IL18_HORSE
ID IL18_HORSE Reviewed; 193 AA.
AC Q9XSQ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Interleukin-18;
DE Short=IL-18;
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;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10541814; DOI=10.1007/s002510050693;
RA Nicolson L., Penha-Goncalves M.N., Keanie J.L., Logan N.A., Argyle D.J.,
RA Onions D.E.;
RT "Cloning and sequencing of horse interleukin-12 and interleukin-18 cDNAs.";
RL Immunogenetics 50:94-97(1999).
CC -!- FUNCTION: Pro-inflammatory cytokine primarily involved in epithelial
CC barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK)
CC cell immune responses. Upon binding to IL18R1 and IL18RAP, forms a
CC signaling ternary complex which activates NF-kappa-B, triggering
CC synthesis of inflammatory mediators. Synergizes with IL12/interleukin-
CC 12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural
CC killer (NK) cells. Involved in transduction of inflammation downstream
CC of pyroptosis: its mature form is specifically released in the
CC extracellular milieu by passing through the gasdermin-D (GSDMD) pore.
CC {ECO:0000250|UniProtKB:Q14116}.
CC -!- SUBUNIT: Forms a ternary complex with ligand-binding receptor subunit
CC IL18R1 and signaling receptor subunit IL18RAP at the plasma membrane.
CC Mature IL18 first binds to IL18R1 forming a low affinity binary
CC complex, which then interacts with IL18RAP to form a high affinity
CC ternary complex that signals inside the cell. Interacts with cargo
CC receptor TMED10; the interaction mediates the translocation from the
CC cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate
CC compartment) and thereby secretion. {ECO:0000250|UniProtKB:Q14116}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14116}.
CC Secreted {ECO:0000250|UniProtKB:Q14116}. Note=The precursor is
CC cytosolic. In response to inflammasome-activating signals, cleaved and
CC secreted. Mature form is secreted and released in the extracellular
CC milieu by passing through the gasdermin-D (GSDMD) pore. In contrast,
CC the precursor form is not released, due to the presence of an acidic
CC region that is proteolytically removed by CASP1 during maturation. The
CC secretion is dependent on protein unfolding and facilitated by the
CC cargo receptor TMED10. {ECO:0000250|UniProtKB:Q14116}.
CC -!- PTM: The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield
CC the active form. {ECO:0000250|UniProtKB:Q14116}.
CC -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
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DR EMBL; Y11131; CAA72013.1; -; mRNA.
DR RefSeq; NP_001075981.1; NM_001082512.1.
DR RefSeq; XP_005611483.1; XM_005611426.2.
DR RefSeq; XP_005611484.1; XM_005611427.2.
DR AlphaFoldDB; Q9XSQ7; -.
DR SMR; Q9XSQ7; -.
DR STRING; 9796.ENSECAP00000040862; -.
DR PaxDb; Q9XSQ7; -.
DR PeptideAtlas; Q9XSQ7; -.
DR PRIDE; Q9XSQ7; -.
DR Ensembl; ENSECAT00000029890; ENSECAP00000040862; ENSECAG00000015261.
DR GeneID; 100034216; -.
DR KEGG; ecb:100034216; -.
DR CTD; 3606; -.
DR VGNC; VGNC:19006; IL18.
DR GeneTree; ENSGT00390000001053; -.
DR HOGENOM; CLU_113349_0_0_1; -.
DR InParanoid; Q9XSQ7; -.
DR OMA; GKNFCLY; -.
DR OrthoDB; 1190337at2759; -.
DR TreeFam; TF336297; -.
DR Proteomes; UP000002281; Chromosome 7.
DR Bgee; ENSECAG00000015261; Expressed in blood and 22 other tissues.
DR ExpressionAtlas; Q9XSQ7; baseline.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; ISS:UniProtKB.
DR GO; GO:0045515; F:interleukin-18 receptor binding; ISS:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:Ensembl.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0030101; P:natural killer cell activation; IEA:Ensembl.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IEA:Ensembl.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IEA:Ensembl.
DR GO; GO:0042119; P:neutrophil activation; IEA:Ensembl.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IEA:Ensembl.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; IEA:Ensembl.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IEA:Ensembl.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; IEA:Ensembl.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; IEA:Ensembl.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0042088; P:T-helper 1 type immune response; IEA:Ensembl.
DR GO; GO:0070328; P:triglyceride homeostasis; IEA:Ensembl.
DR InterPro; IPR015529; IL-18.
DR InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR008996; IL1/FGF.
DR Pfam; PF00340; IL1; 1.
DR PIRSF; PIRSF015162; Interleukin_18; 1.
DR PRINTS; PR01933; INTRLEUKIN18.
DR SUPFAM; SSF50353; SSF50353; 1.
PE 2: Evidence at transcript level;
KW Cytokine; Cytoplasm; Inflammatory response; Reference proteome; Secreted.
FT PROPEP 1..36
FT /evidence="ECO:0000250|UniProtKB:P70380"
FT /id="PRO_0000015341"
FT CHAIN 37..193
FT /note="Interleukin-18"
FT /id="PRO_0000015342"
SQ SEQUENCE 193 AA; 22058 MW; 4D81535E9004ECAF CRC64;
MAAGPVEDNC ISLVEMKFID NTLYFVAEND ENLESDYFGR LEPKLSIIRN LNDQVLFINQ
GNQPVFEDMP DSDCTDNAPQ TVFIIYMYKD SLTRGLAVTI SVKCEKTSTL SCKNKIISFK
EMSPPENIND EGNDIIFFQR SVPGHDDKIQ FESSLYKGYF LACEKENDLF KLILKEKDEN
GDKSVMFTVQ NQN