ID IL2_MOUSE Reviewed; 169 AA. AC P04351; P97945; Q791T3; DT 20-MAR-1987, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-1987, sequence version 1. DT 27-MAR-2024, entry version 196. DE RecName: Full=Interleukin-2; DE Short=IL-2; DE AltName: Full=T-cell growth factor; DE Short=TCGF; DE Flags: Precursor; GN Name=Il2; Synonyms=Il-2; 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 [GENOMIC DNA]. RC STRAIN=BALB/cJ; RX PubMed=6240025; DOI=10.1093/nar/12.24.9323; RA Fuse A., Fujita T., Yasumitsu H., Kashima N., Hasegawa K., Taniguchi T.; RT "Organization and structure of the mouse interleukin-2 gene."; RL Nucleic Acids Res. 12:9323-9331(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=B10BR; RX PubMed=2578624; DOI=10.1038/313402a0; RA Kashima N., Nishi-Takaoka C., Fujita T., Taki S., Yamada G., Hamuro J., RA Taniguchi T.; RT "Unique structure of murine interleukin-2 as deduced from cloned cDNAs."; RL Nature 313:402-404(1985). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; RX PubMed=3918306; DOI=10.1073/pnas.82.1.68; RA Yokota T., Arai N., Lee F., Rennick D., Mosmann T., Arai K.; RT "Use of a cDNA expression vector for isolation of mouse interleukin 2 cDNA RT clones: expression of T-cell growth-factor activity after transfection of RT monkey cells."; RL Proc. Natl. Acad. Sci. U.S.A. 82:68-72(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3003564; DOI=10.1007/bf00417597; RA Degrave W., Simons G., Devos R., Plaetinck G., Remaut E., Tavernier J., RA Fiers W.; RT "Cloning and structure of a mouse interleukin-2 chromosomal gene."; RL Mol. Biol. Rep. 11:57-61(1986). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=10779485; DOI=10.1101/gr.10.4.446; RA Lyons P.A., Armitage N., Argentina F., Denny P., Hill N.J., Lord C.J., RA Wilusz M.B., Peterson L.B., Wicker L.S., Todd J.A.; RT "Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of RT mouse chromosome 3: identification of a candidate segment of ancestral DNA RT by haplotype mapping."; RL Genome Res. 10:446-453(2000). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; TISSUE=Spleen; RA Ma R.Z., Teuscher C.; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-63. RC STRAIN=RF; TISSUE=Spleen; RX PubMed=1420317; DOI=10.1016/0167-4781(92)90174-x; RA Matesanz F., Alcina A., Pellicer A.; RT "A new cDNA sequence for the murine interleukin-2 gene."; RL Biochim. Biophys. Acta 1132:335-336(1992). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-63. RC STRAIN=CAST/EiJ, and RF/J; TISSUE=Spleen; RX PubMed=8319981; DOI=10.1007/bf00188809; RA Matesanz F., Alcina A., Pellicer A.; RT "Existence of at least five interleukin-2 molecules in different mouse RT strains."; RL Immunogenetics 38:300-303(1993). RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=9814585; DOI=10.1155/1998/19567; RA Reya T., Bassiri H., Biancaniello R., Carding S.R.; RT "Thymic stromal-cell abnormalities and dysregulated T-cell development in RT IL-2-deficient mice."; RL Dev. Immunol. 5:287-302(1998). RN [11] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY DENDRITIC CELLS. RX PubMed=11526406; DOI=10.1038/ni0901-882; RA Granucci F., Vizzardelli C., Pavelka N., Feau S., Persico M., Virzi E., RA Rescigno M., Moro G., Ricciardi-Castagnoli P.; RT "Inducible IL-2 production by dendritic cells revealed by global gene RT expression analysis."; RL Nat. Immunol. 