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    IL15 interleukin 15 [ Homo sapiens (human) ]

    Gene ID: 3600, updated on 11-Nov-2018

    Summary

    Official Symbol
    IL15provided by HGNC
    Official Full Name
    interleukin 15provided by HGNC
    Primary source
    HGNC:HGNC:5977
    See related
    Ensembl:ENSG00000164136 MIM:600554; Vega:OTTHUMG00000133418
    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-15
    Summary
    The protein encoded by this gene is a cytokine that regulates T and natural killer cell activation and proliferation. This cytokine and interleukine 2 share many biological activities. They are found to bind common hematopoietin receptor subunits, and may compete for the same receptor, and thus negatively regulate each other's activity. The number of CD8+ memory cells is shown to be controlled by a balance between this cytokine and IL2. This cytokine induces the activation of JAK kinases, as well as the phosphorylation and activation of transcription activators STAT3, STAT5, and STAT6. Studies of the mouse counterpart suggested that this cytokine may increase the expression of apoptosis inhibitor BCL2L1/BCL-x(L), possibly through the transcription activation activity of STAT6, and thus prevent apoptosis. Alternatively spliced transcript variants of this gene have been reported. [provided by RefSeq, Feb 2011]
    Expression
    Ubiquitous expression in spleen (RPKM 3.4), thyroid (RPKM 2.4) and 23 other tissues See more
    Orthologs

    Genomic context

    See IL15 in Genome Data Viewer
    Location:
    4q31.21
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 4 NC_000004.12 (141636596..141733987)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (142557749..142655140)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 2432 Neighboring gene long intergenic non-protein coding RNA 2276 Neighboring gene inositol polyphosphate-4-phosphatase type II B Neighboring gene ribosomal protein L5 pseudogene 13 Neighboring gene LSM3 homolog, U6 small nuclear RNA and mRNA degradation associated pseudogene 4

    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 Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    NHGRI GWAS Catalog

    Description
    Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia.
    NHGRI GWA Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 modulates expression of the cytokines IL1beta, IL3, IL6, IL10, IL13, IL15, IFNbeta2A, IFNgamma, IFNomega, TNFalpha, VEGF, VEGF B, and LIF in PBMCs and MDMs PubMed
    Nef nef IL-1beta, IL-12, and IL-15 are factors involved in the upregulation of IFN-gamma expression in coculture between Nef-pulsed iDCs and NK cells PubMed
    nef Exogenous HIV-1 Nef protein induces the proliferation of unstimulated and suboptimally stimulated normal human PBMC through upregulation of IL-15 synthesis in the monocyte/macrophage population PubMed
    Tat tat HIV-1 Tat upregulates the expression of interleukin 15 (IL15) gene in mammary epithelial cells PubMed
    capsid 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
    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 is able to reduce MIP-1alpha secretion from IL-15-stimulated monocyte cells PubMed
    gag HIV-1 Matrix slightly enhances TNF-alpha and IFN-gamma secretion induced by IL-15 monocyte stimulation and counteracts IL-4 mediated inhibition of the production of these cytokines 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

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
      Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
    • Cytokines and Inflammatory Response, organism-specific biosystem (from WikiPathways)
      Cytokines and Inflammatory Response, organism-specific biosystemInflammation is a protective response to infection by the immune system that requires communication between different classes of immune cells to coordinate their actions. Acute inflammation is an imp...
    • Development and heterogeneity of the ILC family, organism-specific biosystem (from WikiPathways)
      Development and heterogeneity of the ILC family, organism-specific biosystemDevelopment and heterogeneity of the ILC family. ILCs develop from distinct progenitors in the fetal liver or bone marrow and then develop into mature ILCs in the periphery. Different transcription f...
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • Herpes simplex infection, organism-specific biosystem (from KEGG)
      Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
    • Herpes simplex infection, conserved biosystem (from KEGG)
      Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Intestinal immune network for IgA production, organism-specific biosystem (from KEGG)
      Intestinal immune network for IgA production, organism-specific biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Intestinal immune network for IgA production, conserved biosystem (from KEGG)
      Intestinal immune network for IgA production, conserved biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
      Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
    • Jak-STAT signaling pathway, conserved biosystem (from KEGG)
      Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
    • Rheumatoid arthritis, organism-specific biosystem (from KEGG)
      Rheumatoid arthritis, organism-specific biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • Rheumatoid arthritis, conserved biosystem (from KEGG)
      Rheumatoid arthritis, conserved biosystemRheumatoid arthritis (RA) is a chronic autoimmune joint disease where persistent inflammation affects bone remodeling leading to progressive bone destruction. In RA, abnormal activation of the immune...
    • Signaling by Interleukins, organism-specific biosystem (from REACTOME)
      Signaling by Interleukins, organism-specific biosystemInterleukins are low molecular weight proteins that bind to cell surface receptors and act in an autocrine and/or paracrine fashion. They were first identified as factors produced by leukocytes but a...
    • TNF signaling pathway, organism-specific biosystem (from KEGG)
      TNF signaling pathway, organism-specific biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...
    • TNF signaling pathway, conserved biosystem (from KEGG)
      TNF signaling pathway, conserved biosystemTumor necrosis factor (TNF), as a critical cytokine, can induce a wide range of intracellular signal pathways including apoptosis and cell survival as well as inflammation and immunity. Activated TNF...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC9721

