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Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)

 IL18_MOUSE              Reviewed;         192 AA.
P70380;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
15-JUL-1998, sequence version 2.
02-JUN-2021, entry version 163.
RecName: Full=Interleukin-18;
Short=IL-18;
AltName: Full=Interferon gamma-inducing factor;
Short=IFN-gamma-inducing factor;
AltName: Full=Interleukin-1 gamma;
Short=IL-1 gamma;
Flags: Precursor;
Name=Il18 {ECO:0000312|MGI:MGI:107936}; Synonyms=Igif;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
TISSUE=Liver;
PubMed=7477296; DOI=10.1038/378088a0;
Okamura H., Tsutui H., Komatsu T., Yutsudo M., Hakura A., Tanimoto T.,
Torigoe K., Okura T., Nukada Y., Hattori K., Akita K., Namba M., Tanabe F.,
Konishi K., Fukuda S., Kurimoto M.;
"Cloning of a new cytokine that induces IFN-gamma production by T cells.";
Nature 378:88-91(1995).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=FVB/N; TISSUE=Colon;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project:
the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 1-191.
STRAIN=NOD; TISSUE=Pancreas;
PubMed=9022080; DOI=10.1172/jci119181;
Rothe H., Jenkins N.A., Copeland N.G., Kolb H.;
"Active stage of autoimmune diabetes is associated with the expression of a
novel cytokine, IGIF, which is located near Idd2.";
J. Clin. Invest. 99:469-474(1997).
[4]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Brain, and Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: A proinflammatory cytokine primarily involved in polarized T-
helper 1 (Th1) cell and natural killer (NK) cell immune responses. Upon
binding to IL18R1 and IL18RAP, forms a signaling ternary complex which
activates NF-kappa-B, triggering synthesis of inflammatory mediators.
Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-
helper 1 (Th1) cells and natural killer (NK) cells.
{ECO:0000250|UniProtKB:Q14116}.
-!- SUBUNIT: Forms a ternary complex with ligand-binding receptor subunit
IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane.
Mature IL18 first binds to IL18R1 forming a low affinity binary
complex, which then interacts with IL18RAP to form a high affinity
ternary complex that signals inside the cell. Interacts with cargo
receptor TMED10; the interaction mediates the translocation from the
cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate
compartment) and thereby secretion. {ECO:0000250|UniProtKB:Q14116}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14116}.
Secreted {ECO:0000250|UniProtKB:Q14116}. Note=The secretion is
dependent on protein unfolding and facilitated by the cargo receptor
TMED10; it results in protein translocation from the cytoplasm into the
ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed
by vesicle entry and secretion. {ECO:0000250|UniProtKB:Q14116}.
-!- PTM: The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield
the active form. {ECO:0000250}.
-!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; D49949; BAA08705.1; -; mRNA.
EMBL; BC024384; AAH24384.1; -; mRNA.
EMBL; U66244; AAB49753.1; -; mRNA.
CCDS; CCDS40622.1; -.
PIR; S60226; S60226.
RefSeq; NP_032386.1; NM_008360.1.
RefSeq; XP_006510089.1; XM_006510026.1.
RefSeq; XP_006510090.1; XM_006510027.3.
RefSeq; XP_006510091.1; XM_006510028.3.
SMR; P70380; -.
DIP; DIP-950N; -.
STRING; 10090.ENSMUSP00000054591; -.
PhosphoSitePlus; P70380; -.
PaxDb; P70380; -.
PRIDE; P70380; -.
ProteomicsDB; 266967; -.
Antibodypedia; 1287; 942 antibodies.
DNASU; 16173; -.
Ensembl; ENSMUST00000180021; ENSMUSP00000137193; ENSMUSG00000039217.
Ensembl; ENSMUST00000214117; ENSMUSP00000151002; ENSMUSG00000039217.
GeneID; 16173; -.
KEGG; mmu:16173; -.
