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IL4 interleukin 4 [ Homo sapiens (human) ]

Gene ID: 3565, updated on 16-Feb-2020

Summary

Official Symbol
IL4provided by HGNC
Official Full Name
interleukin 4provided by HGNC
Primary source
HGNC:HGNC:6014
See related
Ensembl:ENSG00000113520 MIM:147780
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
BSF1; IL-4; BCGF1; BSF-1; BCGF-1
Summary
The protein encoded by this gene is a pleiotropic cytokine produced by activated T cells. This cytokine is a ligand for interleukin 4 receptor. The interleukin 4 receptor also binds to IL13, which may contribute to many overlapping functions of this cytokine and IL13. STAT6, a signal transducer and activator of transcription, has been shown to play a central role in mediating the immune regulatory signal of this cytokine. This gene, IL3, IL5, IL13, and CSF2 form a cytokine gene cluster on chromosome 5q, with this gene particularly close to IL13. This gene, IL13 and IL5 are found to be regulated coordinately by several long-range regulatory elements in an over 120 kilobase range on the chromosome. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
Expression
Low expression observed in reference dataset See more
Orthologs

Genomic context

See IL4 in Genome Data Viewer
Location:
5q31.1
Exon count:
5
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 5 NC_000005.10 (132673986..132682678)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (132009678..132018370)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene RAD50 double strand break repair protein Neighboring gene Th2 cytokine locus control region Neighboring gene T helper type 2 locus control region associated RNA Neighboring gene uncharacterized LOC105379176 Neighboring gene interleukin 13 Neighboring gene kinesin family member 3A Neighboring gene septin 8 Neighboring gene cyclin I family member 2

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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 replication in resting peripheral blood CD4 T cells is rescued by IL4; IL4 rescues resting peripheral blood CD4 T cells from HIV-1-induced T cell death PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 induces release of IL-4 in CD4+ T cells PubMed
env HIV-1 gp120 cooperates with BAFF and cytokines IL-4 and IL-10 to activate mannose C-type lectin receptors-expressing B cells PubMed
env HIV-1 gp120 upregulates IL-4-induced IgE production through the regulation of the nitric oxide pathway PubMed
env Molecular interactions of CD2 with LFA-3 and CD28 with B7-1 in conjunction with TCR occupancy prevent T cells from programmed apoptosis mediated by binding of CD4 to HIV-1 gp120, resulting in increased levels of IL-2 and IL-4 secretion from the T cells PubMed
env Antigen-induced interleukin 4 secretion is markedly reduced in HIV-1 gp120-treated T cells PubMed
Envelope surface glycoprotein gp160, precursor env Pretreatment of CD4+ cells with HIV-1 gp160 significantly reduces PHA-induced secretion of IFN-gamma and IL-2 but augments IL-4 production PubMed
Nef nef HIV-1 Nef suppresses immunoglobulin class-switch DNA recombination by inducing IkappaBalpha and SOCS proteins, which block CD154, IL-4 and IL-10 cytokine signaling via NF-kappaB and STAT transcription factors PubMed
Tat tat HIV-1 Tat significantly decreases TNF-alpha and IL-6 secretion but increases IL-4 levels in human hepatocellular carcinoma cells PubMed
tat Monocytes treated with HIV-1 clade C Tat show significant upregulation of anti-inflammatory cytokines, IL-4 and IL-10, as compared to clade B Tat-treated cultures PubMed
tat Activation of IL-4/STAT6 signaling partially contributes to HIV-1 Tat-induced Kaposi's sarcoma-associated herpes virus (KSHV) replication PubMed
tat HIV-1 Tat upregulates IL-4 expression in Jurkat T-cells PubMed
tat HIV-1 Tat induces IL-4 and IL-13 release from basophils, leading to dysregulation of the IgE/Fc epsilon RI network PubMed
Vif vif HIV-1 Vif upregulates the expression of interleukin 4 (IL4) in Vif-expression T cells PubMed
Vpr vpr HIV-1 Vpr suppresses expression of IL-4 through suppression of NF-kappa B activity via the induction of I kappa B alpha 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 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 blocks IL-4 downregulation of interferon gamma and TNF-alpha PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC79402

Gene Ontology Provided by GOA

Function Evidence Code Pubs
cytokine activity IEA
Inferred from Electronic Annotation
more info
 
growth factor activity NAS
Non-traceable Author Statement
more info
PubMed 
interleukin-4 receptor binding TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
B cell differentiation TAS
Traceable Author Statement
more info
PubMed 
T cell activation IGI
Inferred from Genetic Interaction
more info
PubMed 
T-helper 2 cell cytokine production IDA
Inferred from Direct Assay
more info
PubMed 
activation of Janus kinase activity IGI
Inferred from Genetic Interaction
more info
PubMed 
cholesterol metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
connective tissue growth factor biosynthetic process TAS
Traceable Author Statement
more info
PubMed 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
dendritic cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
immune response TAS
Traceable Author Statement
more info
PubMed 
myeloid dendritic cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of complement-dependent cytotoxicity IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of endothelial cell apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of epithelial cell migration IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of neuroinflammatory response IC
Inferred by Curator
more info
 
negative regulation of osteoclast differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of tumor necrosis factor biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
neuroinflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of ATP biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of B cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of MHC class II biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of T cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of T cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of amyloid-beta clearance ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cellular respiration ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of gene expression IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-13 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of isotype switching to IgE isotypes ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of isotype switching to IgG isotypes ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of macroautophagy ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of receptor-mediated endocytosis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of tyrosine phosphorylation of STAT protein IGI
Inferred from Genetic Interaction
more info
PubMed 
regulation of immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of isotype switching TAS
Traceable Author Statement
more info
PubMed 
regulation of phosphorylation ISS
Inferred from Sequence or Structural Similarity
more info
 
type 2 immune response TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
interleukin-4
Names
B cell growth factor 1
B_cell stimulatory factor 1
binetrakin
interleukin 4 variant 2
lymphocyte stimulatory factor 1
pitrakinra

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_023252.1 RefSeqGene

    Range
    5309..13998
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000589.4NP_000580.1  interleukin-4 isoform 1 precursor

    See identical proteins and their annotated locations for NP_000580.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    BC067514, CD640452, M13982
    Consensus CDS
    CCDS4158.1
    UniProtKB/Swiss-Prot
    P05112
    UniProtKB/TrEMBL
    D4HNR6
    Related
    ENSP00000231449.2, ENST00000231449.7
    Conserved Domains (1) summary
    pfam00727
    Location:28149
    IL4; Interleukin 4
  2. NM_001354990.1NP_001341919.1  interleukin-4 isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (3) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC004039, JX878389
    Consensus CDS
    CCDS87322.1
    Related
    ENSP00000480581.1, ENST00000622422.1
    Conserved Domains (1) summary
    cl11518
    Location:177
    IL4; Interleukin 4
  3. NM_172348.3NP_758858.1  interleukin-4 isoform 2 precursor

    See identical proteins and their annotated locations for NP_758858.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the 5' region, compared to variant 1, resulting an isoform (2) that lacks an internal region, as compared to isoform 1.
    Source sequence(s)
    AB102862, BC067514, CD640452, M13982
    Consensus CDS
    CCDS4159.1
    UniProtKB/Swiss-Prot
    P05112
    UniProtKB/TrEMBL
    Q5FC01
    Related
    ENSP00000325190.3, ENST00000350025.2
    Conserved Domains (1) summary
    pfam00727
    Location:28133
    IL4; Interleukin 4

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p13 Primary Assembly

    Range
    132673986..132682678
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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