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P05112 (IL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 176. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-4

Short name=IL-4
Alternative name(s):
B-cell stimulatory factor 1
Short name=BSF-1
Binetrakin
Lymphocyte stimulatory factor 1
Pitrakinra
Gene names
Name:IL4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length153 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes.

Subcellular location

Secreted.

Involvement in disease

Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.19

Sequence similarities

Belongs to the IL-4/IL-13 family.

Ontologies

Keywords
   Biological processB-cell activation
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   Molecular functionCytokine
Growth factor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell costimulation

Inferred from electronic annotation. Source: Ensembl

B cell differentiation

Traceable author statement PubMed 11418631. Source: UniProtKB

T-helper 1 cell lineage commitment

Inferred from electronic annotation. Source: Ensembl

T-helper 2 cell cytokine production

Inferred from direct assay PubMed 20554961. Source: UniProtKB

T-helper 2 cell differentiation

Inferred from electronic annotation. Source: Ensembl

cellular defense response

Traceable author statement PubMed 10725748. Source: ProtInc

cellular response to mercury ion

Inferred from electronic annotation. Source: Ensembl

chemotaxis

Traceable author statement PubMed 10725748. Source: ProtInc

cholesterol metabolic process

Inferred from sequence or structural similarity PubMed 11971948. Source: UniProtKB

connective tissue growth factor biosynthetic process

Traceable author statement PubMed 11967989. Source: UniProtKB

defense response to protozoan

Inferred from electronic annotation. Source: Ensembl

dendritic cell differentiation

Inferred from direct assay PubMed 21149635. Source: DFLAT

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

female pregnancy

Inferred from electronic annotation. Source: Ensembl

immune response

Traceable author statement Ref.1. Source: ProtInc

innate immune response in mucosa

Inferred from electronic annotation. Source: Ensembl

negative regulation of T-helper 17 cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of acute inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of chronic inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

negative regulation of macrophage activation

Inferred from electronic annotation. Source: Ensembl

negative regulation of nitric oxide biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoclast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18579517. Source: UniProtKB

positive regulation of B cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MHC class II biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T cell differentiation

Inferred from direct assay PubMed 20554961. Source: UniProtKB

positive regulation of T cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of activated T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-10 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-13 production

Inferred from direct assay PubMed 19346497. Source: UniProtKB

positive regulation of isotype switching to IgE isotypes

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of isotype switching to IgG isotypes

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18579517PubMed 19346497PubMed 20554961. Source: UniProtKB

positive regulation of tyrosine phosphorylation of Stat5 protein

Inferred from electronic annotation. Source: Ensembl

regulation of immune response

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of isotype switching

Traceable author statement PubMed 11418631. Source: UniProtKB

regulation of phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of proton transport

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

type 2 immune response

Traceable author statement PubMed 11676128. Source: UniProtKB

   Cellular_componentexternal side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular space

Traceable author statement PubMed 11418631. Source: UniProtKB

   Molecular_functiongrowth factor activity

Non-traceable author statement PubMed 11418631. Source: UniProtKB

interleukin-4 receptor binding

Traceable author statement PubMed 11418631. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10PubMed 18243101PubMed 23597562PubMed 8266078. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

IL13RA1P785523EBI-367025,EBI-1391535
IL4RP243947EBI-367025,EBI-367009

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P05112-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P05112-2)

Also known as: Short; IL-4delta2;

The sequence of this isoform differs from the canonical sequence as follows:
     46-61: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 153129Interleukin-4
PRO_0000015532

Amino acid modifications

Glycosylation621N-linked (GlcNAc...) Ref.7
Disulfide bond27 ↔ 151 Ref.7 Ref.16
Disulfide bond48 ↔ 89 Ref.7 Ref.16
Disulfide bond70 ↔ 123 Ref.7 Ref.16

Natural variations

Alternative sequence46 – 6116Missing in isoform 2.
VSP_002672
Natural variant271C → R.
Corresponds to variant rs4986964 [ dbSNP | Ensembl ].
VAR_020392

Secondary structure

.................... 153
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Long) [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: 8725BF64B34D45F7

FASTA15317,492
        10         20         30         40         50         60 
MGLTSQLLPP LFFLLACAGN FVHGHKCDIT LQEIIKTLNS LTEQKTLCTE LTVTDIFAAS 

        70         80         90        100        110        120 
KNTTEKETFC RAATVLRQFY SHHEKDTRCL GATAQQFHRH KQLIRFLKRL DRNLWGLAGL 

       130        140        150 
NSCPVKEANQ STLENFLERL KTIMREKYSK CSS 

« Hide

Isoform 2 (Short) (IL-4delta2) [UniParc].

