IL18 (interleukin 18)

Gene

• Entrez ID: 3606
• Gene name: Interleukin 18
• Gene symbol: IL18
• Synonyms: IGIF, IL-18, IL-1g, IL1F4
• Chromosome: 11
• Chromosome location: 11q23.1
• Summary: The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT004304	hsa-miR-346	qRT-PCR, Luciferase reporter assay, Western blot, Northern blot	19342689
MIRT054556	hsa-miR-197-3p	Microarray, qRT-PCR	23710316
MIRT438748	hsa-miR-130a-3p	ELISA, Luciferase reporter assay, qRT-PCR	24801815
MIRT733710	hsa-miR-24-3p	Microarray, qRT-PCR	28057018

Transcription factors

Transcription factor	Regulation	Reference
HDAC9	Unknown	11944905
NFKB1	Activation	15963597;17399992
NFKB1	Unknown	10227974
RELA	Activation	15963597;17399992
RELA	Unknown	10227974
SPI1	Unknown	14991611

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IMP	21147091
GO:0001525	Process	Angiogenesis	IDA	11466388
GO:0005125	Function	Cytokine activity	IDA	14528293, 25500532
GO:0005125	Function	Cytokine activity	ISS
GO:0005125	Function	Cytokine activity	TAS	11598150
GO:0005515	Function	Protein binding	IPI	19104048, 25261253, 32296183
GO:0005576	Component	Extracellular region	TAS	11598150
GO:0005615	Component	Extracellular space	IDA	21323571
GO:0005829	Component	Cytosol	TAS
GO:0006954	Process	Inflammatory response	IDA	21147091
GO:0007267	Process	Cell-cell signaling	TAS	9792649
GO:0008283	Process	Cell population proliferation	IEA
GO:0010744	Process	Positive regulation of macrophage derived foam cell differentiation	ISS
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IDA	21321938
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030101	Process	Natural killer cell activation	IEA
GO:0030155	Process	Regulation of cell adhesion	IDA	11477102
GO:0030431	Process	Sleep	ISS	11506998
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IDA	21147091
GO:0032148	Process	Activation of protein kinase B activity	IDA	21321938
GO:0032602	Process	Chemokine production	TAS	11598150
GO:0032609	Process	Interferon-gamma production	TAS	10227975
GO:0032616	Process	Interleukin-13 production	TAS	10227975
GO:0032725	Process	Positive regulation of granulocyte macrophage colony-stimulating factor production	IDA	20027291
GO:0032729	Process	Positive regulation of interferon-gamma production	IDA	10653850, 14528293, 19088061, 20027291
GO:0032740	Process	Positive regulation of interleukin-17 production	IDA	16482511
GO:0032819	Process	Positive regulation of natural killer cell proliferation	IDA	19088061
GO:0034105	Process	Positive regulation of tissue remodeling	IC	16482511
GO:0035655	Process	Interleukin-18-mediated signaling pathway	IDA	21321938, 25500532
GO:0035655	Process	Interleukin-18-mediated signaling pathway	TAS
GO:0042088	Process	T-helper 1 type immune response	IDA	8766574
GO:0042092	Process	Type 2 immune response	TAS	11905033
GO:0042104	Process	Positive regulation of activated T cell proliferation	IDA	8766574
GO:0042119	Process	Neutrophil activation	IEA
GO:0042267	Process	Natural killer cell mediated cytotoxicity	IEA
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	10903731
GO:0042632	Process	Cholesterol homeostasis	ISS
GO:0045515	Function	Interleukin-18 receptor binding	IDA	14528293, 25500532
GO:0045630	Process	Positive regulation of T-helper 2 cell differentiation	ISS
GO:0045662	Process	Negative regulation of myoblast differentiation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	24615654
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	21321938
GO:0050729	Process	Positive regulation of inflammatory response	IC	16482511
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	25500532
GO:0051142	Process	Positive regulation of NK T cell proliferation	IDA	19088061
GO:0051897	Process	Positive regulation of protein kinase B signaling	IDA	21321938
GO:0070328	Process	Triglyceride homeostasis	ISS
GO:0071407	Process	Cellular response to organic cyclic compound	IDA	21147091
GO:0120162	Process	Positive regulation of cold-induced thermogenesis	ISS	26656097
GO:0150078	Process	Positive regulation of neuroinflammatory response	TAS	26753638
GO:1901224	Process	Positive regulation of NIK/NF-kappaB signaling	IEA
GO:2000556	Process	Positive regulation of T-helper 1 cell cytokine production	IDA	10653850

Other IDs

• MIM: 600953
• HGNC: 5986
• e!Ensembl: ENSG00000150782

Protein

• UniProt ID: Q14116
• Protein name: Interleukin-18 (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
• Protein function: A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). 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). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (Probable) (PubMed:10653850).
• PDB: 1J0S, 2VXT, 3F62, 3WO2, 3WO3, 3WO4, 4EEE, 4EKX, 4HJJ, 4R6U, 4XFS, 4XFT, 4XFU
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00340	IL1	72 → 185	Interleukin-1 / 18	Domain

• Sequence:

  MAAEPVEDNCINFVAMKFIDNTLYFIAEDDENLESDYFGKLESKLSVIRNLNDQVLFIDQ
  GNRPLFEDMTDSDCRDNAPRTIFIISMYKDSQPRGMAVTISVKCEKISTLSCENKIISFK
  EMNPPDNIKDTKSDIIFFQRSVPGHDNKMQFESSSYEGYFLACEKERDLFKLILKKEDEL
  GDRSIMFTVQNED

• Sequence length: 193