IL18_HUMAN
ID IL18_HUMAN Reviewed; 193 AA.
AC Q14116; O75599; Q6FGY3; Q6WWJ7;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Interleukin-18 {ECO:0000303|PubMed:14528293, ECO:0000303|PubMed:25261253, ECO:0000303|PubMed:25500532};
DE Short=IL-18 {ECO:0000303|PubMed:14528293, ECO:0000303|PubMed:25261253, ECO:0000303|PubMed:25500532};
DE AltName: Full=Iboctadekin;
DE AltName: Full=Interferon gamma-inducing factor {ECO:0000303|PubMed:14528293, ECO:0000303|PubMed:25500532};
DE Short=IFN-gamma-inducing factor {ECO:0000303|PubMed:14528293, ECO:0000303|PubMed:25500532};
DE AltName: Full=Interleukin-1 gamma;
DE Short=IL-1 gamma;
DE Flags: Precursor;
GN Name=IL18 {ECO:0000312|HGNC:HGNC:5986}; Synonyms=IGIF, IL1F4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8666798;
RA Ushio S., Namba M., Okura T., Hattori K., Nukada Y., Akita K., Tanabe F.,
RA Konishi K., Micallef M., Fujii M., Torigoe K., Tanimoto T., Fukuda S.,
RA Ikeda M., Okamura H., Kurimoto M.;
RT "Cloning of the cDNA for human IFN-gamma-inducing factor, expression in
RT Escherichia coli, and studies on the biologic activities of the protein.";
RL J. Immunol. 156:4274-4279(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC CLEAVAGE, AND
RP ALTERNATIVE SPLICING.
RX PubMed=15326478; DOI=10.1038/sj.onc.1208036;
RA Gaggero A., De Ambrosis A., Mezzanzanica D., Piazza T., Rubartelli A.,
RA Figini M., Canevari S., Ferrini S.;
RT "A novel isoform of pro-interleukin-18 expressed in ovarian tumors is
RT resistant to caspase-1 and -4 processing.";
RL Oncogene 23:7552-7560(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Yong D., Guixin D., Lihua H., Haitao W.;
RT "Cloning and sequencing of the cDNA for precursor hIL-18.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Liu J., Peng X., Yuan J., Qiang B.;
RT "Cloning of human interleukin 18 cDNA.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Urinary bladder;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-193 (ISOFORM 1).
RC TISSUE=Peripheral blood;
RA Conti B., Kim S.J., Tinti C., Chun H.S., Joh T.H.;
RL Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP FUNCTION.
RX PubMed=10653850; DOI=10.1093/intimm/12.2.151;
RA Tominaga K., Yoshimoto T., Torigoe K., Kurimoto M., Matsui K., Hada T.,
RA Okamura H., Nakanishi K.;
RT "IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from
RT human T cells.";
RL Int. Immunol. 12:151-160(2000).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP INDUCTION BY ENDOCANNABINOID ANANDAMIDE, AND SUBCELLULAR LOCATION.
RX PubMed=23955712; DOI=10.1038/nm.3265;
RA Jourdan T., Godlewski G., Cinar R., Bertola A., Szanda G., Liu J., Tam J.,
RA Han T., Mukhopadhyay B., Skarulis M.C., Ju C., Aouadi M., Czech M.P.,
RA Kunos G.;
RT "Activation of the Nlrp3 inflammasome in infiltrating macrophages by
RT endocannabinoids mediates beta cell loss in type 2 diabetes.";
RL Nat. Med. 19:1132-1140(2013).
RN [13]
RP STRUCTURE BY NMR OF 37-193, FUNCTION, SUBUNIT, AND MUTAGENESIS OF LYS-40;
RP LEU-41; LYS-44; ARG-49; ASP-53; MET-69; ASP-71; ARG-94; MET-96; LYS-115;
RP LYS-120; ASP-134; ARG-140 AND ASP-168.
