UniProtKB - Q14116 (IL18_HUMAN)
Interleukin-18
IL18
Functioni
Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850).
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 (PubMed:10653850).
Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744).
4 PublicationsGO - Molecular functioni
- cytokine activity Source: UniProtKB
- interleukin-18 receptor binding Source: UniProtKB
GO - Biological processi
- activation of protein kinase B activity Source: BHF-UCL
- angiogenesis Source: UniProtKB
- cell-cell signaling Source: ProtInc
- cell population proliferation Source: Ensembl
- cellular response to organic cyclic compound Source: UniProtKB
- cholesterol homeostasis Source: BHF-UCL
- defense response to Gram-positive bacterium Source: UniProtKB
- establishment of skin barrier Source: UniProtKB
- inflammatory response Source: UniProtKB
- interleukin-18-mediated signaling pathway Source: UniProtKB
- lipopolysaccharide-mediated signaling pathway Source: UniProtKB
- MAPK cascade Source: UniProtKB
- natural killer cell activation Source: Ensembl
- natural killer cell mediated cytotoxicity Source: Ensembl
- negative regulation of myoblast differentiation Source: Ensembl
- neutrophil activation Source: Ensembl
- positive regulation of activated T cell proliferation Source: UniProtKB
- positive regulation of chemokine production Source: UniProtKB
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
- positive regulation of inflammatory response Source: UniProtKB
- positive regulation of interferon-gamma production Source: UniProtKB
- positive regulation of interleukin-13 production Source: UniProtKB
- positive regulation of interleukin-17 production Source: BHF-UCL
- positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
- positive regulation of natural killer cell proliferation Source: BHF-UCL
- positive regulation of neuroinflammatory response Source: ARUK-UCL
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of NIK/NF-kappaB signaling Source: Ensembl
- positive regulation of NK T cell proliferation Source: BHF-UCL
- positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
- positive regulation of protein kinase B signaling Source: BHF-UCL
- positive regulation of smooth muscle cell proliferation Source: BHF-UCL
- positive regulation of T-helper 1 cell cytokine production Source: UniProtKB
- positive regulation of T-helper 2 cell differentiation Source: BHF-UCL
- positive regulation of tissue remodeling Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of tyrosine phosphorylation of STAT protein Source: CACAO
- regulation of cell adhesion Source: UniProtKB
- sleep Source: UniProtKB
- T-helper 1 type immune response Source: UniProtKB
- triglyceride homeostasis Source: BHF-UCL
- type 2 immune response Source: UniProtKB
Keywordsi
Molecular function | Cytokine |
Biological process | Inflammatory response |
Enzyme and pathway databases
PathwayCommonsi | Q14116 |
Reactomei | R-HSA-448706, Interleukin-1 processing R-HSA-5620971, Pyroptosis R-HSA-6783783, Interleukin-10 signaling R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-9012546, Interleukin-18 signaling [Q14116-2] R-HSA-9660826, Purinergic signaling in leishmaniasis infection |
SignaLinki | Q14116 |
SIGNORi | Q14116 |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-183 PublicationsShort name: IL-183 Publications Alternative name(s): Iboctadekin Interferon gamma-inducing factor2 Publications Short name: IFN-gamma-inducing factor2 Publications Interleukin-1 gamma Short name: IL-1 gamma |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5986, IL18 |
MIMi | 600953, gene |
neXtProti | NX_Q14116 |
VEuPathDBi | HostDB:ENSG00000150782 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Extracellular region or secreted
- Secreted 3 Publications
Note: The precursor is cytosolic (PubMed:33883744). In response to inflammasome-activating signals, cleaved and secreted (PubMed:33883744). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (PubMed:32272059).2 Publications
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: BHF-UCL
Keywords - Cellular componenti
