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    IL2 interleukin 2 [ Homo sapiens (human) ]

    Gene ID: 3558, updated on 4-Jun-2023

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See IL2 in Genome Data Viewer
    Location:
    4q27
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_03 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (122451470..122456725, complement)
    RS_2023_03 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (125755609..125760864, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (123372625..123377880, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene bridge-like lipid transfer protein family member 1 Neighboring gene NANOG hESC enhancer GRCh37_chr4:123226936-123227466 Neighboring gene adenosine deaminase domain containing 1 Neighboring gene Sharpr-MPRA regulatory region 4201 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:123495468-123496667

    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

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

    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

    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 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-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 heart contraction IEA
    Inferred from Electronic Annotation
    more info
     
    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
     
    involved_in negative regulation of protein phosphorylation 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 positive regulation of tyrosine phosphorylation of STAT protein IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein kinase C-activating G protein-coupled receptor signaling pathway 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 transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in tyrosine phosphorylation of STAT protein 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

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

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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
      4771..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
      P01585, P60568
      UniProtKB/TrEMBL
      Q0GK43
      Related
      ENSP00000226730.5, ENST00000226730.5
      Conserved Domains (1) summary
      pfam00715
      Location:7150
      IL2; Interleukin 2

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_03

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      125755609..125760864 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)