IL2 interleukin 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IL2provided by HGNC
Official Full Name: interleukin 2provided by HGNC
Primary source: HGNC:HGNC:6001
See related: Ensembl:ENSG00000109471 MIM:147680; AllianceGenome:HGNC:6001
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: IL-2; TCGF; lymphokine
Summary: This gene is a member of the interleukin 2 (IL2) cytokine subfamily which includes IL4, IL7, IL9, IL15, IL21, erythropoietin, and thrombopoietin. The protein encoded by this gene is a secreted cytokine produced by activated CD4+ and CD8+ T lymphocytes, that is important for the proliferation of T and B lymphocytes. The receptor of this cytokine (IL2R) is a heterotrimeric protein complex whose gamma chain is also shared by IL4 and IL7. The expression of this gene in mature thymocytes is monoallelic, which represents an unusual regulatory mode for controlling the precise expression of a single gene. The targeted disruption of a similar gene in mice leads to ulcerative colitis-like disease, which suggests an essential role of this gene in the immune response to antigenic stimuli. [provided by RefSeq, Sep 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in cytokine storm inflammatory response.
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 4q27

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (122451470..122456725, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (125755609..125760864, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (123372625..123377880, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study.
Title: Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study.
CD38 in SLE CD4 T cells promotes Ca[2+] flux and suppresses interleukin-2 production by enhancing the expression of GM2 on the surface membrane.
Title: CD38 in SLE CD4 T cells promotes Ca(2+) flux and suppresses interleukin-2 production by enhancing the expression of GM2 on the surface membrane.
Plasma Levels of Interleukin 2 (IL-2) Associated with Hearing Loss Evaluation in the Elderly.
Title: Plasma Levels of Interleukin 2 (IL-2) Associated with Hearing Loss Evaluation in the Elderly.
Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line.
Title: Differential requirement for IL-2 and IL-23 in the differentiation and effector functions of Th17/ILC3-like cells in a human T cell line.
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.
Title: PGE(2) inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.
IL2RA rs2104286 and IL2 rs2069762 polymorphisms may be associated with bipolar disorder and its clinical findings.
Title: IL2RA rs2104286 and IL2 rs2069762 polymorphisms may be associated with bipolar disorder and its clinical findings.
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.
Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue.
Title: Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue.
The soluble IL-2 receptor alpha/CD25 as a modulator of IL-2 function.
Title: The soluble IL-2 receptor α/CD25 as a modulator of IL-2 function.
The Effect of Interleukin-2 -330 T/G Polymorphism in People with Schizophrenia Among The Batak and Javanese Ethnic Groups.
Title: The Effect of Interleukin-2 -330 T/G Polymorphism in People with Schizophrenia Among The Batak and Javanese Ethnic Groups.

Submit: New GeneRIF Correction See all GeneRIFs (581)

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 study for celiac disease identifies risk variants in the region harboring IL2 and IL21. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study in alopecia areata implicates both innate and adaptive immunity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple common variants for celiac disease influencing immune gene expression. EBI GWAS Catalog EBI GWAS CatalogPubMed
Newly identified genetic risk variants for celiac disease related to the immune response. 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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Protein interactions

