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Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)

 IL18_BOVIN              Reviewed;         193 AA.
Q9TU73; A9QWR6; Q3SZF6;
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
02-JUN-2021, entry version 130.
RecName: Full=Interleukin-18;
Short=IL-18;
AltName: Full=Interferon gamma-inducing factor;
Short=IFN-gamma-inducing factor;
AltName: Full=Interleukin-1 gamma;
Short=IL-1 gamma;
Flags: Precursor;
Name=IL18; Synonyms=IGIF;
Bos taurus (Bovine).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
Bovinae; Bos.
NCBI_TaxID=9913;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=10547157; DOI=10.1089/107999099313118;
Shoda L.K., Zarlenga D.S., Hirano A., Brown W.C.;
"Cloning of a cDNA encoding bovine interleukin-18 and analysis of IL-18
expression in macrophages and its IFN-gamma-inducing activity.";
J. Interferon Cytokine Res. 19:1169-1177(1999).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Belted Galloway; TISSUE=Peripheral blood;
U.S. Veterinary Immune Reagent Network;
Hudgens T., Tompkins D., Baldwin C.L.;
"U.S. veterinary immune reagent network: expressed bovine gene sequences.";
Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Crossbred X Angus; TISSUE=Ileum;
NIH - Mammalian Gene Collection (MGC) project;
Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
-!- FUNCTION: A proinflammatory cytokine primarily involved in polarized T-
helper 1 (Th1) cell and natural killer (NK) cell immune responses. Upon
binding to IL18R1 and IL18RAP, forms a signaling ternary complex which
activates NF-kappa-B, triggering synthesis of inflammatory mediators.
Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-
helper 1 (Th1) cells and natural killer (NK) cells.
{ECO:0000250|UniProtKB:Q14116}.
-!- SUBUNIT: Forms a ternary complex with ligand-binding receptor subunit
IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane.
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. Interacts with cargo
receptor TMED10; the interaction mediates the translocation from the
cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate
compartment) and thereby secretion. {ECO:0000250|UniProtKB:Q14116}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14116}.
Secreted {ECO:0000250|UniProtKB:Q14116}. Note=The secretion is
dependent on protein unfolding and facilitated by the cargo receptor
TMED10; it results in protein translocation from the cytoplasm into the
ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed
by vesicle entry and secretion. {ECO:0000250|UniProtKB:Q14116}.
-!- PTM: The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield
the active form. {ECO:0000250}.
-!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
---------------------------------------------------------------------------
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EMBL; AF124789; AAF08686.1; -; mRNA.
EMBL; EU276078; ABX72076.1; -; mRNA.
EMBL; BC102879; AAI02880.1; -; mRNA.
RefSeq; NP_776516.1; NM_174091.2.
SMR; Q9TU73; -.
STRING; 9913.ENSBTAP00000055793; -.
PaxDb; Q9TU73; -.
Ensembl; ENSBTAT00000065052; ENSBTAP00000055793; ENSBTAG00000000277.
GeneID; 281249; -.
KEGG; bta:281249; -.
CTD; 3606; -.
VGNC; VGNC:30126; IL18.
eggNOG; ENOG502SDJZ; Eukaryota.
GeneTree; ENSGT00390000001053; -.
HOGENOM; CLU_113349_0_0_1; -.
InParanoid; Q9TU73; -.
OMA; INPPDNI; -.
OrthoDB; 1190337at2759; -.
TreeFam; TF336297; -.
Proteomes; UP000009136; Chromosome 15.
Bgee; ENSBTAG00000000277; Expressed in abdominal lymph node and 95 other tissues.
ExpressionAtlas; Q9TU73; baseline and differential.
GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
GO; GO:0005125; F:cytokine activity; ISS:UniProtKB.
GO; GO:0045515; F:interleukin-18 receptor binding; ISS:UniProtKB.
GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO; GO:0035655; P:interleukin-18-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
GO; GO:0030101; P:natural killer cell activation; IEA:Ensembl.
GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
GO; GO:0042119; P:neutrophil activation; IEA:Ensembl.
GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Ensembl.
GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
GO; GO:0032740; P:positive regulation of interleukin-17 production; IEA:Ensembl.
GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IEA:Ensembl.
GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IEA:Ensembl.
GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
GO; GO:0051142; P:positive regulation of NK T cell proliferation; IEA:Ensembl.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
GO; GO:0042088; P:T-helper 1 type immune response; IEA:Ensembl.
GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
InterPro; IPR015529; IL-18.