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cytokine activity IEA
    Inferred from Electronic Annotation
    more info
     
    cytokine receptor binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    NK T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    aging IEA
    Inferred from Electronic Annotation
    more info
     
    cell maturation IEA
    Inferred from Electronic Annotation
    more info
     
    cell-cell signaling TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to vitamin D IEA
    Inferred from Electronic Annotation
    more info
     
    extrathymic T cell selection IEA
    Inferred from Electronic Annotation
    more info
     
    hyaluronan metabolic process IEA
    Inferred from Electronic Annotation
    more info
     
    immune response IEA
    Inferred from Electronic Annotation
    more info
     
    inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    interleukin-15-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    interleukin-15-mediated signaling pathway TAS
    Traceable Author Statement
    more info
     
    lymph node development IEA
    Inferred from Electronic Annotation
    more info
     
    natural killer cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cold-induced thermogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    negative regulation of smooth muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of immune response IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of inflammatory response IC
    Inferred by Curator
    more info
    PubMed 
    positive regulation of interleukin-17 production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of natural killer cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of natural killer cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of protein O-linked glycosylation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of tissue remodeling IC
    Inferred by Curator
    more info
    PubMed 
    positive regulation of tyrosine phosphorylation of STAT protein IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of defense response to virus by host IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of signaling receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    skeletal muscle atrophy IEA
    Inferred from Electronic Annotation
    more info
     
    tyrosine phosphorylation of STAT protein IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    Golgi apparatus TAS
    Traceable Author Statement
    more info
    PubMed 
    cell surface IEA
    Inferred from Electronic Annotation
    more info
     
    cytoplasm TAS
    Traceable Author Statement
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    endosome TAS
    Traceable Author Statement
    more info
     
    extracellular region NAS
    Non-traceable Author Statement
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    nuclear speck IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     

    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_029605.1 RefSeqGene

      Range
      5001..102392
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000585.4NP_000576.1  interleukin-15 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_000576.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the shortest transcript and encodes the longer isoform (1, also known as 48aa(LSP)-IL15).
      Source sequence(s)
      AA897685, AC096774, AC118480, BX116580, CX761071
      Consensus CDS
      CCDS3755.1
      UniProtKB/Swiss-Prot
      P40933
      Related
      ENSP00000323505.4, OTTHUMP00000164617, ENST00000320650.8, OTTHUMT00000257279
      Conserved Domains (1) summary
      pfam02372
      Location:33154
      IL15; Interleukin 15
    2. NM_172175.2NP_751915.1  interleukin-15 isoform 2 preproprotein

      See identical proteins and their annotated locations for NP_751915.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and contains an alternate exon in the 5' coding region. This variant uses an alternate downstream start codon, compared to variant 1. Isoform 2 (also known as (21aa(SSP)-IL15) has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AA897685, AC096774, AK290619, BX116580, CX761071
      Consensus CDS
      CCDS3756.1
      UniProtKB/Swiss-Prot
      P40933
      Related
      ENSP00000422271.1, OTTHUMP00000218093, ENST00000514653.5, OTTHUMT00000360354
      Conserved Domains (1) summary
      pfam02372
      Location:10127
      IL15; Interleukin 15

    RNA

    1. NR_037840.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) has an alternate 5' exon, compared to variant 3. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with translation of the longest ORF; translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AA897685, AC096774, BC018149, CX761071

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p12 Primary Assembly

      Range
      141636596..141733987
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_172174.2: Suppressed sequence

      Description
      NM_172174.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
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