IL4_HUMAN
ID IL4_HUMAN Reviewed; 153 AA.
AC P05112; Q14630; Q6NZ77;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Interleukin-4;
DE Short=IL-4;
DE AltName: Full=B-cell stimulatory factor 1;
DE Short=BSF-1;
DE AltName: Full=Binetrakin;
DE AltName: Full=Lymphocyte stimulatory factor 1;
DE AltName: Full=Pitrakinra;
DE Flags: Precursor;
GN Name=IL4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=3016727; DOI=10.1073/pnas.83.16.5894;
RA Yokota T., Otsuka T., Mosmann T., Banchereau J., Defrance T., Blanchard D.,
RA de Vries J.E., Lee F., Arai K.;
RT "Isolation and characterization of a human interleukin cDNA clone,
RT homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and
RT T-cell-stimulating activities.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5894-5898(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2535858;
RA Arai N., Nomura D., Villaret D., Malefijt R.D., Seiki M., Yoshida M.,
RA Minoshima S., Fukuyama R., Maekawa M., Kudoh J., Shimizu N., Yokota K.,
RA Abe E., Yokota T., Takebe Y., Arai K.;
RT "Complete nucleotide sequence of the chromosomal gene for human IL-4 and
RT its expression.";
RL J. Immunol. 142:274-282(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=7806280; DOI=10.1007/bf00188440;
RA Klein S.C., Golverdingen J., Bouwens A.G.M., Tilanus M.G.J.;
RT "An alternatively spliced interleukin 4 form in lymphoid cells.";
RL Immunogenetics 41:57-57(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
RX PubMed=3257560; DOI=10.1093/nar/16.2.772;
RA Eder A., Krafft-Czepa H., Krammer P.H.;
RT "The 5' region of the human interleukin 4 gene: structure and potential
RT regulatory elements.";
RL Nucleic Acids Res. 16:772-772(1988).
RN [7]
RP PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-62, AND DISULFIDE BONDS.
RX PubMed=1993171; DOI=10.1021/bi00220a011;
RA Carr C., Aykent S., Kimack N.M., Levine A.D.;
RT "Disulfide assignments in recombinant mouse and human interleukin 4.";
RL Biochemistry 30:1515-1523(1991).
RN [8]
RP FUNCTION.
RX PubMed=2521231;
RA Delespesse G., Sarfati M., Peleman R.;
RT "Influence of recombinant IL-4, IFN-alpha, and IFN-gamma on the production
RT of human IgE-binding factor (soluble CD23).";
RL J. Immunol. 142:134-138(1989).
RN [9]
RP FUNCTION.
RX PubMed=2971718;
RA Defrance T., Vanbervliet B., Pene J., Banchereau J.;
RT "Human recombinant IL-4 induces activated B lymphocytes to produce IgG and
RT IgM.";
RL J. Immunol. 141:2000-2005(1988).
RN [10]
RP FUNCTION.
RX PubMed=7721895; DOI=10.1074/jbc.270.16.9630;
RA Malabarba M.G., Kirken R.A., Rui H., Koettnitz K., Kawamura M.,
RA O'Shea J.J., Kalthoff F.S., Farrar W.L.;
RT "Activation of JAK3, but not JAK1, is critical to interleukin-4 (IL4)
RT stimulated proliferation and requires a membrane-proximal region of IL4
RT receptor alpha.";
RL J. Biol. Chem. 270:9630-9637(1995).
RN [11]
RP DISULFIDE BONDS, AND 3D-STRUCTURE MODELING.
RX PubMed=1946344; DOI=10.1002/prot.340110204;
RA Curtis B.M., Presnell S.R., Srinivasan S., Sassenfeld H., Klinke R.,
RA Jeffery E., Cosman D., March C.J., Cohen F.E.;
RT "Experimental and theoretical studies of the three-dimensional structure of
RT human interleukin-4.";
RL Proteins 11:111-119(1991).
RN [12]
RP STRUCTURE BY NMR.
RX PubMed=1932028; DOI=10.1021/bi00110a004;
RA Redfield C., Smith L.J., Boyd J., Lawrence G.M.P., Edwards R.G.,
RA Smith R.A.G., Dobson C.M.;
RT "Secondary structure and topology of human interleukin 4 in solution.";
RL Biochemistry 30:11029-11035(1991).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS).
