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IL15 interleukin 15 [ Homo sapiens (human) ]

Gene ID: 3600, updated on 28-Oct-2024

Summary

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Official Symbol
IL15provided by HGNC
Official Full Name
interleukin 15provided by HGNC
Primary source
HGNC:HGNC:5977
See related
Ensembl:ENSG00000164136 MIM:600554; AllianceGenome:HGNC:5977
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
mouse all
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Genomic context

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See IL15 in Genome Data Viewer
Location:
4q31.21
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (141636583..141733987)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (144953939..145051309)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (142557736..142655140)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr4:142252666-142253865 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:142299040-142299540 Neighboring gene long intergenic non-protein coding RNA 2432 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:142501441-142502640 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:142546083-142546797 Neighboring gene long intergenic non-protein coding RNA 2276 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21938 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:142628696-142629196 Neighboring gene MPRA-validated peak5125 silencer Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:142803658-142804281 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:142804282-142804904 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:142823512-142824114 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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. Increased IL-15 production of muscle cells in polymyositis and dermatomyositis. Sugiura T, et al. Int Immunol, 2002 Aug. PMID 12147628
  2. Role of interleukin 15 and interleukin 18 in inflammatory response. Liew FY, et al. Ann Rheum Dis, 2002 Nov. PMID 12379638, Free PMC Article
  3. Interleukin 15 levels in serum may predict a severe disease course in patients with early arthritis. González-Álvaro I, et al. PLoS One, 2011. PMID 22242124, Free PMC Article
  4. Genetic variants in IL15 associate with progression of joint destruction in rheumatoid arthritis: a multicohort study. Knevel R, et al. Ann Rheum Dis, 2012 Oct. PMID 22440823
  5. IL-15 positively regulates IL-21 production in celiac disease mucosa. Sarra M, et al. Mucosal Immunol, 2013 Mar. PMID 22785229

See all (504) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Elevated IL-15 levels in systemic lupus erythematosus: potential pathogenesis insight and therapeutic target.
    Title: Elevated IL-15 levels in systemic lupus erythematosus: potential pathogenesis insight and therapeutic target.
  2. IL-15 gene mutation as a molecular risk factor in acute lymphoid leukemia.
    Title: IL-15 gene mutation as a molecular risk factor in acute lymphoid leukemia.
  3. Interleukin-15 is a hair follicle immune privilege guardian.
    Title: Interleukin-15 is a hair follicle immune privilege guardian.
  4. Immunocytokines with target cell-restricted IL-15 activity for treatment of B cell malignancies.
    Title: Immunocytokines with target cell-restricted IL-15 activity for treatment of B cell malignancies.
  5. Abnormal M1 polarization of placental macrophage induced by IL-15/STAT5 activation in VVC may lead to adverse pregnancy outcomes.
    Title: Abnormal M1 polarization of placental macrophage induced by IL-15/STAT5 activation in VVC may lead to adverse pregnancy outcomes.
  6. Investigating the interplay of hematological parameters, CD markers, genetic polymorphisms, and database mutations in the IL15 gene in acute myeloid leukemia patients.
    Title: Investigating the interplay of hematological parameters, CD markers, genetic polymorphisms, and database mutations in the IL15 gene in acute myeloid leukemia patients.
  7. The roles of different forms of IL-15 in human melanoma progression.
    Title: The roles of different forms of IL-15 in human melanoma progression.
  8. The role of interleukin-15 in the development and treatment of hematological malignancies.
    Title: The role of interleukin-15 in the development and treatment of hematological malignancies.
  9. Myc controls NK cell development, IL-15-driven expansion, and translational machinery.
    Title: Myc controls NK cell development, IL-15-driven expansion, and translational machinery.
  10. Counteracting Interleukin-15 to Elucidate Its Modes of Action in Physiology and Pathology.
    Title: Counteracting Interleukin-15 to Elucidate Its Modes of Action in Physiology and Pathology.
Submit: New GeneRIF Correction See all GeneRIFs (423)

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
Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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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 PubChem

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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

Homology

Clone Names

  • MGC9721

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 cytokine 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 NK T cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell maturation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell-cell signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in extrathymic T cell selection IEA
Inferred from Electronic Annotation
more info
  
involved_in immune response IEA
Inferred from Electronic Annotation
more info
  
involved_in interleukin-15-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in lymph node development IEA
Inferred from Electronic Annotation
more info
  
involved_in macrophage differentiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in natural killer cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in natural killer cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in neutrophil activation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in neutrophil activation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of T cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of cell population proliferation TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of cytokine production IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
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 natural killer cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of natural killer cell proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of phagocytosis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of protein O-linked glycosylation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of tissue remodeling IC
Inferred by Curator
more info
 PubMed 
involved_in regulation of T cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of defense response to virus by host IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in tyrosine phosphorylation of STAT protein IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus TAS
Traceable Author Statement
more info
 PubMed 
located_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in endosome TAS
Traceable Author Statement
more info
  
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear speck IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
interleukin-15

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

  1. NG_029605.2 RefSeqGene

    Range
    4988..102392
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000585.5 → NP_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
    D3DNZ2, O00440, O43512, P40933, Q495Z8, Q6FGX7, Q93058, Q9UBA3
    Related
    ENSP00000323505.4, ENST00000320650.9
    Conserved Domains (1) summary
    pfam02372
    Location:33 → 154
    IL15; Interleukin 15

  2. NM_172175.3 → NP_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, AC118480, AK290619, BX116580, CX761071
    Consensus CDS
    CCDS3756.1
    UniProtKB/Swiss-Prot
    P40933
    Related
    ENSP00000422271.1, ENST00000514653.5
    Conserved Domains (1) summary
    pfam02372
    Location:10 → 127
    IL15; Interleukin 15

RNA

  1. NR_037840.3 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, AC118480, BC018149, CX761071

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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
    141636583..141733987
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    144953939..145051309
    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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P40933.1 GenPept UniProtKB/Swiss-Prot:P40933

Gene LinkOut

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Chemical Information
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