of interleukin- beta in solution by three-and four-dimensional nuclear magnetic resonance spectroscopy |
| 8i1b |  | A comparison of the high resolution structures of human and murine interleukin-1b |
| 9ilb |  | Human interleukin-1 beta |
- Links (links to other resources describing this domain)
-