IL18

Protein identityUniProt · HPA

UniProt accession

Q14116

Gene

IL18

Ensembl

ENSG00000150782

Chromosome

11

Canonical length

193 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Nucleoplasm,Golgi apparatus,Cytosol

Secretome location

Secreted to blood

OverviewNCBI Gene

The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family that is constitutively found as a precursor within the cytoplasm of a variety of cells including macrophages and keratinocytes. The inactive IL-18 precursor is processed to its active form by caspase-1, and is capable of stimulating interferon gamma production, and of regulating both T helper (Th) 1 and Th2 responses. This cytokine has been implicated in the injury of different organs, and in potentially fatal conditions characterized by a cytokine storm. In humans, IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

193 residues, UniProt reviewed canonical sequence.

>Q14116|IL18
     1  MAAEPVEDNC INFVAMKFID NTLYFIAEDD ENLESDYFGK LESKLSVIRN LNDQVLFIDQ
    61  GNRPLFEDMT DSDCRDNAPR TIFIISMYKD SQPRGMAVTI SVKCEKISTL SCENKIISFK
   121  EMNPPDNIKD TKSDIIFFQR SVPGHDNKMQ FESSSYEGYF LACEKERDLF KLILKKEDEL
   181  GDRSIMFTVQ NED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL18 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

141 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for IL18 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.28

gnomAD pLI

0.03

gnomAD missense Z

1.52

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• cell population proliferation
• cell-cell signaling
• cellular response to lipopolysaccharide
• cholesterol homeostasis
• cytokine-mediated signaling pathway
• defense response to Gram-positive bacterium
• establishment of skin barrier
• immune response
• inflammatory response
• interleukin-18-mediated signaling pathway
• natural killer cell activation
• natural killer cell mediated cytotoxicity
• negative regulation of myoblast differentiation
• neutrophil activation
• positive regulation of activated T cell proliferation
• positive regulation of chemokine production
• positive regulation of cold-induced thermogenesis
• positive regulation of granulocyte macrophage colony-stimulating factor production
• positive regulation of inflammatory response
• positive regulation of interleukin-13 production
• positive regulation of interleukin-17 production
• positive regulation of macrophage derived foam cell differentiation
• positive regulation of natural killer cell proliferation
• positive regulation of neuroinflammatory response
• positive regulation of NF-kappaB transcription factor activity
• positive regulation of NK T cell proliferation
• positive regulation of non-canonical NF-kappaB signal transduction
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of smooth muscle cell proliferation
• positive regulation of T-helper 1 cell cytokine production
• positive regulation of T-helper 2 cell differentiation
• positive regulation of tissue remodeling
• positive regulation of transcription by RNA polymerase II
• positive regulation of type II interferon production
• positive regulation of tyrosine phosphorylation of STAT protein
• regulation of cell adhesion
• sleep
• T-helper 1 type immune response
• triglyceride homeostasis
• type 2 immune response

Molecular functions

• cytokine activity
• interleukin-18 receptor binding

Cellular components

• cytosol
• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Interleukin-1 family
• Cytokine IL1/FGF
• Interleukin-1 / 18
• Interleukin-18

KeywordsUniProt

• Cytokine
• Cytoplasm
• Inflammatory response
• Secreted

InteractionsUniProt · HPA

Protein binding partners of IL18 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IL18RAP