IL18_RAT
ID IL18_RAT Reviewed; 194 AA.
AC P97636; O88749; P97637; Q541E6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 25-MAY-2022, entry version 144.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RC STRAIN=Sprague-Dawley; TISSUE=Adrenal gland;
RX PubMed=8999896; DOI=10.1074/jbc.272.4.2035;
RA Conti B., Jahng J.W., Tinti C., Son J.H., Joh T.H.;
RT "Induction of interferon-gamma inducing factor in the adrenal cortex.";
RL J. Biol. Chem. 272:2035-2037(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=9702748; DOI=10.1038/sj.mp.4000389;
RA Culhane A.C., Hall M.D., Rothwell N.J., Luheshi G.N.;
RT "Cloning of rat brain interleukin-18 cDNA.";
RL Mol. Psychiatry 3:362-366(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RC STRAIN=New England Deaconess Hospital; TISSUE=Adrenal gland;
RA Kim S.-J., Kim C.-S., Song K.-Y., Kim J.-S., Jung K.-S.;
RT "Cloning of the cDNA for interleukin-18 in PC12 and expression in
RT Escherichia coli.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RC STRAIN=Fischer 344;
RX PubMed=12787406; DOI=10.1046/j.1523-1755.2003.00077.x;
RA Garcia G.E., Xia Y., Ku G., Johnson R.J., Wilson C.B., Feng L.;
RT "IL-18 translational inhibition restricts IFN-gamma expression in
RT crescentic glomerulonephritis.";
RL Kidney Int. 64:160-169(2003).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Beta;
CC IsoId=P97636-1; Sequence=Displayed;
CC Name=Alpha;
CC IsoId=P97636-2; Sequence=VSP_002659;
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; U77776; AAC53009.1; -; mRNA.
DR EMBL; U77777; AAC53010.1; -; mRNA.
DR EMBL; AJ222813; CAA11001.1; -; mRNA.
DR EMBL; AY258448; AAP14669.1; -; mRNA.
DR EMBL; AY077842; AAL77211.1; -; mRNA.
DR RefSeq; NP_062038.1; NM_019165.1. [P97636-1]
DR AlphaFoldDB; P97636; -.
DR SMR; P97636; -.
DR STRING; 10116.ENSRNOP00000013093; -.
DR BindingDB; P97636; -.
DR PaxDb; P97636; -.
DR GeneID; 29197; -.
DR KEGG; rno:29197; -.
DR UCSC; RGD:2889; rat. [P97636-1]
DR CTD; 3606; -.
DR RGD; 2889; Il18.
DR eggNOG; ENOG502SDJZ; Eukaryota.
DR InParanoid; P97636; -.
DR OrthoDB; 1301385at2759; -.
DR PhylomeDB; P97636; -.
DR TreeFam; TF336297; -.
DR PRO; PR:P97636; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IMP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IDA:RGD.
DR GO; GO:0048546; P:digestive tract morphogenesis; IEP:RGD.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0007611; P:learning or memory; TAS:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0030101; P:natural killer cell activation; ISO:RGD.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:RGD.
DR GO; GO:0033030; P:negative regulation of neutrophil apoptotic process; IMP:RGD.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:RGD.
DR GO; GO:0042119; P:neutrophil activation; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:RGD.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:2000504; P:positive regulation of blood vessel remodeling; IDA:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:RGD.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IDA:RGD.
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:0032731; P:positive regulation of interleukin-1 beta production; IEP:RGD.
DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:RGD.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:RGD.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISO:RGD.
DR GO; GO:2000256; P:positive regulation of male germ cell proliferation; IDA:RGD.
DR GO; GO:0032819; P:positive regulation of natural killer cell proliferation; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0051142; P:positive regulation of NK T cell proliferation; ISO:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:RGD.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR GO; GO:0043117; P:positive regulation of vascular permeability; IMP:RGD.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0045188; P:regulation of circadian sleep/wake cycle, non-REM sleep; TAS:UniProtKB.
DR GO; GO:0009409; P:response to cold; IEP:RGD.
DR GO; GO:0055093; P:response to hyperoxia; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IMP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009314; P:response to radiation; IEP:RGD.
DR GO; GO:0030431; P:sleep; IDA:UniProtKB.
DR GO; GO:0042088; P:T-helper 1 type immune response; ISS:UniProtKB.
DR GO; GO:0070328; P:triglyceride homeostasis; ISO:RGD.
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 Alternative splicing; Cytokine; Cytoplasm; Inflammatory response;
KW Reference proteome; Secreted.
FT PROPEP 1..36
FT /evidence="ECO:0000250|UniProtKB:P70380"
FT /id="PRO_0000015349"
FT CHAIN 37..194
FT /note="Interleukin-18"
FT /id="PRO_0000015350"
FT VAR_SEQ 121..139
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:8999896"
FT /id="VSP_002659"
FT CONFLICT 4..5
FT /note="MS -> IP (in Ref. 2; CAA11001 and 4; AAL77211)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="I -> M (in Ref. 2; CAA11001 and 4; AAL77211)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 194 AA; 22303 MW; E2089AD6F1798450 CRC64;
MAAMSEEGSC VNFKEMMFID NTLYLIPEDN GDLESDHFGR LHCTTAVIRS INDQVLFVDK
RNPPVFEDMP DIDRTANESQ TRLIIYMYKD SEVRGLAVTL SVKDGRMSTL SCKNKIISFE
EMNPPENIDD IKSDLIFFQK RVPGHNKMEF ESSLYEGHFL ACQKEDDAFK LVLKRKDENG
DKSVMFTLTN LHQS
