The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine can bind to, and may be a ligand for interleukin 18 receptor (IL18R1/IL-1Rrp). This cytokine also binds to interleukin 18 binding protein (IL18BP), an inhibitory binding protein of interleukin 18 (IL18), and subsequently forms a complex with IL18 receptor beta subunit, and through which it inhibits the activity of IL18. This gene along with eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Five alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
Function
Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.
Biological Process
Cellular response to lipopolysaccharideManual Assertion Based On ExperimentIBA:GO_Central
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Immune response2 PublicationsNAS:UniProtKB
Inflammatory responseManual Assertion Based On ExperimentIBA:GO_Central
Inflammatory response to antigenic stimulusManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of interleukin-6 productionManual Assertion Based On ExperimentIGI:ARUK-UCL
Negative regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of gene expressionManual Assertion Based On ExperimentIBA:GO_Central
Regulation of inflammatory responseManual Assertion Based On ExperimentIGI:ARUK-UCL
Cellular Location
Cytoplasm, cytosol; Nucleus; Secreted. Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions (PubMed:20935647).
Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation (PubMed:18390730).
The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059).
PTM
Proteolytically converted to the mature form by CASP1.
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