IL33 interleukin 33 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL33provided by HGNC
Official Full Name: interleukin 33provided by HGNC
Primary source: HGNC:HGNC:16028
See related: Ensembl:ENSG00000137033 MIM:608678; AllianceGenome:HGNC:16028
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DVS27; IL1F11; NF-HEV; NFEHEV; C9orf26
Summary: 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]
Expression: Ubiquitous expression in urinary bladder (RPKM 34.7), lung (RPKM 27.3) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p24.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (6215149..6257983)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (6220289..6263045)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (6215149..6257983)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.
Title: TL1A is an epithelial alarmin that cooperates with IL-33 for initiation of allergic airway inflammation.
IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1.
Title: IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1.
Zinc finger protein 263 upregulates interleukin 33 and suppresses autophagy to accelerate the malignant progression of non-small cell lung cancer.
Title: Zinc finger protein 263 upregulates interleukin 33 and suppresses autophagy to accelerate the malignant progression of non-small cell lung cancer.
Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases.
Title: Interleukin-33/serum stimulation-2 pathway: Regulatory mechanisms and emerging implications in immune and inflammatory diseases.
[PATHOGENIC MEMORY THE2 CELLS INDUCE CONJUNCTIVAL ITCH VIA IL-33-ST2-CGRP AXIS].
Title: [PATHOGENIC MEMORY THE2 CELLS INDUCE CONJUNCTIVAL ITCH VIA IL-33-ST2-CGRP AXIS].
Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.
Title: Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease.
The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.
Title: The Alarmin Triad-IL-25, IL-33, and TSLP-Serum Levels and Their Clinical Implications in Chronic Spontaneous Urticaria.
Lack of S1PR2 in Macrophage Ameliorates Sepsis-associated Lung Injury through Inducing IL-33-mediated Type 2 Immunity.
Title: Lack of S1PR2 in Macrophage Ameliorates Sepsis-associated Lung Injury through Inducing IL-33-mediated Type 2 Immunity.
Tumor-infiltrating mast cells stimulate ICOS[+] regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.
Title: Tumor-infiltrating mast cells stimulate ICOS(+) regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.
P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33.
Title: P2X7 Receptor-Induced Human Mast Cell Degranulation Is Enhanced by Interleukin 33.

Submit: New GeneRIF Correction See all GeneRIFs (694)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. EBI GWAS Catalog EBI GWAS CatalogPubMed
A large-scale, consortium-based genomewide association study of asthma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study link novel loci to endometriosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of periodontal pathogen colonization. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
In vitro infection with HIV-1 subtype B upregulates IL-33 expression in primary human astrocytes and SKNMC cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-57740 (e-PCR)
- UniSTS:27910

D9S2078 (e-PCR)
- UniSTS:25864

RH47407 (e-PCR)
- UniSTS:79761

RH46528 (e-PCR)
- UniSTS:9396

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables interleukin-33 receptor binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to mechanical stimulus	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in extrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in interleukin-33-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in macrophage differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in microglial cell activation involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in microglial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of T-helper 1 type immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of inflammatory response to wounding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of leukocyte migration	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of macrophage proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of CD80 production	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of CD86 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of MHC class I biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of MHC class II biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of cellular defense response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytokine production	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of interleukin-13 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-4 production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of interleukin-5 production	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of interleukin-6 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macrophage activation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of macrophage activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuroinflammatory response	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within positive regulation of nitric-oxide synthase biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info	PubMed
acts_upstream_of positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type 2 immune response	IEA Inferred from Electronic Annotation more info
involved_in protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in type 2 immune response	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in transport vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: interleukin-33

Names: DVS27-related protein; interleukin-1 family member 11; nuclear factor for high endothelial venules; nuclear factor from high endothelial venules

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047209.1 RefSeqGene

Range

5659..47835

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001199640.2 → NP_001186569.1 interleukin-33 isoform b

See identical proteins and their annotated locations for NP_001186569.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b, also known as 2) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AB024518, AI610794, AK303943, BC047085, DB477860

