Interleukin-18 (IL18)
The protein contains 193 amino acids for an estimated molecular weight of 22326 Da.
A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850). (updated: June 20, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
(right-click above to access to more options from the contextual menu)
No binding partner found
Biological Process
Activation of protein kinase B activity
Angiogenesis
Cell population proliferation
Cell-cell signaling
Cellular response to organic cyclic compound
Chemokine biosynthetic process
Chemokine production
Cholesterol homeostasis
Cytokine-mediated signaling pathway
Granulocyte macrophage colony-stimulating factor biosynthetic process
Immune response
Inflammatory response
Interferon-gamma biosynthetic process
Interferon-gamma production
Interleukin-13 biosynthetic process
Interleukin-13 production
Interleukin-18-mediated signaling pathway
Interleukin-2 biosynthetic process
Interleukin-6 production
Lipopolysaccharide-mediated signaling pathway
MAPK cascade
Natural killer cell activation
Natural killer cell mediated cytotoxicity
Negative regulation of myoblast differentiation
Neutrophil activation
Positive regulation of activated T cell proliferation
Positive regulation of chemokine production
Positive regulation of cold-induced thermogenesis
Positive regulation of gene expression
Positive regulation of granulocyte macrophage colony-stimulating factor production
Positive regulation of inflammatory response
Positive regulation of interferon-gamma production
Positive regulation of interleukin-13 production
Positive regulation of interleukin-17 production
Positive regulation of macrophage derived foam cell differentiation
Positive regulation of natural killer cell proliferation
Positive regulation of neuroinflammatory response
Positive regulation of NF-kappaB import into nucleus
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of NK T cell proliferation
Positive regulation of phosphatidylinositol 3-kinase signaling
Positive regulation of protein kinase B signaling
Positive regulation of smooth muscle cell proliferation
Positive regulation of T-helper 1 cell cytokine production
Positive regulation of T-helper 2 cell differentiation
Positive regulation of tissue remodeling
Positive regulation of transcription by RNA polymerase II
Positive regulation of tyrosine phosphorylation of STAT protein
Purinergic nucleotide receptor signaling pathway
Regulation of cell adhesion
Sleep
T-helper 1 cell cytokine production
T-helper 1 type immune response
Triglyceride homeostasis
Type 2 immune response
The reference OMIM entry for this protein is 600953
Interleukin 18; il18
Interferon-gamma-inducing factor; igif
CLONING
Okamura et al. (1995) cloned an interferon-gamma (IFNG; 147570)-inducing factor that augments natural killer (NK) cell activity in spleen cells. The gene encodes a precursor protein of 192 amino acids and a mature protein of 157 amino acids. Messenger RNAs for the gene, designated IGIF by them, and for interleukin-12 (IL12; see 161560) were readily detected in Kupffer cells and activated macrophages. Recombinant IGIF induced IFNG more potently than did IL12, which is also a NK-cell stimulatory factor. Administration of anti-IGIF antibodies prevented liver damage in mice inoculated with Propionibacterium acnes and challenged with lipopolysaccharide that induces toxic shock. Okamura et al. (1995) speculated that IGIF may be involved in the development of Th1 cells and also in mechanisms of tissue injury in inflammatory reactions. The interferon-gamma-inducing factor is also known as interleukin-18 (Sarvetnick, 1997).GENE STRUCTURE
Sanchez et al. (2009) noted that the IL18 gene contains 6 exons.MAPPING
By analysis of a human/rodent somatic cell hybrid panel and radiation hybrid analysis, Nolan et al. (1998) mapped the IL18 gene to 11q22.2-q22.3, close to the DRD2 (126450) gene.GENE FUNCTION
The adhesion of circulating cancer cells to capillary endothelia is a critical step in the initiation of metastasis. Vidal-Vanaclocha et al. (2000) reported results demonstrating a role for interleukin-1-beta (IL1B; 147720) and IL18 in the development of hepatic metastases of melanoma in vivo. In vitro, soluble products from mouse melanoma cells stimulated hepatic sinusoidal endothelium to sequentially release tumor necrosis factor-alpha (TNFA; 191160), IL1B, and IL18. The IL18 cytokine increased expression of vascular cell adhesion molecule-1 (VCAM1; 192225) and the adherence of melanoma cells. Shida et al. (2001) found that 30% of normal subjects had a detectable, functionally inactive IL18 fragment, which they termed IL18 type 2, bound to IgM in plasma. The level of IL18 type 2 was 10- to 100-fold higher than that of conventional, active IL18 type 1 in these subjects. Using RT-PCR, immunoblot, and immunofluorescence microscopy analyses, Sugawara et al. (2001) demonstrated that oral epithelial cells express IL18 mRNA and the 24-kD IL18 precursor protein. ELISA analysis showed that stimulation of the cells with proteinase-3 (PRTN3; 177020) and lipopolysaccharide (LPS) after IFNG priming leads to intracellular production and secretion of the 18-kD bioactive form of IL18 in a caspase-1 (CASP1; 147678)-independent fashion. Cell fractionation and immunoblot analyses indicated that PRTN3 acts on the cell surface after the IFNG priming, not intracellularly. Sugawara et al. (2001) proposed that PRTN3 together with LPS and IFNG may be involved in mucosal inflammation, such as periodontitis. Pizarro et al. (1999) detected increased IL18 mRNA and protein expression in intestinal epithelial cells and lamina propria mononuclear cells in Crohn disease tissue compared with ulcerative colitis (see 266600) and normal tissue. By immunohistochemical analysis, Corbaz et al. (2002) showed that IL18-binding protein (IL18BP; 604113) expression in intestinal tissue is increased in endothelial cells as well as cells of the submucosa and overlying lymphoid aggregates in Crohn disease patients compared with controls. Immunofluorescent microscopy demonstrated colocalization with macrophage and endothelial cell markers, but n ... More on the omim web site
July 2, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600953 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed