ID IL5_HUMAN Reviewed; 134 AA. AC P05113; Q13840; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 13-AUG-1987, sequence version 1. DT 27-MAR-2024, entry version 221. DE RecName: Full=Interleukin-5; DE Short=IL-5; DE AltName: Full=B-cell differentiation factor I; DE AltName: Full=Eosinophil differentiation factor; DE AltName: Full=T-cell replacing factor; DE Short=TRF; DE Flags: Precursor; GN Name=IL5; 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=3024129; DOI=10.1093/nar/14.22.9149; RA Azuma C., Tanabe T., Konishi M., Kinashi T., Noma T., Matsuda F., RA Yaoita Y., Takatsu K., Hammarstroem L., Smith C.I.E., Severinson E., RA Honjo T.; RT "Cloning of cDNA for human T-cell replacing factor (interleukin-5) and RT comparison with the murine homologue."; RL Nucleic Acids Res. 14:9149-9158(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2824500; DOI=10.1016/s0021-9258(18)49295-2; RA Tanabe T., Konishi M., Mizuta T., Noma T., Honjo T.; RT "Molecular cloning and structure of the human interleukin-5 gene."; RL J. Biol. Chem. 262:16580-16584(1987). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3498940; DOI=10.1073/pnas.84.19.6629; RA Campbell H.D., Tucker W.Q.J., Hort Y., Martinson M.E., Mayo G., RA Clutterbuck E.J., Sanderson C.J., Young I.G.; RT "Molecular cloning, nucleotide sequence, and expression of the gene RT encoding human eosinophil differentiation factor (interleukin 5)."; RL Proc. Natl. Acad. Sci. U.S.A. 84:6629-6633(1987). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2823259; DOI=10.1073/pnas.84.21.7388; RA Yokota T., Coffman R.L., Hagiwara H., Rennick D.M., Takebe Y., Yokota K., RA Gemmell L., Shrader B., Yang G., Meyerson P., Luh J., Hoy P., Pene J., RA Briere F., Spits H., Banchereau J., de Vries J., Lee F.D., Arai N., RA Arai K.; RT "Isolation and characterization of lymphokine cDNA clones encoding mouse RT and human IgA-enhancing factor and eosinophil colony-stimulating factor RT activities: relationship to interleukin 5."; RL Proc. Natl. Acad. Sci. U.S.A. 84:7388-7392(1987). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RA Honjo T., Takatsu K., Severinson E.; RL Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=2653458; RA Clutterbuck E.J., Hirst E.M., Sanderson C.J.; RT "Human interleukin-5 (IL-5) regulates the production of eosinophils in RT human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL- RT 6, and GMCSF."; RL Blood 73:1504-1512(1989). RN [9] RP PROTEIN SEQUENCE OF 20-134, DISULFIDE BONDS, GLYCOSYLATION AT THR-22 AND RP ASN-47, AND LACK OF GLYCOSYLATION AT ASN-90. RX PubMed=2361960; DOI=10.1093/oxfordjournals.jbchem.a123041; RA Minamitake Y., Kodama S., Katayama T., Adachi H., Tanaka S., Tsujimoto M.; RT "Structure of recombinant human interleukin 5 produced by Chinese hamster RT ovary cells."; RL J. Biochem. 