RX PubMed=1400355; DOI=10.2210/pdb2int/pdb;
RA Walter M.R., Cook W.J., Zhao B.G., Cameron R.P. Jr., Ealick S.E.,
RA Walter R.L. Jr., Reichert P., Nagabhushan T.L., Trotta P.P., Bugg C.E.;
RT "Crystal structure of recombinant human interleukin-4.";
RL J. Biol. Chem. 267:20371-20376(1992).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
RX PubMed=1511746; DOI=10.1016/0014-5793(92)80739-4;
RA Wlodaver A., Pavlovsky A., Gustchina A.;
RT "Crystal structure of human recombinant interleukin-4 at 2.25-A
RT resolution.";
RL FEBS Lett. 309:59-64(1992).
RN [15]
RP STRUCTURE BY NMR.
RX PubMed=1569578; DOI=10.1016/0022-2836(92)90457-u;
RA Smith L.J., Redfield C., Boyd J., Lawrence G.M.P., Edwards R.G.,
RA Smith R.A.G., Dobson C.M.;
RT "Human interleukin 4. The solution structure of a four-helix bundle
RT protein.";
RL J. Mol. Biol. 224:899-904(1992).
RN [16]
RP STRUCTURE BY NMR.
RX PubMed=1567880; DOI=10.1021/bi00132a026;
RA Powers R., Garret D.S., March C.J., Frieden E.A., Gronenborn A.M.,
RA Clore G.M.;
RT "1H, 15N, 13C, and 13CO assignments of human interleukin-4 using three-
RT dimensional double- and triple-resonance heteronuclear magnetic resonance
RT spectroscopy.";
RL Biochemistry 31:4334-4346(1992).
RN [17]
RP STRUCTURE BY NMR.
RX PubMed=1567881; DOI=10.1021/bi00132a027;
RA Garret D.S., Powers R., March C.J., Frieden E.A., Clore G.M.,
RA Gronenborn A.M.;
RT "Determination of the secondary structure and folding topology of human
RT interleukin-4 using three-dimensional heteronuclear magnetic resonance
RT spectroscopy.";
RL Biochemistry 31:4347-4353(1992).
RN [18]
RP STRUCTURE BY NMR.
RX PubMed=1609277; DOI=10.1126/science.256.5064.1673;
RA Powers R., Garret D.S., March C.J., Frieden E.A., Gronenborn A.M.,
RA Clore G.M.;
RT "Three-dimensional solution structure of human interleukin-4 by
RT multidimensional heteronuclear magnetic resonance spectroscopy.";
RL Science 256:1673-1677(1992).
RN [19]
RP MUTAGENESIS, AND STRUCTURE BY NMR.
RX PubMed=8151703; DOI=10.1006/jmbi.1994.1245;
RA Mueller T., Dieckmann T., Sebald W., Oschkinat H.;
RT "Aspects of receptor binding and signalling of interleukin-4 investigated
RT by site-directed mutagenesis and NMR spectroscopy.";
RL J. Mol. Biol. 237:423-436(1994).
RN [20]
RP COMPARISON OF STRUCTURES.
RX PubMed=7664036; DOI=10.1038/nsb0594-301;
RA Smith L.J., Redfield C., Smith R.A.G., Dobson C.M., Clore G.M.,
RA Gronenborn A.M., Walter M.R., Naganbushan T.L., Wlodawer A.;
RT "Comparison of four independently determined structures of human
RT recombinant interleukin-4.";
RL Nat. Struct. Biol. 1:301-310(1994).
RN [21] {ECO:0007744|PDB:1IAR}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 25-153 IN COMPLEX WITH IL4R,
RP DISULFIDE BONDS, AND FUNCTION.
RX PubMed=10219247; DOI=10.1016/S0092-8674(00)80736-9;
RA Hage T., Sebald W., Reinemer P.;
RT "Crystal structure of the interleukin-4/receptor alpha chain complex
RT reveals a mosaic binding interface.";
RL Cell 97:271-281(1999).
