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IL16 interleukin 16 [ Homo sapiens (human) ]

Gene ID: 3603, updated on 1-Aug-2020

Summary

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Official Symbol
IL16provided by HGNC
Official Full Name
interleukin 16provided by HGNC
Primary source
HGNC:HGNC:5980
See related
Ensembl:ENSG00000172349 MIM:603035
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
LCF; NIL16; PRIL16; prIL-16
Summary
The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]
Expression
Broad expression in lymph node (RPKM 15.8), spleen (RPKM 12.1) and 20 other tissues See more
Orthologs
mouse all

Genomic context

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See IL16 in Genome Data Viewer
Location:
15q25.1
Exon count:
22
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 15 NC_000015.10 (81196879..81314058)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (81474941..81605104)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene talin rod domain containing 1 Neighboring gene cilia and flagella associated protein 161 Neighboring gene acidic nuclear phosphoprotein 32 family member B pseudogene 3 Neighboring gene TMC3 antisense RNA 1 Neighboring gene StAR related lipid transfer domain containing 5 Neighboring gene transmembrane channel like 3 Neighboring gene uncharacterized LOC102723985

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
  • 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. IL-16 expression is increased in the skin and sera of patients with systemic sclerosis. Kawabata K, et al. Rheumatology (Oxford), 2020 Mar 1. PMID 31377804
  2. Cytokine Diversity in Human Peripheral Blood Eosinophils: Profound Variability of IL-16. Ma M, et al. J Immunol, 2019 Jul 15. PMID 31182481, Free PMC Article
  3. The Impact of IL-16 3'UTR Polymorphism rs859 on Lung Carcinoma Susceptibility among Chinese Han Individuals. Zhuo M, et al. Biomed Res Int, 2018. PMID 30671474, Free PMC Article
  4. Elevated IL-16 expression is associated with development of immune dysfunction in children with autism. Ahmad SF, et al. Psychopharmacology (Berl), 2019 Feb. PMID 30456538
  5. The role of IL‑16 gene polymorphisms in endometriosis. Matalliotakis M, et al. Int J Mol Med, 2018 Mar. PMID 29328375, Free PMC Article

See all (166) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The regional up-regulation of IL-16 in the skin is not only associated with skin sclerosis, but also with systemic IL-16 activation. IL-16 may play a role in the pathogenesis of SSc. Moreover, serum IL-16 levels may be useful as a biomarker for determining the severity of the skin sclerosis.
    Title: IL-16 expression is increased in the skin and sera of patients with systemic sclerosis.
  2. A moderate increase in total dietary fat resulted in a 2.7-fold reduction in eosinophil IL-16 content among C57BL/6-IL5tg mice.
    Title: Cytokine Diversity in Human Peripheral Blood Eosinophils: Profound Variability of IL-16.
  3. Study uncover a role for IL-16/mir-125a in systemic lupus erythematosus (SLE) and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this.
    Title: IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation.
  4. genetic variant rs859 of IL-16 3'UTR was associated with lung cancer risk in Chinese Han population
    Title: The Impact of <i>IL-16</i> 3'UTR Polymorphism rs859 on Lung Carcinoma Susceptibility among Chinese Han Individuals.
  5. IL-16 modulates macrophage polarization through regulating IL-10, IL-1a and IL-6 expression. Mir-145 is involved in M2 macrophage polarization by targeting IL-16 and enhancing IL-10 expression.
    Title: IL-16 regulates macrophage polarization as a target gene of mir-145-3p.
  6. IL-16 mRNA and protein expression was significantly induced in children with autism spectrum disorder compared with typically developing children.
    Title: Elevated IL-16 expression is associated with development of immune dysfunction in children with autism.
  7. IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive, while IL-12 might inhibit the immune response. IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.
    Title: [Effect of interleukin-6 and interleukin-12 on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers].
  8. The present study demonstrated no association between IL-2 (T-330G), IL-16 (T-295C), and IL-17 (A-7383G) genotypes and CP in an Iranian population.
    Title: Interleukin-2, -16, and -17 gene polymorphisms in Iranian patients with chronic periodontitis.
  9. rs11556218 is associated with endometriosis in Greek women, probably by resulting in the aberrant expression of IL16
    Title: The role of IL‑16 gene polymorphisms in endometriosis.
  10. There was a decreased frequency of IL16 rs4778889 CC genotype carriers among women with gestational diabetes mellitus, however, there was no significant difference in the distribution of alleles.
    Title: IL16 and IL18 gene polymorphisms in women with gestational diabetes.
Submit: New GeneRIF Correction See all GeneRIFs (113)

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

NHGRI GWAS Catalog

Description
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.
NHGRI GWA 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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Replication interactions

Interaction Pubs
Knockdown of interleukin 16 (IL16) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env IL-16 induces rapid translocation of PKC from the cytosol to the membrane in CD4+ cells; PKC inhibitors completely block IL-16-induced lymphocyte migration as well as the motile response induced by HIV-1 gp120 and anti-CD4 antibody binding to CD4 PubMed
Tat tat Recombinant IL-16 inhibits HIV-1 Tat activation of the HIV-1 LTR promoter 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

  • FLJ16806, FLJ42735, FLJ44234

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CD4 receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
CD4 receptor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
cytokine activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
Process Evidence Code Pubs
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
  
immune response TAS
Traceable Author Statement
more info
 PubMed 
induction of positive chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
leukocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
positive regulation of inflammatory response IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of interleukin-1 alpha production IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of interleukin-12 production IDA
Inferred from Direct Assay
more info
 PubMed 
positive regulation of interleukin-6 production IDA
Inferred from Direct Assay
more info
 PubMed 
regulation of calcium ion transport IDA
Inferred from Direct Assay
more info
 PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
Flemming body IDA
Inferred from Direct Assay
more info
  
cytosol IDA
Inferred from Direct Assay
more info
  
cytosol TAS
Traceable Author Statement
more info
  
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
  
plasma membrane IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
pro-interleukin-16
Names
lymphocyte chemoattractant factor
neuronal interleukin 16
prointerleukin 16

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_029933.1 RefSeqGene

    Range
    5001..120886
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001172128.2 → NP_001165599.1  pro-interleukin-16 isoform 3

    See identical proteins and their annotated locations for NP_001165599.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has multiple differences and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) is longer, compared to isoform 1.
    Source sequence(s)
    AC036196, AC103858
    Consensus CDS
    CCDS53966.1
    UniProtKB/Swiss-Prot
    Q14005
    Related
    ENSP00000378155.2, ENST00000394660.6
    Conserved Domains (2) summary
    smart00228
    Location:1233 → 1319
    PDZ; Domain present in PSD-95, Dlg, and ZO-1/2
    cd00992
    Location:217 → 300
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

  2. NM_001352684.2 → NP_001339613.1  pro-interleukin-16 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC036196, AC103858
    Conserved Domains (3) summary
    smart00228
    Location:624 → 710
    PDZ; Domain present in PSD-95, Dlg, and ZO-1/2
    cd00992
    Location:501 → 578
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cl27818
    Location:250 → 345
    COG1615; Uncharacterized membrane protein, UPF0182 family [Function unknown]

  3. NM_001352685.2 → NP_001339614.1  pro-interleukin-16 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC036196, AC103858
    Conserved Domains (3) summary
    smart00228
    Location:1063 → 1149
    PDZ; Domain present in PSD-95, Dlg, and ZO-1/2
    cd00992
    Location:47 → 130
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cl27818
    Location:690 → 785
    COG1615; Uncharacterized membrane protein, UPF0182 family [Function unknown]

  4. NM_001352686.1 → NP_001339615.1  pro-interleukin-16 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC036196, AC103858, AY324389
    Conserved Domains (3) summary
    smart00228
    Location:1284 → 1370
    PDZ; Domain present in PSD-95, Dlg, and ZO-1/2
    cd00992
    Location:268 → 351
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cl27818
    Location:911 → 1006
    COG1615; Uncharacterized membrane protein, UPF0182 family [Function unknown]

  5. NM_004513.6 → NP_004504.3  pro-interleukin-16 isoform 1

    See identical proteins and their annotated locations for NP_004504.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform (1).
    Source sequence(s)
    AC103858
    Consensus CDS
    CCDS10317.1
    UniProtKB/Swiss-Prot
    Q14005
    UniProtKB/TrEMBL
    Q9UME6
    Related
    ENSP00000378147.2, ENST00000394652.6
    Conserved Domains (3) summary
    smart00228
    Location:533 → 619
    PDZ; Domain present in PSD-95, Dlg, and ZO-1/2
    cd00992
    Location:410 → 487
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
    cl23717
    Location:347 → 432
    crotonase-like; Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. ...

  6. NM_172217.5 → NP_757366.2  pro-interleukin-16 isoform 2

    See identical proteins and their annotated locations for NP_757366.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and and 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) is longer at the N-terminus compared to isoform 1.
    Source sequence(s)
    AC036196, AC103858
    Consensus CDS
    CCDS42069.1
    UniProtKB/Swiss-Prot
    Q14005
    Related
    ENSP00000302935.4, ENST00000302987.8
    Conserved Domains (2) summary
    smart00228
    Location:1234 → 1320
    PDZ; Domain present in PSD-95, Dlg, and ZO-1/2
    cd00992
    Location:217 → 300
    PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

RNA

  1. NR_148035.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC036196, AC103858

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p13 Primary Assembly

    Range
    81196879..81314058
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14005.4 GenPept UniProtKB/Swiss-Prot:Q14005

Gene LinkOut

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