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IL2 interleukin 2 [ Homo sapiens (human) ]

Gene ID: 3558, updated on 27-Sep-2020

Summary

Official Symbol
IL2provided by HGNC
Official Full Name
interleukin 2provided by HGNC
Primary source
HGNC:HGNC:6001
See related
Ensembl:ENSG00000109471 MIM:147680
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

Genomic context

See IL2 in Genome Data Viewer
Location:
4q27
Exon count:
4
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 4 NC_000004.12 (122451470..122456725, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (123372625..123377650, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene KIAA1109 Neighboring gene adenosine deaminase domain containing 1 Neighboring gene IL21 antisense RNA 1 Neighboring gene interleukin 21 Neighboring gene Bardet-Biedl syndrome 12 Neighboring gene centrin 4, pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21.
GeneReviews: Not available
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.
GeneReviews: Not available
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
GeneReviews: Not available
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
GeneReviews: Not available
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.
GeneReviews: Not available
Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.
GeneReviews: Not available
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.
GeneReviews: Not available
Genome-wide association study of celiac disease in North America confirms FRMD4B as new celiac locus.
GeneReviews: Not available
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GeneReviews: Not available
Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy.
GeneReviews: Not available
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
GeneReviews: Not available
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.
GeneReviews: Not available
Multiple common variants for celiac disease influencing immune gene expression.
GeneReviews: Not available
Newly identified genetic risk variants for celiac disease related to the immune response.
GeneReviews: Not available

HIV-1 interactions

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

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
carbohydrate binding IEA
Inferred from Electronic Annotation
more info
 
cytokine activity IDA
Inferred from Direct Assay
more info
PubMed 
glycosphingolipid binding IEA
Inferred from Electronic Annotation
more info
 
growth factor activity TAS
Traceable Author Statement
more info
PubMed 
interleukin-2 receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
interleukin-2 receptor binding TAS
Traceable Author Statement
more info
PubMed 
kappa-type opioid receptor binding IEA
Inferred from Electronic Annotation
more info
 
kinase activator activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
MAPK cascade TAS
Traceable Author Statement
more info
 
T cell differentiation TAS
Traceable Author Statement
more info
PubMed 
adaptive immune response IEA
Inferred from Electronic Annotation
more info
 
cell adhesion TAS
Traceable Author Statement
more info
PubMed 
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
 
gene expression IEA
Inferred from Electronic Annotation
more info
 
immune response TAS
Traceable Author Statement
more info
PubMed 
interleukin-2-mediated signaling pathway TAS
Traceable Author Statement
more info
 
leukocyte activation involved in immune response IDA
Inferred from Direct Assay
more info
PubMed 
natural killer cell activation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of B cell apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of T-helper 17 cell differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of apoptotic process TAS
Traceable Author Statement
more info
PubMed 
negative regulation of heart contraction IEA
Inferred from Electronic Annotation
more info
 
negative regulation of inflammatory response IEA
Inferred from Electronic Annotation
more info
 
negative regulation of lymphocyte proliferation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein phosphorylation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of B cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of activated T cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell growth TAS
Traceable Author Statement
more info
PubMed 
positive regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of cytosolic calcium ion concentration IEA
Inferred from Electronic Annotation
more info
 
positive regulation of dendritic spine development IEA
Inferred from Electronic Annotation
more info
 
positive regulation of immunoglobulin secretion IEA
Inferred from Electronic Annotation
more info
 
positive regulation of inflammatory response IC
Inferred by Curator
more info
PubMed 
positive regulation of interferon-gamma production IEA
Inferred from Electronic Annotation
more info
 
positive regulation of interleukin-17 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of isotype switching to IgG isotypes IEA
Inferred from Electronic Annotation
more info
 
positive regulation of kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of regulatory T cell differentiation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of tissue remodeling IC
Inferred by Curator
more info
PubMed 
positive regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
positive regulation of tyrosine phosphorylation of STAT protein IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase C-activating G protein-coupled receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
regulation of T cell homeostatic proliferation IEA
Inferred from Electronic Annotation
more info
 
regulation of regulatory T cell differentiation TAS
Traceable Author Statement
more info
 
response to ethanol IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
interleukin-2
Names
T cell growth factor
aldesleukin
involved in regulation of T-cell clonal expansion

NCBI Reference Sequences (RefSeq)

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

  1. NG_016779.1 RefSeqGene

    Range
    5001..10026
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000586.4NP_000577.2  interleukin-2 precursor

    See identical proteins and their annotated locations for NP_000577.2

    Status: REVIEWED

    Source sequence(s)
    AC022489
    Consensus CDS
    CCDS3726.1
    UniProtKB/Swiss-Prot
    P60568
    UniProtKB/TrEMBL
    Q0GK43
    Related
    ENSP00000226730.4, ENST00000226730.4
    Conserved Domains (1) summary
    pfam00715
    Location:7150
    IL2; Interleukin 2

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 Primary Assembly

    Range
    122451470..122456725 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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