UCSC; uc009pju.1; mouse.
CTD; 3606; -.
MGI; MGI:107936; Il18.
eggNOG; ENOG502SDJZ; Eukaryota.
GeneTree; ENSGT00390000001053; -.
HOGENOM; CLU_113349_0_0_1; -.
InParanoid; P70380; -.
OMA; INPPDNI; -.
PhylomeDB; P70380; -.
BioGRID-ORCS; 16173; 0 hits in 52 CRISPR screens.
ChiTaRS; Il18; mouse.
PRO; PR:P70380; -.
Proteomes; UP000000589; Chromosome 9.
RNAct; P70380; protein.
Bgee; ENSMUSG00000039217; Expressed in epithelium of stomach and 268 other tissues.
ExpressionAtlas; P70380; baseline and differential.
Genevisible; P70380; MM.
GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
GO; GO:0005737; C:cytoplasm; ISO:MGI.
GO; GO:0005615; C:extracellular space; IDA:MGI.
GO; GO:0005125; F:cytokine activity; IDA:MGI.
GO; GO:0045515; F:interleukin-18 receptor binding; ISS:UniProtKB.
GO; GO:0032148; P:activation of protein kinase B activity; ISO:MGI.
GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
GO; GO:0008283; P:cell population proliferation; IDA:MGI.
GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISO:MGI.
GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI.
GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:UniProtKB.
GO; GO:0006955; P:immune response; TAS:MGI.
GO; GO:0006954; P:inflammatory response; IGI:MGI.
GO; GO:0035655; P:interleukin-18-mediated signaling pathway; IDA:MGI.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:MGI.
GO; GO:0000165; P:MAPK cascade; ISO:MGI.
GO; GO:0030101; P:natural killer cell activation; IDA:MGI.
GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:MGI.
GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:MGI.
GO; GO:0033030; P:negative regulation of neutrophil apoptotic process; ISO:MGI.
GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
GO; GO:0042119; P:neutrophil activation; IDA:MGI.
GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
GO; GO:2000504; P:positive regulation of blood vessel remodeling; ISO:MGI.
GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISO:MGI.
GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:MGI.
GO; GO:0032736; P:positive regulation of interleukin-13 production; TAS:UniProtKB.
GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL.
GO; GO:2000256; P:positive regulation of male germ cell proliferation; ISO:MGI.
GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:MGI.
GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:MGI.
GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IMP:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
GO; GO:0043117; P:positive regulation of vascular permeability; ISO:MGI.
GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
GO; GO:0001666; P:response to hypoxia; ISO:MGI.
GO; GO:0030431; P:sleep; ISS:UniProtKB.
GO; GO:0042088; P:T-helper 1 type immune response; ISS:UniProtKB.
GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL.
InterPro; IPR015529; IL-18.
InterPro; IPR000975; IL-1_fam.
InterPro; IPR008996; IL1/FGF.
Pfam; PF00340; IL1; 1.
PIRSF; PIRSF015162; Interleukin_18; 1.
PRINTS; PR01933; INTRLEUKIN18.
SUPFAM; SSF50353; SSF50353; 1.
1: Evidence at protein level;
Cytokine; Cytoplasm; Direct protein sequencing; Inflammatory response;
Reference proteome; Secreted.
