IL11_MOUSE
ID IL11_MOUSE Reviewed; 199 AA.
AC P47873;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Interleukin-11 {ECO:0000305};
DE Short=IL-11;
DE Flags: Precursor;
GN Name=Il11 {ECO:0000312|MGI:MGI:107613};
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], AND FUNCTION.
RX PubMed=8913282;
RA Morris J.C., Finnerty H., Bennet F., Turner K.J., Wood C.R.;
RT "Molecular cloning and characterization of murine interleukin-11.";
RL Exp. Hematol. 24:1369-1376(1996).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF TRP-168; ARG-172; ARG-190 AND LEU-193.
RX PubMed=10026196; DOI=10.1074/jbc.274.9.5755;
RA Barton V.A., Hudson K.R., Heath J.K.;
RT "Identification of three distinct receptor binding sites of murine
RT interleukin-11.";
RL J. Biol. Chem. 274:5755-5761(1999).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY OXIDATIVE STRESS.
RX PubMed=22253262; DOI=10.1126/scisignal.2002056;
RA Nishina T., Komazawa-Sakon S., Yanaka S., Piao X., Zheng D.M., Piao J.H.,
RA Kojima Y., Yamashina S., Sano E., Putoczki T., Doi T., Ueno T., Ezaki J.,
RA Ushio H., Ernst M., Tsumoto K., Okumura K., Nakano H.;
RT "Interleukin-11 links oxidative stress and compensatory proliferation.";
RL Sci. Signal. 5:RA5-RA5(2012).
RN [4]
RP FUNCTION.
RX PubMed=23948300; DOI=10.1016/j.ccr.2013.06.017;
RA Putoczki T.L., Thiem S., Loving A., Busuttil R.A., Wilson N.J.,
RA Ziegler P.K., Nguyen P.M., Preaudet A., Farid R., Edwards K.M., Boglev Y.,
RA Luwor R.B., Jarnicki A., Horst D., Boussioutas A., Heath J.K., Sieber O.M.,
RA Pleines I., Kile B.T., Nash A., Greten F.R., McKenzie B.S., Ernst M.;
RT "Interleukin-11 is the dominant IL-6 family cytokine during
RT gastrointestinal tumorigenesis and can be targeted therapeutically.";
RL Cancer Cell 24:257-271(2013).
CC -!- FUNCTION: Cytokine that stimulates the proliferation of hematopoietic
CC stem cells and megakaryocyte progenitor cells and induces megakaryocyte
CC maturation resulting in increased platelet production (PubMed:8913282).
CC Also promotes the proliferation of hepatocytes in response to liver
CC damage (PubMed:22253262). Binding to its receptor formed by IL6ST and
CC either IL11RA1 or IL11RA2 activates a signaling cascade that promotes
CC cell proliferation, also in the context of various cancers
CC (PubMed:10026196, PubMed:23948300). Signaling leads to the activation
CC of intracellular protein kinases and the phosphorylation of STAT3
CC (PubMed:23948300, PubMed:22253262). The interaction with the membrane-
CC bound IL11RA and IL6ST stimulates 'classic signaling', whereas the
CC binding of IL11 and soluble IL11RA to IL6ST stimulates 'trans-
CC signaling' (By similarity). {ECO:0000250|UniProtKB:P20809,
CC ECO:0000269|PubMed:10026196, ECO:0000269|PubMed:22253262,
CC ECO:0000269|PubMed:23948300, ECO:0000269|PubMed:8913282}.
CC -!- SUBUNIT: Interacts with either IL11RA1 or IL11RA2 to associate with
CC IL6ST, giving rise to a multimeric signaling complex.
CC {ECO:0000269|PubMed:10026196}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22253262}.
CC -!- INDUCTION: Up-regulated in hepatocytes by oxidative stress caused by
CC liver damage. {ECO:0000269|PubMed:22253262}.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
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DR EMBL; U03421; AAC52941.1; -; mRNA.
DR CCDS; CCDS39740.1; -.
DR RefSeq; NP_032376.1; NM_008350.4.
DR AlphaFoldDB; P47873; -.
DR SMR; P47873; -.
DR DIP; DIP-5780N; -.
