ID IL11_HUMAN Reviewed; 199 AA.
AC P20809; B4DQV5; Q96EB4;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 27-MAR-2024, entry version 200.
DE RecName: Full=Interleukin-11 {ECO:0000305};
DE Short=IL-11;
DE AltName: Full=Adipogenesis inhibitory factor {ECO:0000303|PubMed:1828438};
DE Short=AGIF {ECO:0000303|PubMed:1828438};
DE AltName: INN=Oprelvekin;
DE Flags: Precursor;
GN Name=IL11 {ECO:0000312|HGNC:HGNC:5966};
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] (ISOFORM 1), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=2145578; DOI=10.1073/pnas.87.19.7512;
RA Paul S.R., Bennett F., Calvetti J.A., Kelleher K., Wood C.R.,
RA O'Hara R.M. Jr., Leary A.C., Sibley B.S., Clark S.C., Williams D.A.,
RA Yang Y.-C.;
RT "Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-
RT derived lymphopoietic and hematopoietic cytokine.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:7512-7516(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RC TISSUE=Bone marrow;
RX PubMed=1828438; DOI=10.1016/0014-5793(91)80587-s;
RA Kawashima I., Ohsumi J., Mita-Honjo K., Shimoda-Takano K., Ishikawa H.,
RA Sakakibara S., Miyadai K., Takiguchi Y.;
RT "Molecular cloning of cDNA encoding adipogenesis inhibitory factor and
RT identity with interleukin-11.";
RL FEBS Lett. 283:199-202(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1386338; DOI=10.1016/0888-7543(92)90158-o;
RA McKinley D., Wu Q., Yang-Feng T., Yang Y.C.;
RT "Genomic sequence and chromosomal location of human interleukin-11 gene
RT (IL11).";
RL Genomics 13:814-819(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANTS MET-108 AND
RP HIS-112.
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
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, SUBUNIT, AND MUTAGENESIS OF HIS-182 AND ASP-186.
RX PubMed=12919066; DOI=10.1042/bj20030459;
RA Harmegnies D., Wang X.M., Vandenbussche P., Leon A., Vusio P.,
RA Groetzinger J., Jacques Y., Goormaghtigh E., Devreese B., Content J.;
RT "Characterization of a potent human interleukin-11 agonist.";
RL Biochem. J. 375:23-32(2003).
RN [9]
RP FUNCTION, AND SUBUNIT.
RX PubMed=30279168; DOI=10.1126/scisignal.aar7388;
RA Lamertz L., Rummel F., Polz R., Baran P., Hansen S., Waetzig G.H.,
RA Moll J.M., Floss D.M., Scheller J.;
RT "Soluble gp130 prevents interleukin-6 and interleukin-11 cluster signaling
RT but not intracellular autocrine responses.";
RL Sci. Signal. 11:0-0(2018).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 23-199.
RX PubMed=25195742; DOI=10.1107/s1399004714012267;
RA Putoczki T.L., Dobson R.C., Griffin M.D.W.;
RT "The structure of human interleukin-11 reveals receptor-binding site
RT features and structural differences from interleukin-6.";
RL Acta Crystallogr. D 70:2277-2285(2014).
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:2145578).
CC Also promotes the proliferation of hepatocytes in response to liver
CC damage. Binding to its receptor formed by IL6ST and IL11RA activates a
CC signaling cascade that promotes cell proliferation (PubMed:12919066).
CC Signaling leads to the activation of intracellular protein kinases and
CC the phosphorylation of STAT3. The interaction with the membrane-bound
CC IL11RA and IL6ST stimulates 'classic signaling', whereas the binding of
CC IL11 and soluble IL11RA to IL6ST stimulates 'trans-signaling'
CC (PubMed:30279168). {ECO:0000250|UniProtKB:P47873,
CC ECO:0000269|PubMed:12919066, ECO:0000269|PubMed:2145578,
CC ECO:0000269|PubMed:30279168}.
CC -!- SUBUNIT: Interacts with IL11RA to associate with IL6ST, giving rise to
CC a multimeric signaling complex. {ECO:0000269|PubMed:12919066,
CC ECO:0000269|PubMed:30279168}.
CC -!- INTERACTION:
CC P20809; P43364: MAGEA11; NbExp=4; IntAct=EBI-751694, EBI-739552;
CC P20809; P43364-2: MAGEA11; NbExp=3; IntAct=EBI-751694, EBI-10178634;
CC P20809; P25815: S100P; NbExp=2; IntAct=EBI-751694, EBI-743700;
CC P20809; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-751694, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1828438,
CC ECO:0000269|PubMed:2145578}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P20809-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P20809-2; Sequence=VSP_046936;
CC -!- PHARMACEUTICAL: Available under the name Neumega (Wyeth). Used for the
CC prevention of severe thrombocytopenia and the reduction of the need for
CC platelet transfusion following myelosuppressive chemotherapy.
CC -!- SIMILARITY: Belongs to the IL-6 superfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Neumega; Note=Clinical information on Neumega;
CC URL="https://www.drugs.com/cdi/neumega.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-11 entry;
CC URL="https://en.wikipedia.org/wiki/Interleukin_11";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il11/";
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DR EMBL; M57765; AAA59132.1; -; mRNA.
DR EMBL; X58377; CAA41266.1; -; mRNA.
DR EMBL; AY207429; AAO13493.1; -; Genomic_DNA.
DR EMBL; AK298973; BAG61067.1; -; mRNA.
DR EMBL; AC020922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012506; AAH12506.1; -; mRNA.
DR CCDS; CCDS12923.1; -. [P20809-1]
DR CCDS; CCDS59423.1; -. [P20809-2]
DR PIR; A42830; B38285.
DR RefSeq; NP_000632.1; NM_000641.3. [P20809-1]
DR RefSeq; NP_001254647.1; NM_001267718.1. [P20809-2]
DR PDB; 4MHL; X-ray; 2.09 A; A=23-199.
DR PDB; 6O4O; X-ray; 1.62 A; A=32-199.
DR PDB; 8DPS; EM; 3.47 A; B/E=32-199.
DR PDB; 8DPT; EM; 4.00 A; B/E=32-199.
DR PDB; 8DPU; X-ray; 3.78 A; B/E/H/K/N/Q=22-199.
DR PDB; 8DPV; X-ray; 1.48 A; A=32-199.
DR PDB; 8DPW; X-ray; 1.80 A; A=32-199.
DR PDBsum; 4MHL; -.
DR PDBsum; 6O4O; -.
DR PDBsum; 8DPS; -.
DR PDBsum; 8DPT; -.
DR PDBsum; 8DPU; -.
DR PDBsum; 8DPV; -.
DR PDBsum; 8DPW; -.
DR AlphaFoldDB; P20809; -.
DR EMDB; EMD-27641; -.
DR EMDB; EMD-27642; -.
DR SASBDB; P20809; -.
DR SMR; P20809; -.
DR BioGRID; 109803; 13.
DR DIP; DIP-3775N; -.
DR IntAct; P20809; 4.
DR STRING; 9606.ENSP00000264563; -.
DR iPTMnet; P20809; -.
DR PhosphoSitePlus; P20809; -.
DR BioMuta; IL11; -.
DR DMDM; 124294; -.
DR MassIVE; P20809; -.
DR PaxDb; 9606-ENSP00000264563; -.
DR PeptideAtlas; P20809; -.
DR ProteomicsDB; 53795; -. [P20809-1]
DR Antibodypedia; 19559; 515 antibodies from 37 providers.
DR DNASU; 3589; -.
DR Ensembl; ENST00000264563.7; ENSP00000264563.1; ENSG00000095752.7. [P20809-1]
DR Ensembl; ENST00000585513.1; ENSP00000467355.1; ENSG00000095752.7. [P20809-1]
DR Ensembl; ENST00000590625.5; ENSP00000465705.1; ENSG00000095752.7. [P20809-2]
DR GeneID; 3589; -.
DR KEGG; hsa:3589; -.
DR MANE-Select; ENST00000264563.7; ENSP00000264563.1; NM_000641.4; NP_000632.1.
DR UCSC; uc002qks.3; human. [P20809-1]
DR AGR; HGNC:5966; -.
DR CTD; 3589; -.
DR DisGeNET; 3589; -.
DR GeneCards; IL11; -.
DR HGNC; HGNC:5966; IL11.
DR HPA; ENSG00000095752; Tissue enhanced (brain).
DR MIM; 147681; gene.
DR neXtProt; NX_P20809; -.
DR OpenTargets; ENSG00000095752; -.
DR PharmGKB; PA29781; -.
DR VEuPathDB; HostDB:ENSG00000095752; -.
