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Details on Person UniProt:O95760 IL33

Class:Id	ReferenceGeneProduct:232689
_chainChangeLog	chain:1-270 added on Sat February 7 2015;propeptide:1-94 added on Sat February 7 2015;chain:95-270 added on Sat February 7 2015;chain:99-270 added on Sat February 7 2015;chain:109-270 added on Sat February 7 2015
_displayName	UniProt:O95760 IL33
_timestamp	2024-11-03 19:41:24
chain	chain:1-270 propeptide:1-94 chain:95-270 chain:99-270 chain:109-270
checksum	7C158069196EF636
comment	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, PubMed:19841166). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines (PubMed:17853410, PubMed:18836528). Also involved in activation of mast cells, basophils, eosinophils and natural killer cells (PubMed:17853410, PubMed:18836528). Acts as an enhancer of polarization of alternatively activated macrophages (PubMed:19841166). Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury (PubMed:17853410, PubMed:18836528). Induces rapid UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (By similarity).FUNCTION 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 pro-inflammatory activation (PubMed:18787100).SUBUNIT Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP (PubMed:19836339, PubMed:23980170). Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).SUBUNIT (Microbial infection) Interacts (in reduced form) with H.polygyrus ARI.INTERACTION Secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore following cleavage by CELA1 (PubMed:35794369). 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).ALTERNATIVE PRODUCTS Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.INDUCTION By infection with the parasite H.polygyrus.DOMAIN The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.PTM The full-length protein can be released from cells and is able to signal via the IL1RL1/ST2 receptor. However, proteolytic processing by CELA1, CSTG/cathepsin G and ELANE/neutrophil elastase produces C-terminal peptides that are more active than the unprocessed full length protein (PubMed:22307629, PubMed:35794369). May also be proteolytically processed by calpains (PubMed:19596270, PubMed:22307629). 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, PubMed:19439663) but could not be confirmed in vivo (PubMed:19465481) suggesting that IL33 is probably not a direct substrate for that caspase (PubMed:19439663, PubMed:19465481).MISCELLANEOUS Constitutively active.SIMILARITY Belongs to the IL-1 family. Highly divergent.
created	[InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53
description	recommendedName: Interleukin-33 shortName: IL-33 alternativeName: Interleukin-1 family member 11 shortName: IL-1F11 alternativeName: Nuclear factor from high endothelial venules shortName: NF-HEV component recommendedName: Interleukin-33 (95-270) /component component recommendedName: Interleukin-33 (99-270) /component component recommendedName: Interleukin-33 (109-270) /component
geneName	IL33 C9orf26 IL1F11 NFHEV
identifier	O95760
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Chromosome Cytokine Cytoplasm Cytoplasmic vesicle Direct protein sequencing Nucleus Proteomics identification Reference proteome Secreted Transcription
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	IL33
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8999570] ENSEMBL:ENSG00000137033 IL33 [Homo sapiens]
secondaryIdentifier	IL33_HUMAN B2R8L1 B4DJ35 B4E1Q9 D3DRI5 E7EAX4 Q2YEJ5
sequenceLength	270
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8967892] UniProt:O95760-1 IL33 [Homo sapiens] [ReferenceIsoform:8967893] UniProt:O95760-2 IL33 [Homo sapiens] [ReferenceIsoform:8967894] UniProt:O95760-3 IL33 [Homo sapiens] [ReferenceIsoform:8967895] UniProt:O95760-4 IL33 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:448567] IL33 [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:6783057] PolyUb-IL33 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:6783145] IL33 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9016606] IL33(1-178) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9016609] IL33(109-270) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9016610] IL33(99-270) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9016611] IL33 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9016615] IL33(95-270) [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9016623] IL33(179-270) [cytosol] [Homo sapiens]
(referenceSequence)	[GroupModifiedResidue:6783147] ubiquitinylated lysine (PolyUb [nucleoplasm]) at unknown position
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No pathways have been reviewed or authored by UniProt:O95760 IL33 (232689)