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Protein

Interleukin-18

Gene

IL18

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

A proinflammatory cytokine primarily involved in polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (Probable). 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 (Probable) (PubMed:10653850).Curated3 Publications

GO - Molecular functioni

  • cytokine activity Source: UniProtKB
  • interleukin-18 receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionCytokine
Biological processInflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-448706 Interleukin-1 processing
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-9012546 Interleukin-18 signaling
SIGNORiQ14116

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-183 Publications
Short 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
Name:IL18Imported
Synonyms:IGIF, IL1F4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000150782.11
HGNCiHGNC:5986 IL18
MIMi600953 gene
neXtProtiNX_Q14116

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40K → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi41L → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi44K → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi49R → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi53D → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi69M → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi71D → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi94R → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi96M → A: Impairs binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi115K → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production. 1 Publication1
Mutagenesisi120K → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production. 1 Publication1
Mutagenesisi134D → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP resulting in impaired IFNG production. 1 Publication1
Mutagenesisi140R → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi144G → A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication1
Mutagenesisi145H → A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication1
Mutagenesisi146D → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication1
Mutagenesisi148K → A: Abolishes binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication1
Mutagenesisi168D → A: Reduces binding to IL18R1 and the ability to induce IFNG production. 1 Publication1
Mutagenesisi183R → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication1
Mutagenesisi186M → A: Reduces binding of the preformed binary complex of IL18 and IL18R1 to IL18RAP. 1 Publication1

Organism-specific databases

DisGeNETi3606
OpenTargetsiENSG00000150782
PharmGKBiPA29802

Chemistry databases

ChEMBLiCHEMBL1741305

Polymorphism and mutation databases

BioMutaiIL18
DMDMi3219817

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000153431 – 36By similarityAdd BLAST36
ChainiPRO_000001534437 – 193Interleukin-18Add BLAST157

Post-translational modificationi

The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form.2 Publications

Proteomic databases

EPDiQ14116
MaxQBiQ14116
PaxDbiQ14116
PeptideAtlasiQ14116
PRIDEiQ14116
ProteomicsDBi59823

2D gel databases

OGPiQ14116

PTM databases

iPTMnetiQ14116
PhosphoSitePlusiQ14116

Miscellaneous databases

PMAP-CutDBiQ14116

Expressioni

Inductioni

In macrophages, release is increased by endocannabinoid anandamide/AEA.1 Publication

Gene expression databases

BgeeiENSG00000150782 Expressed in 194 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_IL18
ExpressionAtlasiQ14116 baseline and differential
GenevisibleiQ14116 HS

Organism-specific databases

HPAiCAB007772
HPA003980

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).3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109819, 12 interactors
DIPiDIP-3785N
IntActiQ14116, 5 interactors
MINTiQ14116
STRINGi9606.ENSP00000280357

Structurei

Secondary structure

1193
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ14116
SMRiQ14116
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14116

Family & Domainsi

Sequence similaritiesi

Belongs to the IL-1 family.Curated

Phylogenomic databases

eggNOGiENOG410J3U9 Eukaryota
ENOG410ZGS8 LUCA
GeneTreeiENSGT00390000001053
HOGENOMiHOG000048723
HOVERGENiHBG000388
InParanoidiQ14116
KOiK05482
OMAiYKGYFLA
OrthoDBiEOG091G0NGF
PhylomeDBiQ14116
TreeFamiTF336297

Family and domain databases

InterProiView protein in InterPro
IPR015529 IL-18
IPR000975 IL-1_fam
IPR008996 IL1/FGF
PANTHERiPTHR45200 PTHR45200, 1 hit
PfamiView protein in Pfam
PF00340 IL1, 1 hit
PIRSFiPIRSF015162 Interleukin_18, 1 hit
PRINTSiPR01933 INTRLEUKIN18
SUPFAMiSSF50353 SSF50353, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q14116-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:193
Mass (Da):22,326
Last modified:November 1, 1996 - v1
Checksum:i323C62C203788D55
GO
Isoform 2 (identifier: Q14116-2) [UniParc]FASTAAdd to basket
Also known as: Delta3pro-IL-18

The sequence of this isoform differs from the canonical sequence as follows:
     27-30: Missing.