DR eggNOG; ENOG502RZVA; Eukaryota.
DR GeneTree; ENSGT00390000007165; -.
DR HOGENOM; CLU_119797_0_0_1; -.
DR InParanoid; P20809; -.
DR OMA; WAYRAFI; -.
DR OrthoDB; 4636833at2759; -.
DR PhylomeDB; P20809; -.
DR TreeFam; TF337294; -.
DR PathwayCommons; P20809; -.
DR Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions.
DR SignaLink; P20809; -.
DR SIGNOR; P20809; -.
DR BioGRID-ORCS; 3589; 11 hits in 1142 CRISPR screens.
DR ChiTaRS; IL11; human.
DR GeneWiki; Interleukin_11; -.
DR GenomeRNAi; 3589; -.
DR Pharos; P20809; Tbio.
DR PRO; PR:P20809; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P20809; Protein.
DR Bgee; ENSG00000095752; Expressed in islet of Langerhans and 121 other cell types or tissues.
DR ExpressionAtlas; P20809; baseline and differential.
DR Genevisible; P20809; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; IDA:UniProtKB.
DR GO; GO:0005142; F:interleukin-11 receptor binding; NAS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; NAS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0045444; P:fat cell differentiation; NAS:UniProtKB.
DR GO; GO:0038154; P:interleukin-11-mediated signaling pathway; IDA:UniProt.
DR GO; GO:0030219; P:megakaryocyte differentiation; NAS:UniProtKB.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA: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; INTERLEUKIN 11; 1.
DR PANTHER; PTHR16922:SF0; INTERLEUKIN-11; 1.
DR Pfam; PF07400; IL11; 1.
DR PRINTS; PR01943; INTLKN11MAML.
DR PRINTS; PR01927; INTRLEUKIN11.
DR SUPFAM; SSF47266; 4-helical cytokines; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytokine; Growth factor;
KW Pharmaceutical; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..199
FT /note="Interleukin-11"
FT /id="PRO_0000015618"
FT REGION 182..190
FT /note="Important for interaction with IL11RA and for the
FT stimulation of cell proliferation"
FT /evidence="ECO:0000305"
FT SITE 168
FT /note="Important for interaction with IL6ST and for the
FT stimulation of cell proliferation"
FT /evidence="ECO:0000250|UniProtKB:P47873"
FT VAR_SEQ 1..79
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046936"
FT VARIANT 108
FT /note="V -> M (in dbSNP:rs4252576)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016313"
FT VARIANT 112
FT /note="R -> H (in dbSNP:rs4252548)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016314"
FT MUTAGEN 182
FT /note="H->V: Increases affinity for IL11RA and stimulation
FT of cell proliferation."
FT /evidence="ECO:0000269|PubMed:12919066"
FT MUTAGEN 186
FT /note="D->A: Strongly increases affinity for IL11RA and
FT stimulation of cell proliferation."
FT /evidence="ECO:0000269|PubMed:12919066"
FT MUTAGEN 186
FT /note="D->V: Increases affinity for IL11RA and stimulation
FT of cell proliferation."
FT /evidence="ECO:0000269|PubMed:12919066"
FT CONFLICT 175
FT /note="H -> L (in Ref. 7; AAH12506)"
FT /evidence="ECO:0000305"
FT HELIX 35..63
FT /evidence="ECO:0007829|PDB:6O4O"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:6O4O"
FT HELIX 90..114
FT /evidence="ECO:0007829|PDB:6O4O"
FT HELIX 117..122
FT /evidence="ECO:0007829|PDB:6O4O"
FT HELIX 125..146
FT /evidence="ECO:0007829|PDB:6O4O"
FT HELIX 167..196
FT /evidence="ECO:0007829|PDB:6O4O"
SQ SEQUENCE 199 AA; 21429 MW; F292BF8B34F4096D CRC64;
MNCVCRLVLV VLSLWPDTAV APGPPPGPPR VSPDPRAELD STVLLTRSLL ADTRQLAAQL
RDKFPADGDH NLDSLPTLAM SAGALGALQL PGVLTRLRAD LLSYLRHVQW LRRAGGSSLK
TLEPELGTLQ ARLDRLLRRL QLLMSRLALP QPPPDPPAPP LAPPSSAWGG IRAAHAILGG
LHLTLDWAVR GLLLLKTRL
//