Protein	Gene	Interaction	Pubs
Asp	asp	ASP-YL9 peptide (89YLYNSLLQL97) induces release of IL-2, IFN-gamma, TNF-alpha, or MIP-1beta in antigen-specific CD8+ T-cells	PubMed
Envelope surface glycoprotein gp120	env	HIV-1 gp120-treated myeloid dendritic cell (mDC) downregulates IL-2 and IFN-gamma production compared to LPS-treated mDC	PubMed
	env	HIV-1 gp120 upregulates IL2 secretion in TZM-bl cells	PubMed
	env	HIV-1 gp120 exerts a dose-dependent reduction of IL-2 mRNA expression, IL-2 production, and surface IL-2 receptor expression in CD4+ lymphocytes	PubMed
	env	HIV-1 gp120-specific cell mediated cytotoxicity (CMC) is enhanced by IL-2 or the combination of IL-2 and IFN-alpha	PubMed
	env	Secretion of IL-2 and IFN-gamma stimulated with anti-CD3 antibodies is inhibited by HIV-1 gp120 in T cell lines	PubMed
	env	Binding of HIV-1 gp120 to CD4 downregulates Bcl-2 protein in CD4+ T lymphocytes and facilitates Fas/Fas-ligand triggered apoptosis; addition of IL-2 rescues CD4+ T cells from CD4/gp120-induced Bcl-2 down modulation and apoptosis induction	PubMed
	env	CCR5- and CXCR4-tropic HIV-1 gp120 proteins suppress the ability of NK cells to proliferate in the presence of IL-2	PubMed
	env	IL-2-induced activation of JAK/STAT5 in human CD4+ T cells is inhibited by HIV-1 gp120 and anti-CD4 antibodies	PubMed
	env	In the presence of HIV-1 gp120, stimulation through the CD28 pathway partially restores IL-2 and IFN-gamma production by T cell lines in response to anti-CD3 antibodies	PubMed
	env	Proliferative responses of lymphocytes to cytomegalovirus are inhibited by relatively high concentrations (greater than or equal to 10 micrograms/ml) of recombinant HIV-1 envelope glycoprotein and this immunosuppression is completely overcome by IL2	PubMed
	env	HIV-1 gp120 and anti-CD4 antibodies induce a specific, significant decrease in the binding activity of NF-AT, NF-kappa B and AP-1, which leads to an inhibition of IL-2 production and cell proliferation	PubMed
	env	Molecular interactions of CD2 with LFA-3 and CD28 with B7-1 in conjunction with TCR occupancy prevent T cells from programmed apoptosis mediated by binding of CD4 to HIV-1 gp120, resulting in increased levels of IL-2 and IL-4 secretion from the T cells	PubMed
Envelope surface glycoprotein gp160, precursor	env	Pretreatment of CD4+ cells with HIV-1 gp160 significantly reduces PHA-induced secretion of IFN-gamma and IL-2 but augments IL-4 production	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 or gp120 synthetic peptides induce the production of interleukin (IL)-1 and tumor necrosis factor (TNF); in contrast, gp41 or gp120 synthetic peptides are able to depress the production of interferon (IFN)-alpha, IFN-gamma, and IL-2	PubMed
	env	An HIV-1 gp41 peptide (amino acid residues 581-597) inhibits both protein kinase C (PKC)-dependent interleukin 2 (IL 2) production and the [Ca2+]i influx-dependent but PKC-independent induction of IL 2 receptor expression	PubMed
Nef	nef	HIV-1 Nef-mediated CTLA-4 downregulation is associated with upregulation of IL-2 production in infected primary CD4+ T-cells	PubMed
	nef	HIV-1 Nef upregulates IL2 secretion when Jurkat cells are stimulated with both CD3 and CD28	PubMed
	nef	Primary quiescent CD4+ T lymphocytes release both TNF-alpha and IL-2 in response to the treatment with exosomes from cells infected by HIV-1, but not by delta-Nef HIV-1 or Nef (62EEEE/AAAA65) HIV-1 strains	PubMed
	nef	HIV-1 Nef induces the production of IL-2 and interferon-gamma in human T cells	PubMed
	nef	HIV-1 Nef increases IL-2 secretion when Jurkat and primary human CD4 T cells are stimulated through the T cell receptor and the co-stimulus receptor (CD28); this effect depends on Nef myristoylation	PubMed
	nef	HIV-1 Nef inhibits the induction of interleukin 2-directed gene expression	PubMed
	nef	The overall level of IL2 secretion in HIV-1/SIV chimeric Nef expressing cells is higher than that in HIV-1 Nef expressing cells, suggesting that the N-terminal half of Nef harbors molecular determinants that are responsible for T-cell activation	PubMed
	nef	The upregulation of IL2 is impaired by HIV-1 Nef in sub-optimally activated/resting T cells	PubMed
	nef	HIV-1 Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation	PubMed
	nef	Upon TcR triggering with antigens, HIV-1 Nef specifically downregulates IL-2 and interferon-gamma production in human T cells	PubMed
	nef	HIV-1 Nef suppresses the IL-2-dependent proliferation of CD4+ cells; this suppression is due to the enhanced production of several lymphokines, including interferon-gamma	PubMed
Tat	tat	HIV-1 Tat upregulates IL-2 and IFN-gamma production in stimulated CD8+ T cells	PubMed
	tat	HIV-1 Tat upregulates IL-2 expression in activated T-cells and Jurkat T-cells through activation of the IL-2 promoter, an effect involving NF-kappa B, NFAT, and cyclic nucleoside phosphodiesterase 4	PubMed
	tat	Four mutations (C27S, K51T, R55L, and G79A) on HIV-1 Tat result in the loss of the deleterious effects of Tat on the expression of MHC I, IL-2, and CD25 genes compared with wild-type Tat in Jurkat cells	PubMed
	tat	HIV-1 Tat downregulates IL-2 expression in Jurkat T-cells stably transfected with Tat, H9 T-cells, as well as other T-cells, through an effect on the rel/AP1 complex and IL-2 promoter, resulting in functional unresponsiveness in T-cells	PubMed
	tat	Treatment of T lymphocytes with IL-2, IL-6 and TNFalpha increases CDK9 and cyclin T1 protein levels, suggesting a mechanism for activation of HIV-1 Tat function and reactivation of HIV-1 in CD4+ T lymphocytes harboring a latent provirus	PubMed
	tat	HIV-1 Tat downregulates IL-2 expression in T-cells by inhibiting CD26 which interferes with the delivery or amplification of a signal necessary for IL-2 production	PubMed
Vpr	vpr	HIV-1 Vpr upregulates the gene expression of IL-2 in human monocyte-derived dendritic cells	PubMed
	vpr	HIV-1 Vpr suppresses expression of IL-2 through suppression of NF-kappa B activity via the induction of I kappa B alpha	PubMed
capsid	gag	PLA-p24- or p24-loaded human monocyte-derived dendritic cells enhance HIV-1-specific T-cell response by increased levels of IFN-gamma and IL-2 in comparison with PLA-loaded cells alone	PubMed
	gag	Levels of p24 are significantly higher in cell cultures from HIV-1-exposed infants compared to healthy controls after immune activation by IL-2 or GM-CSF	PubMed
	gag	Unactivated memory CD4+ T cells infected by HIV-1 in the presence of IL-2 and IL-15 alone or IL-6/IL-7/TNF-alpha combination, upregulate granzyme B and HIV-1 CA production	PubMed
	gag	IL-2 enhances HIV-1 p24 Gag expression in STAT5delta silenced CD8-depleted PBMCs of HIV-positive individuals	PubMed
	gag	IFN-gamma and/or IL-2 responses characterized by secreting cells contribute more to the HIV-1 CA specific response in acute infection early disease (AIED) than in chronically infected individuals	PubMed
integrase	gag-pol	Treatment of resting CD4+ T cells with cytokines IL-2, IL-4, IL-7, or IL15 enhances HIV-1 IN mutant D116N to generate de novo virus production	PubMed
matrix	gag	HIV-1 matrix protein colocalizes with syndecan-2, syndecan-4, and CD44v3 on activated CD4+ T cells to modulate TNF-alpha and IL2 production	PubMed
	gag	IL-2-induced down modulation of CD28 is completely prevented by p17 MA, and cells derived from p17-stimulated cultures show a strong Tc1 polarization	PubMed
	gag	HIV-1 Matrix upregulates levels of IL-2, IL-12 and IL-15 in natural killer cells and induces natural killer cell proliferation	PubMed
	gag	HIV-1 Matrix enhances lymphocyte proliferation and IL-2 induced production of interferon gamma and TNF-alpha	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC138391P1 (e-PCR)
- UniSTS:270868