107:292-297(1990). RN [10] RP DISULFIDE BONDS. RX PubMed=2037074; DOI=10.1016/0014-5793(91)80553-f; RA Proudfoot A.E.I., Davies J.G., Turcatti G., Wingfield P.T.; RT "Human interleukin-5 expressed in Escherichia coli: assignment of the RT disulfide bridges of the purified unglycosylated protein."; RL FEBS Lett. 283:61-64(1991). RN [11] RP FUNCTION, AND INTERACTION WITH IL5RA AND CSF2RB. RX PubMed=1495999; DOI=10.1073/pnas.89.15.7041; RA Tavernier J., Tuypens T., Plaetinck G., Verhee A., Fiers W., Devos R.; RT "Molecular basis of the membrane-anchored and two soluble isoforms of the RT human interleukin 5 receptor alpha subunit."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7041-7045(1992). RN [12] RP FUNCTION. RX PubMed=7613138; DOI=10.1159/000236985; RA Alam R., Pazdrak K., Stafford S., Forsythe P.; RT "The interleukin-5/receptor interaction activates Lyn and Jak2 tyrosine RT kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak- RT STAT pathways in eosinophils."; RL Int. Arch. Allergy Immunol. 107:226-227(1995). RN [13] RP FUNCTION. RX PubMed=9010276; DOI=10.1046/j.1365-2249.1997.d01-884.x; RA Ochiai K., Kagami M., Matsumura R., Tomioka H.; RT "IL-5 but not interferon-gamma (IFN-gamma) inhibits eosinophil apoptosis by RT up-regulation of bcl-2 expression."; RL Clin. Exp. Immunol. 107:198-204(1997). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), DISULFIDE BONDS, AND SUBUNIT. RX PubMed=8483502; DOI=10.1038/363172a0; RA Milburn M.V., Hassell A.M., Lambert M.H., Jordan S.R., Proudfoot A.E.I., RA Graber P., Wells T.N.C.; RT "A novel dimer configuration revealed by the crystal structure at 2.4-A RT resolution of human interleukin-5."; RL Nature 363:172-176(1993). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 19-134 IN COMPLEX WITH IL5RA, AND RP DISULFIDE BONDS. RX PubMed=22153509; DOI=10.1016/j.str.2011.08.015; RA Patino E., Kotzsch A., Saremba S., Nickel J., Schmitz W., Sebald W., RA Mueller T.D.; RT "Structure analysis of the IL-5 ligand-receptor complex reveals a wrench- RT like architecture for IL-5Ralpha."; RL Structure 19:1864-1875(2011). RN [16] {ECO:0007744|PDB:3VA2} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 23-134 IN COMPLEX WITH IL5RA, RP DISULFIDE BONDS, SUBUNIT, AND FUNCTION. RX PubMed=22528658; DOI=10.1002/pro.2072; RA Kusano S., Kukimoto-Niino M., Hino N., Ohsawa N., Ikutani M., Takaki S., RA Sakamoto K., Hara-Yokoyama M., Shirouzu M., Takatsu K., Yokoyama S.; RT "Structural basis of interleukin-5 dimer recognition by its alpha RT receptor."; RL Protein Sci. 21:850-864(2012). CC -!- FUNCTION: Homodimeric cytokine expressed predominantly by T-lymphocytes CC and NK cells that plays an important role in the survival, CC differentiation, and chemotaxis of eosinophils (PubMed:2653458, CC PubMed:9010276). Acts also on activated and resting B-cells to induce CC immunoglobulin production, growth, and differentiation (By similarity). CC Mechanistically, exerts its biological effects through a receptor CC composed of IL5RA subunit and the cytokine receptor common subunit CC beta/CSF2RB (PubMed:1495999, PubMed:22528658). Binding to the receptor CC leads to activation of various kinases including LYN, SYK and JAK2 and CC thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways CC respectively (PubMed:7613138). {ECO:0000250|UniProtKB:P04401, CC ECO:0000269|PubMed:1495999, ECO:0000269|PubMed:22528658, CC ECO:0000269|PubMed:2653458, ECO:0000269|PubMed:7613138, CC ECO:0000269|PubMed:9010276}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:8483502, PubMed:22528658). CC Interacts with IL5RA (PubMed:1495999, PubMed:22153509). Interacts with CC CSF2RB (PubMed:1495999). {ECO:0000269|PubMed:1495999, CC ECO:0000269|PubMed:22153509, ECO:0000269|PubMed:22528658, CC ECO:0000269|PubMed:8483502}. CC -!