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IL33 Gene(Protein Coding)

Interleukin 33

GCID:
GC09P006206
GIFtS:
58
Genes Participants
UDN Logo

Aliases for IL33 Gene

Aliases for IL33 Gene

  • Interleukin 33 2 3 5
  • Nuclear Factor From High Endothelial Venules 3 4
  • Nuclear Factor For High Endothelial Venules 2 3
  • Interleukin-1 Family Member 11 3 4
  • DVS27-Related Protein 2 3
  • C9orf26 3 4
  • IL1F11 3 4
  • NF-HEV 3 4
  • Chromosome 9 Open Reading Frame 26 (NF-HEV) 2
  • Interleukin-1 Family, Member 11 2
  • Interleukin-33 3
  • IL-1F11 4
  • NFEHEV 3
  • DVS27 3
  • IL-33 4
  • NFHEV 4

External Ids for IL33 Gene

Previous HGNC Symbols for IL33 Gene

  • C9orf26

Summaries for IL33 Gene

Entrez Gene Summary for IL33 Gene

  • 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]

GeneCards Summary for IL33 Gene

IL33 (Interleukin 33) is a Protein Coding gene. Diseases associated with IL33 include Idiopathic Achalasia and Allergic Conjunctivitis. Among its related pathways are Th2 Differentiation Pathway and Innate Immune System. GO annotations related to this gene include cytokine activity.

UniProtKB/Swiss-Prot for IL33 Gene

  • 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).

  • 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).

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IL33 Gene

Genomics for IL33 Gene

Products:

  1. Regulatory Element

Regulatory Elements for IL33 Gene

Enhancers for IL33 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH09G006238 1.1 FANTOM5 ENCODE 14.9 +24.1 24060 0.8 ELF3 SOX13 TBP FOXA2 ATF1 SAP130 MLX DMAP1 HBP1 ZNF644 IL33 ENSG00000228132
GH09G006217 0.9 Ensembl ENCODE 0.7 +2.8 2838 1.4 STAT1 TAF1 JUN MAX CEBPB EP300 BRCA1 RFX5 GATA2 STAT3 IL33 ENSG00000228132
GH09G006229 0.6 ENCODE 0.4 +14.9 14936 1.5 GATA2 POLR2A JUN CEBPB FOS EP300 CHD2 IL33 ENSG00000228132
GH09G006272 1.1 Ensembl ENCODE 0.2 +57.1 57067 0.4 ELF3 FOXA2 ARID4B RAD21 YY1 FOS CREM CEBPB NR2F2 NFIL3 ENSG00000228132 IL33
GH09G006226 0.4 ENCODE 0.4 +11.8 11787 0.2 GATA2 IL33 ENSG00000228132
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around IL33 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the IL33 gene promoter:

Genomic Location for IL33 Gene

Chromosome:
9
Start:
6,215,149 bp from pter
End:
6,257,983 bp from pter
Size:
42,835 bases
Orientation:
Plus strand

Genomic View for IL33 Gene

Genes around IL33 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IL33 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IL33 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for IL33 Gene

Proteins for IL33 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for IL33 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95760-IL33_HUMAN
    Recommended name:
    Interleukin-33
    Protein Accession:
    O95760
    Secondary Accessions:
    • B2R8L1
    • B4DJ35
    • B4E1Q9
    • D3DRI5
    • E7EAX4
    • Q2YEJ5

    Protein attributes for IL33 Gene

    Size:
    270 amino acids
    Molecular mass:
    30759 Da
    Quaternary structure:
    • Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP.

    Three dimensional structures from OCA and Proteopedia for IL33 Gene

    Alternative splice isoforms for IL33 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IL33 Gene

Protein Expression for IL33 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for IL33 Gene

  • 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.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for IL33 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for IL33
  • Santa Cruz Biotechnology (SCBT) Antibodies for IL33

Assay Products

  • Enzo Life Sciences assays for IL33
  • Abcam assays for IL33

No data available for DME Specific Peptides for IL33 Gene

Domains & Families for IL33 Gene

Gene Families for IL33 Gene

HGNC:

Protein Domains for IL33 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for IL33 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O95760

UniProtKB/Swiss-Prot:

IL33_HUMAN :
  • The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.
  • Belongs to the IL-1 family. Highly divergent.
Domain:
  • The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.
Family:
  • Belongs to the IL-1 family. Highly divergent.
genes like me logo Genes that share domains with IL33: view

Function for IL33 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for IL33 Gene

UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot 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 proinflammatory activation (PubMed:18787100).

Gene Ontology (GO) - Molecular Function for IL33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005125 cytokine activity IDA 19841166
GO:0005515 protein binding IPI 16286016
genes like me logo Genes that share ontologies with IL33: view
genes like me logo Genes that share phenotypes with IL33: view

Animal Models for IL33 Gene

MGI Knock Outs for IL33:

Animal Model Products

miRNA for IL33 Gene

miRTarBase miRNAs that target IL33

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for IL33 Gene

Localization for IL33 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IL33 Gene

Nucleus. Chromosome. Cytoplasmic vesicle, secretory vesicle. Secreted. Note=Associates with heterochromatin and mitotic chromosomes (PubMed:17185418).

