Summary: Interleukin 11
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Interleukin 11 Edit Wikipedia article
|, AGIF, IL-11, interleukin 11|
|RNA expression pattern|
|View/Edit Human||View/Edit Mouse|
IL-11 is a multifunctional cytokine first isolated in 1990 from bone marrow-derived stromal cells. It is a key regulator of multiple events in hematopoiesis, most notably the stimulation of megakaryocyte maturation. It is also known under the names adipogenesis inhibitory factor (AGIF) and oprelvekin.
The human IL-11 gene, consisting of 5 exons and 4 introns, is located on chromosome 19, and encodes a 23 kDa protein. IL-11 is a member of the IL-6-type cytokine family, distinguished based on their use of the common co-receptor gp130. Signal specificity is provided by the IL-11Rα subunit.
Signal transduction is initiated upon binding of IL-11 to IL-11Ralpha and gp130, facilitating the homodimerization of gp130 molecules. This permits gp130-associated Janus kinases (JAK) to become activated and phosphorylate intracellular tyrosine residues on gp130.
IL-11 has been demonstrated to improve platelet recovery after chemotherapy-induced thrombocytopenia, induce acute phase proteins, modulate antigen-antibody responses, participate in the regulation of bone cell proliferation and differentiation IL-11 causes bone-resorption. It stimulates the growth of certain lymphocytes and, in the murine model, stimulates an increase in the cortical thickness and strength of long bones. In addition to having lymphopoietic/hematopoietic and osteotrophic properties, it has functions in many other tissues, including the brain, gut, testis and bone.
As a signaling molecule, interleukin 11 has a variety of functions associated with its receptor interleukin 11 receptor alpha; such functions include placentation and to some extent of decidualization. IL11 has been expressed to have a role during implantation of the blastocyst in the endometrium of the uterus; as the blastocyst is imbedded within the endometrium, the extravillous trophoblasts will invade the maternal spiral arteries for stability and the transfer of essential life-sustaining elements via the maternal and fetal circulatory systems. This process is highly regulated due to detrimental consequences that can arise from aberrations of the placentation process: poor infiltration of the trophoblasts may result in preeclampsia while severely invasive trophoblasts may resolve in placenta accreta, increta or percreta; all defects which most likely would result in the early demise of the embryo and/or negative effects upon the mother. IL11 has been shown to be present in the decidua and chorionic villi to regulate the extent in which the placenta implants itself; regulations to ensure the well-being of the mother but also the normal growth and survival of the fetus. A murine knockout model has been produced for this particular gene, with initial studies involving IL11 role in bone pathologies but have since progressed to fertility research; further research utilizes endometrial and gestational tissue from humans.
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- McKinley D, Wu Q, Yang-Feng T, Yang YC (1992). "Genomic sequence and chromosomal location of human interleukin-11 gene (IL11)". Genomics. 13 (3): 814–9. doi:10.1016/0888-7543(92)90158-O. PMID 1386338.
- Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O'Hara RM, Leary AC, Sibley B, Clark SC, Williams DA (1990). "Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine". Proc. Natl. Acad. Sci. U.S.A. 87 (19): 7512–6. doi:10.1073/pnas.87.19.7512. PMC . PMID 2145578.
- Kawashima I, Ohsumi J, Mita-Honjo K, Shimoda-Takano K, Ishikawa H, Sakakibara S, Miyadai K, Takiguchi Y (1991). "Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11". FEBS Lett. 283 (2): 199–202. doi:10.1016/0014-5793(91)80587-S. PMID 1828438.
- Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G, Schaper F (August 2003). "Principles of interleukin (IL)-6-type cytokine signalling and its regulation". Biochem. J. 374 (Pt 1): 1–20. doi:10.1042/BJ20030407. PMC . PMID 12773095.
- Sims NA, Jenkins BJ, Nakamura A, Quinn JM, Li R, Gillespie MT, Ernst M, Robb L, Martin TJ (July 2005). "Interleukin-11 receptor signaling is required for normal bone remodeling.". Journal of Bone and Mineral Research. 20 (7): 1093–102. doi:10.1359/JBMR.050209. PMID 15940362.