RX PubMed=14528293; DOI=10.1038/nsb993;
RA Kato Z., Jee J., Shikano H., Mishima M., Ohki I., Ohnishi H., Li A.,
RA Hashimoto K., Matsukuma E., Omoya K., Yamamoto Y., Yoneda T., Hara T.,
RA Kondo N., Shirakawa M.;
RT "The structure and binding mode of interleukin-18.";
RL Nat. Struct. Biol. 10:966-971(2003).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TMED10.
RX PubMed=32272059; DOI=10.1016/j.cell.2020.03.031;
RA Zhang M., Liu L., Lin X., Wang Y., Li Y., Guo Q., Li S., Sun Y., Tao X.,
RA Zhang D., Lv X., Zheng L., Ge L.;
RT "A Translocation Pathway for Vesicle-Mediated Unconventional Protein
RT Secretion.";
RL Cell 181:637-652(2020).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=33883744; DOI=10.1038/s41586-021-03478-3;
RA Xia S., Zhang Z., Magupalli V.G., Pablo J.L., Dong Y., Vora S.M., Wang L.,
RA Fu T.M., Jacobson M.P., Greka A., Lieberman J., Ruan J., Wu H.;
RT "Gasdermin D pore structure reveals preferential release of mature
RT interleukin-1.";
RL Nature 593:607-611(2021).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 37-193, PROTEOLYTIC CLEAVAGE, AND
RP SUBUNIT.
RX PubMed=25261253; DOI=10.1016/j.febslet.2014.09.019;
RA Wei H., Wang D., Qian Y., Liu X., Fan S., Yin H.S., Wang X.;
RT "Structural basis for the specific recognition of IL-18 by its alpha
RT receptor.";
RL FEBS Lett. 588:3838-3843(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 37-193, FUNCTION, MUTAGENESIS OF
RP GLY-144; HIS-145; ASP-146; LYS-148; ARG-183 AND MET-186, AND SUBUNIT.
RX PubMed=25500532; DOI=10.1038/ncomms6340;
RA Tsutsumi N., Kimura T., Arita K., Ariyoshi M., Ohnishi H., Yamamoto T.,
RA Zuo X., Maenaka K., Park E.Y., Kondo N., Shirakawa M., Tochio H., Kato Z.;
RT "The structural basis for receptor recognition of human interleukin-18.";
RL Nat. Commun. 5:5340-5340(2014).
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:10653850). Upon binding to IL18R1 and
CC IL18RAP, forms a signaling ternary complex which activates NF-kappa-B,
CC triggering synthesis of inflammatory mediators (PubMed:14528293,
CC PubMed:25500532). Synergizes with IL12/interleukin-12 to induce IFNG
CC synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells
CC (PubMed:10653850). Involved in transduction of inflammation downstream
CC of pyroptosis: its mature form is specifically released in the
CC extracellular milieu by passing through the gasdermin-D (GSDMD) pore
CC (PubMed:33883744). {ECO:0000269|PubMed:10653850,
CC ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25500532,
CC ECO:0000269|PubMed:33883744}.
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 (PubMed:25261253,
CC PubMed:14528293, PubMed:25500532). Interacts with cargo receptor
CC TMED10; the interaction mediates the translocation from the cytoplasm
CC into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment)
CC and thereby secretion (PubMed:32272059). {ECO:0000269|PubMed:14528293,
CC ECO:0000269|PubMed:25261253, ECO:0000269|PubMed:25500532,
CC ECO:0000269|PubMed:32272059}.
CC -!- INTERACTION:
CC Q14116; Q15847: ADIRF; NbExp=3; IntAct=EBI-3910835, EBI-7162516;
CC Q14116; Q13478: IL18R1; NbExp=2; IntAct=EBI-3910835, EBI-9817499;
CC Q14116; Q9IW12; Xeno; NbExp=2; IntAct=EBI-3910835, EBI-15748155;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32272059}. Secreted
CC {ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:32272059,
CC ECO:0000269|PubMed:33883744}. Note=The precursor is cytosolic
CC (PubMed:33883744). In response to inflammasome-activating signals,
CC cleaved and secreted (PubMed:33883744). Mature form is secreted and
CC released in the extracellular milieu by passing through the gasdermin-D
CC (GSDMD) pore (PubMed:33883744). 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 (PubMed:33883744).
