IL4_MOUSE
ID IL4_MOUSE Reviewed; 140 AA.
AC P07750;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Interleukin-4;
DE Short=IL-4;
DE AltName: Full=B-cell IgG differentiation factor;
DE AltName: Full=B-cell growth factor 1;
DE AltName: Full=B-cell stimulatory factor 1;
DE Short=BSF-1;
DE AltName: Full=IGG1 induction factor;
DE AltName: Full=Lymphocyte stimulatory factor 1;
DE Flags: Precursor;
GN Name=Il4; Synonyms=Il-4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3005865; DOI=10.1038/319640a0;
RA Noma Y., Sideras P., Naito T., Bergstedt-Lindqvist S., Azuma C.,
RA Severinson E., Tanabe T., Kinashi T., Matsuda F., Yaoita Y., Honjo T.;
RT "Cloning of cDNA encoding the murine IgG1 induction factor by a novel
RT strategy using SP6 promoter.";
RL Nature 319:640-646(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BALB/cJ;
RX PubMed=3029676; DOI=10.1093/nar/15.1.333;
RA Otsuka T., Villaret D., Yokota T., Takebe Y., Lee F., Arai N., Arai K.;
RT "Structural analysis of the mouse chromosomal gene encoding interleukin 4
RT which expresses B cell, T cell and mast cell stimulating activities.";
RL Nucleic Acids Res. 15:333-344(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=3083412; DOI=10.1073/pnas.83.7.2061;
RA Lee F., Yokota T., Otsuka T., Meyerson P., Villaret D., Coffman R.,
RA Mosmann T., Rennick D., Roehm N., Smith C., Zlotnik A., Arai K.;
RT "Isolation and characterization of a mouse interleukin cDNA clone that
RT expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-
RT stimulating activities.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:2061-2065(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=3498301; DOI=10.1007/978-1-4684-5323-2_22;
RA Sideras P., Bergstedt-Lindqvist S., Severinson E., Noma Y., Naito T.,
RA Azuma C., Tanabe T., Kinashi T., Matsude F., Yaoita Y., Honjo T.;
RT "IgG1 induction factor: a single molecular entity with multiple biological
RT functions.";
RL Adv. Exp. Med. Biol. 213:227-236(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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 PARTIAL PROTEIN SEQUENCE, 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 [7]
RP FUNCTION.
RX PubMed=8624821; DOI=10.1016/s1074-7613(00)80439-2;
RA Kaplan M.H., Schindler U., Smiley S.T., Grusby M.J.;
RT "Stat6 is required for mediating responses to IL-4 and for development of
RT Th2 cells.";
RL Immunity 4:313-319(1996).
RN [8]
RP FUNCTION.
RX PubMed=25847241; DOI=10.1074/jbc.m114.622126;
RA Edukulla R., Singh B., Jegga A.G., Sontake V., Dillon S.R., Madala S.K.;
RT "Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-
RT 31RA Expression.";
RL J. Biol. Chem. 290:13510-13520(2015).
RN [9]
RP FUNCTION.
RX PubMed=26416964; DOI=10.1083/jcb.201501059;
RA Terawaki S., Camosseto V., Prete F., Wenger T., Papadopoulos A.,
RA Rondeau C., Combes A., Rodriguez Rodrigues C., Vu Manh T.P., Fallet M.,
RA English L., Santamaria R., Soares A.R., Weil T., Hammad H., Desjardins M.,
RA Gorvel J.P., Santos M.A., Gatti E., Pierre P.;
RT "RUN and FYVE domain-containing protein 4 enhances autophagy and lysosome
RT tethering in response to Interleukin-4.";
RL J. Cell Biol. 210:1133-1152(2015).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25772794; DOI=10.1007/s10519-015-9714-x;
RA Moon M.L., Joesting J.J., Blevins N.A., Lawson M.A., Gainey S.J.,
RA Towers A.E., McNeil L.K., Freund G.G.;
RT "IL-4 Knock Out Mice Display Anxiety-Like Behavior.";
RL Behav. Genet. 45:451-460(2015).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28202615; DOI=10.4049/jimmunol.1601546;
RA Brombacher T.M., Nono J.K., De Gouveia K.S., Makena N., Darby M.,
RA Womersley J., Tamgue O., Brombacher F.;
RT "IL-13-Mediated Regulation of Learning and Memory.";
RL J. Immunol. 198:2681-2688(2017).