Note: Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4.
Show »
Length:189
Mass (Da):21,896
Checksum:iA8BA275CF713A4B6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti66F → L in AAC27787 (Ref. 3) Curated1
Sequence conflicti86S → R in AAC27787 (Ref. 3) Curated1
Sequence conflicti191N → S in AAC27787 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04493427 – 30Missing in isoform 2. 1 Publication4

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
CCDSiCCDS44731.1 [Q14116-1]
CCDS58180.1 [Q14116-2]
RefSeqiNP_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]
UniGeneiHs.83077

Genome annotation databases

EnsembliENST00000280357; ENSP00000280357; ENSG00000150782 [Q14116-1]
ENST00000524595; ENSP00000434561; ENSG00000150782 [Q14116-2]
ENST00000528832; ENSP00000434161; ENSG00000150782 [Q14116-1]
GeneIDi3606
KEGGihsa:3606
UCSCiuc001pnb.2 human [Q14116-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS44731.1 [Q14116-1]
CCDS58180.1 [Q14116-2]
RefSeqiNP_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]
UniGeneiHs.83077

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1J0SNMR-A37-193[»]
2VXTX-ray1.49I37-193[»]
3F62X-ray2.00B37-193[»]
3WO2X-ray2.33A/B/C/D37-193[»]
3WO3X-ray3.10A/C/E/G/I/K37-193[»]
3WO4X-ray3.10A37-193[»]
4EEEX-ray2.71B/D37-193[»]
4EKXX-ray1.75B/D37-193[»]
4HJJX-ray2.10A37-192[»]
4R6UX-ray2.80B/D37-193[»]
4XFSX-ray1.91A/B37-193[»]
4XFTX-ray2.00A/B37-193[»]
4XFUX-ray2.85A/B37-193[»]
ProteinModelPortaliQ14116
SMRiQ14116
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109819, 12 interactors
DIPiDIP-3785N
IntActiQ14116, 5 interactors
MINTiQ14116
STRINGi9606.ENSP00000280357

Chemistry databases

ChEMBLiCHEMBL1741305

PTM databases

iPTMnetiQ14116
PhosphoSitePlusiQ14116

Polymorphism and mutation databases

BioMutaiIL18
DMDMi3219817

2D gel databases

OGPiQ14116

Proteomic databases

EPDiQ14116
MaxQBiQ14116
PaxDbiQ14116
PeptideAtlasiQ14116
PRIDEiQ14116
ProteomicsDBi59823

Protocols and materials databases

DNASUi3606
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000280357; ENSP00000280357; ENSG00000150782 [Q14116-1]
ENST00000524595; ENSP00000434561; ENSG00000150782 [Q14116-2]
ENST00000528832; ENSP00000434161; ENSG00000150782 [Q14116-1]
GeneIDi3606
KEGGihsa:3606
UCSCiuc001pnb.2 human [Q14116-1]

Organism-specific databases

CTDi3606
DisGeNETi3606
EuPathDBiHostDB:ENSG00000150782.11
GeneCardsiIL18
HGNCiHGNC:5986 IL18
HPAiCAB007772
HPA003980
MIMi600953 gene
neXtProtiNX_Q14116
OpenTargetsiENSG00000150782
PharmGKBiPA29802
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J3U9 Eukaryota
ENOG410ZGS8 LUCA
GeneTreeiENSGT00390000001053
HOGENOMiHOG000048723
HOVERGENiHBG000388
InParanoidiQ14116
KOiK05482
OMAiYKGYFLA
OrthoDBiEOG091G0NGF
PhylomeDBiQ14116
TreeFamiTF336297

Enzyme and pathway databases

ReactomeiR-HSA-448706 Interleukin-1 processing
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-9012546 Interleukin-18 signaling
SIGNORiQ14116

Miscellaneous databases

EvolutionaryTraceiQ14116
GeneWikiiInterleukin_18
GenomeRNAii3606
PMAP-CutDBiQ14116
PROiPR:Q14116
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000150782 Expressed in 194 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_IL18
ExpressionAtlasiQ14116 baseline and differential
GenevisibleiQ14116 HS

Family and domain databases

InterProiView protein in InterPro
IPR015529 IL-18
IPR000975 IL-1_fam
IPR008996 IL1/FGF
PANTHERiPTHR45200 PTHR45200, 1 hit
PfamiView protein in Pfam
PF00340 IL1, 1 hit
PIRSFiPIRSF015162 Interleukin_18, 1 hit
PRINTSiPR01933 INTRLEUKIN18
SUPFAMiSSF50353 SSF50353, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIL18_HUMAN
AccessioniPrimary (citable) accession number: Q14116
Secondary accession number(s): O75599, Q6FGY3, Q6WWJ7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 174 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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