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

Summary

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

Location:: 4q31.21

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (141636583..141733987)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (144953939..145051309)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (142557736..142655140)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
IL-15 induced bystander activation of CD8[+] T cells may mediate endothelium injury through NKG2D in Hantaan virus infection.
Title: IL-15 induced bystander activation of CD8(+) T cells may mediate endothelium injury through NKG2D in Hantaan virus infection.
The effects of ageing, BMI and physical activity on blood IL-15 levels: A systematic review and meta-analyses.
Title: The effects of ageing, BMI and physical activity on blood IL-15 levels: A systematic review and meta-analyses.
Circulating myokines IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity.
Title: Circulating myokines IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity.

Submit: New GeneRIF Correction See all GeneRIFs (420)

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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

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 positive regulation of tyrosine phosphorylation of STAT protein	IBA Inferred from Biological aspect of Ancestor more info
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

NG_029605.2 RefSeqGene

Range

4988..102392

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

141636583..141733987

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

144953939..145051309

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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.