IL2 (e-PCR)
- UniSTS:266092

SHGC4-74 (e-PCR)
- UniSTS:87670

SHGC-59515 (e-PCR)
- UniSTS:13438

IL2 (e-PCR)
- UniSTS:479872

D4S3227 (e-PCR)
- UniSTS:61060

GDB:625818 (e-PCR)
- UniSTS:158367

GDB:625821 (e-PCR)
- UniSTS:158368

RH119686 (e-PCR)
- UniSTS:133055

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables carbohydrate binding	IEA Inferred from Electronic Annotation more info
enables cytokine activity	IDA Inferred from Direct Assay more info	PubMed
enables glycosphingolipid binding	IEA Inferred from Electronic Annotation more info
enables growth factor activity	TAS Traceable Author Statement more info	PubMed
enables interleukin-2 receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables interleukin-2 receptor binding	TAS Traceable Author Statement more info	PubMed
enables kappa-type opioid receptor binding	IEA Inferred from Electronic Annotation more info
enables kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in T cell differentiation	TAS Traceable Author Statement more info	PubMed
involved_in activated T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in cell adhesion	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway via STAT	IDA Inferred from Direct Assay more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in interleukin-2-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in leukocyte activation involved in immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell activation	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within negative regulation of B cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of T-helper 17 cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of lymphocyte proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of B cell proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of activated T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell growth	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of dendritic spine development	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of immunoglobulin production	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in positive regulation of interleukin-17 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of isotype switching to IgG isotypes	IEA Inferred from Electronic Annotation more info
acts_upstream_of positive regulation of plasma cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of regulatory T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of tissue remodeling	IC Inferred by Curator more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of type II interferon production	IEA Inferred from Electronic Annotation more info
involved_in regulation of CD4-positive, alpha-beta T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of T cell homeostatic proliferation	IEA Inferred from Electronic Annotation more info
involved_in response to ethanol	IEA Inferred from Electronic Annotation more info
involved_in response to tacrolimus	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
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 extracellular space	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: interleukin-2

Names: T cell growth factor; aldesleukin; involved in regulation of T-cell clonal expansion

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.