IL5_HUMAN
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 03-AUG-2022, entry version 212.
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/";
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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; 2.
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 GlyGen; P05113; 2 sites.
DR iPTMnet; P05113; -.
DR PhosphoSitePlus; P05113; -.
DR BioMuta; IL5; -.
DR DMDM; 124341; -.
DR PaxDb; P05113; -.
DR PeptideAtlas; P05113; -.
DR PRIDE; P05113; -.
DR ABCD; P05113; 12 sequenced antibodies.
DR Antibodypedia; 4146; 800 antibodies from 40 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 CTD; 3567; -.
DR DisGeNET; 3567; -.
DR GeneCards; IL5; -.
DR HGNC; HGNC:6016; IL5.
DR HPA; ENSG00000113525; Tissue enhanced (brain, 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; RWRVKKF; -.
DR OrthoDB; 1469027at2759; -.
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; 7 hits in 1064 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 tissues.
DR ExpressionAtlas; P05113; baseline and differential.
DR Genevisible; P05113; HS.
DR GO; GO:0005576; C:extracellular region; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; TAS: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:0005137; F:interleukin-5 receptor binding; TAS:ProtInc.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; 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 GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR000186; IL-5.
DR Pfam; PF02025; IL5; 1.
DR PRINTS; PR00432; INTERLEUKIN5.
DR SUPFAM; SSF47266; SSF47266; 1.
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