- INTERACTION: CC P05113; P32927: CSF2RB; NbExp=2; IntAct=EBI-2435811, EBI-1809771; CC P05113; Q01344: IL5RA; NbExp=2; IntAct=EBI-2435811, EBI-1759442; CC P05113; Q01344-2: IL5RA; NbExp=4; IntAct=EBI-2435811, EBI-15957545; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2653458}. CC -!- SIMILARITY: Belongs to the IL-5 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-5 entry; CC URL="https://en.wikipedia.org/wiki/Interleukin_5"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/il5/"; 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; X04688; CAA28390.1; -; mRNA. DR EMBL; J03478; AAA74469.1; -; Genomic_DNA. DR EMBL; J02971; AAA98620.1; -; Genomic_DNA. DR EMBL; X12705; CAA31210.1; -; mRNA. DR EMBL; X12706; CAA31211.1; -; Genomic_DNA. DR EMBL; AF353265; AAK19759.1; -; Genomic_DNA. DR EMBL; BC066282; AAH66282.1; -; mRNA. DR CCDS; CCDS4156.1; -. DR PIR; A28477; A28477. DR RefSeq; NP_000870.1; NM_000879.2. DR RefSeq; XP_011541675.1; XM_011543373.2. DR RefSeq; XP_011541676.1; XM_011543374.2. DR PDB; 1HUL; X-ray; 2.40 A; A/B=24-131. DR PDB; 3QT2; X-ray; 2.55 A; C/D/E/F=19-134. DR PDB; 3VA2; X-ray; 2.70 A; A/B=23-134. DR PDBsum; 1HUL; -. DR PDBsum; 3QT2; -. DR PDBsum; 3VA2; -. DR AlphaFoldDB; P05113; -. DR SMR; P05113; -. DR BioGRID; 109781; 4. DR DIP; DIP-28N; -. DR IntAct; P05113; 2. DR STRING; 9606.ENSP00000231454; -. DR BindingDB; P05113; -. DR ChEMBL; CHEMBL1169600; -. DR DrugBank; DB06612; Mepolizumab. DR DrugBank; DB01411; Pranlukast. DR DrugBank; DB06602; Reslizumab. DR DrugCentral; P05113; -. DR GlyCosmos; P05113; 2 sites, No reported glycans. DR GlyGen; P05113; 2 sites. DR iPTMnet; P05113; -. DR PhosphoSitePlus; P05113; -. DR BioMuta; IL5; -. DR DMDM; 124341; -. DR PaxDb; 9606-ENSP00000231454; -. DR PeptideAtlas; P05113; -. DR ABCD; P05113; 12 sequenced antibodies. DR Antibodypedia; 4146; 935 antibodies from 42 providers. DR DNASU; 3567; -. DR Ensembl; ENST00000231454.6; ENSP00000231454.1; ENSG00000113525.10. DR GeneID; 3567; -. DR KEGG; hsa:3567; -. DR MANE-Select; ENST00000231454.6; ENSP00000231454.1; NM_000879.3; NP_000870.1. DR UCSC; uc003kxe.1; human. DR AGR; HGNC:6016; -. DR CTD; 3567; -. DR DisGeNET; 3567; -. DR GeneCards; IL5; -. DR HGNC; HGNC:6016; IL5. DR HPA; ENSG00000113525; Tissue enriched (testis). DR MIM; 147850; gene. DR neXtProt; NX_P05113; -. DR OpenTargets; ENSG00000113525; -. DR PharmGKB; PA29833; -. DR VEuPathDB; HostDB:ENSG00000113525; -. DR eggNOG; ENOG502RWD8; Eukaryota. DR GeneTree; ENSGT00390000016991; -. DR HOGENOM; CLU_156269_0_0_1; -. DR InParanoid; P05113; -. DR OMA; VPTHKNH; -. DR OrthoDB; 4626282at2759; -. DR PhylomeDB; P05113; -. DR TreeFam; TF338422; -. DR PathwayCommons; P05113; -. 