Tbio IL33 Interleukin-33

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• O95760
• B2R8L1
• B4DJ35
• B4E1Q9
• D3DRI5
• E7EAX4
• Q2YEJ5
• IL-33

Gene Name

• IL33

Ensembl ID

• ENST00000381434
• ENSP00000370842
• ENSG00000137033
• ENST00000417746
• ENSP00000394039
• ENST00000456383
• ENSP00000414238
• ENST00000611532
• ENSP00000478858

Symbol

• C9orf26
• IL1F11
• NFHEV
• DVS27
• IL1F11
• NF-HEV
• NFEHEV
• C9orf26

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.98
biological term	0.98
gene perturbation	0.98
disease	0.66
phenotype	0.62

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1804.43   (req: < 5)

Gene RIFs: 411   (req: <= 3)

Antibodies: 993   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1804.43   (req: >= 5)

Gene RIFs: 411   (req: > 3)

Antibodies: 993   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (8)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
asthma	EFO_0000270	3	3	0	1.5	75.6
eosinophil count	EFO_0004842	2	2	2		64.6
serum metabolite measurement	EFO_0005653	2	1	2		61.7
eosinophil percentage of leukocytes	EFO_0007991	1	2	2		58
childhood onset asthma	EFO_0004591	1	1	0	1.1	32.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
asthma	EFO_0000270	0	1.5	75.6
eosinophil count	EFO_0004842	2		64.6
serum metabolite measurement	EFO_0005653	2		61.7
eosinophil percentage of leukocytes	EFO_0007991	2		58
childhood onset asthma	EFO_0004591	0	1.1	32.5

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Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	interleukin 33	VGNC:4763	737537
Macaque	interleukin 33		717301
Mouse	interleukin 33	MGI:1924375	77125
Rat	interleukin 33	RGD:1311155	361749
Dog	interleukin 33	VGNC:41982	403810

Species	Name	OMA	EggNOG	Inparanoid
Chimp	interleukin 33
Macaque	interleukin 33
Mouse	interleukin 33
Rat	interleukin 33
Dog	interleukin 33

Protein Structure (2 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-O95760-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 2 of 2

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (20)

Reactome (14)

KEGG (4)

WikiPathways (2)

Cytokine Signaling in Immune system (R-HSA-1280215)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Deubiquitination	278 targets	R-HSA-5688426
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Interleukin-1 family signaling	140 targets	R-HSA-446652
Reactome	Interleukin-33 signaling	3 targets	R-HSA-9014843

Name	Explore in Pharos	Explore in Source
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Deubiquitination	278 targets	R-HSA-5688426
Immune System	2246 targets	R-HSA-168256
Interleukin-1 family signaling	140 targets	R-HSA-446652
Interleukin-33 signaling	3 targets	R-HSA-9014843

Gene Ontology Terms (28)

Functions (1)

Components (5)

Processes (22)

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Items per page:

10

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GO Term	Evidence	Assigned by
cytokine activity	Inferred from Direct Assay (IDA)	BHF-UCL

Protein-Protein Interactions (176)

Explore Interacting Targets

1 – 10 of 176

• See Interactions on String-DB

IL1RL1

Tbio

Novelty: 0.00541949

Score: 0.999

Data Source: Reactome,STRINGDB

GATA3

Tbio

Family: TF

Novelty: 0.00071141

Score: 0.978

Data Source: STRINGDB

USP21

Tbio

Family: Enzyme

Novelty: 0.11434352

Score: 0.968

Data Source: Reactome,STRINGDB

MYD88

Tbio

Novelty: 0.00037931

Score: 0.963

Data Source: Reactome,STRINGDB

IRAK1

Tchem

Family: Kinase

Novelty: 0.00170873

Score: 0.942

Data Source: Reactome,STRINGDB

TRAF6

Tbio

Novelty: 0.00109366

Score: 0.942

Data Source: Reactome,STRINGDB

IRAK4

Tchem

Family: Kinase

Novelty: 0.00344058

Score: 0.939

Data Source: Reactome,STRINGDB

TSLP

Tbio

Novelty: 0.00140333

Score: 0.934

Data Source: STRINGDB

IL1RAP

Tclin

Novelty: 0.01115915

Score: 0.926

Data Source: Reactome,STRINGDB

IL13

Tbio

Novelty: 0.00021435

Score: 0.9

Data Source: STRINGDB

Publication Statistics

PubMed Score  1804.43

PubMed score by year

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PubTator Score  836.83

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Chromosome
Complete proteome
Cytokine
Cytoplasmic vesicle
Direct protein sequencing
Nucleus
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

allergy
asthma
childhood onset asthma
eosinophil count
eosinophil percentage of leukocytes
neutrophil percentage of leukocytes
serum metabolite measurement
sum of eosinophil and basophil counts

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
mortality/aging
nervous system phenotype