InterPro; IPR000975; IL-1_fam.
InterPro; IPR008996; IL1/FGF.
Pfam; PF00340; IL1; 1.
PIRSF; PIRSF015162; Interleukin_18; 1.
PRINTS; PR01933; INTRLEUKIN18.
SUPFAM; SSF50353; SSF50353; 1.
2: Evidence at transcript level;
Cytokine; Cytoplasm; Inflammatory response; Reference proteome; Secreted.
PROPEP 1..36
/evidence="ECO:0000250"
/id="PRO_0000015337"
CHAIN 37..193
/note="Interleukin-18"
/id="PRO_0000015338"
SEQUENCE 193 AA; 22347 MW; 65720F199DEA49C4 CRC64;
MAAEQVEDYC ISFVEMKFIN NTLYFVAEND EDLESDHFGK LEPKLSIIRN LNDQVLFINQ
GNQPVFEDMP DSDCSDNAPQ TIFIIYMYKD SLTRGLAVTI SVQCKKMSTL SCENKIVSFK
EMNPPDNIDN EESDIIFFQR SVPGHDDKIQ FESSLYKGYF LACKKENDLF KLILKKQDDN
RDKSVMFTVQ NQN


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Pathways :
WP1836: Interferon gamma signaling
WP868: estrogen signalling
WP2292: Chemokine signaling pathway
WP1225: estrogen signalling
WP1993: angiogenesis overview
WP1654: gamma-Hexachlorocyclohexane degradation
WP760: estrogen signalling
WP2199: Seed Development
WP866: EBV LMP1 signaling
WP262: EBV LMP1 signaling
WP1224: EBV LMP1 signaling
WP32: Translation Factors
WP1886: Post-translational modification: gamma carboxylation and hypusine formation
WP542: Electron Transport Chain
WP152: FGF signaling pathway
WP758: EBV LMP1 signaling
WP2152: BDNF
WP537: Translation Factors
WP2006: Squamous cell TarBase
WP1722: Th1/Th2
WP272: Blood Clotting Cascade
WP1839: Interleukin-1 signaling
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP444: Signaling of Hepatocyte Growth Factor Receptor

Related Genes :
[IL18 IGIF IL1F4] Interleukin-18 (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Il18 Igif] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[Il18 Igif] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL18 IGIF] Interleukin-18 (IL-18) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma)
[IL36G IL1E IL1F9 IL1H1 IL1RP2 UNQ2456/PRO5737] Interleukin-36 gamma (IL-1-related protein 2) (IL-1RP2) (Interleukin-1 epsilon) (IL-1 epsilon) (Interleukin-1 family member 9) (IL-1F9) (Interleukin-1 homolog 1) (IL-1H1)
[TICAM1 PRVTIRB TRIF] TIR domain-containing adapter molecule 1 (TICAM-1) (Proline-rich, vinculin and TIR domain-containing protein B) (Putative NF-kappa-B-activating protein 502H) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (MyD88-3) (TIR domain-containing adapter protein inducing IFN-beta)
[IL18R1 IL1RRP] Interleukin-18 receptor 1 (IL-18R-1) (IL-18R1) (EC 3.2.2.6) (CD218 antigen-like family member A) (CDw218a) (IL1 receptor-related protein) (IL-1Rrp) (IL1R-rp) (Interleukin-18 receptor alpha) (IL-18R-alpha) (IL-18Ralpha) (CD antigen CD218a)
[IL6 IFNB2] Interleukin-6 (IL-6) (B-cell stimulatory factor 2) (BSF-2) (CTL differentiation factor) (CDF) (Hybridoma growth factor) (Interferon beta-2) (IFN-beta-2)
[IFNG] Interferon gamma (IFN-gamma)
[IL2RG] Cytokine receptor common subunit gamma (Interleukin-2 receptor subunit gamma) (IL-2 receptor subunit gamma) (IL-2R subunit gamma) (IL-2RG) (gammaC) (p64) (CD antigen CD132)
[IL18RAP IL1R7] Interleukin-18 receptor accessory protein (IL-18 receptor accessory protein) (IL-18RAcP) (EC 3.2.2.6) (Accessory protein-like) (AcPL) (CD218 antigen-like family member B) (CDw218b) (IL-1R accessory protein-like) (IL-1RAcPL) (Interleukin-1 receptor 7) (IL-1R-7) (IL-1R7) (Interleukin-18 receptor accessory protein-like) (Interleukin-18 receptor beta) (IL-18R-beta) (IL-18Rbeta) (CD antigen CD218b)