Consensus CDS

CCDS56563.1

UniProtKB/TrEMBL

A0A1I9RI51

Related

ENSP00000414238.2, ENST00000456383.3

Conserved Domains (1) summary

pfam15095
Location:5 → 226

IL33; Interleukin 33
NM_001199641.2 → NP_001186570.1 interleukin-33 isoform c

See identical proteins and their annotated locations for NP_001186570.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame segment compared to variant 1. The resulting isoform (c, also known as 3) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AB024518, AI610794, AK295908, BC047085

Consensus CDS

CCDS56564.1

UniProtKB/TrEMBL

A0A1I9RI50

Related

ENSP00000394039.2, ENST00000417746.6

Conserved Domains (1) summary

pfam15095
Location:31 → 142

IL33; Interleukin 33
NM_001314044.2 → NP_001300973.1 interleukin-33 isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 4, and 5 all encode the same isoform (a).

Source sequence(s)

AB024518, AI610794, DA713547

Consensus CDS

CCDS6468.1

UniProtKB/Swiss-Prot

B2R8L1, B4DJ35, B4E1Q9, D3DRI5, E7EAX4, O95760, Q2YEJ5

UniProtKB/TrEMBL

A0A1I9RI51

Conserved Domains (1) summary

pfam15095
Location:5 → 268

IL33; Interleukin 33
NM_001314045.2 → NP_001300974.1 interleukin-33 isoform a precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 4, and 5 all encode the same isoform (a).

Source sequence(s)

AB024518, AI610794, DA439244

Consensus CDS

CCDS6468.1

UniProtKB/Swiss-Prot

B2R8L1, B4DJ35, B4E1Q9, D3DRI5, E7EAX4, O95760, Q2YEJ5

UniProtKB/TrEMBL

A0A1I9RI51

Conserved Domains (1) summary

pfam15095
Location:5 → 268

IL33; Interleukin 33
NM_001314046.2 → NP_001300975.1 interleukin-33 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (d) has the same N- and C-termini but is shorter compared to isoform a. Variants 6 and 7 both encode the same isoform (d).

Source sequence(s)

AB024518, AI610794, DB266668

UniProtKB/TrEMBL

A0A1I9RI51

Conserved Domains (1) summary

pfam15095
Location:5 → 262

IL33; Interleukin 33
NM_001314047.2 → NP_001300976.1 interleukin-33 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' UTR and uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (d) has the same N- and C-termini but is shorter compared to isoform a. Variants 6 and 7 both encode the same isoform (d).

Source sequence(s)

AB024518, AI610794, DA713547, DA719342

UniProtKB/TrEMBL

A0A1I9RI51

Conserved Domains (1) summary

pfam15095
Location:5 → 262

IL33; Interleukin 33
NM_001314048.2 → NP_001300977.1 interleukin-33 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (8) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (e) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AB024518, AI610794, DB199599, HQ641439

Consensus CDS

CCDS83341.1

UniProtKB/Swiss-Prot

O95760

Related

ENSP00000478858.1, ENST00000611532.4

Conserved Domains (1) summary

pfam15095
Location:5 → 226

IL33; Interleukin 33
NM_001353802.2 → NP_001340731.1 interleukin-33 isoform f

Status: REVIEWED

Description

Transcript Variant: This variant (9) lacks alternate exons in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The promoter and 5' terminal exon sequence is from an endogenous retroviral LTR (PMID: 28715472). The resulting isoform (f),has a distinct N-terminus and is shorter than isoform 1. The encoded protein is expressed in a subset of colon cancer cells.

Source sequence(s)

AL353741

UniProtKB/TrEMBL

A0A1I9RI51

Conserved Domains (1) summary

pfam15095
Location:1 → 227

IL33; Interleukin 33
NM_033439.4 → NP_254274.1 interleukin-33 isoform a precursor

See identical proteins and their annotated locations for NP_254274.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a, also known as 1). Variants 1, 4, and 5 all encode the same isoform (a).

Source sequence(s)

AB024518, AI610794, BC047085, DB477860

Consensus CDS

CCDS6468.1

UniProtKB/Swiss-Prot

B2R8L1, B4DJ35, B4E1Q9, D3DRI5, E7EAX4, O95760, Q2YEJ5

UniProtKB/TrEMBL

A0A1I9RI51

Related

ENSP00000507310.1, ENST00000682010.1

Conserved Domains (1) summary

pfam15095
Location:5 → 268

IL33; Interleukin 33