Checksum: 3B621F60D0F0D261
Show »

FASTA13715,797

References

« Hide 'large scale' references
[1]"Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities."
Yokota T., Otsuka T., Mosmann T., Banchereau J., Defrance T., Blanchard D., de Vries J.E., Lee F., Arai K.
Proc. Natl. Acad. Sci. U.S.A. 83:5894-5898(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression."
Arai N., Nomura D., Villaret D., Malefijt R.D., Seiki M., Yoshida M., Minoshima S., Fukuyama R., Maekawa M., Kudoh J., Shimizu N., Yokota K., Abe E., Yokota T., Takebe Y., Arai K.
J. Immunol. 142:274-282(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"An alternatively spliced interleukin 4 form in lymphoid cells."
Klein S.C., Golverdingen J., Bouwens A.G.M., Tilanus M.G.J.
Immunogenetics 41:57-57(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]SeattleSNPs variation discovery resource
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Blood.
[6]"The 5' region of the human interleukin 4 gene: structure and potential regulatory elements."
Eder A., Krafft-Czepa H., Krammer P.H.
Nucleic Acids Res. 16:772-772(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
[7]"Disulfide assignments in recombinant mouse and human interleukin 4."
Carr C., Aykent S., Kimack N.M., Levine A.D.
Biochemistry 30:1515-1523(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-62, DISULFIDE BONDS.
[8]"Crystal structure of recombinant human interleukin-4."
Walter M.R., Cook W.J., Zhao B.G., Cameron R.P. Jr., Ealick S.E., Walter R.L. Jr., Reichert P., Nagabhushan T.L., Trotta P.P., Bugg C.E.
J. Biol. Chem. 267:20371-20376(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS).
[9]"Crystal structure of human recombinant interleukin-4 at 2.25-A resolution."
Wlodaver A., Pavlovsky A., Gustchina A.
FEBS Lett. 309:59-64(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
[10]"Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface."
Hage T., Sebald W., Reinemer P.
Cell 97:271-281(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 25-153 IN COMPLEX WITH IL4RALPHA.
[11]"Secondary structure and topology of human interleukin 4 in solution."
Redfield C., Smith L.J., Boyd J., Lawrence G.M.P., Edwards R.G., Smith R.A.G., Dobson C.M.
Biochemistry 30:11029-11035(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[12]"Human interleukin 4. The solution structure of a four-helix bundle protein."
Smith L.J., Redfield C., Boyd J., Lawrence G.M.P., Edwards R.G., Smith R.A.G., Dobson C.M.
J. Mol. Biol. 224:899-904(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[13]"1H, 15N, 13C, and 13CO assignments of human interleukin-4 using three-dimensional double- and triple-resonance heteronuclear magnetic resonance spectroscopy."
Powers R., Garret D.S., March C.J., Frieden E.A., Gronenborn A.M., Clore G.M.
Biochemistry 31:4334-4346(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[14]"Determination of the secondary structure and folding topology of human interleukin-4 using three-dimensional heteronuclear magnetic resonance spectroscopy."
Garret D.S., Powers R., March C.J., Frieden E.A., Clore G.M., Gronenborn A.M.
Biochemistry 31:4347-4353(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[15]"Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy."
Powers R., Garret D.S., March C.J., Frieden E.A., Gronenborn A.M., Clore G.M.
Science 256:1673-1677(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[16]"Experimental and theoretical studies of the three-dimensional structure of human interleukin-4."
Curtis B.M., Presnell S.R., Srinivasan S., Sassenfeld H., Klinke R., Jeffery E., Cosman D., March C.J., Cohen F.E.
Proteins 11:111-119(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS, 3D-STRUCTURE MODELING.
[17]"Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy."
Mueller T., Dieckmann T., Sebald W., Oschkinat H.
J. Mol. Biol. 237:423-436(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS, STRUCTURE BY NMR.
[18]"Comparison of four independently determined structures of human recombinant interleukin-4."
Smith L.J., Redfield C., Smith R.A.G., Dobson C.M., Clore G.M., Gronenborn A.M., Walter M.R., Naganbushan T.L., Wlodawer A.
Nat. Struct. Biol. 1:301-310(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: COMPARISON OF STRUCTURES.
[19]"Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis."
Zee R.Y.L., Cook N.R., Cheng S., Reynolds R., Erlich H.A., Lindpaintner K., Ridker P.M.
Hum. Mol. Genet. 13:389-396(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M13982 mRNA. Translation: AAA59149.1.
M23442 Genomic DNA. Translation: AAA59150.1.
X81851 mRNA. Translation: CAA57444.1.
AF395008 Genomic DNA. Translation: AAK71324.1.
BC066277 mRNA. Translation: AAH66277.1.
BC067514 mRNA. Translation: AAH67514.1.
BC070123 mRNA. Translation: AAH70123.1.
X06750 Genomic DNA. Translation: CAA29925.1.
CCDSCCDS4158.1. [P05112-1]
CCDS4159.1. [P05112-2]
PIRA25946. A30546.
RefSeqNP_000580.1. NM_000589.3. [P05112-1]
NP_758858.1. NM_172348.2. [P05112-2]
UniGeneHs.73917.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1BBNNMR-A25-153[»]
1BCNNMR-A25-153[»]
1CYLNMR-A25-153[»]
1HIJX-ray3.00A25-153[»]
1HIKX-ray2.60A25-153[»]
1HZIX-ray2.05A25-153[»]
1IARX-ray2.30A25-153[»]
1ILLmodel-425-153[»]
1ITEmodel-A25-153[»]
1ITINMR-A25-153[»]
1ITLNMR-A25-153[»]
1ITMNMR-A25-153[»]
1RCBX-ray2.25A25-153[»]
2B8UX-ray1.80A25-153[»]
2B8XX-ray1.70A25-153[»]
2B8YX-ray1.80A25-153[»]
2B8ZX-ray2.50A25-153[»]
2B90X-ray2.10A25-153[»]
2B91X-ray2.00A25-153[»]
2CYKNMR-A25-153[»]
2D48X-ray1.65A25-153[»]
2INTX-ray2.35A25-153[»]
3BPLX-ray2.93A25-153[»]
3BPNX-ray3.02A25-153[»]
3QB7X-ray3.24A/B25-153[»]
ProteinModelPortalP05112.
SMRP05112. Positions 25-153.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109779. 4 interactions.
DIPDIP-3222N.
IntActP05112. 3 interactions.
MINTMINT-90320.
STRING9606.ENSP00000231449.

