IL15 interleukin 15 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: IL15provided by HGNC
Official Full Name: interleukin 15provided by HGNC
Primary source: HGNC:5977
See related: Ensembl:ENSG00000164136; HPRD:02776; 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]

Genomic context

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Location :: 4q31

Sequence :: Chromosome: 4; NC_000004.11 (142557749..142655140)

See IL15 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

IL-15 or IL-7 priming of the RasGRP/SOS pathway contributes to the increased ERK responsiveness and reduces the threshold above which signaling cascades are initiated, thereby predisposing for autoimmunity.
Title: IL-7- and IL-15-mediated TCR sensitization enables T cell responses to self-antigens.
IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.
Title: IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors.
Paracrine and transpresentation functions of IL-15 are mediated by diverse splice form of IL-15Ralpha.
Title: Paracrine and transpresentation functions of IL-15 are mediated by diverse splice versions of IL-15Rα in human monocytes and dendritic cells.
IFN-gamma and TNF-alpha play an important role in regulating the expression of IL-15 and IL-15Ralpha on the surface of HUVECs.
Title: Expression of interleukin-15 and its receptor on the surface of stimulated human umbilical vein endothelial cells.
study found in the structure of the IL-15-IL-15Ralpha-IL-2Rbeta-gamma(c) quaternary complex, IL-15 binds to IL-2Rbeta and gamma(c) in a heterodimer nearly indistinguishable from the IL-2-IL-2Ralpha-IL-2Rbeta-gamma(c) complex, despite their different receptor-binding chemistries; IL-15 and IL-2 induced similar signals
Title: Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.
IL-15 represses miR-29b via induction of Myc/NF-kappaBp65/Hdac-1, resulting in Dnmt3b overexpression and DNA hypermethylation.
Title: Aberrant overexpression of IL-15 initiates large granular lymphocyte leukemia through chromosomal instability and DNA hypermethylation.
IL-15 in the amniotic fluid is significantly higher in the third trimester of pregnancy than in the second trimester.
Title: Analysis of the concentrations of interleukin 15 in amniotic fluid in the second and the third trimesters of pregnancy.
Il-15 levels were not significantly different the amniotic fluid of fetuses with normal karyotypes and with chromosome abnormalities.
Title: Second-trimester IL-15 and IL-18 levels in the amniotic fluid of fetuses with normal karyotypes and with chromosome abnormalities.
These single-nucleotide polymorphisms were also significant after correction for multiple testing. CONCLUSION: Genetic variants in IL-15 are associated with progression of joint destruction in rheumatoid arthritis
Title: Genetic variants in IL15 associate with progression of joint destruction in rheumatoid arthritis: a multicohort study.
there is an altered expression of LIF and IL-15 in the endometrium of women with recurrent implantation failure
Title: Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells.

Submit: New GeneRIF Correction See all (219)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

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

HIV-1 protein interactions

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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, p27	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
matrix	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 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

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P40933	Q13261	IL15RA	HPRD	PubMed
P40933	P14784	IL2RB	HPRD	PubMed
P40933	P31785	IL2RG	HPRD	PubMed
BioGRID:109813	BioGRID:106848	APP	BioGRID	PubMed	Reconstituted Complex
BioGRID:109813	BioGRID:112654	STAT5B	BioGRID	PubMed	Two-hybrid
BioGRID:109813	BioGRID:113039	TRAF3	BioGRID	PubMed	Two-hybrid
BioGRID:109813	BioGRID:119050	ZNRD1	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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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...
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...
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...

General gene information

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Markers

D4S3176 (e-PCR)
- UniSTS:77331

IL15 (e-PCR), detects polymorphism
- UniSTS:266090

NoName (e-PCR)
- UniSTS:482732

RH103394 (e-PCR)
- UniSTS:97720

Genotypes

See IL15 SNP Geneview Report
See IL15 SNP Genotype Report
See IL15 SNP Variation Viewer Report

Homology

Homologs of the IL15 gene: The IL15 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

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
lymph node development	IEA Inferred from Electronic Annotation more info
natural killer cell differentiation	IEA Inferred from Electronic Annotation more info
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 tissue remodeling	IC Inferred by Curator more info	PubMed
positive regulation of tyrosine phosphorylation of Stat3 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
signal transduction	TAS Traceable Author Statement more info	PubMed
skeletal muscle atrophy	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	TAS Traceable Author Statement more info	PubMed
cytoplasm	TAS Traceable Author Statement more info	PubMed
endosome	TAS Traceable Author Statement more info	PubMed
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular space	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane	TAS Traceable Author Statement more info	PubMed
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: interleukin-15

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

NG_029605.1 RefSeqGene

Range

5001..102392

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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

ENSP00000296545, OTTHUMP00000164616, ENST00000296545, OTTHUMT00000257278

Conserved Domains (1) summary

pfam02372
Location:33 – 160
Blast Score: 402

IL15; Interleukin 15
NM_172175.2 → NP_751915.1 interleukin-15 isoform 2 preproprotein

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

UniProtKB/TrEMBL

Q6FGX7

Conserved Domains (1) summary

pfam02372
Location:6 – 133
Blast Score: 386

IL15; Interleukin 15

RNA

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 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

142557749..142655140

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

138287515..138384970

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

142342674..142440065

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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
genomic	ABBA01069990.1 (34270..131725)	None
genomic	AC096774.1	None
genomic	AC118480.3 (55320..106490)	None
genomic	AF176907.1	None
genomic	AMYH01014575.1 (29674..127065)	None
genomic	CH471056.2	EAX05083.1
		EAX05084.1
		EAX05085.1
		EAX05086.1
		EAX05087.1
genomic	CS112464.1	CAJ13397.1
genomic	CS163144.1	CAJ32191.1
genomic	CS401671.1	CAL40354.1
genomic	GM040149.1	CAS97649.1
genomic	HC087890.1	CBI67687.1
genomic	JA143001.1	CCA64045.1
genomic	X91233.1	CAA62616.1
mRNA	AA897685.1	None
mRNA	AF031167.1	AAB97518.1
mRNA	AK122993.1	BAG53839.1
mRNA	AK290619.1	BAF83308.1
mRNA	AY720442.1	AAU21241.1
mRNA	BC018149.2	AAH18149.1
mRNA	BC100961.1	AAI00962.1
mRNA	BC100962.1	AAI00963.1
mRNA	BC100963.1	AAI00964.1
mRNA	BX116580.1	None
mRNA	CA443264.1	None
mRNA	CR541980.1	CAG46777.1
mRNA	CR542007.1	CAG46804.1
mRNA	CX761071.1	None
mRNA	CX785233.1	None
mRNA	U14407.1	AAA21551.1
mRNA	X94222.1	CAA63913.1
mRNA	X94223.1	CAA63914.1
mRNA	Z38000.1	CAA86100.1
other-genetic	DQ890548.2	ABM92165.1
other-genetic	DQ893709.2	ABM84635.1
other-genetic	DQ893710.2	ABM84636.1