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:3083412). Induces the expression of
CC class II MHC molecules on resting B-cells (PubMed:3498301). Enhances
CC both secretion and cell surface expression of IgE and IgG1
CC (PubMed:3498301). Regulates also the expression of the low affinity Fc
CC receptor for IgE (CD23) on both lymphocytes and monocytes (By
CC similarity). Positively regulates IL31RA expression in macrophages.
CC Stimulates autophagy in dendritic cells by interfering with mTORC1
CC signaling and through the induction of RUFY4 (PubMed:26416964). In
CC addition, plays a critical role in higher functions of the normal
CC brain, such as memory and learning (PubMed:25772794, PubMed:28202615).
CC Upon binding to IL4, IL4R receptor dimerizes either with the common
CC IL2R gamma chain/IL2RG to produce the type 1 signaling complex, located
CC mainly on hematopoietic cells, or with the IL13RA1 to produce the type
CC 2 complex, which is expressed also on nonhematopoietic cells.
CC Engagement of both types of receptors initiates JAK3 and to a lower
CC extend JAK1 phosphorylation leading to activation of the signal
CC transducer and activator of transcription 6/STAT6 (PubMed:8624821,
CC PubMed:25847241). {ECO:0000250|UniProtKB:P05112,
CC ECO:0000269|PubMed:25772794, ECO:0000269|PubMed:25847241,
CC ECO:0000269|PubMed:28202615, ECO:0000269|PubMed:3083412,
CC ECO:0000269|PubMed:3498301, ECO:0000269|PubMed:8624821}.
CC -!- SUBUNIT: Interacts with IL4R. Interacts with IL13RA1.
CC {ECO:0000250|UniProtKB:P05112, ECO:0000269|PubMed:25772794,
CC ECO:0000269|PubMed:25847241, ECO:0000269|PubMed:28202615,
CC ECO:0000269|PubMed:3083412, ECO:0000269|PubMed:3498301,
CC ECO:0000269|PubMed:8624821}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant mice demonstrate anxiety-like
CC behavior in comparison to WT mice (PubMed:25772794). In addition, they
CC show impaired cognitive function (PubMed:28202615).
CC {ECO:0000269|PubMed:25772794, ECO:0000269|PubMed:28202615}.
CC -!- SIMILARITY: Belongs to the IL-4/IL-13 family. {ECO:0000305}.
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DR EMBL; X03532; CAA27233.1; -; mRNA.
DR EMBL; X05064; CAA28731.1; -; Genomic_DNA.
DR EMBL; X05252; CAA28873.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X05253; CAA28874.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M13238; AAA39307.1; -; mRNA.
DR EMBL; M25892; AAA39298.1; -; mRNA.
DR EMBL; BC027514; AAH27514.1; -; mRNA.
DR CCDS; CCDS24682.1; -.
DR PIR; A25870; IIMSG1.
DR RefSeq; NP_067258.1; NM_021283.2.
DR AlphaFoldDB; P07750; -.
DR SMR; P07750; -.
DR IntAct; P07750; 1.
DR STRING; 10090.ENSMUSP00000000889; -.
DR GlyGen; P07750; 3 sites.
DR PhosphoSitePlus; P07750; -.
DR PaxDb; P07750; -.
DR PRIDE; P07750; -.
DR ABCD; P07750; 1 sequenced antibody.
DR Antibodypedia; 14502; 1772 antibodies from 47 providers.
DR DNASU; 16189; -.
DR Ensembl; ENSMUST00000000889; ENSMUSP00000000889; ENSMUSG00000000869.
DR GeneID; 16189; -.
DR KEGG; mmu:16189; -.
DR UCSC; uc007iwq.2; mouse.
DR CTD; 3565; -.
DR MGI; MGI:96556; Il4.
DR VEuPathDB; HostDB:ENSMUSG00000000869; -.
DR eggNOG; KOG3886; Eukaryota.
DR GeneTree; ENSGT00390000013108; -.
DR HOGENOM; CLU_154691_0_0_1; -.
DR InParanoid; P07750; -.
DR OMA; SCMELTV; -.
DR OrthoDB; 1495672at2759; -.
DR PhylomeDB; P07750; -.
DR TreeFam; TF336383; -.
