IL3_HUMAN
ID IL3_HUMAN Reviewed; 152 AA.
AC P08700; Q6GS87;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 03-AUG-2022, entry version 201.
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3497843; DOI=10.1016/0378-1119(87)90254-x;
RA Dorssers L., Burger H., Bot F., Delwel R., Geurts van Kessel A.H.M.,
RA Loewenberg B., Wagemaker G.;
RT "Characterization of a human multilineage-colony-stimulating factor cDNA
RT clone identified by a conserved noncoding sequence in mouse interleukin-
RT 3.";
RL Gene 55:115-124(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3127463;
RA Otsuka T., Miyajima A., Brown N., Otsu K., Abrams J., Saeland S., Caux C.,
RA de Waal Malefijt R., de Vries J., Meyerson P., Yokota K., Gemmel L.,
RA Rennick D., Lee F., Arai N., Arai K., Yokota T.;
RT "Isolation and characterization of an expressible cDNA encoding human IL-3.
RT Induction of IL-3 mRNA in human T cell clones.";
RL J. Immunol. 140:2288-2295(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3489530; DOI=10.1016/0092-8674(86)90360-0;
RA Yang Y.-C., Ciarletta A.B., Temple P.A., Chung M.P., Kovacic S.,
RA Witek-Giannotti J.S., Leary A.C., Kriz R., Donahue R.E., Wong G.G.,
RA Clark S.C.;
RT "Human IL-3 (multi-CSF): identification by expression cloning of a novel
RT hematopoietic growth factor related to murine IL-3.";
RL Cell 47:3-10(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-15 AND SER-27.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-27.
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 [7]
RP NUCLEOTIDE SEQUENCE OF 20-152, AND VARIANT SER-27.
RX PubMed=2544122; DOI=10.1111/j.1749-6632.1989.tb22418.x;
RA Urdal D.L., Price V., Sassenfeld H.M., Cosman D., Gillis S., Park L.S.;
RT "Molecular characterization of colony-stimulating factors and their
RT receptors: human interleukin-3.";
RL Ann. N. Y. Acad. Sci. 554:167-176(1989).
RN [8]
RP FUNCTION, AND INDUCTION BY T-CELL RECEPTOR/CD3 PATHWAY.
RX PubMed=2556442; DOI=10.1172/jci114352;
RA Guba S.C., Stella G., Turka L.A., June C.H., Thompson C.B., Emerson S.G.;
RT "Regulation of interleukin 3 gene induction in normal human T cells.";
RL J. Clin. Invest. 84:1701-1706(1989).
RN [9]
RP FUNCTION.
RX PubMed=10779277; DOI=10.1111/j.1365-2222.1993.tb00274.x;
RA Okayama Y., Begishvili T.B., Church M.K.;
RT "Comparison of mechanisms of IL-3 induced histamine release and IL-3
RT priming effect on human basophils.";
RL Clin. Exp. Allergy 23:901-910(1993).
RN [10]
RP FUNCTION.
RX PubMed=12816992; DOI=10.4049/jimmunol.171.1.142;
RA Khapli S.M., Mangashetti L.S., Yogesha S.D., Wani M.R.;
RT "IL-3 acts directly on osteoclast precursors and irreversibly inhibits
RT receptor activator of NF-kappa B ligand-induced osteoclast differentiation
RT by diverting the cells to macrophage lineage.";
RL J. Immunol. 171:142-151(2003).
RN [11]
RP FUNCTION.
RX PubMed=23226269; DOI=10.1371/journal.pone.0050375;
RG Alzheimer's Disease Neuroimaging Initiative;
RA Luo X.J., Li M., Huang L., Nho K., Deng M., Chen Q., Weinberger D.R.,
RA Vasquez A.A., Rijpkema M., Mattay V.S., Saykin A.J., Shen L., Fernandez G.,
RA Franke B., Chen J.C., Chen X.N., Wang J.K., Xiao X., Qi X.B., Xiang K.,
RA Peng Y.M., Cao X.Y., Li Y., Shi X.D., Gan L., Su B.;
RT "The interleukin 3 gene (IL3) contributes to human brain volume variation
RT by regulating proliferation and survival of neural progenitors.";
RL PLoS ONE 7:e50375-e50375(2012).
RN [12]
RP FUNCTION.
RX PubMed=27862234; DOI=10.1002/jcb.25790;
RA Lopez C., Zamorano P., Teuber S., Salas M., Otth C., Hidalgo M.A.,
RA Concha I., Zambrano A.;
RT "Interleukin-3 Prevents Cellular Death Induced by Oxidative Stress in
RT HEK293 Cells.";
RL J. Cell. Biochem. 118:1330-1340(2017).
