IL2_MOUSE
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 03-AUG-2022, entry version 187.
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}.
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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 GlyGen; P04351; 1 site.
DR PhosphoSitePlus; P04351; -.
DR PaxDb; P04351; -.
DR PRIDE; P04351; -.
DR ABCD; P04351; 2 sequenced antibodies.
DR Antibodypedia; 4147; 2022 antibodies from 47 providers.
DR DNASU; 16183; -.
DR Ensembl; ENSMUST00000029275; ENSMUSP00000029275; ENSMUSG00000027720.
DR GeneID; 16183; -.
DR KEGG; mmu:16183; -.
DR UCSC; uc008pai.3; mouse.
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; 1491449at2759; -.
DR PhylomeDB; P04351; -.
DR TreeFam; TF338200; -.
DR BioGRID-ORCS; 16183; 2 hits in 113 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 tissues.
DR Genevisible; P04351; MM.
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: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:0045822; P:negative regulation of heart contraction; 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:0032729; P:positive regulation of interferon-gamma production; IDA: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: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 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; IPR000779; IL-2.
DR InterPro; IPR030477; IL-2_CS.
DR Pfam; PF00715; IL2; 1.
DR PRINTS; PR00265; INTERLEUKIN2.
DR SMART; SM00189; IL2; 1.
DR SUPFAM; SSF47266; SSF47266; 1.
DR PROSITE; PS00424; INTERLEUKIN_2; 1.
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