Cytoplasm, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 40 | K → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 41 | L → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 44 | K → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 49 | R → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 53 | D → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 69 | M → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 71 | D → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 94 | R → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 96 | M → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 115 | K → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production. 1 Publication | 1 | |
Mutagenesisi | 120 | K → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production. 1 Publication | 1 | |
Mutagenesisi | 134 | D → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production. 1 Publication | 1 | |
Mutagenesisi | 140 | R → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 144 | G → A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication | 1 | |
Mutagenesisi | 145 | H → A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication | 1 | |
Mutagenesisi | 146 | D → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication | 1 | |
Mutagenesisi | 148 | K → A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication | 1 | |
Mutagenesisi | 168 | D → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication | 1 | |
Mutagenesisi | 183 | R → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication | 1 | |
Mutagenesisi | 186 | M → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 3606 |
OpenTargetsi | ENSG00000150782 |
PharmGKBi | PA29802 |
Miscellaneous databases
Pharosi | Q14116, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1741305 |
Genetic variation databases
BioMutai | IL18 |
DMDMi | 3219817 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
PropeptideiPRO_0000015343 | 1 – 36 | By similarityAdd BLAST | 36 | |
ChainiPRO_0000015344 | 37 – 193 | Interleukin-18Add BLAST | 157 |
Post-translational modificationi
Proteomic databases
CPTACi | CPTAC-1249 CPTAC-1250 CPTAC-1431 CPTAC-1432 CPTAC-1433 CPTAC-1434 CPTAC-1435 CPTAC-705 |
EPDi | Q14116 |
jPOSTi | Q14116 |
MassIVEi | Q14116 |
MaxQBi | Q14116 |
PaxDbi | Q14116 |
PeptideAtlasi | Q14116 |
PRIDEi | Q14116 |
ProteomicsDBi | 59823 [Q14116-1] 67779 |
2D gel databases
OGPi | Q14116 |
PTM databases
GlyGeni | Q14116, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q14116 |
PhosphoSitePlusi | Q14116 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000150782, Expressed in lower esophagus mucosa and 210 other tissues |
ExpressionAtlasi | Q14116, baseline and differential |
Genevisiblei | Q14116, HS |
Organism-specific databases
HPAi | ENSG00000150782, Tissue enhanced (esophagus, skin) |
Interactioni
Subunit structurei
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 (PubMed:25261253, PubMed:14528293, PubMed:25500532).
Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).
4 PublicationsBinary interactionsi
Q14116
With | #Exp. | IntAct |
---|---|---|
ADIRF [Q15847] | 3 | EBI-3910835,EBI-7162516 |
IL18R1 [Q13478] | 2 | EBI-3910835,EBI-9817499 |
Q9IW12 from Ectromelia virus. | 2 | EBI-3910835,EBI-15748155 |
GO - Molecular functioni
- cytokine activity Source: UniProtKB
- interleukin-18 receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 109819, 21 interactors |
DIPi | DIP-3785N |
IntActi | Q14116, 11 interactors |
MINTi | Q14116 |
STRINGi | 9606.ENSP00000280357 |
Miscellaneous databases
RNActi | Q14116, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q14116 |
SMRi | Q14116 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q14116 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502SDJZ, Eukaryota |
GeneTreei | ENSGT00390000001053 |
HOGENOMi | CLU_113349_0_0_1 |
InParanoidi | Q14116 |
OMAi | GKNFCLY |
OrthoDBi | 1190337at2759 |
PhylomeDBi | Q14116 |
TreeFami | TF336297 |
Family and domain databases
InterProi | View protein in InterPro IPR015529, IL-18 IPR000975, IL-1_fam IPR008996, IL1/FGF |
Pfami | View protein in Pfam PF00340, IL1, 1 hit |
PIRSFi | PIRSF015162, Interleukin_18, 1 hit |
PRINTSi | PR01933, INTRLEUKIN18 |
SUPFAMi | SSF50353, SSF50353, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAAEPVEDNC INFVAMKFID NTLYFIAEDD ENLESDYFGK LESKLSVIRN
60 70 80 90 100
LNDQVLFIDQ GNRPLFEDMT DSDCRDNAPR TIFIISMYKD SQPRGMAVTI
110 120 130 140 150
SVKCEKISTL SCENKIISFK EMNPPDNIKD TKSDIIFFQR SVPGHDNKMQ
160 170 180 190
FESSSYEGYF LACEKERDLF KLILKKEDEL GDRSIMFTVQ NED
The sequence of this isoform differs from the canonical sequence as follows:
27-30: Missing.