DR Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR BioGRID-ORCS; 16189; 0 hits in 108 CRISPR screens.
DR ChiTaRS; Il4; mouse.
DR PRO; PR:P07750; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P07750; protein.
DR Bgee; ENSMUSG00000000869; Expressed in embryonic brain and 65 other tissues.
DR ExpressionAtlas; P07750; baseline and differential.
DR Genevisible; P07750; MM.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005136; F:interleukin-4 receptor binding; IEA:InterPro.
DR GO; GO:0050798; P:activated T cell proliferation; IDA:MGI.
DR GO; GO:0042976; P:activation of Janus kinase activity; ISO:MGI.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0042113; P:B cell activation; IDA:MGI.
DR GO; GO:0031296; P:B cell costimulation; IDA:MGI.
DR GO; GO:0042100; P:B cell proliferation; IDA:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0042832; P:defense response to protozoan; IMP:MGI.
DR GO; GO:0097028; P:dendritic cell differentiation; ISO:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IDA:MGI.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA:BHF-UCL.
DR GO; GO:0048289; P:isotype switching to IgE isotypes; IDA:MGI.
DR GO; GO:0048291; P:isotype switching to IgG isotypes; IDA:MGI.
DR GO; GO:0042116; P:macrophage activation; ISO:MGI.
DR GO; GO:0045342; P:MHC class II biosynthetic process; IDA:MGI.
DR GO; GO:0001774; P:microglial cell activation; ISO:MGI.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISO:MGI.
DR GO; GO:0002674; P:negative regulation of acute inflammatory response; ISO:MGI.
DR GO; GO:1903845; P:negative regulation of cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; ISO:MGI.
DR GO; GO:1903660; P:negative regulation of complement-dependent cytotoxicity; ISO:MGI.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:0010633; P:negative regulation of epithelial cell migration; ISO:MGI.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:MGI.
DR GO; GO:0043031; P:negative regulation of macrophage activation; ISO:MGI.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IDA:MGI.
DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:MGI.
DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:ARUK-UCL.
DR GO; GO:0070351; P:negative regulation of white fat cell proliferation; IDA:CACAO.
DR GO; GO:0150076; P:neuroinflammatory response; ISO:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:MGI.
DR GO; GO:1900223; P:positive regulation of amyloid-beta clearance; IDA:ARUK-UCL.
DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0050871; P:positive regulation of B cell activation; IDA:MGI.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:1901857; P:positive regulation of cellular respiration; IDA:ARUK-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:2000424; P:positive regulation of eosinophil chemotaxis; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; ISO:MGI.
DR GO; GO:0048295; P:positive regulation of isotype switching to IgE isotypes; IDA:MGI.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IDA:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:MGI.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:MGI.
DR GO; GO:0071677; P:positive regulation of mononuclear cell migration; ISO:MGI.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:MGI.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; IDA:ARUK-UCL.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:MGI.
DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
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; IDA:MGI.
DR GO; GO:0050776; P:regulation of immune response; IDA:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:MGI.
DR GO; GO:0010155; P:regulation of proton transport; ISO:MGI.
DR GO; GO:0042110; P:T cell activation; ISO:MGI.
DR GO; GO:0042098; P:T cell proliferation; IDA:MGI.
DR GO; GO:0002296; P:T-helper 1 cell lineage commitment; IGI:MGI.
DR GO; GO:0045064; P:T-helper 2 cell differentiation; IDA:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:MGI.
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 Autophagy; B-cell activation; Cytokine; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..20
FT CHAIN 21..140
FT /note="Interleukin-4"
FT /id="PRO_0000015538"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..107
FT /evidence="ECO:0000269|PubMed:1993171"
FT DISULFID 47..87
FT /evidence="ECO:0000269|PubMed:1993171"
FT DISULFID 69..114
FT /evidence="ECO:0000269|PubMed:1993171"
SQ SEQUENCE 140 AA; 15834 MW; E43CE16195DE051F CRC64;
MGLNPQLVVI LLFFLECTRS HIHGCDKNHL REIIGILNEV TGEGTPCTEM DVPNVLTATK
NTTESELVCR ASKVLRIFYL KHGKTPCLKK NSSVLMELQR LFRAFRCLDS SISCTMNESK
STSLKDFLES LKSIMQMDYS