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IL33 gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 5
mitochondrion 2
plasma membrane 1

Gene Ontology (GO) - Cellular Components for IL33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005694 chromosome IEA --
genes like me logo Genes that share ontologies with IL33: view

Pathways & Interactions for IL33 Gene

genes like me logo Genes that share pathways with IL33: view

Gene Ontology (GO) - Biological Process for IL33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002282 microglial cell activation involved in immune response IEA --
GO:0002686 negative regulation of leukocyte migration IEA --
GO:0002826 negative regulation of T-helper 1 type immune response IEA --
GO:0002830 positive regulation of type 2 immune response IEA --
GO:0006351 transcription, DNA-templated IEA --
genes like me logo Genes that share ontologies with IL33: view

No data available for SIGNOR curated interactions for IL33 Gene

Drugs & Compounds for IL33 Gene

Products:

  1. Drug
No Compound Related Data Available

Transcripts for IL33 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for IL33 Gene

(10) REFSEQ mRNAs :
(9) Additional mRNA sequences :
(135) Selected AceView cDNA sequences:
(5) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for IL33 Gene

Interleukin 33:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for IL33 Gene

No ASD Table

Relevant External Links for IL33 Gene

GeneLoc Exon Structure for
IL33
ECgene alternative splicing isoforms for
IL33

Expression for IL33 Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for IL33 Gene

mRNA expression in normal human tissues for IL33 Gene
mRNA expression by BioGPS for IL33 GenemRNA expression by GTEx for IL33 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IL33 Gene

This gene is overexpressed in Gallbladder (15.0), Lymph node (10.4), Uterus (8.7), and Pancreas (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for IL33 Gene



NURSA nuclear receptor signaling pathways regulating expression of IL33 Gene:

IL33

SOURCE GeneReport for Unigene cluster for IL33 Gene:

Hs.731660

mRNA Expression by UniProt/SwissProt for IL33 Gene:

O95760-IL33_HUMAN
Tissue specificity: Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.

Evidence on tissue expression from TISSUES for IL33 Gene

  • Heart(4.6)
  • Nervous system(4.4)
  • Adrenal gland(4.2)
  • Lung(3.2)
  • Lymph node(2.9)
  • Skin(2.8)
  • Intestine(2.7)
  • Spleen(2.7)
  • Blood(2.6)
  • Muscle(2.3)
  • Liver(2.2)
genes like me logo Genes that share expression patterns with IL33: view

Primer Products

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for IL33 Gene

Orthologs for IL33 Gene

This gene was present in the common ancestor of mammals.

Orthologs for IL33 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia IL33 34 35
  • 99.75 (n)
cow
(Bos Taurus)
 Mammalia IL33 34 35
  • 77.69 (n)
dog
(Canis familiaris)
 Mammalia IL33 34 35
  • 76.95 (n)
rat
(Rattus norvegicus)
 Mammalia Il33 34
  • 70.4 (n)
mouse
(Mus musculus)
 Mammalia Il33 34 16 35
  • 69.99 (n)
Species where no ortholog for IL33 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for IL33 Gene

ENSEMBL:
Gene Tree for IL33 (if available)
TreeFam:
Gene Tree for IL33 (if available)

Paralogs for IL33 Gene

No data available for Paralogs for IL33 Gene

Variants for IL33 Gene

Sequence variations from dbSNP and Humsavar for IL33 Gene

SNP ID Clin Chr 09 pos Sequence Context AA Info Type
rs193920852 Uncertain significance 6,256,067(+) CTGGA(A/G)TGTTT intron-variant, reference, missense
rs1000009411 -- 6,212,856(+) AAACA(A/T)CAATT upstream-variant-2KB
rs1000038492 -- 6,242,726(+) TCTTT(C/T)GTGGC intron-variant
rs1000144867 -- 6,248,538(+) TGGAT(G/T)TGCCT intron-variant, utr-variant-5-prime
rs1000184077 -- 6,235,141(+) GCTCA(A/G)GTGAT intron-variant, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for IL33 Gene

Variant ID Type Subtype PubMed ID
dgv7386n100 CNV gain 25217958
esv2674589 CNV deletion 23128226
esv2761483 CNV loss 21179565
esv3544466 CNV deletion 23714750
esv3619394 CNV gain 21293372
nsv1019912 CNV loss 25217958
nsv1029665 CNV gain 25217958
nsv521598 CNV loss 19592680
nsv613205 CNV loss 21841781
nsv831496 CNV gain 17160897

Variation tolerance for IL33 Gene

Residual Variation Intolerance Score: 40.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.83; 47.86% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for IL33 Gene

Human Gene Mutation Database (HGMD)
IL33
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IL33

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IL33 Gene

Disorders for IL33 Gene

MalaCards: The human disease database

(11) MalaCards diseases for IL33 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
idiopathic achalasia
  • achalasia
allergic conjunctivitis
  • conjunctivitis allergic
kimura disease
  • angiolymphoid hyperplasia with eosinophilia
conjunctivitis
  • madras eye
allergic contact dermatitis
  • dermatitis allergic contact
- elite association - COSMIC cancer census association via MalaCards
Search IL33 in MalaCards View complete list of genes associated with diseases

Relevant External Links for IL33

Genetic Association Database (GAD)
IL33
Human Genome Epidemiology (HuGE) Navigator
IL33
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
IL33
genes like me logo Genes that share disorders with IL33: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IL33 Gene

Publications for IL33 Gene

  1. Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. (PMID: 12819012) Baekkevold E.S. … Girard J.-P. (Am. J. Pathol. 2003) 2 3 4 22 64
  2. Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. (PMID: 19204726) Chapuis J. … Lambert J.C. (Mol. Psychiatry 2009) 3 22 46 64
  3. Interleukin-33 is biologically active independently of caspase-1 cleavage. (PMID: 19465481) Talabot-Ayer D. … Palmer G. (J. Biol. Chem. 2009) 3 4 22 64
  4. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. (PMID: 19559631) Luthi A.U. … Martin S.J. (Immunity 2009) 3 4 22 64
  5. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? (PMID: 18836528) Moussion C. … Girard J.P. (PLoS ONE 2008) 3 4 22 64

Products for IL33 Gene

Sources for IL33 Gene

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