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 66 | F → L in AAC27787 (Ref. 3) Curated | 1 | |
Sequence conflicti | 86 | S → R in AAC27787 (Ref. 3) Curated | 1 | |
Sequence conflicti | 191 | N → S in AAC27787 (Ref. 3) Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044934 | 27 – 30 | Missing in isoform 2. 1 Publication | 4 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D49950 mRNA Translation: BAA08706.1 AY266351 mRNA Translation: AAP92112.1 AF077611 mRNA Translation: AAC27787.1 AY044641 mRNA Translation: AAK95950.1 CR541973 mRNA Translation: CAG46771.1 CR542001 mRNA Translation: CAG46798.1 AP002007 Genomic DNA No translation available. AP002884 Genomic DNA No translation available. CH471065 Genomic DNA Translation: EAW67184.1 BC007007 mRNA Translation: AAH07007.1 BC007461 mRNA Translation: AAH07461.1 U90434 mRNA Translation: AAB50010.1 |
CCDSi | CCDS44731.1 [Q14116-1] CCDS58180.1 [Q14116-2] |
RefSeqi | NP_001230140.1, NM_001243211.1 [Q14116-2] NP_001553.1, NM_001562.3 [Q14116-1] XP_011541107.1, XM_011542805.1 [Q14116-2] XP_011541108.1, XM_011542806.2 [Q14116-1] |
Genome annotation databases
Ensembli | ENST00000280357.12; ENSP00000280357.7; ENSG00000150782.12 ENST00000524595.5; ENSP00000434561.1; ENSG00000150782.12 [Q14116-2] ENST00000528832.1; ENSP00000434161.1; ENSG00000150782.12 |
GeneIDi | 3606 |
KEGGi | hsa:3606 |
MANE-Selecti | ENST00000280357.12; ENSP00000280357.7; NM_001562.4; NP_001553.1 |
UCSCi | uc001pnb.2, human [Q14116-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Interleukin-1 entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D49950 mRNA Translation: BAA08706.1 AY266351 mRNA Translation: AAP92112.1 AF077611 mRNA Translation: AAC27787.1 AY044641 mRNA Translation: AAK95950.1 CR541973 mRNA Translation: CAG46771.1 CR542001 mRNA Translation: CAG46798.1 AP002007 Genomic DNA No translation available. AP002884 Genomic DNA No translation available. CH471065 Genomic DNA Translation: EAW67184.1 BC007007 mRNA Translation: AAH07007.1 BC007461 mRNA Translation: AAH07461.1 U90434 mRNA Translation: AAB50010.1 |
CCDSi | CCDS44731.1 [Q14116-1] CCDS58180.1 [Q14116-2] |
RefSeqi | NP_001230140.1, NM_001243211.1 [Q14116-2] NP_001553.1, NM_001562.3 [Q14116-1] XP_011541107.1, XM_011542805.1 [Q14116-2] XP_011541108.1, XM_011542806.2 [Q14116-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1J0S | NMR | - | A | 37-193 | [»] | |
2VXT | X-ray | 1.49 | I | 37-193 | [»] | |
3F62 | X-ray | 2.00 | B | 37-193 | [»] | |
3WO2 | X-ray | 2.33 | A/B/C/D | 37-193 | [»] | |
3WO3 | X-ray | 3.10 | A/C/E/G/I/K | 37-193 | [»] | |
3WO4 | X-ray | 3.10 | A | 37-193 | [»] | |
4EEE | X-ray | 2.71 | B/D | 37-193 | [»] | |
4EKX | X-ray | 1.75 | B/D | 37-193 | [»] | |
4HJJ | X-ray | 2.10 | A | 37-192 | [»] | |
4R6U | X-ray | 2.80 | B/D | 37-193 | [»] | |
4XFS | X-ray | 1.91 | A/B | 37-193 | [»] | |
4XFT | X-ray | 2.00 | A/B | 37-193 | [»] | |
4XFU | X-ray | 2.85 | A/B | 37-193 | [»] | |
AlphaFoldDBi | Q14116 | |||||
SMRi | Q14116 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109819, 21 interactors |
DIPi | DIP-3785N |
IntActi | Q14116, 11 interactors |
MINTi | Q14116 |
