ID IL3_MOUSE Reviewed; 166 AA. AC P01586; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 177. DE RecName: Full=Interleukin-3; DE Short=IL-3; DE AltName: Full=Hematopoietic growth factor; DE AltName: Full=Mast cell growth factor; DE Short=MCGF; DE AltName: Full=Multipotential colony-stimulating factor; DE AltName: Full=P-cell-stimulating factor; DE Flags: Precursor; GN Name=Il3; Synonyms=Csfmu, Il-3; 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=6420702; DOI=10.1038/307233a0; RA Fung M.-C., Hapel A.J., Ymer S., Cohen D.R., Johnson R.M., Campbell H.D., RA Young I.G.; RT "Molecular cloning of cDNA for murine interleukin-3."; RL Nature 307:233-237(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6322187; DOI=10.1073/pnas.81.4.1070; RA Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., RA Cantor H., Arai K.; RT "Isolation and characterization of a mouse cDNA clone that expresses mast- RT cell growth-factor activity in monkey cells."; RL Proc. Natl. Acad. Sci. U.S.A. 81:1070-1074(1984). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3918308; DOI=10.1073/pnas.82.2.316; RA Miyatake S., Yokota T., Lee F., Arai K.; RT "Structure of the chromosomal gene for murine interleukin 3."; RL Proc. Natl. Acad. Sci. U.S.A. 82:316-320(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3926497; DOI=10.1111/j.1432-1033.1985.tb09020.x; RA Campbell H.D., Ymer S., Fung M.-C., Young I.G.; RT "Cloning and nucleotide sequence of the murine interleukin-3 gene."; RL Eur. J. Biochem. 150:297-304(1985). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=DDD; RX PubMed=3935516; DOI=10.1016/0378-1119(85)90114-3; RA Todokoro K., Yamamoto A., Amanuma H., Ikawa Y.; RT "Isolation and characterization of a genomic DDD mouse interleukin-3 RT gene."; RL Gene 39:103-107(1985). RN [6] RP GLYCOSYLATION AT ASN-42 AND ASN-112, AND DISULFIDE BONDS. RX PubMed=1445902; DOI=10.1021/bi00161a053; RA Knepper T.P., Arbogast B., Schreurs J., Deinzer M.L.; RT "Determination of the glycosylation patterns, disulfide linkages, and RT protein heterogeneities of baculovirus-expressed mouse interleukin-3 by RT mass spectrometry."; RL Biochemistry 31:11651-11659(1992). RN [7] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=9446636; RA Mach N., Lantz C.S., Galli S.J., Reznikoff G., Mihm M., Small C., RA Granstein R., Beissert S., Sadelain M., Mulligan R.C., Dranoff G.; RT "Involvement of interleukin-3 in delayed-type hypersensitivity."; RL Blood 91:778-783(1998). RN [8] RP FUNCTION IN JAK2 ACTIVATION. RX PubMed=8378315; DOI=10.1073/pnas.90.18.8429; RA Silvennoinen O., Witthuhn B.A., Quelle F.W., Cleveland J.L., Yi T., RA Ihle J.N.; RT "Structure of the murine Jak2 protein-tyrosine kinase and its role in RT interleukin 3 signal transduction."; RL Proc. Natl. Acad. Sci. U.S.A. 90:8429-8433(1993). RN [9] RP FUNCTION IN STAT5 ACTIVATION. RX PubMed=10376805; DOI=10.1016/s0898-6568(98)00049-7; RA Jaster R., Tschirch E., Bittorf T., Brock J.; RT "Role of STAT5 in interferon-alpha signal transduction in Ba/F3 cells."; RL Cell. Signal. 11:331-335(1999). RN [10] RP FUNCTION. RX PubMed=31990690; DOI=10.1172/jci.insight.133652; RA Tong Y., Lear T.B., Evankovich J., Chen Y., Londino J.D., Myerburg M.M., RA Zhang Y., Popescu I.D., McDyer J.F., McVerry B.J., Lockwood K.C., RA Jurczak M.J., Liu Y., Chen B.B.; RT "The RNFT2/IL-3Ralpha axis regulates IL-3 signaling and innate immunity."; RL JCI Insight 5:0-0(2020). RN [11] RP STRUCTURE BY NMR OF 33-156, AND DISULFIDE BOND. RX PubMed=21329364; DOI=10.1021/bi101810f; RA Yao S., Young I.G., Norton R.S., Murphy J.M.; RT "Murine interleukin-3: structure, dynamics, and conformational RT heterogeneity in solution."; RL Biochemistry 50:2464-2477(2011). CC -!