RN [13]
RP FUNCTION IN ACTIVATION OF BASOPHILS.
RX PubMed=32889153; DOI=10.1016/j.cyto.2020.155268;
RA Hong L., Tang Y., Pan S., Xu M., Shi Y., Gao S., Sui C., He C., Zheng K.,
RA Tang R., Shi Z., Wang Q., Wang H.;
RT "Interleukin 3-induced GITR promotes the activation of human basophils.";
RL Cytokine 136:155268-155268(2020).
RN [14]
RP STRUCTURE BY NMR.
RX PubMed=8676386; DOI=10.1006/jmbi.1996.0337;
RA Feng Y., Klein B.K., McWherter C.A.;
RT "Three-dimensional solution structure and backbone dynamics of a variant of
RT human interleukin-3.";
RL J. Mol. Biol. 259:524-541(1996).
RN [15] {ECO:0007744|PDB:5UV8, ECO:0007744|PDB:5UWC}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 31-152, DISULFIDE BONDS,
RP INTERACTION WITH IL3RA, AND FUNCTION.
RX PubMed=29374162; DOI=10.1038/s41467-017-02633-7;
RA Broughton S.E., Hercus T.R., Nero T.L., Kan W.L., Barry E.F., Dottore M.,
RA Cheung Tung Shing K.S., Morton C.J., Dhagat U., Hardy M.P., Wilson N.J.,
RA Downton M.T., Schieber C., Hughes T.P., Lopez A.F., Parker M.W.;
RT "A dual role for the N-terminal domain of the IL-3 receptor in cell
RT signalling.";
RL Nat. Commun. 9:386-386(2018).
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 (PubMed:2556442). Stimulates also mature basophils,
CC eosinophils, and monocytes to become functionally activated
CC (PubMed:10779277, PubMed:32889153). In addition, plays an important
CC role in neural cell proliferation and survival (PubMed:23226269).
CC Participates as well in bone homeostasis and inhibits osteoclast
CC differentiation by preventing NF-kappa-B nuclear translocation and
CC activation (PubMed:12816992). Mechanistically, exerts its biological
CC effects through a receptor composed of IL3RA subunit and a signal
CC transducing subunit IL3RB (PubMed:29374162). Receptor stimulation
CC results in the rapid activation of JAK2 kinase activity leading to
CC STAT5-mediated transcriptional program (By similarity). Alternatively,
CC contributes to cell survival under oxidative stress in non-
CC hematopoietic systems by activating pathways mediated by PI3K/AKT and
CC ERK (PubMed:27862234). {ECO:0000250|UniProtKB:P01586,
CC ECO:0000269|PubMed:10779277, ECO:0000269|PubMed:12816992,
CC ECO:0000269|PubMed:23226269, ECO:0000269|PubMed:2556442,
CC ECO:0000269|PubMed:27862234, ECO:0000269|PubMed:29374162,
CC ECO:0000269|PubMed:32889153}.
CC -!- SUBUNIT: Interacts with IL3RA (PubMed:29374162).
CC {ECO:0000269|PubMed:29374162}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Activated T-cells, mast cells, natural killer
CC cells.
CC -!- INDUCTION: Upon activation of the T-cell receptor/CD3 pathway and can
CC be augmented by coactivation of the CD3 and CD28 pathways.
CC {ECO:0000269|PubMed:2556442}.
CC -!- SIMILARITY: Belongs to the IL-3 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/IL3ID60.html";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il3/";
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DR EMBL; M14743; AAA59146.1; -; mRNA.
DR EMBL; M20137; AAA59147.1; -; mRNA.
DR EMBL; M17115; AAA35725.1; -; mRNA.
DR EMBL; AF365976; AAK38378.1; -; Genomic_DNA.
DR EMBL; AC004511; AAC08706.1; -; Genomic_DNA.
DR EMBL; BC066272; AAH66272.1; -; mRNA.
DR EMBL; BC066273; AAH66273.1; -; mRNA.
DR EMBL; BC066276; AAH66276.1; -; mRNA.
DR EMBL; BC069472; AAH69472.1; -; mRNA.
DR CCDS; CCDS4149.1; -.
DR PIR; A24427; A24427.
DR RefSeq; NP_000579.2; NM_000588.3.
DR PDB; 1JLI; NMR; -; A=34-144.
DR PDB; 5UV8; X-ray; 2.70 A; B/I=31-152.