Polymorphism databases

DMDM124337.

Proteomic databases

PaxDbP05112.
PRIDEP05112.

Protocols and materials databases

DNASU3565.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000231449; ENSP00000231449; ENSG00000113520. [P05112-1]
ENST00000350025; ENSP00000325190; ENSG00000113520. [P05112-2]
GeneID3565.
KEGGhsa:3565.
UCSCuc003kxk.2. human. [P05112-1]

Organism-specific databases

CTD3565.
GeneCardsGC05P132009.
H-InvDBHIX0164435.
HGNCHGNC:6014. IL4.
MIM147780. gene.
601367. phenotype.
neXtProtNX_P05112.
PharmGKBPA197.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG266404.
HOGENOMHOG000254781.
HOVERGENHBG000290.
InParanoidP05112.
KOK05430.
OMAKEKYSKC.
OrthoDBEOG7SJD75.
PhylomeDBP05112.
TreeFamTF336383.

Enzyme and pathway databases

SignaLinkP05112.

Gene expression databases

ArrayExpressP05112.
BgeeP05112.
CleanExHS_IL4.
GenevestigatorP05112.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR002354. IL-4.
IPR001325. IL-4/IL-13.
IPR018096. IL-4/IL-13_CS.
[Graphical view]
PANTHERPTHR11456. PTHR11456. 1 hit.
PfamPF00727. IL4. 1 hit.
[Graphical view]
PIRSFPIRSF001941. Interleukin_4. 1 hit.
PRINTSPR00431. INTERLEUKIN4.
SMARTSM00190. IL4_13. 1 hit.
[Graphical view]
SUPFAMSSF47266. SSF47266. 1 hit.
PROSITEPS00838. INTERLEUKIN_4_13. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05112.
GeneWikiInterleukin_4.
GenomeRNAi3565.
NextBio13920.
PROP05112.
SOURCESearch...

Entry information

Entry nameIL4_HUMAN
AccessionPrimary (citable) accession number: P05112
Secondary accession number(s): Q14630, Q6NZ77
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: July 9, 2014
This is version 176 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM