{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q14116","secondaryAccessions":["O75599","Q6FGY3","Q6WWJ7"],"uniProtkbId":"IL18_HUMAN","entryAudit":{"firstPublicDate":"1998-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-11-01","entryVersion":214,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14528293"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25261253"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25500532"}],"value":"Interleukin-18"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14528293"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25261253"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25500532"}],"value":"IL-18"}]},"alternativeNames":[{"fullName":{"value":"Iboctadekin"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14528293"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25500532"}],"value":"Interferon gamma-inducing factor"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14528293"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25500532"}],"value":"IFN-gamma-inducing factor"}]},{"fullName":{"value":"Interleukin-1 gamma"},"shortNames":[{"value":"IL-1 gamma"}]}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:5986"}],"value":"IL18"},"synonyms":[{"value":"IGIF"},{"value":"IL1F4"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10653850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14528293"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25500532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33883744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993714"}],"value":"Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). 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, PubMed:37993714). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (PubMed:10653850). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14528293"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25261253"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25500532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32272059"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993714"}],"value":"Forms a ternary complex with ligand-binding receptor subunit IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane (PubMed:14528293, PubMed:25261253, PubMed:25500532, PubMed:37993714). 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 (PubMed:14528293, PubMed:25261253, PubMed:25500532). Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q14116","intActId":"EBI-3910835"},"interactantTwo":{"uniProtKBAccession":"Q15847","geneName":"ADIRF","intActId":"EBI-7162516"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14116","intActId":"EBI-3910835"},"interactantTwo":{"uniProtKBAccession":"Q13478","geneName":"IL18R1","intActId":"EBI-9817499"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14116","intActId":"EBI-3910835"},"interactantTwo":{"uniProtKBAccession":"P48594","geneName":"SERPINB4","intActId":"EBI-1055490"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q14116","intActId":"EBI-3910835"},"interactantTwo":{"uniProtKBAccession":"Q9IW12","intActId":"EBI-15748155"},"numberOfExperiments":2,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32272059"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33883744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993714"}],"value":"The precursor is cytosolic (PubMed:33883744). In response to inflammasome-activating signals, cleaved and secreted (PubMed:33883744, PubMed:37993712, PubMed:37993714). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744, PubMed:37993714). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1, CASP4 or CASP5 during maturation (PubMed:33883744, PubMed:37993714). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (PubMed:32272059)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32272059"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33883744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9334240"}],"value":"Cytoplasm, cytosol","id":"SL-0091"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23955712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32272059"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33883744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993714"}],"value":"Secreted","id":"SL-0243"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q14116-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"Delta3pro-IL-18"}],"isoformIds":["Q14116-2"],"sequenceIds":["VSP_044934"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15326478"}],"value":"Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4"}],"commentType":"TISSUE SPECIFICITY","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23955712"}],"value":"In macrophages, release is increased by endocannabinoid anandamide/AEA"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15326478"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25261253"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33883744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"37993714"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9334240"}],"value":"The pro-IL-18 precursor is processed by CASP1, CASP4 or CASP5 to yield its mature, active form (PubMed:15326478, PubMed:25261253, PubMed:37993712, PubMed:37993714, PubMed:9334240). The pro-IL-18 precursor features autoinhibitory interactions between the propeptide and the post-cleavage-site region, preventing recognition by the IL18R1 receptor (PubMed:37993714). Processing by CASP1, CASP4 or CASP5 induces conformational changes to generate critical receptor-binding sites (PubMed:37993714). The mature form is then secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744, PubMed:37993714). In contrast, cleavage by CASP3 inactivates IL18 (PubMed:37993714, PubMed:9334240)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the IL-1 family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/Interleukin_1","ftp":false,"note":"Interleukin-1 entry"}],"features":[{"type":"Propeptide","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":36,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9334240"}],"featureId":"PRO_0000015343"},{"type":"Chain","location":{"start":{"value":37,"modifier":"EXACT"},"end":{"value":193,"modifier":"EXACT"}},"description":"Interleukin-18","featureId":"PRO_0000015344"},{"type":"Site","location":{"start":{"value":36,"modifier":"EXACT"},"end":{"value":37,"modifier":"EXACT"}},"description":"Cleavage; by CASP1, CASP4 and 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