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IL-33

OverviewProducts

Domain

The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.

Function

Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:29045903). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury.

In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets. This form is rapidely lost upon angiogenic or proinflammatory activation.

Post-translational modifications

The full-length protein can be released from cells and is able to signal via the IL1RL1/ST2 receptor. However, proteolytic processing by CSTG/cathepsin G and ELANE/neutrophil elastase produces C-terminal peptides that are more active than the unprocessed full-length protein. May also be proteolytically processed by calpains. Proteolytic cleavage mediated by apoptotic caspases including CASP3 and CASP7 results in IL33 inactivation. In vitro proteolytic cleavage by CASP1 was reported (PubMed:16286016) but could not be confirmed in vivo (PubMed:19465481) suggesting that IL33 is probably not a direct substrate for that caspase.

Sequence similarities

Belongs to the IL-1 family. Highly divergent.

Cellular localization

  • Nucleus
  • (Microbial infection) Upon infection with H.polygyrus, tethered to the nucleus by the H.polygyrus parasitic protein ARI.
  • Nucleus
  • Chromosome
  • Cytoplasm
  • Cytoplasmic vesicle
  • Secretory vesicle
  • Secreted
  • Associates with heterochromatin and mitotic chromosomes. 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.

Alternative names

  • Interleukin-33
  • IL-33
  • Il33

Database links

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

  • Cardiovascular
  • Immuno-oncology

Molecular weight

29991Da