2:882-888(2001). RN [12] RP FUNCTION. RX PubMed=14614860; DOI=10.1016/s1074-7613(03)00292-9; RA Zhu J., Cote-Sierra J., Guo L., Paul W.E.; RT "Stat5 activation plays a critical role in Th2 differentiation."; RL Immunity 19:739-748(2003). RN [13] RP FUNCTION. RX PubMed=27018889; DOI=10.1038/nchembio.2056; RA Smith G.A., Uchida K., Weiss A., Taunton J.; RT "Essential biphasic role for JAK3 catalytic activity in IL-2 receptor RT signaling."; RL Nat. Chem. Biol. 12:373-379(2016). RN [14] RP 3D-STRUCTURE MODELING. RX PubMed=8262055; DOI=10.1002/j.1460-2075.1993.tb06206.x; RA Zurawski S., Vega F. Jr., Doyel E.L., Huyghe B., Flaherty K., McKay D.B., RA Zurawski G.; RT "Definition and spatial location of mouse interleukin-2 residues that RT interact with its heterotrimeric receptor."; RL EMBO J. 12:5113-5119(1993). RN [15] {ECO:0007744|PDB:4YQX, ECO:0007744|PDB:4YUE} RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 47-169, AND DISULFIDE BOND. RX PubMed=25992858; DOI=10.1016/j.immuni.2015.04.015; RA Spangler J.B., Tomala J., Luca V.C., Jude K.M., Dong S., Ring A.M., RA Votavova P., Pepper M., Kovar M., Garcia K.C.; RT "Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation RT through Distinct Conformational Mechanisms."; RL Immunity 42:815-825(2015). CC -!- FUNCTION: Cytokine produced by activated CD4-positive helper T-cells CC and to a lesser extend activated CD8-positive T-cells and natural CC killer (NK) cells that plays pivotal roles in the immune response and CC tolerance (PubMed:9814585, PubMed:14614860). Binds to a receptor CC complex composed of either the high-affinity trimeric IL-2R CC (IL2RA/CD25, IL2RB/CD122 and IL2RG/CD132) or the low-affinity dimeric CC IL-2R (IL2RB and IL2RG). Interaction with the receptor leads to CC oligomerization and conformation changes in the IL-2R subunits CC resulting in downstream signaling starting with phosphorylation of JAK1 CC and JAK3. In turn, JAK1 and JAK3 phosphorylate the receptor to form a CC docking site leading to the phosphorylation of several substrates CC including STAT5 (PubMed:14614860, PubMed:27018889). This process leads CC to activation of several pathways including STAT, phosphoinositide-3- CC kinase/PI3K and mitogen-activated protein kinase/MAPK pathways. CC Functions as a T-cell growth factor and can increase NK-cell cytolytic CC activity as well. Promotes strong proliferation of activated B-cells CC and subsequently immunoglobulin production. Plays a pivotal role in CC regulating the adaptive immune system by controlling the survival and CC proliferation of regulatory T-cells, which are required for the CC maintenance of immune tolerance (PubMed:14614860). Moreover, CC participates in the differentiation and homeostasis of effector T-cell CC subsets, including Th1, Th2, Th17 as well as memory CD8-positive T- CC cells (PubMed:9814585). {ECO:0000250|UniProtKB:P60568, CC ECO:0000269|PubMed:9814585}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Produced by immune cells including dendritic cells. CC In contrast, macrophages do not produce IL2 upon bacterial stimulation. CC {ECO:0000269|PubMed:11526406}. CC -!- INDUCTION: By bacterial infection. {ECO:0000269|PubMed:11526406}. CC -!