IL18_MOUSE
ID IL18_MOUSE Reviewed; 192 AA.
AC P70380;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Interleukin-18;
DE Short=IL-18;
DE AltName: Full=Interferon gamma-inducing factor;
DE Short=IFN-gamma-inducing factor;
DE AltName: Full=Interleukin-1 gamma;
DE Short=IL-1 gamma;
DE Flags: Precursor;
GN Name=Il18 {ECO:0000312|MGI:MGI:107936}; Synonyms=Igif;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=7477296; DOI=10.1038/378088a0;
RA Okamura H., Tsutui H., Komatsu T., Yutsudo M., Hakura A., Tanimoto T.,
RA Torigoe K., Okura T., Nukada Y., Hattori K., Akita K., Namba M., Tanabe F.,
RA Konishi K., Fukuda S., Kurimoto M.;
RT "Cloning of a new cytokine that induces IFN-gamma production by T cells.";
RL Nature 378:88-91(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-191.
RC STRAIN=NOD; TISSUE=Pancreas;
RX PubMed=9022080; DOI=10.1172/jci119181;
RA Rothe H., Jenkins N.A., Copeland N.G., Kolb H.;
RT "Active stage of autoimmune diabetes is associated with the expression of a
RT novel cytokine, IGIF, which is located near Idd2.";
RL J. Clin. Invest. 99:469-474(1997).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=26638072; DOI=10.1016/j.cell.2015.10.048;
RA Levy M., Thaiss C.A., Zeevi D., Dohnalova L., Zilberman-Schapira G.,
RA Mahdi J.A., David E., Savidor A., Korem T., Herzig Y., Pevsner-Fischer M.,
RA Shapiro H., Christ A., Harmelin A., Halpern Z., Latz E., Flavell R.A.,
RA Amit I., Segal E., Elinav E.;
RT "Microbiota-modulated metabolites shape the intestinal microenvironment by
RT regulating NLRP6 inflammasome signaling.";
RL Cell 163:1428-1443(2015).
RN [6]
RP FUNCTION.
RX PubMed=26638073; DOI=10.1016/j.cell.2015.10.072;
RA Nowarski R., Jackson R., Gagliani N., de Zoete M.R., Palm N.W., Bailis W.,
RA Low J.S., Harman C.C., Graham M., Elinav E., Flavell R.A.;
RT "Epithelial IL-18 equilibrium controls barrier function in colitis.";
RL Cell 163:1444-1456(2015).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=30392956; DOI=10.1016/j.cell.2018.09.047;
RA Hara H., Seregin S.S., Yang D., Fukase K., Chamaillard M., Alnemri E.S.,
RA Inohara N., Chen G.Y., Nunez G.;
RT "The NLRP6 inflammasome recognizes lipoteichoic acid and regulates Gram-
RT positive pathogen infection.";
RL Cell 175:1651-1664(2018).
CC -!- FUNCTION: Pro-inflammatory cytokine primarily involved in epithelial
CC barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK)
CC cell immune responses (PubMed:26638072, PubMed:26638073). Upon binding
CC to IL18R1 and IL18RAP, forms a signaling ternary complex which
CC activates NF-kappa-B, triggering synthesis of inflammatory mediators
CC (By similarity). Synergizes with IL12/interleukin-12 to induce IFNG
CC synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (By
CC similarity). Involved in transduction of inflammation downstream of
CC pyroptosis: its mature form is specifically released in the
CC extracellular milieu by passing through the gasdermin-D (GSDMD) pore
CC (PubMed:30392956). {ECO:0000250|UniProtKB:Q14116,
CC ECO:0000269|PubMed:26638072, ECO:0000269|PubMed:26638073,
CC ECO:0000269|PubMed:30392956}.
CC -!- SUBUNIT: Forms a ternary complex with ligand-binding receptor subunit
CC IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane.
CC Mature IL18 first binds to IL18R1 forming a low affinity binary
CC complex, which then interacts with IL18RAP to form a high affinity
CC ternary complex that signals inside the cell. Interacts with cargo
CC receptor TMED10; the interaction mediates the translocation from the
CC cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate
CC compartment) and thereby secretion. {ECO:0000250|UniProtKB:Q14116}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14116}.
CC Secreted {ECO:0000269|PubMed:30392956}. Note=The precursor is cytosolic
CC (By similarity). In response to inflammasome-activating signals,
CC cleaved and secreted (By similarity). Mature form is secreted and
CC released in the extracellular milieu by passing through the gasdermin-D
CC (GSDMD) pore (PubMed:30392956). In contrast, the precursor form is not
CC released, due to the presence of an acidic region that is
CC proteolytically removed by CASP1 during maturation (By similarity). The
CC secretion is dependent on protein unfolding and facilitated by the
CC cargo receptor TMED10 (By similarity). {ECO:0000250|UniProtKB:Q14116,
CC ECO:0000269|PubMed:30392956}.