RN [22] {ECO:0007744|PDB:1HZI}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 25-153, DISULFIDE BONDS,
RP FUNCTION, MUTAGENESIS OF GLU-33, AND INTERACTION WITH IL4R.
RX PubMed=11526337; DOI=10.1107/s0907444901009799;
RA Hulsmeyer M., Scheufler C., Dreyer M.K.;
RT "Structure of interleukin 4 mutant E9A suggests polar steering in receptor-
RT complex formation.";
RL Acta Crystallogr. 57:1334-1336(2001).
RN [23] {ECO:0007744|PDB:3BPL, ECO:0007744|PDB:3BPN}
RP X-RAY CRYSTALLOGRAPHY (2.93 ANGSTROMS) OF 25-153, DISULFIDE BONDS,
RP INTERACTION WITH IL13RA1, AND FUNCTION.
RX PubMed=18243101; DOI=10.1016/j.cell.2007.12.030;
RA LaPorte S.L., Juo Z.S., Vaclavikova J., Colf L.A., Qi X., Heller N.M.,
RA Keegan A.D., Garcia K.C.;
RT "Molecular and structural basis of cytokine receptor pleiotropy in the
RT interleukin-4/13 system.";
RL Cell 132:259-272(2008).
RN [24]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR.
RX PubMed=14681304; DOI=10.1093/hmg/ddh039;
RA Zee R.Y.L., Cook N.R., Cheng S., Reynolds R., Erlich H.A., Lindpaintner K.,
RA Ridker P.M.;
RT "Polymorphism in the P-selectin and interleukin-4 genes as determinants of
RT stroke: a population-based, prospective genetic analysis.";
RL Hum. Mol. Genet. 13:389-396(2004).
CC -!- FUNCTION: Cytokine secreted primarily by mast cells, T-cells,
CC eosinophils, and basophils that plays a role in regulating antibody
CC production, hematopoiesis and inflammation, and the development of
CC effector T-cell responses (PubMed:3016727, PubMed:1993171). Induces the
CC expression of class II MHC molecules on resting B-cells. Enhances both
CC secretion and cell surface expression of IgE and IgG1 (PubMed:1993171).
CC Regulates also the expression of the low affinity Fc receptor for IgE
CC (CD23) on both lymphocytes and monocytes (PubMed:2521231). Positively
CC regulates IL31RA expression in macrophages. Stimulates autophagy in
CC dendritic cells by interfering with mTORC1 signaling and through the
CC induction of RUFY4. In addition, plays a critical role in higher
CC functions of the normal brain, such as memory and learning (By
CC similarity). Upon binding to IL4, IL4R receptor dimerizes either with
CC the common IL2R gamma chain/IL2RG to produce the type 1 signaling
CC complex, located mainly on hematopoietic cells, or with the IL13RA1 to
CC produce the type 2 complex, which is expressed also on nonhematopoietic
CC cells (PubMed:10219247, PubMed:11526337, PubMed:18243101). Engagement
CC of both types of receptors initiates JAK3 and to a lower extend JAK1
CC phosphorylation leading to activation of the signal transducer and
CC activator of transcription 6/STAT6 (PubMed:7721895).
CC {ECO:0000250|UniProtKB:P07750, ECO:0000269|PubMed:10219247,
CC ECO:0000269|PubMed:11526337, ECO:0000269|PubMed:18243101}.
CC -!- SUBUNIT: Interacts with IL4R (PubMed:10219247, PubMed:11526337).
CC Interacts with IL13RA1 (PubMed:18243101). {ECO:0000269|PubMed:10219247,
CC ECO:0000269|PubMed:11526337}.
CC -!- INTERACTION:
CC P05112; P78552: IL13RA1; NbExp=3; IntAct=EBI-367025, EBI-1391535;
CC P05112; P24394: IL4R; NbExp=7; IntAct=EBI-367025, EBI-367009;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=P05112-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, IL-4delta2;
CC IsoId=P05112-2; Sequence=VSP_002672;
CC -!- DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute
CC neurologic event leading to death of neural tissue of the brain and
CC resulting in loss of motor, sensory and/or cognitive function. Ischemic
CC strokes, resulting from vascular occlusion, is considered to be a
CC highly complex disease consisting of a group of heterogeneous disorders
CC with multiple genetic and environmental risk factors.
