ID   IL18_BOSTR              Reviewed;         193 AA.
AC   Q5I931;
DT   17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2005, sequence version 1.
DT   25-MAY-2022, entry version 48.
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   Boselaphus tragocamelus (Nilgai).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Boselaphus.
OX   NCBI_TaxID=9917;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Saini M., Swarup D., Yadav M.P., Singh G.R., Arora B.M., Chandra P.,
RA   Das D.K., Gupta P.K.;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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; AY842499; AAW34191.1; -; mRNA.
DR   AlphaFoldDB; Q5I931; -.
DR   SMR; Q5I931; -.
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:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR   GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR   GO; GO:0006955; P:immune response; IEA:InterPro.
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: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:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR   GO; GO:2000556; P:positive regulation of T-helper 1 cell cytokine production; ISS:UniProtKB.
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; Secreted.
FT   PROPEP          1..36
FT                   /evidence="ECO:0000250|UniProtKB:P70380"
FT                   /id="PRO_0000253503"
FT   CHAIN           37..193
FT                   /note="Interleukin-18"
FT                   /id="PRO_0000253504"
SQ   SEQUENCE   193 AA;  22130 MW;  75B6671696EE4A8D CRC64;
     MAAEQVEDNC ISFVEMKFIN NTLYFVAEND EDLESDHFGK LEPKLSIIRN LNDQVLFINQ
     GNQPVFEDMP DSDCPDNAPQ TIFIIYMYKD SLTRGLAVTI SVQCKKMSTL SCENKIVSFK
     EMNPPDNIDN EGSDIIFFQR SVPGHDDKIQ FESSLYKGYF LACKKENDLF KLILKKQDDN
     GDKSVTFTVQ NQH