CC -!- PTM: The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield
CC the active form. {ECO:0000250|UniProtKB:Q14116}.
CC -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
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DR EMBL; D49949; BAA08705.1; -; mRNA.
DR EMBL; BC024384; AAH24384.1; -; mRNA.
DR EMBL; U66244; AAB49753.1; -; mRNA.
DR CCDS; CCDS40622.1; -.
DR PIR; S60226; S60226.
DR RefSeq; NP_032386.1; NM_008360.1.
DR RefSeq; XP_006510089.1; XM_006510026.1.
DR RefSeq; XP_006510090.1; XM_006510027.3.
DR RefSeq; XP_006510091.1; XM_006510028.3.
DR AlphaFoldDB; P70380; -.
DR SMR; P70380; -.
DR DIP; DIP-950N; -.
DR STRING; 10090.ENSMUSP00000054591; -.
DR PhosphoSitePlus; P70380; -.
DR PaxDb; P70380; -.
DR PRIDE; P70380; -.
DR ProteomicsDB; 266967; -.
DR ABCD; P70380; 1 sequenced antibody.
DR Antibodypedia; 1287; 883 antibodies from 47 providers.
DR DNASU; 16173; -.
DR Ensembl; ENSMUST00000180021; ENSMUSP00000137193; ENSMUSG00000039217.
DR Ensembl; ENSMUST00000214117; ENSMUSP00000151002; ENSMUSG00000039217.
DR GeneID; 16173; -.
DR KEGG; mmu:16173; -.
DR UCSC; uc009pju.1; mouse.
DR CTD; 3606; -.
DR MGI; MGI:107936; Il18.
DR VEuPathDB; HostDB:ENSMUSG00000039217; -.
DR eggNOG; ENOG502SDJZ; Eukaryota.
DR GeneTree; ENSGT00390000001053; -.
DR HOGENOM; CLU_113349_0_0_1; -.
DR InParanoid; P70380; -.
DR OMA; GKNFCLY; -.
DR PhylomeDB; P70380; -.
DR BioGRID-ORCS; 16173; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Il18; mouse.
DR PRO; PR:P70380; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P70380; protein.
DR Bgee; ENSMUSG00000039217; Expressed in epithelium of stomach and 220 other tissues.
DR ExpressionAtlas; P70380; baseline and differential.
DR Genevisible; P70380; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0045515; F:interleukin-18 receptor binding; ISS:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; ISO:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:BHF-UCL.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0061436; P:establishment of skin barrier; IMP:UniProtKB.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; TAS:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:MGI.
DR GO; GO:0006954; P:inflammatory response; IGI:MGI.
DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:MGI.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0030101; P:natural killer cell activation; IDA:MGI.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IDA:MGI.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:MGI.
DR GO; GO:0033030; P:negative regulation of neutrophil apoptotic process; ISO:MGI.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0042119; P:neutrophil activation; IDA:MGI.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:2000504; P:positive regulation of blood vessel remodeling; ISO:MGI.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:MGI.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; TAS:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL.
DR GO; GO:2000256; P:positive regulation of male germ cell proliferation; ISO:MGI.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:MGI.
DR GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0043117; P:positive regulation of vascular permeability; ISO:MGI.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0030431; P:sleep; ISS:UniProtKB.
DR GO; GO:0042088; P:T-helper 1 type immune response; ISS:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL.
DR InterPro; IPR015529; IL-18.
DR InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR008996; IL1/FGF.
DR Pfam; PF00340; IL1; 1.
DR PIRSF; PIRSF015162; Interleukin_18; 1.
DR PRINTS; PR01933; INTRLEUKIN18.
DR SUPFAM; SSF50353; SSF50353; 1.
PE 1: Evidence at protein level;
KW Cytokine; Cytoplasm; Direct protein sequencing; Inflammatory response;
KW Reference proteome; Secreted.
FT PROPEP 1..35
FT /evidence="ECO:0000269|PubMed:7477296"
FT /id="PRO_0000015345"
FT CHAIN 36..192
FT /note="Interleukin-18"
FT /id="PRO_0000015346"
FT CONFLICT 183..185
FT /note="MFT -> IS (in Ref. 3; AAB49753)"
FT /evidence="ECO:0000305"
SQ 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