CC The secretion is dependent on protein unfolding and facilitated by the
CC cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:32272059,
CC ECO:0000269|PubMed:33883744}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14116-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta3pro-IL-18;
CC IsoId=Q14116-2; Sequence=VSP_044934;
CC -!- INDUCTION: In macrophages, release is increased by endocannabinoid
CC anandamide/AEA. {ECO:0000269|PubMed:23955712}.
CC -!- PTM: The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield
CC the active form. {ECO:0000269|PubMed:15326478,
CC ECO:0000269|PubMed:25261253}.
CC -!- MISCELLANEOUS: [Isoform 2]: Expressed in ovarian carcinoma but
CC undetectable in normal ovarian epithelial cells. Resistant to
CC proteolytic activation by caspase-1 and -4. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-1 entry;
CC URL="https://en.wikipedia.org/wiki/Interleukin_1";
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DR EMBL; D49950; BAA08706.1; -; mRNA.
DR EMBL; AY266351; AAP92112.1; -; mRNA.
DR EMBL; AF077611; AAC27787.1; -; mRNA.
DR EMBL; AY044641; AAK95950.1; -; mRNA.
DR EMBL; CR541973; CAG46771.1; -; mRNA.
DR EMBL; CR542001; CAG46798.1; -; mRNA.
DR EMBL; AP002007; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67184.1; -; Genomic_DNA.
DR EMBL; BC007007; AAH07007.1; -; mRNA.
DR EMBL; BC007461; AAH07461.1; -; mRNA.
DR EMBL; U90434; AAB50010.1; -; mRNA.
DR CCDS; CCDS44731.1; -. [Q14116-1]
DR CCDS; CCDS58180.1; -. [Q14116-2]
DR RefSeq; NP_001230140.1; NM_001243211.1. [Q14116-2]
DR RefSeq; NP_001553.1; NM_001562.3. [Q14116-1]
DR RefSeq; XP_011541107.1; XM_011542805.1. [Q14116-2]
DR RefSeq; XP_011541108.1; XM_011542806.2. [Q14116-1]
DR PDB; 1J0S; NMR; -; A=37-193.
DR PDB; 2VXT; X-ray; 1.49 A; I=37-193.
DR PDB; 3F62; X-ray; 2.00 A; B=37-193.
DR PDB; 3WO2; X-ray; 2.33 A; A/B/C/D=37-193.
DR PDB; 3WO3; X-ray; 3.10 A; A/C/E/G/I/K=37-193.
DR PDB; 3WO4; X-ray; 3.10 A; A=37-193.
DR PDB; 4EEE; X-ray; 2.71 A; B/D=37-193.
DR PDB; 4EKX; X-ray; 1.75 A; B/D=37-193.
DR PDB; 4HJJ; X-ray; 2.10 A; A=37-192.
DR PDB; 4R6U; X-ray; 2.80 A; B/D=37-193.
DR PDB; 4XFS; X-ray; 1.91 A; A/B=37-193.
DR PDB; 4XFT; X-ray; 2.00 A; A/B=37-193.
DR PDB; 4XFU; X-ray; 2.85 A; A/B=37-193.
DR PDBsum; 1J0S; -.
DR PDBsum; 2VXT; -.
DR PDBsum; 3F62; -.
DR PDBsum; 3WO2; -.
DR PDBsum; 3WO3; -.
DR PDBsum; 3WO4; -.
DR PDBsum; 4EEE; -.
DR PDBsum; 4EKX; -.
DR PDBsum; 4HJJ; -.
DR PDBsum; 4R6U; -.
DR PDBsum; 4XFS; -.
DR PDBsum; 4XFT; -.
DR PDBsum; 4XFU; -.
DR AlphaFoldDB; Q14116; -.
DR SMR; Q14116; -.
DR BioGRID; 109819; 21.
DR DIP; DIP-3785N; -.
DR IntAct; Q14116; 11.
DR MINT; Q14116; -.
DR STRING; 9606.ENSP00000280357; -.
DR ChEMBL; CHEMBL1741305; -.
DR GlyGen; Q14116; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14116; -.