CC {ECO:0000269|PubMed:14681304}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the IL-4/IL-13 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il4/";
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DR EMBL; M13982; AAA59149.1; -; mRNA.
DR EMBL; M23442; AAA59150.1; -; Genomic_DNA.
DR EMBL; X81851; CAA57444.1; -; mRNA.
DR EMBL; AF395008; AAK71324.1; -; Genomic_DNA.
DR EMBL; BC066277; AAH66277.1; -; mRNA.
DR EMBL; BC067514; AAH67514.1; -; mRNA.
DR EMBL; BC070123; AAH70123.1; -; mRNA.
DR EMBL; X06750; CAA29925.1; -; Genomic_DNA.
DR CCDS; CCDS4158.1; -. [P05112-1]
DR CCDS; CCDS4159.1; -. [P05112-2]
DR PIR; A30546; A25946.
DR RefSeq; NP_000580.1; NM_000589.3. [P05112-1]
DR RefSeq; NP_758858.1; NM_172348.2. [P05112-2]
DR PDB; 1BBN; NMR; -; A=25-153.
DR PDB; 1BCN; NMR; -; A=25-153.
DR PDB; 1CYL; NMR; -; A=25-153.
DR PDB; 1HIJ; X-ray; 3.00 A; A=25-153.
DR PDB; 1HIK; X-ray; 2.60 A; A=25-153.
DR PDB; 1HZI; X-ray; 2.05 A; A=25-153.
DR PDB; 1IAR; X-ray; 2.30 A; A=25-153.
DR PDB; 1ITI; NMR; -; A=25-153.
DR PDB; 1ITL; NMR; -; A=25-153.
DR PDB; 1ITM; NMR; -; A=25-153.
DR PDB; 1RCB; X-ray; 2.25 A; A=25-153.
DR PDB; 2B8U; X-ray; 1.80 A; A=25-153.
DR PDB; 2B8X; X-ray; 1.70 A; A=25-153.
DR PDB; 2B8Y; X-ray; 1.80 A; A=25-153.
DR PDB; 2B8Z; X-ray; 2.50 A; A=25-153.
DR PDB; 2B90; X-ray; 2.10 A; A=25-153.
DR PDB; 2B91; X-ray; 2.00 A; A=25-153.
DR PDB; 2CYK; NMR; -; A=25-153.
DR PDB; 2D48; X-ray; 1.65 A; A=25-153.
DR PDB; 2INT; X-ray; 2.35 A; A=25-153.
DR PDB; 3BPL; X-ray; 2.93 A; A=25-153.
DR PDB; 3BPN; X-ray; 3.02 A; A=25-153.
DR PDB; 3QB7; X-ray; 3.24 A; A/B=25-153.
DR PDB; 4YDY; X-ray; 2.00 A; I/J=25-153.
DR PDB; 5FHX; X-ray; 2.55 A; A=30-153.
DR PDB; 6OEL; X-ray; 3.10 A; A=25-153.
DR PDBsum; 1BBN; -.
DR PDBsum; 1BCN; -.
DR PDBsum; 1CYL; -.
DR PDBsum; 1HIJ; -.
DR PDBsum; 1HIK; -.
DR PDBsum; 1HZI; -.
DR PDBsum; 1IAR; -.
DR PDBsum; 1ITI; -.
DR PDBsum; 1ITL; -.
DR PDBsum; 1ITM; -.
DR PDBsum; 1RCB; -.
DR PDBsum; 2B8U; -.
DR PDBsum; 2B8X; -.
DR PDBsum; 2B8Y; -.
DR PDBsum; 2B8Z; -.
DR PDBsum; 2B90; -.
DR PDBsum; 2B91; -.
DR PDBsum; 2CYK; -.
DR PDBsum; 2D48; -.
DR PDBsum; 2INT; -.
DR PDBsum; 3BPL; -.
DR PDBsum; 3BPN; -.
DR PDBsum; 3QB7; -.
DR PDBsum; 4YDY; -.
DR PDBsum; 5FHX; -.
DR PDBsum; 6OEL; -.