DR IntAct; P47873; 1.
DR STRING; 10090.ENSMUSP00000092492; -.
DR PhosphoSitePlus; P47873; -.
DR PaxDb; P47873; -.
DR PRIDE; P47873; -.
DR Antibodypedia; 19559; 456 antibodies from 37 providers.
DR DNASU; 16156; -.
DR Ensembl; ENSMUST00000094892; ENSMUSP00000092492; ENSMUSG00000004371.
DR GeneID; 16156; -.
DR KEGG; mmu:16156; -.
DR UCSC; uc009eyo.2; mouse.
DR CTD; 3589; -.
DR MGI; MGI:107613; Il11.
DR VEuPathDB; HostDB:ENSMUSG00000004371; -.
DR eggNOG; ENOG502RZVA; Eukaryota.
DR GeneTree; ENSGT00390000007165; -.
DR InParanoid; P47873; -.
DR OMA; LLHRQMQ; -.
DR OrthoDB; 1469507at2759; -.
DR PhylomeDB; P47873; -.
DR TreeFam; TF337294; -.
DR BioGRID-ORCS; 16156; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Il11; mouse.
DR PRO; PR:P47873; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P47873; protein.
DR Bgee; ENSMUSG00000004371; Expressed in gastrula and 61 other tissues.
DR ExpressionAtlas; P47873; baseline and differential.
DR Genevisible; P47873; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005125; F:cytokine activity; IDA:MGI.
DR GO; GO:0008083; F:growth factor activity; ISS:UniProtKB.
DR GO; GO:0005142; F:interleukin-11 receptor binding; IPI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0046888; P:negative regulation of hormone secretion; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR Gene3D; 1.20.1250.10; -; 1.
DR InterPro; IPR009079; 4_helix_cytokine-like_core.
DR InterPro; IPR020438; IL-11.
DR InterPro; IPR020412; IL-11_mml.
DR PANTHER; PTHR16922; PTHR16922; 1.
DR Pfam; PF07400; IL11; 1.
DR PRINTS; PR01943; INTLKN11MAML.
DR PRINTS; PR01927; INTRLEUKIN11.
DR SUPFAM; SSF47266; SSF47266; 1.
PE 1: Evidence at protein level;
KW Cytokine; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..199
FT /note="Interleukin-11"
FT /id="PRO_0000015620"
FT REGION 182..190
FT /note="Important for interaction with IL11RA and for the
FT stimulation of cell proliferation"
FT /evidence="ECO:0000250|UniProtKB:P20809, ECO:0000305"
FT SITE 168
FT /note="Important for interaction with IL6ST and for the
FT stimulation of cell proliferation"
FT /evidence="ECO:0000269|PubMed:10026196"
FT MUTAGEN 168
FT /note="W->A: Slightly increases IL11RA binding. Abolishes
FT interaction with IL6ST. Abolishes stimulation of cell
FT proliferation."
FT /evidence="ECO:0000269|PubMed:10026196"
FT MUTAGEN 172
FT /note="R->A: No effect on IL11RA binding. Decreases
FT stimulation of cell proliferation."
FT /evidence="ECO:0000269|PubMed:10026196"
FT MUTAGEN 190
FT /note="R->A: Srongly reduces IL11RA binding and stimulation
FT of cell proliferation."
FT /evidence="ECO:0000269|PubMed:10026196"
FT MUTAGEN 193
FT /note="L->A: Impairs IL11RA binding and mildly reduces
FT stimulation of cell proliferation."
FT /evidence="ECO:0000269|PubMed:10026196"
SQ SEQUENCE 199 AA; 21522 MW; 904FF7DBA896625A CRC64;
MNCVCRLVLV VLSLWPDRVV APGPPAGSPR VSSDPRADLD SAVLLTRSLL ADTRQLAAQM
RDKFPADGDH SLDSLPTLAM SAGTLGSLQL PGVLTRLRVD LMSYLRHVQW LRRAGGPSLK
TLEPELGALQ ARLERLLRRL QLLMSRLALP QAAPDQPVIP LGPPASAWGS IRAAHAILGG
LHLTLDWAVR GLLLLKTRL