DR PhosphoSitePlus; Q14116; -.
DR BioMuta; IL18; -.
DR DMDM; 3219817; -.
DR OGP; Q14116; -.
DR CPTAC; CPTAC-1249; -.
DR CPTAC; CPTAC-1250; -.
DR CPTAC; CPTAC-1431; -.
DR CPTAC; CPTAC-1432; -.
DR CPTAC; CPTAC-1433; -.
DR CPTAC; CPTAC-1434; -.
DR CPTAC; CPTAC-1435; -.
DR CPTAC; CPTAC-705; -.
DR EPD; Q14116; -.
DR jPOST; Q14116; -.
DR MassIVE; Q14116; -.
DR MaxQB; Q14116; -.
DR PaxDb; Q14116; -.
DR PeptideAtlas; Q14116; -.
DR PRIDE; Q14116; -.
DR ProteomicsDB; 59823; -. [Q14116-1]
DR ProteomicsDB; 67779; -.
DR ABCD; Q14116; 25 sequenced antibodies.
DR Antibodypedia; 1287; 883 antibodies from 47 providers.
DR CPTC; Q14116; 4 antibodies.
DR DNASU; 3606; -.
DR Ensembl; ENST00000280357.12; ENSP00000280357.7; ENSG00000150782.12. [Q14116-1]
DR Ensembl; ENST00000524595.5; ENSP00000434561.1; ENSG00000150782.12. [Q14116-2]
DR Ensembl; ENST00000528832.1; ENSP00000434161.1; ENSG00000150782.12. [Q14116-1]
DR GeneID; 3606; -.
DR KEGG; hsa:3606; -.
DR MANE-Select; ENST00000280357.12; ENSP00000280357.7; NM_001562.4; NP_001553.1.
DR UCSC; uc001pnb.2; human. [Q14116-1]
DR CTD; 3606; -.
DR DisGeNET; 3606; -.
DR GeneCards; IL18; -.
DR HGNC; HGNC:5986; IL18.
DR HPA; ENSG00000150782; Tissue enhanced (esophagus, skin).
DR MIM; 600953; gene.
DR neXtProt; NX_Q14116; -.
DR OpenTargets; ENSG00000150782; -.
DR PharmGKB; PA29802; -.
DR VEuPathDB; HostDB:ENSG00000150782; -.
DR eggNOG; ENOG502SDJZ; Eukaryota.
DR GeneTree; ENSGT00390000001053; -.
DR HOGENOM; CLU_113349_0_0_1; -.
DR InParanoid; Q14116; -.
DR OMA; GKNFCLY; -.
DR OrthoDB; 1190337at2759; -.
DR PhylomeDB; Q14116; -.
DR TreeFam; TF336297; -.
DR PathwayCommons; Q14116; -.
DR Reactome; R-HSA-448706; Interleukin-1 processing.
DR Reactome; R-HSA-5620971; Pyroptosis.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-9012546; Interleukin-18 signaling. [Q14116-2]
DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection.
DR SignaLink; Q14116; -.
DR SIGNOR; Q14116; -.
DR BioGRID-ORCS; 3606; 38 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; Q14116; -.
DR GeneWiki; Interleukin_18; -.
DR GenomeRNAi; 3606; -.
DR Pharos; Q14116; Tbio.
DR PRO; PR:Q14116; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q14116; protein.
DR Bgee; ENSG00000150782; Expressed in lower esophagus mucosa and 171 other tissues.
DR ExpressionAtlas; Q14116; baseline and differential.
DR Genevisible; Q14116; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005125; F:cytokine activity; IDA:UniProtKB.
DR GO; GO:0045515; F:interleukin-18 receptor binding; IDA:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:BHF-UCL.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0030101; P:natural killer cell activation; IEA:Ensembl.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0042119; P:neutrophil activation; IEA:Ensembl.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; TAS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IDA:BHF-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; TAS:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISS:BHF-UCL.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:BHF-UCL.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; TAS:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:BHF-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; IDA:UniProtKB.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISS:BHF-UCL.
DR GO; GO:0034105; P:positive regulation of tissue remodeling; IC:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:CACAO.