DR AlphaFoldDB; P05112; -.
DR BMRB; P05112; -.
DR SMR; P05112; -.
DR BioGRID; 109779; 3.
DR CORUM; P05112; -.
DR DIP; DIP-3222N; -.
DR IntAct; P05112; 3.
DR MINT; P05112; -.
DR STRING; 9606.ENSP00000231449; -.
DR ChEMBL; CHEMBL3712894; -.
DR DrugBank; DB06560; Pascolizumab.
DR DrugCentral; P05112; -.
DR GlyGen; P05112; 1 site.
DR iPTMnet; P05112; -.
DR PhosphoSitePlus; P05112; -.
DR BioMuta; IL4; -.
DR DMDM; 124337; -.
DR MassIVE; P05112; -.
DR PaxDb; P05112; -.
DR PeptideAtlas; P05112; -.
DR PRIDE; P05112; -.
DR ProteomicsDB; 51797; -. [P05112-1]
DR ProteomicsDB; 51798; -. [P05112-2]
DR ABCD; P05112; 8 sequenced antibodies.
DR Antibodypedia; 14502; 1772 antibodies from 47 providers.
DR DNASU; 3565; -.
DR Ensembl; ENST00000231449.7; ENSP00000231449.2; ENSG00000113520.11. [P05112-1]
DR Ensembl; ENST00000350025.2; ENSP00000325190.3; ENSG00000113520.11. [P05112-2]
DR GeneID; 3565; -.
DR KEGG; hsa:3565; -.
DR MANE-Select; ENST00000231449.7; ENSP00000231449.2; NM_000589.4; NP_000580.1.
DR UCSC; uc003kxk.3; human. [P05112-1]
DR CTD; 3565; -.
DR DisGeNET; 3565; -.
DR GeneCards; IL4; -.
DR HGNC; HGNC:6014; IL4.
DR HPA; ENSG00000113520; Not detected.
DR MIM; 147780; gene.
DR MIM; 601367; phenotype.
DR neXtProt; NX_P05112; -.
DR OpenTargets; ENSG00000113520; -.
DR PharmGKB; PA197; -.
DR VEuPathDB; HostDB:ENSG00000113520; -.
DR eggNOG; KOG3886; Eukaryota.
DR GeneTree; ENSGT00390000013108; -.
DR HOGENOM; CLU_154691_0_0_1; -.
DR InParanoid; P05112; -.
DR OMA; SCMELTV; -.
DR PhylomeDB; P05112; -.
DR TreeFam; TF336383; -.
DR PathwayCommons; P05112; -.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-9012546; Interleukin-18 signaling.
DR SignaLink; P05112; -.
DR SIGNOR; P05112; -.
DR BioGRID-ORCS; 3565; 6 hits in 1067 CRISPR screens.
DR EvolutionaryTrace; P05112; -.
DR GeneWiki; Interleukin_4; -.
DR GenomeRNAi; 3565; -.
DR Pharos; P05112; Tbio.
DR PRO; PR:P05112; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P05112; protein.
DR Bgee; ENSG00000113520; Expressed in oocyte and 95 other tissues.
DR ExpressionAtlas; P05112; baseline and differential.
DR Genevisible; P05112; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; NAS:UniProtKB.
DR GO; GO:0005136; F:interleukin-4 receptor binding; TAS:UniProtKB.
DR GO; GO:0042976; P:activation of Janus kinase activity; IGI:ARUK-UCL.
DR GO; GO:0031296; P:B cell costimulation; IBA:GO_Central.
DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR GO; GO:0097028; P:dendritic cell differentiation; IDA:DFLAT.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0002227; P:innate immune response in mucosa; IBA:GO_Central.
DR GO; GO:0042116; P:macrophage activation; IGI:ARUK-UCL.
DR GO; GO:0001774; P:microglial cell activation; IBA:GO_Central.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IDA:UniProtKB.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1903845; P:negative regulation of cellular response to transforming growth factor beta stimulus; IDA:UniProtKB.
DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; IBA:GO_Central.
DR GO; GO:1903660; P:negative regulation of complement-dependent cytotoxicity; IMP:AgBase.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IMP:AgBase.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; IDA:CACAO.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IGI:ARUK-UCL.
DR GO; GO:0043031; P:negative regulation of macrophage activation; IBA:GO_Central.
DR GO; GO:0150079; P:negative regulation of neuroinflammatory response; IC:ARUK-UCL.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; ISS:UniProtKB.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IBA:GO_Central.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0150076; P:neuroinflammatory response; ISS:ARUK-UCL.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; ISS:ARUK-UCL.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IGI:ARUK-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:ARUK-UCL.
DR GO; GO:1901857; P:positive regulation of cellular respiration; ISS:ARUK-UCL.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IBA:GO_Central.
DR GO; GO:2000424; P:positive regulation of eosinophil chemotaxis; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IGI:ARUK-UCL.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IDA:UniProtKB.
DR GO; GO:0048295; P:positive regulation of isotype switching to IgE isotypes; ISS:UniProtKB.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IBA:GO_Central.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISS:UniProtKB.
DR GO; GO:0071677; P:positive regulation of mononuclear cell migration; IBA:GO_Central.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IBA:GO_Central.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISS:ARUK-UCL.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IDA:UniProtKB.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IGI:ARUK-UCL.
DR GO; GO:0050776; P:regulation of immune response; ISS:UniProtKB.
DR GO; GO:0045191; P:regulation of isotype switching; TAS:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0042110; P:T cell activation; IGI:BHF-UCL.
DR GO; GO:0045064; P:T-helper 2 cell differentiation; IBA:GO_Central.
DR GO; GO:0042092; P:type 2 immune response; TAS:UniProtKB.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR002354; IL-4.
DR InterPro; IPR001325; IL-4/IL-13.
DR InterPro; IPR018096; IL-4/IL-13_CS.
DR PANTHER; PTHR47401; PTHR47401; 1.
DR Pfam; PF00727; IL4; 1.
DR PIRSF; PIRSF001941; Interleukin_4; 1.
DR PRINTS; PR00431; INTERLEUKIN4.
DR SMART; SM00190; IL4_13; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00838; INTERLEUKIN_4_13; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; B-cell activation; Cytokine;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT CHAIN 25..153
FT /note="Interleukin-4"
FT /id="PRO_0000015532"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1993171"
FT DISULFID 27..151
FT /evidence="ECO:0000269|PubMed:10219247,
FT ECO:0000269|PubMed:11526337, ECO:0000269|PubMed:18243101,
FT ECO:0000269|PubMed:1993171"
FT DISULFID 48..89
FT /evidence="ECO:0000269|PubMed:10219247,
FT ECO:0000269|PubMed:11526337, ECO:0000269|PubMed:18243101,
FT ECO:0000269|PubMed:1993171"
FT DISULFID 70..123
FT /evidence="ECO:0000269|PubMed:10219247,
FT ECO:0000269|PubMed:11526337, ECO:0000269|PubMed:18243101"
FT VAR_SEQ 46..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7806280"
FT /id="VSP_002672"
FT VARIANT 27
FT /note="C -> R (in dbSNP:rs4986964)"
FT /id="VAR_020392"
FT MUTAGEN 33
FT /note="E->A: About 500-fold lower interaction with IL4R
FT than WT."
FT /evidence="ECO:0000269|PubMed:11526337"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:1BBN"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:2D48"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:5FHX"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:2D48"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:2D48"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:2D48"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:1CYL"
FT HELIX 65..83
FT /evidence="ECO:0007829|PDB:2D48"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:2D48"
FT HELIX 94..118
FT /evidence="ECO:0007829|PDB:2D48"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:2D48"
FT HELIX 133..151
FT /evidence="ECO:0007829|PDB:2D48"
SQ SEQUENCE 153 AA; 17492 MW; 8725BF64B34D45F7 CRC64;
MGLTSQLLPP LFFLLACAGN FVHGHKCDIT LQEIIKTLNS LTEQKTLCTE LTVTDIFAAS
KNTTEKETFC RAATVLRQFY SHHEKDTRCL GATAQQFHRH KQLIRFLKRL DRNLWGLAGL
NSCPVKEANQ STLENFLERL KTIMREKYSK CSS
