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 11-NOV-2015, entry version 149. DE RecName: Full=Interleukin-18; DE Short=IL-18; DE AltName: Full=Iboctadekin; 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; Synonyms=IGIF, IL1F4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Tanabe F., Konishi K., Micallef M., Fujii M., Torigoe K., Tanimoto T., RA Fukuda S., Ikeda M., Okamura H., Kurimoto M.; RT "Cloning of the cDNA for human IFN-gamma-inducing factor, expression RT in Escherichia coli, and studies on the biologic activities of the RT protein."; RL J. Immunol. 156:4274-4279(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEOLYTIC PROCESSING, 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., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 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., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). CC -!- FUNCTION: Augments natural killer cell activity in spleen cells CC and stimulates interferon gamma production in T-helper type I CC cells. CC -!- INTERACTION: CC Q13478:IL18R1; NbExp=2; IntAct=EBI-3910835, EBI-9817499; CC -!- SUBCELLULAR LOCATION: Secreted. 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 Note=Expressed in ovarian carcinoma but undetectable in normal CC ovarian epithelial cells. Resistant to proteolytic activation by CC caspase-1 and -4.; CC -!- PTM: The pro-IL-18 precursor is processed by CASP1 or CASP4 to CC yield the active form. {ECO:0000269|PubMed:15326478}. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_011542806.1. [Q14116-1] DR UniGene; Hs.83077; -. 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 ProteinModelPortal; Q14116; -. DR SMR; Q14116; 37-193. DR BioGrid; 109819; 10. DR DIP; DIP-3785N; -. DR IntAct; Q14116; 2. DR STRING; 9606.ENSP00000280357; -. DR PhosphoSite; Q14116; -. DR BioMuta; IL18; -. DR DMDM; 3219817; -. DR OGP; Q14116; -. DR MaxQB; Q14116; -. DR PaxDb; Q14116; -. DR PRIDE; Q14116; -. DR DNASU; 3606; -. DR Ensembl; ENST00000280357; ENSP00000280357; ENSG00000150782. [Q14116-1] DR Ensembl; ENST00000524595; ENSP00000434561; ENSG00000150782. [Q14116-2] DR Ensembl; ENST00000528832; ENSP00000434161; ENSG00000150782. [Q14116-1] DR GeneID; 3606; -. DR KEGG; hsa:3606; -. DR UCSC; uc001pna.2; human. [Q14116-1] DR UCSC; uc009yym.2; human. DR CTD; 3606; -. DR GeneCards; IL18; -. DR HGNC; HGNC:5986; IL18. DR HPA; CAB007772; -. DR HPA; CAB027385; -. DR HPA; HPA003980; -. DR MIM; 600953; gene. DR neXtProt; NX_Q14116; -. DR PharmGKB; PA29802; -. DR eggNOG; ENOG410J3U9; Eukaryota. DR eggNOG; ENOG410ZGS8; LUCA. DR GeneTree; ENSGT00390000001053; -. DR HOGENOM; HOG000048723; -. DR HOVERGEN; HBG000388; -. DR InParanoid; Q14116; -. DR KO; K05482; -. DR OMA; PVFEDMP; -. DR OrthoDB; EOG7SR4NN; -. DR PhylomeDB; Q14116; -. DR TreeFam; TF336297; -. DR Reactome; R-HSA-448706; Interleukin-1 processing. DR EvolutionaryTrace; Q14116; -. DR GeneWiki; Interleukin_18; -. DR GenomeRNAi; 3606; -. DR NextBio; 14093; -. DR PMAP-CutDB; Q14116; -. DR PRO; PR:Q14116; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q14116; -. DR CleanEx; HS_IL18; -. DR ExpressionAtlas; Q14116; baseline and differential. DR Genevisible; Q14116; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005125; F:cytokine activity; TAS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB. DR GO; GO:0042033; P:chemokine biosynthetic process; TAS:UniProtKB. DR GO; GO:0042253; P:granulocyte macrophage colony-stimulating factor biosynthetic process; TAS:UniProtKB. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB. DR GO; GO:0042095; P:interferon-gamma biosynthetic process; TAS:UniProtKB. DR GO; GO:0042231; P:interleukin-13 biosynthetic process; TAS:UniProtKB. DR GO; GO:0042094; P:interleukin-2 biosynthetic process; TAS: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:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. 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; IC:BHF-UCL. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:BHF-UCL. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IDA:BHF-UCL. DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IDA:BHF-UCL. DR GO; GO:0042346; P:positive regulation of NF-kappaB import into nucleus; IEA:Ensembl. DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IDA:BHF-UCL. DR GO; GO:0034105; P:positive regulation of tissue remodeling; IC:BHF-UCL. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 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:0042092; P:type 2 immune response; TAS:UniProtKB. DR InterPro; IPR008996; Cytokine_IL1-like. DR InterPro; IPR015529; IL-18. DR InterPro; IPR000975; IL-1_fam. DR PANTHER; PTHR11326; PTHR11326; 1. 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; Complete proteome; Cytokine; KW Reference proteome; Secreted. FT PROPEP 1 36 {ECO:0000250}. FT /FTId=PRO_0000015343. FT CHAIN 37 193 Interleukin-18. FT /FTId=PRO_0000015344. FT VAR_SEQ 27 30 Missing (in isoform 2). FT {ECO:0000303|PubMed:15326478}. FT /FTId=VSP_044934. FT CONFLICT 66 66 F -> L (in Ref. 3; AAC27787). FT {ECO:0000305}. FT CONFLICT 86 86 S -> R (in Ref. 3; AAC27787). FT {ECO:0000305}. FT CONFLICT 191 191 N -> S (in Ref. 3; AAC27787). FT {ECO:0000305}. FT STRAND 42 49 {ECO:0000244|PDB:2VXT}. FT STRAND 55 58 {ECO:0000244|PDB:2VXT}. FT STRAND 64 67 {ECO:0000244|PDB:2VXT}. FT HELIX 71 76 {ECO:0000244|PDB:2VXT}. FT TURN 77 81 {ECO:0000244|PDB:2VXT}. FT STRAND 83 91 {ECO:0000244|PDB:2VXT}. FT TURN 92 94 {ECO:0000244|PDB:2VXT}. FT STRAND 95 111 {ECO:0000244|PDB:2VXT}. FT HELIX 113 115 {ECO:0000244|PDB:2VXT}. FT STRAND 118 121 {ECO:0000244|PDB:2VXT}. FT STRAND 126 131 {ECO:0000244|PDB:2VXT}. FT STRAND 137 142 {ECO:0000244|PDB:2VXT}. FT STRAND 145 156 {ECO:0000244|PDB:2VXT}. FT STRAND 159 166 {ECO:0000244|PDB:2VXT}. FT STRAND 169 176 {ECO:0000244|PDB:2VXT}. FT TURN 178 180 {ECO:0000244|PDB:4HJJ}. FT HELIX 183 185 {ECO:0000244|PDB:2VXT}. FT STRAND 187 191 {ECO:0000244|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 //