DR PDB; 5UWC; X-ray; 2.40 A; I=31-152.
DR PDB; 6NMY; X-ray; 3.30 A; I/J=31-144.
DR PDBsum; 1JLI; -.
DR PDBsum; 5UV8; -.
DR PDBsum; 5UWC; -.
DR PDBsum; 6NMY; -.
DR AlphaFoldDB; P08700; -.
DR SMR; P08700; -.
DR BioGRID; 109777; 3.
DR DIP; DIP-6N; -.
DR IntAct; P08700; 1.
DR STRING; 9606.ENSP00000296870; -.
DR DrugBank; DB01025; Amlexanox.
DR DrugBank; DB09221; Polaprezinc.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR GlyGen; P08700; 2 sites.
DR BioMuta; IL3; -.
DR DMDM; 124330; -.
DR PaxDb; P08700; -.
DR PeptideAtlas; P08700; -.
DR PRIDE; P08700; -.
DR ProteomicsDB; 52158; -.
DR TopDownProteomics; P08700; -.
DR Antibodypedia; 14353; 832 antibodies from 40 providers.
DR DNASU; 3562; -.
DR Ensembl; ENST00000296870.3; ENSP00000296870.2; ENSG00000164399.5.
DR GeneID; 3562; -.
DR KEGG; hsa:3562; -.
DR MANE-Select; ENST00000296870.3; ENSP00000296870.2; NM_000588.4; NP_000579.2.
DR UCSC; uc003kwe.2; human.
DR CTD; 3562; -.
DR DisGeNET; 3562; -.
DR GeneCards; IL3; -.
DR HGNC; HGNC:6011; IL3.
DR HPA; ENSG00000164399; Not detected.
DR MIM; 147740; gene.
DR neXtProt; NX_P08700; -.
DR OpenTargets; ENSG00000164399; -.
DR PharmGKB; PA29830; -.
DR VEuPathDB; HostDB:ENSG00000164399; -.
DR eggNOG; ENOG502TD4X; Eukaryota.
DR GeneTree; ENSGT00940000163393; -.
DR HOGENOM; CLU_144877_0_0_1; -.
DR InParanoid; P08700; -.
DR OMA; IKDGDWN; -.
DR OrthoDB; 1415445at2759; -.
DR PhylomeDB; P08700; -.
DR TreeFam; TF338567; -.
DR PathwayCommons; P08700; -.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8939247; RUNX1 regulates transcription of genes involved in interleukin signaling.
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR SignaLink; P08700; -.
DR SIGNOR; P08700; -.
DR BioGRID-ORCS; 3562; 29 hits in 1062 CRISPR screens.
DR EvolutionaryTrace; P08700; -.
DR GeneWiki; Interleukin_3; -.
DR GenomeRNAi; 3562; -.
DR Pharos; P08700; Tbio.
DR PRO; PR:P08700; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P08700; protein.
DR Bgee; ENSG00000164399; Expressed in calcaneal tendon and 3 other tissues.
DR Genevisible; P08700; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005135; F:interleukin-3 receptor binding; TAS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0035162; P:embryonic hemopoiesis; IDA:DFLAT.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:BHF-UCL.
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..19
FT CHAIN 20..152
FT /note="Interleukin-3"
FT /id="PRO_0000015516"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..103
FT /evidence="ECO:0000269|PubMed:29374162,
FT ECO:0007744|PDB:5UV8"
FT VARIANT 3
FT /note="R -> C (in dbSNP:rs35415145)"
FT /id="VAR_034014"
FT VARIANT 15
FT /note="R -> H (in dbSNP:rs2069787)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_013071"
FT VARIANT 27
FT /note="P -> S (in dbSNP:rs40401)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2544122, ECO:0000269|Ref.4"
FT /id="VAR_013072"
FT VARIANT 60
FT /note="N -> S (in dbSNP:rs35482671)"
FT /id="VAR_034015"
FT HELIX 35..46
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:5UWC"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 91..97
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:5UWC"
FT HELIX 123..140
FT /evidence="ECO:0007829|PDB:5UWC"
SQ SEQUENCE 152 AA; 17233 MW; BB46F23FAC1259A4 CRC64;
MSRLPVLLLL QLLVRPGLQA PMTQTTPLKT SWVNCSNMID EIITHLKQPP LPLLDFNNLN
GEDQDILMEN NLRRPNLEAF NRAVKSLQNA SAIESILKNL LPCLPLATAA PTRHPIHIKD
GDWNEFRRKL TFYLKTLENA QAQQTTLSLA IF