PROPEP 1..35
/id="PRO_0000015345"
CHAIN 36..192
/note="Interleukin-18"
/id="PRO_0000015346"
CONFLICT 183..185
/note="MFT -> IS (in Ref. 3; AAB49753)"
/evidence="ECO:0000305"
SEQUENCE 192 AA; 22135 MW; 8FED938473874D63 CRC64;
MAAMSEDSCV NFKEMMFIDN TLYFIPEENG DLESDNFGRL HCTTAVIRNI NDQVLFVDKR
QPVFEDMTDI DQSASEPQTR LIIYMYKDSE VRGLAVTLSV KDSKMSTLSC KNKIISFEEM
DPPENIDDIQ SDLIFFQKRV PGHNKMEFES SLYEGHFLAC QKEDDAFKLI LKKKDENGDK
SVMFTLTNLH QS


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Pathways :
WP1836: Interferon gamma signaling
WP868: estrogen signalling
WP2292: Chemokine signaling pathway
WP1225: estrogen signalling
WP1993: angiogenesis overview
WP1654: gamma-Hexachlorocyclohexane degradation
WP760: estrogen signalling
WP866: EBV LMP1 signaling
WP2199: Seed Development
WP262: EBV LMP1 signaling
WP1224: EBV LMP1 signaling
WP32: Translation Factors
WP1886: Post-translational modification: gamma carboxylation and hypusine formation
WP542: Electron Transport Chain
WP152: FGF signaling pathway
WP758: EBV LMP1 signaling
WP2152: BDNF
WP537: Translation Factors
WP2006: Squamous cell TarBase
WP1722: Th1/Th2
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP272: Blood Clotting Cascade
WP1839: Interleukin-1 signaling
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP1899: Regulation of Insulin-like Growth Factor (IGF) Activity by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Related Genes :
[IL18 IGIF IL1F4] Interleukin-18 (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Il18 Igif] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Il18 Igif] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL36G IL1E IL1F9 IL1H1 IL1RP2 UNQ2456/PRO5737] Interleukin-36 gamma (IL-1-related protein 2) (IL-1RP2) (Interleukin-1 epsilon) (IL-1 epsilon) (Interleukin-1 family member 9) (IL-1F9) (Interleukin-1 homolog 1) (IL-1H1)
[TICAM1 PRVTIRB TRIF] TIR domain-containing adapter molecule 1 (TICAM-1) (Proline-rich, vinculin and TIR domain-containing protein B) (Putative NF-kappa-B-activating protein 502H) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (MyD88-3) (TIR domain-containing adapter protein inducing IFN-beta)
[IL18R1 IL1RRP] Interleukin-18 receptor 1 (IL-18R-1) (IL-18R1) (EC 3.2.2.6) (CD218 antigen-like family member A) (CDw218a) (IL1 receptor-related protein) (IL-1Rrp) (IL1R-rp) (Interleukin-18 receptor alpha) (IL-18R-alpha) (IL-18Ralpha) (CD antigen CD218a)
[IL6 IFNB2] Interleukin-6 (IL-6) (B-cell stimulatory factor 2) (BSF-2) (CTL differentiation factor) (CDF) (Hybridoma growth factor) (Interferon beta-2) (IFN-beta-2)
[IFNG] Interferon gamma (IFN-gamma)
[IL2RG] Cytokine receptor common subunit gamma (Interleukin-2 receptor subunit gamma) (IL-2 receptor subunit gamma) (IL-2R subunit gamma) (IL-2RG) (gammaC) (p64) (CD antigen CD132)
[IL18RAP IL1R7] Interleukin-18 receptor accessory protein (IL-18 receptor accessory protein) (IL-18RAcP) (EC 3.2.2.6) (Accessory protein-like) (AcPL) (CD218 antigen-like family member B) (CDw218b) (IL-1R accessory protein-like) (IL-1RAcPL) (Interleukin-1 receptor 7) (IL-1R-7) (IL-1R7) (Interleukin-18 receptor accessory protein-like) (Interleukin-18 receptor beta) (IL-18R-beta) (IL-18Rbeta) (CD antigen CD218b)
[IFNG] Interferon gamma (IFN-gamma) (Immune interferon)