[IFNG] Interferon gamma (IFN-gamma) (Immune interferon)
[IFNLR1 IL28RA LICR2] Interferon lambda receptor 1 (IFN-lambda receptor 1) (IFN-lambda-R1) (Cytokine receptor class-II member 12) (Cytokine receptor family 2 member 12) (CRF2-12) (Interleukin-28 receptor subunit alpha) (IL-28 receptor subunit alpha) (IL-28R-alpha) (IL-28RA) (Likely interleukin or cytokine receptor 2) (LICR2)
[Ticam1 Trif] TIR domain-containing adapter molecule 1 (TICAM-1) (Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta) (TIR domain-containing adapter protein inducing IFN-beta)
[IFNL1 IL29 ZCYTO21] Interferon lambda-1 (IFN-lambda-1) (Cytokine Zcyto21) (Interleukin-29) (IL-29)
[IL33 C9orf26 IL1F11 NFHEV] Interleukin-33 (IL-33) (Interleukin-1 family member 11) (IL-1F11) (Nuclear factor from high endothelial venules) (NF-HEV) [Cleaved into: Interleukin-33 (95-270); Interleukin-33 (99-270); Interleukin-33 (109-270)]
[Il18r1] Interleukin-18 receptor 1 (IL-18R-1) (IL-18R1) (EC 3.2.2.6) (CD218 antigen-like family member A) (IL1 receptor-related protein) (IL-1Rrp) (IL1R-rp) (Interleukin-18 receptor alpha) (IL-18R-alpha) (IL-18Ralpha) (CD antigen CD218a)
[Il2rg] Cytokine receptor common subunit gamma (Interleukin-2 receptor subunit gamma) (IL-2 receptor subunit gamma) (IL-2R subunit gamma) (IL-2RG) (gammaC) (p64) (CD antigen CD132)
[IL32 NK4 TAIF] Interleukin-32 (IL-32) (Natural killer cells protein 4) (Tumor necrosis factor alpha-inducing factor)
[IL1B IL1F2] Interleukin-1 beta (IL-1 beta) (Catabolin)
[Ifng] Interferon gamma (IFN-gamma)
[Ifng] Interferon gamma (IFN-gamma)
[IFNG] Interferon gamma (IFN-gamma)
[IFNG] Interferon gamma (IFN-gamma)
[IFNG] Interferon gamma (IFN-gamma)
[IL1R1 IL1R IL1RA IL1RT1] Interleukin-1 receptor type 1 (IL-1R-1) (IL-1RT-1) (IL-1RT1) (EC 3.2.2.6) (CD121 antigen-like family member A) (Interleukin-1 receptor alpha) (IL-1R-alpha) (Interleukin-1 receptor type I) (p80) (CD antigen CD121a) [Cleaved into: Interleukin-1 receptor type 1, membrane form (mIL-1R1) (mIL-1RI); Interleukin-1 receptor type 1, soluble form (sIL-1R1) (sIL-1RI)]
[IFNG] Interferon gamma (BoIFNG) (IFN-gamma)

Bibliography :
[34228995] Characterization of the turbot (Scophthalmus maximus) interleukin-18: Identification of splicing variants, phylogeny, synteny and expression analysis.
[34139296] Inflammatory cytokines and appetite in older hospitalized patients.
[34108686] TIM-3 restrains anti-tumour immunity by regulating inflammasome activation.
[34010066] LncRNA GAS5 inhibits miR-579-3p to activate SIRT1/PGC-1α/Nrf2 signaling pathway to reduce cell pyroptosis in sepsis-associated renal injury.
[33833503] White Tip Silver Needle (Slightly Fermented White Tea) Flavonoids Help Prevent Aging via Antioxidative and Anti-Inflammatory Effects.
[33760111] Cytokine secretion and pyroptosis of cholesteatoma keratinocytes mediated by AIM2 inflammasomes in response to cytoplasmic DNA.
[33185287] Cytokine dysregulation in children with cerebral palsy.
[32983099] Human Autoinflammatory Diseases Mediated by NLRP3-, Pyrin-, NLRP1-, and NLRC4-Inflammasome Dysregulation Updates on Diagnosis, Treatment, and the Respective Roles of IL-1 and IL-18.
[32726630] Neutrophil Caspase-11 Is Essential to Defend against a Cytosol-Invasive Bacterium.
[32556329] Systemic juvenile idiopathic arthritis and recurrent macrophage activation syndrome due to a CASP1 variant causing inflammasome hyperactivation.