- Paiva P, Salamonsen LA, Manuelpillai U, Walker C, Tapia A, Wallace EM, Dimitriadis E (November 2007). "Interleukin-11 promotes migration, but not proliferation, of human trophoblast cells, implying a role in placentation". Endocrinology. 148 (11): 5566–72. doi:10.1210/en.2007-0517. PMID 17702845.
- Chen HF, Lin CY, Chao KH, Wu MY, Yang YS, Ho HN (May 2002). "Defective production of interleukin-11 by decidua and chorionic villi in human anembryonic pregnancy". J. Clin. Endocrinol. Metab. 87 (5): 2320–8. doi:10.1210/jc.87.5.2320. PMID 11994383.
- Yang YC, Yin T (1993). "Interleukin-11 and its receptor.". BioFactors. 4 (1): 15–21. PMID 1292471.
- Bhatia M, Davenport V, Cairo MS (2007). "The role of interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with solid tumors, lymphoma, acute myeloid leukemia and bone marrow failure syndromes.". Leuk. Lymphoma. 48 (1): 9–15. doi:10.1080/10428190600909115. PMID 17325843.
- McKinley D, Wu Q, Yang-Feng T, Yang YC (1992). "Genomic sequence and chromosomal location of human interleukin-11 gene (IL11).". Genomics. 13 (3): 814–9. doi:10.1016/0888-7543(92)90158-O. PMID 1386338.
- Kawashima I, Ohsumi J, Mita-Honjo K, et al. (1991). "Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11.". FEBS Lett. 283 (2): 199–202. doi:10.1016/0014-5793(91)80587-S. PMID 1828438.
- Paul SR, Bennett F, Calvetti JA, et al. (1990). "Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine.". Proc. Natl. Acad. Sci. U.S.A. 87 (19): 7512–6. doi:10.1073/pnas.87.19.7512. PMC . PMID 2145578.
- Wang XY, Fuhrer DK, Marshall MS, Yang YC (1996). "Interleukin-11 induces complex formation of Grb2, Fyn, and JAK2 in 3T3L1 cells.". J. Biol. Chem. 270 (47): 27999–8002. doi:10.1074/jbc.270.47.27999. PMID 7499280.
- Chérel M, Sorel M, Lebeau B, et al. (1995). "Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11.". Blood. 86 (7): 2534–40. PMID 7670098.
- Yamaguchi M, Miki N, Ono M, et al. (1995). "Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer.". Endocrinology. 136 (3): 1072–8. doi:10.1210/en.136.3.1072. PMID 7867561.
- Mehler MF, Rozental R, Dougherty M, et al. (1993). "Cytokine regulation of neuronal differentiation of hippocampal progenitor cells.". Nature. 362 (6415): 62–5. doi:10.1038/362062a0. PMID 8383296.
- Morris JC, Neben S, Bennett F, et al. (1996). "Molecular cloning and characterization of murine interleukin-11.". Exp. Hematol. 24 (12): 1369–76. PMID 8913282.
- Neddermann P, Graziani R, Ciliberto G, Paonessa G (1997). "Functional expression of soluble human interleukin-11 (IL-11) receptor alpha and stoichiometry of in vitro IL-11 receptor complexes with gp130.". J. Biol. Chem. 271 (48): 30986–91. doi:10.1074/jbc.271.48.30986. PMID 8940087.
- Barton VA, Hudson KR, Heath JK (1999). "Identification of three distinct receptor binding sites of murine interleukin-11.". J. Biol. Chem. 274 (9): 5755–61. doi:10.1074/jbc.274.9.5755. PMID 10026196.
- Tacken I, Dahmen H, Boisteau O, et al. (1999). "Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis.". Eur. J. Biochem. 265 (2): 645–55. doi:10.1046/j.1432-1327.1999.00755.x. PMID 10504396.