DR GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0030431; P:sleep; ISS:UniProtKB.
DR GO; GO:0042088; P:T-helper 1 type immune response; IDA:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; ISS:BHF-UCL.
DR GO; GO:0042092; P:type 2 immune response; TAS:UniProtKB.
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 3D-structure; Alternative splicing; Cytokine; Cytoplasm;
KW Inflammatory response; Reference proteome; Secreted.
FT PROPEP 1..36
FT /evidence="ECO:0000250|UniProtKB:P70380"
FT /id="PRO_0000015343"
FT CHAIN 37..193
FT /note="Interleukin-18"
FT /id="PRO_0000015344"
FT VAR_SEQ 27..30
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15326478"
FT /id="VSP_044934"
FT MUTAGEN 40
FT /note="K->A: Reduces binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 41
FT /note="L->A: Impairs binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 44
FT /note="K->A: Reduces binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 49
FT /note="R->A: Reduces binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 53
FT /note="D->A: Reduces binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 69
FT /note="M->A: Impairs binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 71
FT /note="D->A: Impairs binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 94
FT /note="R->A: Impairs binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 96
FT /note="M->A: Impairs binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 115
FT /note="K->A: Reduces binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP resulting in impaired
FT IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 120
FT /note="K->A: Reduces binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP resulting in impaired
FT IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 134
FT /note="D->A: Reduces binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP resulting in impaired
FT IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 140
FT /note="R->A: Reduces binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 144
FT /note="G->A: Abolishes binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP."
FT /evidence="ECO:0000269|PubMed:25500532"
FT MUTAGEN 145
FT /note="H->A: Abolishes binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP."
FT /evidence="ECO:0000269|PubMed:25500532"
FT MUTAGEN 146
FT /note="D->A: Reduces binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP."
FT /evidence="ECO:0000269|PubMed:25500532"
FT MUTAGEN 148
FT /note="K->A: Abolishes binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP."
FT /evidence="ECO:0000269|PubMed:25500532"
FT MUTAGEN 168
FT /note="D->A: Reduces binding to IL18R1 and the ability to
FT induce IFNG production."
FT /evidence="ECO:0000269|PubMed:14528293"
FT MUTAGEN 183
FT /note="R->A: Reduces binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP."
FT /evidence="ECO:0000269|PubMed:25500532"
FT MUTAGEN 186
FT /note="M->A: Reduces binding of the preformed binary
FT complex of IL18 and IL18R1 to IL18RAP."
FT /evidence="ECO:0000269|PubMed:25500532"
FT CONFLICT 66
FT /note="F -> L (in Ref. 3; AAC27787)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="S -> R (in Ref. 3; AAC27787)"
FT /evidence="ECO:0000305"
FT CONFLICT 191
FT /note="N -> S (in Ref. 3; AAC27787)"
FT /evidence="ECO:0000305"
FT STRAND 42..49
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:2VXT"
FT HELIX 71..76
FT /evidence="ECO:0007829|PDB:2VXT"
FT TURN 77..81
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 83..91
FT /evidence="ECO:0007829|PDB:2VXT"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 95..111
FT /evidence="ECO:0007829|PDB:2VXT"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 145..156
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 169..176
FT /evidence="ECO:0007829|PDB:2VXT"
FT TURN 178..180
FT /evidence="ECO:0007829|PDB:4HJJ"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2VXT"
FT STRAND 187..191
FT /evidence="ECO:0007829|PDB:2VXT"
SQ SEQUENCE 193 AA; 22326 MW; 323C62C203788D55 CRC64;
MAAEPVEDNC INFVAMKFID NTLYFIAEDD ENLESDYFGK LESKLSVIRN LNDQVLFIDQ
GNRPLFEDMT DSDCRDNAPR TIFIISMYKD SQPRGMAVTI SVKCEKISTL SCENKIISFK
EMNPPDNIKD TKSDIIFFQR SVPGHDNKMQ FESSSYEGYF LACEKERDLF KLILKKEDEL
GDRSIMFTVQ NED
