IL33
The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
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:16286016).
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 (PubMed:17853410, PubMed:18836528).3 Publications
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 (PubMed:21734074).
This form is rapidely lost upon angiogenic or proinflammatory activation (PubMed:18787100).
Biological Process
Interleukin-33-mediated signaling pathwayISS:ARUK-UCL
Negative regulation of macrophage proliferationISS:ARUK-UCL
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of CD80 productionISS:ARUK-UCL
Positive regulation of CD86 productionISS:ARUK-UCL
Positive regulation of cellular defense responseISS:ARUK-UCL
Positive regulation of chemokine productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cytokine productionManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of gene expressionISS:ARUK-UCL
Positive regulation of inflammatory responseBy SimilarityISS:BHF-UCL
Positive regulation of interleukin-6 productionISS:ARUK-UCL
Positive regulation of macrophage activationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of neuroinflammatory responseManual Assertion Based On ExperimentTAS:ARUK-UCL
Positive regulation of nitric-oxide synthase biosynthetic processISS:ARUK-UCL
Positive regulation of transcription by RNA polymerase IIBy SimilarityISS:BHF-UCL
Positive regulation of tumor necrosis factor productionISS:ARUK-UCL
Cellular Location
Nucleus; Chromosome; Cytoplasm; Cytoplasmic vesicle, secretory vesicle; Secreted. Associates with heterochromatin and mitotic chromosomes (PubMed:17185418).
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
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 (PubMed:19596270).
Proteolytic cleavage mediated by apoptotic caspases including CASP3 and CASP7 results in IL33 inactivation (PubMed:19559631).
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.
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Datasheet