ID   IL9_MOUSE               Reviewed;         144 AA.
AC   P15247;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Interleukin-9;
DE            Short=IL-9;
DE   AltName: Full=Cytokine P40;
DE   AltName: Full=T-cell growth factor P40;
DE   Flags: Precursor;
GN   Name=Il9;
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].
RC   STRAIN=C57BL/6J;
RX   PubMed=2521242; DOI=10.1084/jem.169.1.363;
RA   van Snick J., Goethals A., Renauld J.-C., van Roost E., Uyttenhove C.,
RA   Rubira M.R., Moritz R.L., Simpson R.J.;
RT   "Cloning and characterization of a cDNA for a new mouse T cell growth
RT   factor (P40).";
RL   J. Exp. Med. 169:363-368(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1971295;
RA   Renauld J.-C., Goethals A., Houssiau F., Merz H., van Roost E.,
RA   van Snick J.;
RT   "Human P40/IL-9. Expression in activated CD4+ T cells, genomic
RT   organization, and comparison with the mouse gene.";
RL   J. Immunol. 144:4235-4241(1990).
RN   [3]
RP   PROTEIN SEQUENCE OF 19-144, PYROGLUTAMATE FORMATION AT GLN-19, AND
RP   GLYCOSYLATION AT ASN-50; ASN-78; ASN-101 AND ASN-114.
RX   PubMed=2528451; DOI=10.1111/j.1432-1033.1989.tb21103.x;
RA   Simpson R.J., Moritz R.L., Rubira M.R., Gorman J.J., van Snick J.;
RT   "Complete amino acid sequence of a new murine T-cell growth factor P40.";
RL   Eur. J. Biochem. 183:715-722(1989).
RN   [4]
RP   PROTEIN SEQUENCE OF 118-136.
RX   PubMed=3137580; DOI=10.1073/pnas.85.18.6934;
RA   Uyttenhove C., Simpson R.J., van Snick J.;
RT   "Functional and structural characterization of P40, a mouse glycoprotein
RT   with T-cell growth factor activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:6934-6938(1988).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH IL9R.
RX   PubMed=2145361;
RA   Druez C., Coulie P., Uyttenhove C., Van Snick J.;
RT   "Functional and biochemical characterization of mouse P40/IL-9 receptors.";
RL   J. Immunol. 145:2494-2499(1990).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH IL2RG.
RX   PubMed=7718508; DOI=10.1093/intimm/7.1.115;
RA   Kimura Y., Takeshita T., Kondo M., Ishii N., Nakamura M., Van Snick J.,
RA   Sugamura K.;
RT   "Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor
RT   complex.";
RL   Int. Immunol. 7:115-120(1995).
RN   [7]
RP   FUNCTION.
RX   PubMed=10464327; DOI=10.1074/jbc.274.36.25855;
RA   Demoulin J.B., Van Roost E., Stevens M., Groner B., Renauld J.C.;
RT   "Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene
RT   induction and apoptosis inhibition by interleukin-9.";
RL   J. Biol. Chem. 274:25855-25861(1999).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=11070175; DOI=10.1016/s1074-7613(00)00056-x;
RA   Townsend J.M., Fallon G.P., Matthews J.D., Smith P., Jolin E.H.,
RA   McKenzie N.A.;
RT   "IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary
RT   mastocytosis and goblet cell hyperplasia but not T cell development.";
RL   Immunity 13:573-583(2000).
RN   [9]
RP   FUNCTION.
RX   PubMed=12704113; DOI=10.1128/iai.71.5.2430-2438.2003;
RA   Khan W.I., Richard M., Akiho H., Blennerhasset P.A., Humphreys N.E.,
RA   Grencis R.K., Van Snick J., Collins S.M.;
RT   "Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-
RT   9 neutralization: correlation with worm expulsion in murine nematode
RT   infections.";
RL   Infect. Immun. 71:2430-2438(2003).
RN   [10]
RP   FUNCTION.
RX   PubMed=19433802; DOI=10.1073/pnas.0812530106;
RA   Elyaman W., Bradshaw E.M., Uyttenhove C., Dardalhon V., Awasthi A.,
RA   Imitola J., Bettelli E., Oukka M., van Snick J., Renauld J.C.,
RA   Kuchroo V.K., Khoury S.J.;
RT   "IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+
RT   natural regulatory T cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:12885-12890(2009).
CC   -!- FUNCTION: Multifunctional cytokine secreted mainly by T-helper 2
CC       lymphocytes and also mast cells or NKT cells that plays important roles
CC       in the immune response against parasites (PubMed:11070175,
CC       PubMed:19433802). Affects intestinal epithelial permeability and
CC       adaptive immunity (PubMed:12704113). In addition, induces the
CC       differentiation of specific T-cell subsets such as IL-17 producing
CC       helper T-cells (TH17) and also proliferation and differentiation of
CC       mast cells (PubMed:19433802, PubMed:11070175). Mechanistically, exerts
CC       its biological effects through a receptor composed of IL9R subunit and
CC       a signal transducing subunit IL2RG (PubMed:2145361, PubMed:7718508).
CC       Receptor stimulation results in the rapid activation of JAK1 and JAK3
CC       kinase activities leading to STAT1, STAT3 and STAT5-mediated
CC       transcriptional programs (PubMed:10464327). Induction of
CC       differentiation genes seems to be mediated by STAT1 alone, while
CC       protection of cells from apoptosis depends on STAT3 and STAT5
CC       (PubMed:10464327). {ECO:0000269|PubMed:10464327,
CC       ECO:0000269|PubMed:11070175, ECO:0000269|PubMed:12704113,
CC       ECO:0000269|PubMed:19433802, ECO:0000269|PubMed:2145361,
CC       ECO:0000269|PubMed:7718508}.