- POLYMORPHISM: The poly-Gln region is highly polymorphic. {ECO:0000305}. CC -!- DISRUPTION PHENOTYPE: Mutant mice exhibit lethal autoimmunity and are CC impaired in regulatory T-cell production. After 4 to 5 weeks of birth, CC they develop a thymic disorder resulting in the disruption of thymocyte CC maturation. {ECO:0000269|PubMed:9814585}. CC -!- SIMILARITY: Belongs to the IL-2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X01663; CAA25823.1; -; Genomic_DNA. DR EMBL; X01664; CAA25824.1; -; Genomic_DNA. DR EMBL; X01665; CAA25825.1; -; Genomic_DNA. DR EMBL; X01772; CAA25909.1; -; mRNA. DR EMBL; K02292; AAA39289.1; -; mRNA. DR EMBL; M16762; AAA39281.1; -; Genomic_DNA. DR EMBL; M16760; AAA39281.1; JOINED; Genomic_DNA. DR EMBL; M16761; AAA39281.1; JOINED; Genomic_DNA. DR EMBL; AF195956; AAF32272.1; -; Genomic_DNA. DR EMBL; AF065914; AAD25890.1; -; mRNA. DR EMBL; AL662823; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X66058; CAA46854.1; -; mRNA. DR EMBL; L07574; AAA39326.1; -; Genomic_DNA. DR EMBL; L07576; AAA39328.1; -; Genomic_DNA. DR CCDS; CCDS17316.1; -. DR PIR; A93550; ICMS2. DR PIR; I54512; I54512. DR PIR; I68871; I68871. DR RefSeq; NP_032392.1; NM_008366.3. DR PDB; 4YQX; X-ray; 2.83 A; A/M=47-169. DR PDB; 4YUE; X-ray; 2.19 A; C=47-169. DR PDBsum; 4YQX; -. DR PDBsum; 4YUE; -. DR AlphaFoldDB; P04351; -. DR SMR; P04351; -. DR IntAct; P04351; 1. DR STRING; 10090.ENSMUSP00000029275; -. DR BindingDB; P04351; -. DR ChEMBL; CHEMBL2466; -. DR GlyCosmos; P04351; 1 site, No reported glycans. DR GlyGen; P04351; 1 site. DR PhosphoSitePlus; P04351; -. DR PaxDb; 10090-ENSMUSP00000029275; -. DR ABCD; P04351; 2 sequenced antibodies. DR Antibodypedia; 4147; 2307 antibodies from 49 providers. DR DNASU; 16183; -. DR Ensembl; ENSMUST00000029275.6; ENSMUSP00000029275.6; ENSMUSG00000027720.8. DR GeneID; 16183; -. DR KEGG; mmu:16183; -. DR UCSC; uc008pai.3; mouse. DR AGR; MGI:96548; -. DR CTD; 3558; -. DR MGI; MGI:96548; Il2. DR VEuPathDB; HostDB:ENSMUSG00000027720; -. DR eggNOG; ENOG502RVR5; Eukaryota. DR GeneTree; ENSGT00390000003555; -. DR HOGENOM; CLU_124210_0_0_1; -. DR InParanoid; P04351; -. DR OMA; NGVNNYE; -. DR OrthoDB; 5263670at2759; -. DR PhylomeDB; P04351; -. DR TreeFam; TF338200; -. DR BioGRID-ORCS; 16183; 2 hits in 118 CRISPR screens. DR ChiTaRS; Il2; mouse. DR PRO; PR:P04351; -. DR Proteomes; UP000000589; Chromosome 3. DR RNAct; P04351; Protein. DR Bgee; ENSMUSG00000027720; Expressed in chordate pharynx and 15 other cell types or tissues. DR GO; GO:0005615; C:extracellular space; IDA:MGI. DR GO; GO:0030246; F:carbohydrate binding; ISO:MGI. DR GO; GO:0005125; F:cytokine activity; IDA:MGI. DR GO; GO:0043208; F:glycosphingolipid binding; ISO:MGI. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005134; F:interleukin-2 receptor binding; IDA:MGI. DR GO; GO:0031851; F:kappa-type opioid receptor binding; ISO:MGI. DR GO; GO:0050798; P:activated T cell proliferation; IDA:MGI. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IDA:MGI. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI. DR GO; GO:0010467; P:gene expression; IDA:MGI. DR GO; GO:0038110; P:interleukin-2-mediated signaling pathway; ISO:MGI. DR GO; GO:0002366; P:leukocyte activation involved in immune response; ISO:MGI. DR GO; GO:0046651; P:lymphocyte proliferation; IMP:MGI. DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; ISO:MGI. DR GO; GO:0050728; P:negative regulation of inflammatory response; IMP:MGI. DR GO; GO:0050672; P:negative regulation of lymphocyte proliferation; IMP:MGI. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI. DR GO; GO:2000320; P:negative regulation of T-helper 17 cell differentiation; IGI:BHF-UCL. DR GO; GO:0042104; P:positive regulation of activated T cell proliferation; IDA:MGI. DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:MGI. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:MGI. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISO:MGI. DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IMP:MGI. DR GO; GO:1900100; P:positive regulation of plasma cell differentiation; ISO:MGI. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI. DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISO:MGI. 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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:MGI. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:MGI. DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISO:MGI. DR GO; GO:2000561; P:regulation of CD4-positive, alpha-beta T cell proliferation; IMP:MGI. DR GO; GO:0046013; P:regulation of T cell homeostatic proliferation; IMP:MGI. DR GO; GO:0045471; P:response to ethanol; ISO:MGI. DR GO; GO:0042098; P:T cell proliferation; IDA:MGI. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR000779; IL-2. DR InterPro; IPR030477; IL-2_CS. DR PANTHER; PTHR48399; INTERLEUKIN-2; 1. DR PANTHER; PTHR48399:SF1; INTERLEUKIN-2; 1. DR Pfam; PF00715; IL2; 1. DR PRINTS; PR00265; INTERLEUKIN2. DR SMART; SM00189; IL2; 1. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR PROSITE; PS00424; INTERLEUKIN_2; 1. DR Genevisible; P04351; MM. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cytokine; Disulfide bond; Glycoprotein; KW Growth factor; Immunity; Reference proteome; Secreted; Signal. FT SIGNAL 1..20 FT CHAIN 21..169 FT /note="Interleukin-2" FT /id="PRO_0000015493" FT CARBOHYD 23 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000250" FT DISULFID 92..140 FT /evidence="ECO:0000269|PubMed:25992858, FT ECO:0007744|PDB:4YQX, ECO:0007744|PDB:4YUE" FT VARIANT 26 FT /note="S -> P (in strain: RF/J and CAST/Ei)" FT VARIANT 30 FT /note="S -> P (in strain: RF/J)" FT VARIANT 32..39 FT /note="AEAQQQQQ -> SSSTAEA (in strain: CAST/Ei)" FT VARIANT 32..38 FT /note="AEAQQQQ -> SSSTAEA (in strain: RF/J)" FT CONFLICT 108 FT /note="Q -> E (in Ref. 4; AAA39281)" FT /evidence="ECO:0000305" FT HELIX 47..60 FT /evidence="ECO:0007829|PDB:4YUE" FT HELIX 70..73 FT /evidence="ECO:0007829|PDB:4YQX" FT STRAND 75..79 FT /evidence="ECO:0007829|PDB:4YQX" FT HELIX 87..90 FT /evidence="ECO:0007829|PDB:4YUE" FT HELIX 91..94 FT /evidence="ECO:0007829|PDB:4YUE" FT HELIX 97..103 FT /evidence="ECO:0007829|PDB:4YUE" FT HELIX 118..132 FT /evidence="ECO:0007829|PDB:4YUE" FT STRAND 134..136 FT /evidence="ECO:0007829|PDB:4YQX" FT STRAND 144..148 FT /evidence="ECO:0007829|PDB:4YQX" FT HELIX 149..164 FT /evidence="ECO:0007829|PDB:4YUE" SQ SEQUENCE 169 AA; 19400 MW; B3B17644F6EF83CA CRC64; MYSMQLASCV TLTLVLLVNS APTSSSTSSS TAEAQQQQQQ QQQQQQHLEQ LLMDLQELLS RMENYRNLKL PRMLTFKFYL PKQATELKDL QCLEDELGPL RHVLDLTQSK SFQLEDAENF ISNIRVTVVK LKGSDNTFEC QFDDESATVV DFLRRWIAFC QSIISTSPQ //