[IFNLR1 IL28RA LICR2] Interferon lambda receptor 1 (IFN-lambda receptor 1) (IFN-lambda-R1) (Cytokine receptor class-II member 12) (Cytokine receptor family 2 member 12) (CRF2-12) (Interleukin-28 receptor subunit alpha) (IL-28 receptor subunit alpha) (IL-28R-alpha) (IL-28RA) (Likely interleukin or cytokine receptor 2) (LICR2)
[Ticam1 Trif] TIR domain-containing adapter molecule 1 (TICAM-1) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (TIR domain-containing adapter protein inducing IFN-beta)
[IFNL1 IL29 ZCYTO21] Interferon lambda-1 (IFN-lambda-1) (Cytokine Zcyto21) (Interleukin-29) (IL-29)
[IL33 C9orf26 IL1F11 NFHEV] Interleukin-33 (IL-33) (Interleukin-1 family member 11) (IL-1F11) (Nuclear factor from high endothelial venules) (NF-HEV) [Cleaved into: Interleukin-33 (95-270); Interleukin-33 (99-270); Interleukin-33 (109-270)]
[Il18r1] Interleukin-18 receptor 1 (IL-18R-1) (IL-18R1) (EC 3.2.2.6) (CD218 antigen-like family member A) (IL1 receptor-related protein) (IL-1Rrp) (IL1R-rp) (Interleukin-18 receptor alpha) (IL-18R-alpha) (IL-18Ralpha) (CD antigen CD218a)
[Il2rg] Cytokine receptor common subunit gamma (Interleukin-2 receptor subunit gamma) (IL-2 receptor subunit gamma) (IL-2R subunit gamma) (IL-2RG) (gammaC) (p64) (CD antigen CD132)
[IL32 NK4 TAIF] Interleukin-32 (IL-32) (Natural killer cells protein 4) (Tumor necrosis factor alpha-inducing factor)
[IL1B IL1F2] Interleukin-1 beta (IL-1 beta) (Catabolin)
[Ifng] Interferon gamma (IFN-gamma)
[Ifng] Interferon gamma (IFN-gamma)
[IFNG] Interferon gamma (IFN-gamma)
[IFNG] Interferon gamma (IFN-gamma)
[IFNG] Interferon gamma (IFN-gamma)
[IL1R1 IL1R IL1RA IL1RT1] Interleukin-1 receptor type 1 (IL-1R-1) (IL-1RT-1) (IL-1RT1) (EC 3.2.2.6) (CD121 antigen-like family member A) (Interleukin-1 receptor alpha) (IL-1R-alpha) (Interleukin-1 receptor type I) (p80) (CD antigen CD121a) [Cleaved into: Interleukin-1 receptor type 1, membrane form (mIL-1R1) (mIL-1RI); Interleukin-1 receptor type 1, soluble form (sIL-1R1) (sIL-1RI)]
[IFNG] Interferon gamma (BoIFNG) (IFN-gamma)

Bibliography :
[34280771] Molecular characterization and functional analysis of IL-18 in snakehead (Channa argus) during Aeromonas schubertii and Nocardia seriolae infections.
[34228995] Characterization of the turbot (Scophthalmus maximus) interleukin-18: Identification of splicing variants, phylogeny, synteny and expression analysis.
[34139296] Inflammatory cytokines and appetite in older hospitalized patients.
[34108686] TIM-3 restrains anti-tumour immunity by regulating inflammasome activation.
[34010066] LncRNA GAS5 inhibits miR-579-3p to activate SIRT1/PGC-1α/Nrf2 signaling pathway to reduce cell pyroptosis in sepsis-associated renal injury.
[33833503] White Tip Silver Needle (Slightly Fermented White Tea) Flavonoids Help Prevent Aging via Antioxidative and Anti-Inflammatory Effects.
[33760111] Cytokine secretion and pyroptosis of cholesteatoma keratinocytes mediated by AIM2 inflammasomes in response to cytoplasmic DNA.
[33185287] Cytokine dysregulation in children with cerebral palsy.
[32983099] Human Autoinflammatory Diseases Mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome Dysregulation Updates on Diagnosis, Treatment, and the Respective Roles of IL-1 and IL-18.
[32726630] Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium.