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.
Subunit:
Interacts with SMAD3. Binds IL18R1, but not to IL1R1, with lower affinity than IL18, and does not seem to act as a receptor antagonist for IL18.
Subcellular Location:
Cytoplasm; cytosol. Nucleus. Secreted. Stimulation with IL1B leads to colocalization with SMAD3 mostly in perinuclear regions. Only the CASP1-cleaved mature form translocates into the nucleus upon LPS stimulation.
Tissue Specificity:
In general, low constitutive expression, if any, in healthy tissues; high expression in inflammatory counterparts, including in synovial tissues from individuals with active rheumatoid arthritis. Isoform A, isoform B and isoform C are expressed in testis, colon, placenta, lung and lymph node. Isoform D and isoform E were found only in testis and bone marrow. Whereas only isoform A is found in brain, only isoform B in kidney and only isoform C in heart.
Post-translational modifications:
Proteolytically converted to the mature form by CASP1.
Similarity:
Belongs to the IL-1 family.
SWISS:
Q9NZH6
Gene ID:
27178
Database links:
Entrez Gene: 27178 Human
Omim: 605510 Human
SwissProt: Q9NZH6 Human
Unigene: 166371 Human
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