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Details on Person UniProt:Q14116 IL18
| Class:Id | ReferenceGeneProduct:57232 |
|---|---|
| _chainChangeLog | propeptide:1-36 added on Sat February 7 2015;chain:37-193 added on Sat February 7 2015 |
| _displayName | UniProt:Q14116 IL18 |
| _timestamp | 2024-11-03 19:41:23 |
| chain | propeptide:1-36 chain:37-193 |
| checksum | 323C62C203788D55 |
| comment | FUNCTION 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).SUBUNIT 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).INTERACTION 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).ALTERNATIVE PRODUCTS Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4.INDUCTION In macrophages, release is increased by endocannabinoid anandamide/AEA.PTM 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).SIMILARITY Belongs to the IL-1 family.ONLINE INFORMATION Interleukin-1 entry |
| description | recommendedName: fullName evidence="12 14 15"Interleukin-18 shortName evidence="12 14 15"IL-18 alternativeName: Iboctadekin alternativeName: fullName evidence="12 15"Interferon gamma-inducing factor shortName evidence="12 15"IFN-gamma-inducing factor alternativeName: Interleukin-1 gamma shortName: IL-1 gamma |
| geneName | IL18 IGIF IL1F4 |
| identifier | Q14116 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cytokine Cytoplasm Direct protein sequencing Inflammatory response Proteomics identification Reference proteome Secreted |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | IL18 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:6784994] ENSEMBL:ENSG00000150782 IL18 [Homo sapiens] |
| secondaryIdentifier | IL18_HUMAN O75599 Q6FGY3 Q6WWJ7 |
| sequenceLength | 193 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8968816] UniProt:Q14116-1 IL18 [Homo sapiens] [ReferenceIsoform:8968817] UniProt:Q14116-2 IL18 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:448446] IL18 [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:449023] IL18(37-193) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:449033] IL18(1-193) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:449062] IL18(1-36) [cytosol] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q14116 IL18 (57232)