- Mahboubi K, Biedermann BC, Carroll JM, Pober JS (2000). "IL-11 activates human endothelial cells to resist immune-mediated injury.". J. Immunol. 164 (7): 3837–46. doi:10.4049/jimmunol.164.7.3837. PMID 10725745.
- Barton VA, Hall MA, Hudson KR, Heath JK (2000). "Interleukin-11 signals through the formation of a hexameric receptor complex.". J. Biol. Chem. 275 (46): 36197–203. doi:10.1074/jbc.M004648200. PMID 10948192.
- Curti A, Tafuri A, Ricciardi MR, et al. (2002). "Interleukin-11 induces proliferation of human T-cells and its activity is associated with downregulation of p27(kip1).". Haematologica. 87 (4): 373–80. PMID 11940481.
- Van der Meeren A, Mouthon MA, Gaugler MH, et al. (2002). "Administration of recombinant human IL11 after supralethal radiation exposure promotes survival in mice: interactive effect with thrombopoietin". Radiat. Res. 157 (6): 642–9. doi:10.1667/0033-7587(2002)157[0642:AORHIA]2.0.CO;2. PMID 12005542.
- McCloy MP, Roberts IA, Howarth LJ, et al. (2002). "Interleukin-11 levels in healthy and thrombocytopenic neonates". Pediatr. Res. 51 (6): 756–60. doi:10.1203/00006450-200206000-00016. PMID 12032273.
- Bartz H, Büning-Pfaue F, Türkel O, Schauer U (2002). "Respiratory syncytial virus induces prostaglandin E2, IL-10 and IL-11 generation in antigen presenting cells". Clin. Exp. Immunol. 129 (3): 438–45. doi:10.1046/j.1365-2249.2002.01927.x. PMC . PMID 12197884.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
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This family contains interleukin 11 (approximately 200 residues long). This is a secreted protein that stimulates megakaryocytopoiesis, resulting in increased production of platelets, as well as activating osteoclasts, inhibiting epithelial cell proliferation and apoptosis, and inhibiting macrophage mediator production. These functions may be particularly important in mediating the hematopoietic, osseous and mucosal protective effects of interleukin 11 . Family members seem to be restricted to mammals.
This tab holds annotation information from the InterPro database.
InterPro entry IPR020438
Interleukins (IL) are a group of cytokines that play an important role in the immune system. They modulate inflammation and immunity by regulating growth, mobility and differentiation of lymphoid and other cells.
Interleukin-11 (IL-11) is a pleiotropic cytokine that stimulates megakaryocytopoiesis, resulting in increased production of platelets, as well as activating osteoclasts, inhibiting epithelial cell proliferation and apoptosis, and inhibiting macrophage mediator production. These functions may be particularly important in mediating the hematopoietic, osseous and mucosal protective effects of IL-11 [PUBMED:9416001]. The cytokine also possesses anti-inflammatory activity, and has been proposed as a therapeutic agent in the treatment of chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis [PUBMED:15992047].
This entry represents interleukin-11.
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Cytokines are regulatory peptides that can be produced by various cells for communicating and orchestrating the large multicellular system. Cytokines are key mediators of hematopoiesis, immunity, allergy, inflammation, tissue remodeling, angiogenesis, and embryonic development . This superfamily includes both the long and short chain helical cytokines.
The clan contains the following 25 members:CNTF CSF-1 EPO_TPO Flt3_lig GCSF GM_CSF Hormone_1 IFN-gamma IL10 IL11 IL12 IL13 IL15 IL2 IL22 IL3 IL34 IL4 IL5 IL6 Interferon Leptin LIF_OSM PRF SCF
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_20854 (release 10.0)|
|Author:||Vella Briffa B|
|Number in seed:||1|
|Number in full:||52|
|Average length of the domain:||158.80 aa|
|Average identity of full alignment:||51 %|
|Average coverage of the sequence by the domain:||87.10 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||9|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IL11 domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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