- FUNCTION: Cytokine secreted predominantly by activated T-lymphocytes as CC well as mast cells and osteoblastic cells that controls the production CC and differentiation of hematopoietic progenitor cells into lineage- CC restricted cells. Stimulates also mature basophils, eosinophils, and CC monocytes to become functionally activated. In addition, plays an CC important role in neural cell proliferation and survival. Participates CC as well in bone homeostasis and inhibits osteoclast differentiation by CC preventing NF-kappa-B nuclear translocation and activation. CC Mechanistically, exerts its biological effects through a receptor CC composed of IL3RA subunit and a signal transducing subunit IL3RB (By CC similarity). Receptor stimulation results in the rapid activation of CC JAK2 kinase activity leading to STAT5-mediated transcriptional program CC (PubMed:8378315, PubMed:10376805, PubMed:31990690). Alternatively, CC contributes to cell survival under oxidative stress in non- CC hematopoietic systems by activating pathways mediated by PI3K/AKT and CC ERK (By similarity). {ECO:0000250|UniProtKB:P08700, CC ECO:0000269|PubMed:10376805, ECO:0000269|PubMed:31990690, CC ECO:0000269|PubMed:8378315, ECO:0000269|PubMed:9446636}. CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Activated T-cells, mast cells, natural killer CC cells. CC -!- DISRUPTION PHENOTYPE: IL-3-deficient animals show no abnormalities. CC Analysis of steady-state hematopoiesis demonstrates normal numbers of CC peripheral blood cells, bone marrow and splenic hematopoietic CC progenitors. However, they show impaired contact hypersensitivity CC reactions. {ECO:0000269|PubMed:9446636}. CC -!- SIMILARITY: Belongs to the IL-3 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; K01850; AAA39291.1; -; mRNA. DR EMBL; K01668; AAA39507.1; -; mRNA. DR EMBL; K03233; AAA39293.1; -; Genomic_DNA. DR EMBL; X02732; CAA26514.1; -; Genomic_DNA. DR EMBL; M20128; AAA39308.1; -; Genomic_DNA. DR EMBL; M14394; AAA39308.1; JOINED; Genomic_DNA. DR CCDS; CCDS24693.1; -. DR PIR; A25481; ICMS3. DR RefSeq; NP_034686.2; NM_010556.4. DR PDB; 2L3O; NMR; -; A=33-156. DR PDBsum; 2L3O; -. DR AlphaFoldDB; P01586; -. DR BMRB; P01586; -. DR SMR; P01586; -. DR STRING; 10090.ENSMUSP00000019058; -. DR GlyCosmos; P01586; 2 sites, No reported glycans. DR GlyGen; P01586; 2 sites. DR iPTMnet; P01586; -. DR PaxDb; 10090-ENSMUSP00000019058; -. DR Antibodypedia; 14353; 908 antibodies from 41 providers. DR DNASU; 16187; -. DR Ensembl; ENSMUST00000019058.6; ENSMUSP00000019058.6; ENSMUSG00000018914.6. DR GeneID; 16187; -. DR KEGG; mmu:16187; -. DR UCSC; uc007ixn.1; mouse. DR AGR; MGI:96552; -. DR CTD; 3562; -. DR MGI; MGI:96552; Il3. DR VEuPathDB; HostDB:ENSMUSG00000018914; -. DR eggNOG; ENOG502TD4X; Eukaryota. DR GeneTree; ENSGT00940000163393; -. DR HOGENOM; CLU_1602158_0_0_1; -. DR InParanoid; P01586; -. DR OMA; LDCRTIA; -. DR OrthoDB; 4839138at2759; -. DR PhylomeDB; P01586; -. DR TreeFam; TF338567; -. DR BioGRID-ORCS; 16187; 0 hits in 75 CRISPR screens. DR PRO; PR:P01586; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; P01586; Protein. DR Bgee; ENSMUSG00000018914; Expressed in embryonic cell in blastocyst and 20 other cell types or tissues. DR ExpressionAtlas; P01586; baseline and differential. 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; IDA:MGI. DR GO; GO:0005135; F:interleukin-3 receptor binding; IPI:MGI. DR GO; GO:0001783; P:B cell apoptotic process; IDA:MGI. DR GO; GO:0042100; P:B cell proliferation; IDA:MGI. DR GO; GO:0008283; P:cell population proliferation; IDA:MGI. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:MGI. DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:MGI. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IDA:MGI. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI. DR GO; GO:0030097; P:hemopoiesis; ISO:MGI. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; IDA:MGI. DR GO; GO:0007254; P:JNK cascade; IDA:MGI. DR GO; GO:0033024; P:mast cell apoptotic process; IDA:MGI. DR GO; GO:0070662; P:mast cell proliferation; IDA:MGI. DR GO; GO:0030224; P:monocyte differentiation; IGI:MGI. DR GO; GO:0033028; P:myeloid cell apoptotic process; IDA:MGI. DR GO; GO:0002573; P:myeloid leukocyte differentiation; IGI:MGI. DR GO; GO:0010507; P:negative regulation of autophagy; IDA:MGI. DR GO; GO:0002903; P:negative regulation of B cell apoptotic process; IDA:MGI. DR GO; GO:0033026; P:negative regulation of mast cell apoptotic process; IDA:MGI. DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IDA:MGI. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI. DR GO; GO:1901534; P:positive regulation of hematopoietic progenitor cell differentiation; IGI:MGI. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI. DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IDA:MGI. DR GO; GO:0002763; P:positive regulation of myeloid leukocyte differentiation; IGI: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:0042102; P:positive regulation of T cell proliferation; IDA:MGI. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI. DR GO; GO:0001558; P:regulation of cell growth; IGI:MGI. DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI. DR GO; GO:0006110; P:regulation of glycolytic process; IGI:MGI. DR GO; GO:0035304; P:regulation of protein dephosphorylation; IDA:MGI. DR GO; GO:0009725; P:response to hormone; ISO:MGI. DR GO; GO:0001666; P:response to hypoxia; IGI:MGI. DR GO; GO:0042098; P:T cell proliferation; IDA:MGI. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR002183; IL-3. DR PANTHER; PTHR48401; INTERLEUKIN-3; 1. DR PANTHER; PTHR48401:SF1; INTERLEUKIN-3; 1. DR Pfam; PF02059; IL3; 1. DR PIRSF; PIRSF001939; IL-3; 1. DR PRINTS; PR00430; INTERLEUKIN3. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR Genevisible; P01586; MM. PE 1: Evidence at protein level; KW 3D-structure; Cytokine; Disulfide bond; Glycoprotein; Growth factor; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..26 FT CHAIN 27..166 FT /note="Interleukin-3" FT /id="PRO_0000015519" FT REGION 145..166 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 42 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:1445902" FT CARBOHYD 112 FT /note="N-linked (GlcNAc...) asparagine; partial" FT /evidence="ECO:0000269|PubMed:1445902" FT DISULFID 43..106 FT /evidence="ECO:0000269|PubMed:1445902" FT DISULFID 105..166 FT /evidence="ECO:0000269|PubMed:1445902" FT STRAND 37..41 FT /evidence="ECO:0007829|PDB:2L3O" FT HELIX 44..53 FT /evidence="ECO:0007829|PDB:2L3O" FT HELIX 67..69 FT /evidence="ECO:0007829|PDB:2L3O" FT TURN 71..73 FT /evidence="ECO:0007829|PDB:2L3O" FT HELIX 74..85 FT /evidence="ECO:0007829|PDB:2L3O" FT TURN 86..88 FT /evidence="ECO:0007829|PDB:2L3O" FT HELIX 90..93 FT /evidence="ECO:0007829|PDB:2L3O" FT HELIX 97..106 FT /evidence="ECO:0007829|PDB:2L3O" FT HELIX 124..137 FT /evidence="ECO:0007829|PDB:2L3O" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:2L3O" FT STRAND 151..153 FT /evidence="ECO:0007829|PDB:2L3O" SQ SEQUENCE 166 AA; 18540 MW; F38EE7A9E361CAA2 CRC64; MVLASSTTSI HTMLLLLLML FHLGLQASIS GRDTHRLTRT LNCSSIVKEI IGKLPEPELK TDDEGPSLRN KSFRRVNLSK FVESQGEVDP EDRYVIKSNL QKLNCCLPTS ANDSALPGVF IRDLDDFRKK LRFYMVHLND LETVLTSRPP QPASGSVSPN RGTVEC //