STRINGi | 9606.ENSP00000280357 |
Chemistry databases
ChEMBLi | CHEMBL1741305 |
PTM databases
GlyGeni | Q14116, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q14116 |
PhosphoSitePlusi | Q14116 |
Genetic variation databases
BioMutai | IL18 |
DMDMi | 3219817 |
2D gel databases
OGPi | Q14116 |
Proteomic databases
CPTACi | CPTAC-1249 CPTAC-1250 CPTAC-1431 CPTAC-1432 CPTAC-1433 CPTAC-1434 CPTAC-1435 CPTAC-705 |
EPDi | Q14116 |
jPOSTi | Q14116 |
MassIVEi | Q14116 |
MaxQBi | Q14116 |
PaxDbi | Q14116 |
PeptideAtlasi | Q14116 |
PRIDEi | Q14116 |
ProteomicsDBi | 59823 [Q14116-1] 67779 |
Protocols and materials databases
ABCDi | Q14116, 24 sequenced antibodies |
Antibodypediai | 1287, 961 antibodies from 47 providers |
CPTCi | Q14116, 4 antibodies |
DNASUi | 3606 |
Genome annotation databases
Ensembli | ENST00000280357.12; ENSP00000280357.7; ENSG00000150782.12 ENST00000524595.5; ENSP00000434561.1; ENSG00000150782.12 [Q14116-2] ENST00000528832.1; ENSP00000434161.1; ENSG00000150782.12 |
GeneIDi | 3606 |
KEGGi | hsa:3606 |
MANE-Selecti | ENST00000280357.12; ENSP00000280357.7; NM_001562.4; NP_001553.1 |
UCSCi | uc001pnb.2, human [Q14116-1] |
Organism-specific databases
CTDi | 3606 |
DisGeNETi | 3606 |
GeneCardsi | IL18 |
HGNCi | HGNC:5986, IL18 |
HPAi | ENSG00000150782, Tissue enhanced (esophagus, skin) |
MIMi | 600953, gene |
neXtProti | NX_Q14116 |
OpenTargetsi | ENSG00000150782 |
PharmGKBi | PA29802 |
VEuPathDBi | HostDB:ENSG00000150782 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SDJZ, Eukaryota |
GeneTreei | ENSGT00390000001053 |
HOGENOMi | CLU_113349_0_0_1 |
InParanoidi | Q14116 |
OMAi | GKNFCLY |
OrthoDBi | 1190337at2759 |
PhylomeDBi | Q14116 |
TreeFami | TF336297 |
Enzyme and pathway databases
PathwayCommonsi | Q14116 |
Reactomei | R-HSA-448706, Interleukin-1 processing R-HSA-5620971, Pyroptosis R-HSA-6783783, Interleukin-10 signaling R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-9012546, Interleukin-18 signaling [Q14116-2] R-HSA-9660826, Purinergic signaling in leishmaniasis infection |
SignaLinki | Q14116 |
SIGNORi | Q14116 |
Miscellaneous databases
BioGRID-ORCSi | 3606, 38 hits in 1069 CRISPR screens |
EvolutionaryTracei | Q14116 |
GeneWikii | Interleukin_18 |
GenomeRNAii | 3606 |
Pharosi | Q14116, Tbio |
PROi | PR:Q14116 |
RNActi | Q14116, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000150782, Expressed in lower esophagus mucosa and 210 other tissues |
ExpressionAtlasi | Q14116, baseline and differential |
Genevisiblei | Q14116, HS |
Family and domain databases
InterProi | View protein in InterPro IPR015529, IL-18 IPR000975, IL-1_fam IPR008996, IL1/FGF |
Pfami | View protein in Pfam PF00340, IL1, 1 hit |
PIRSFi | PIRSF015162, Interleukin_18, 1 hit |
PRINTSi | PR01933, INTRLEUKIN18 |
SUPFAMi | SSF50353, SSF50353, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IL18_HUMAN | |
Accessioni | Q14116Primary (citable) accession number: Q14116 Secondary accession number(s): O75599, Q6FGY3, Q6WWJ7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | November 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 195 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families