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-912526; Interleukin receptor SHC signaling. DR SignaLink; P05113; -. DR SIGNOR; P05113; -. DR BioGRID-ORCS; 3567; 8 hits in 1146 CRISPR screens. DR ChiTaRS; IL5; human. DR EvolutionaryTrace; P05113; -. DR GeneWiki; Interleukin_5; -. DR GenomeRNAi; 3567; -. DR Pharos; P05113; Tclin. DR PRO; PR:P05113; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P05113; Protein. DR Bgee; ENSG00000113525; Expressed in right testis and 109 other cell types or tissues. DR ExpressionAtlas; P05113; baseline and differential. DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL. DR GO; GO:0005615; C:extracellular space; IDA:UniProt. DR GO; GO:0005125; F:cytokine activity; IDA:UniProt. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005137; F:interleukin-5 receptor binding; TAS:ProtInc. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0038043; P:interleukin-5-mediated signaling pathway; IDA:UniProt. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IEA:Ensembl. DR GO; GO:0045645; P:positive regulation of eosinophil differentiation; IEA:Ensembl. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IEA:Ensembl. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB. DR GO; GO:0071803; P:positive regulation of podosome assembly; IDA:BHF-UCL. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl. DR Gene3D; 1.20.1250.10; -; 1. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR000186; IL-5. DR PANTHER; PTHR48403; INTERLEUKIN-5; 1. DR PANTHER; PTHR48403:SF1; INTERLEUKIN-5; 1. DR Pfam; PF02025; IL5; 1. DR PRINTS; PR00432; INTERLEUKIN5. DR SUPFAM; SSF47266; 4-helical cytokines; 1. DR Genevisible; P05113; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytokine; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000269|PubMed:2361960" FT CHAIN 20..134 FT /note="Interleukin-5" FT /id="PRO_0000015560" FT SITE 90 FT /note="Not glycosylated" FT /evidence="ECO:0000269|PubMed:2361960" FT CARBOHYD 22 FT /note="O-linked (GalNAc...) threonine" FT /evidence="ECO:0000269|PubMed:2361960" FT CARBOHYD 47 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:2361960" FT DISULFID 63 FT /note="Interchain (with C-105)" FT /evidence="ECO:0000269|PubMed:2037074, FT ECO:0000269|PubMed:22528658" FT DISULFID 105 FT /note="Interchain (with C-63)" FT /evidence="ECO:0000269|PubMed:2037074, FT ECO:0000269|PubMed:22528658" FT CONFLICT 88 FT /note="F -> L (in Ref. 5; CAA31210)" FT /evidence="ECO:0000305" FT HELIX 26..39 FT /evidence="ECO:0007829|PDB:1HUL" FT HELIX 41..45 FT /evidence="ECO:0007829|PDB:1HUL" FT STRAND 51..54 FT /evidence="ECO:0007829|PDB:1HUL" FT STRAND 56..58 FT /evidence="ECO:0007829|PDB:1HUL" FT HELIX 60..62 FT /evidence="ECO:0007829|PDB:1HUL" FT HELIX 64..75 FT /evidence="ECO:0007829|PDB:1HUL" FT HELIX 84..103 FT /evidence="ECO:0007829|PDB:1HUL" FT STRAND 106..111 FT /evidence="ECO:0007829|PDB:1HUL" FT HELIX 112..128 FT /evidence="ECO:0007829|PDB:1HUL" SQ SEQUENCE 134 AA; 15238 MW; DC984467179556A3 CRC64; MRMLLHLSLL ALGAAYVYAI PTEIPTSALV KETLALLSTH RTLLIANETL RIPVPVHKNH QLCTEEIFQG IGTLESQTVQ GGTVERLFKN LSLIKKYIDG QKKKCGEERR RVNQFLDYLQ EFLGVMNTEW IIES //