CC   -!- SUBUNIT: Interacts with IL9R (PubMed:2145361). Interacts with IL2RG
CC       (PubMed:7718508). {ECO:0000269|PubMed:2145361,
CC       ECO:0000269|PubMed:7718508}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- DISRUPTION PHENOTYPE: Deltion mice do not show defects in T-cell
CC       development or differentiation, the generation of naive or antigen-
CC       driven antibody responses, or the expulsion of the intestinal parasitic
CC       nematode Nippostrongylus brasiliensis. However, mastocytosis is
CC       severely impaired in these animals. {ECO:0000269|PubMed:19433802}.
CC   -!- SIMILARITY: Belongs to the IL-7/IL-9 family. {ECO:0000305}.
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DR   EMBL; X14045; CAA32203.1; -; mRNA.
DR   EMBL; M30136; AAA39874.1; -; Genomic_DNA.
DR   CCDS; CCDS26562.1; -.
DR   PIR; JL0089; JL0089.
DR   RefSeq; NP_032399.1; NM_008373.1.
DR   PDB; 7OX4; X-ray; 1.80 A; C=19-144.
DR   PDB; 7XCB; X-ray; 3.40 A; A=21-140.
DR   PDBsum; 7OX4; -.
DR   PDBsum; 7XCB; -.
DR   AlphaFoldDB; P15247; -.
DR   SMR; P15247; -.
DR   STRING; 10090.ENSMUSP00000022019; -.
DR   GlyCosmos; P15247; 4 sites, No reported glycans.
DR   GlyGen; P15247; 4 sites.
DR   iPTMnet; P15247; -.
DR   PhosphoSitePlus; P15247; -.
DR   PaxDb; 10090-ENSMUSP00000022019; -.
DR   Antibodypedia; 14762; 745 antibodies from 39 providers.
DR   DNASU; 16198; -.
DR   Ensembl; ENSMUST00000022019.4; ENSMUSP00000022019.4; ENSMUSG00000021538.4.
DR   GeneID; 16198; -.
DR   KEGG; mmu:16198; -.
DR   UCSC; uc007qso.1; mouse.
DR   AGR; MGI:96563; -.
DR   CTD; 3578; -.
DR   MGI; MGI:96563; Il9.
DR   VEuPathDB; HostDB:ENSMUSG00000021538; -.
DR   eggNOG; ENOG502TDE1; Eukaryota.
DR   GeneTree; ENSGT00390000015384; -.
DR   HOGENOM; CLU_150120_0_0_1; -.
DR   InParanoid; P15247; -.
DR   OMA; IPSDNCP; -.
DR   OrthoDB; 5260311at2759; -.
DR   PhylomeDB; P15247; -.
DR   TreeFam; TF336367; -.
DR   Reactome; R-MMU-8985947; Interleukin-9 signaling.
DR   BioGRID-ORCS; 16198; 2 hits in 76 CRISPR screens.
DR   PRO; PR:P15247; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; P15247; Protein.
DR   Bgee; ENSMUSG00000021538; Expressed in epiblast cell in embryo and 10 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0005125; F:cytokine activity; IGI:MGI.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005140; F:interleukin-9 receptor binding; ISO:MGI.
DR   GO; GO:0030183; P:B cell differentiation; IGI:MGI.
DR   GO; GO:0042100; P:B cell proliferation; IGI:MGI.
DR   GO; GO:0016064; P:immunoglobulin mediated immune response; IGI:MGI.
DR   GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR   GO; GO:0032754; P:positive regulation of interleukin-5 production; IMP:UniProtKB.
DR   GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR   GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IDA:MGI.
DR   InterPro; IPR018049; IL-7/IL-9_CS.
DR   InterPro; IPR020447; IL-9.
DR   PANTHER; PTHR16926; INTERLEUKIN 9; 1.
DR   PANTHER; PTHR16926:SF1; INTERLEUKIN-9; 1.
DR   PRINTS; PR01926; INTERLEUKIN9.
DR   PROSITE; PS00255; INTERLEUKIN_7_9; 1.
DR   Genevisible; P15247; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cytokine; Direct protein sequencing; Glycoprotein;
KW   Growth factor; Pyrrolidone carboxylic acid; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000269|PubMed:2528451"
FT   CHAIN           19..144
FT                   /note="Interleukin-9"
FT                   /id="PRO_0000015628"
FT   MOD_RES         19
FT                   /note="Pyrrolidone carboxylic acid"
FT                   /evidence="ECO:0000269|PubMed:2528451"
FT   CARBOHYD        50
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:2528451"
FT   CARBOHYD        78
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:2528451"
FT   CARBOHYD        101
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:2528451"
FT   CARBOHYD        114
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:2528451"
FT   HELIX           24..37
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   HELIX           41..44
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   STRAND          48..50
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   STRAND          57..60
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   HELIX           70..79
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   HELIX           83..85
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   HELIX           86..101
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   HELIX           105..108
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   STRAND          116..119
FT                   /evidence="ECO:0007829|PDB:7OX4"
FT   HELIX           121..138
FT                   /evidence="ECO:0007829|PDB:7OX4"
SQ   SEQUENCE   144 AA;  16075 MW;  ECD944632CE837C7 CRC64;
     MLVTYILASV LLFSSVLGQR CSTTWGIRDT NYLIENLKDD PPSKCSCSGN VTSCLCLSVP
     TDDCTTPCYR EGLLQLTNAT QKSRLLPVFH RVKRIVEVLK NITCPSFSCE KPCNQTMAGN
     TLSFLKSLLG TFQKTEMQRQ KSRP
//