IL3_MOUSE
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 03-AUG-2022, entry version 169.
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 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). Alternatively, contributes to cell
CC survival under oxidative stress in non-hematopoietic systems by
CC activating pathways mediated by PI3K/AKT and ERK (By similarity).
CC {ECO:0000250|UniProtKB:P08700, ECO:0000269|PubMed:10376805,
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}.
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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 GlyGen; P01586; 2 sites.
DR iPTMnet; P01586; -.
DR PaxDb; P01586; -.
DR PRIDE; P01586; -.
DR Antibodypedia; 14353; 832 antibodies from 40 providers.
DR DNASU; 16187; -.
DR Ensembl; ENSMUST00000019058; ENSMUSP00000019058; ENSMUSG00000018914.
DR GeneID; 16187; -.
DR KEGG; mmu:16187; -.
DR UCSC; uc007ixn.1; mouse.
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; 1495805at2759; -.
DR PhylomeDB; P01586; -.
DR TreeFam; TF338567; -.
DR BioGRID-ORCS; 16187; 0 hits in 70 CRISPR screens.
DR PRO; PR:P01586; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P01586; protein.
DR Bgee; ENSMUSG00000018914; Expressed in vasculature of trunk and 20 other tissues.
DR ExpressionAtlas; P01586; baseline and differential.
DR Genevisible; P01586; MM.
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:0042976; P:activation of Janus kinase activity; IDA: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:0018108; P:peptidyl-tyrosine phosphorylation; 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:0006468; P:protein phosphorylation; IDA: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 Pfam; PF02059; IL3; 1.
DR PIRSF; PIRSF001939; IL-3; 1.
DR PRINTS; PR00430; INTERLEUKIN3.
DR SUPFAM; SSF47266; SSF47266; 1.
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
