Summary: Interleukin 2
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Interleukin". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Interleukin Edit Wikipedia article
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cells (leukocytes). ILs can be divided into four major groups based on distinguishing structural features. However, their amino acid sequence similarity is rather weak (typically 15-25% identity). The human genome encodes more than 50 interleukins and related proteins.
The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune diseases or immune deficiency. The majority of interleukins are synthesized by helper CD4 T lymphocytes, as well as through monocytes, macrophages, and endothelial cells. They promote the development and differentiation of T and B lymphocytes, and hematopoietic cells.
- 1 History and name
- 2 Common families of interleukins
- 3 List of human interleukins
- 4 INNs for pharmaceutical analogues and derivatives
- 5 References
- 6 External links
History and name
The name "interleukin" was chosen in 1979, to replace the various different names used by different research groups to designate interleukin 1 (lymphocyte activating factor, mitogenic protein, T-cell replacing factor III, B-cell activating factor, B-cell differentiation factor, and "Heidikine") and interleukin 2 (TSF, etc.). This decision was taken during the Second International Lymphokine Workshop in Switzerland (27-31 May 1979 in Ermatingen, 'near' Interlaken).
The term interleukin derives from (inter-) "as a means of communication", and (-leukin) "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes". The name is something of a relic; it has since been found that interleukins are produced by a wide variety of body cells. The term was coined by Dr Vern Paetkau, University of Victoria.
Some interleukins are classified as lymphokines, lymphocyte-produced cytokines that mediate immune responses.
Common families of interleukins
|Interleukin 1 / 18|
Crystallographic structure of human interleukin 1B.
Interleukin 1 alpha and interleukin 1 beta (IL1 alpha and IL1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. Two types of IL-1 receptor, each with three extracellular immunoglobulin (Ig)-like domains, limited sequence similarity (28%) and different pharmacological characteristics have been cloned from mouse and human cell lines: these have been termed type I and type II receptors. The receptors both exist in transmembrane (TM) and soluble forms: the soluble IL-1 receptor is thought to be post-translationally derived from cleavage of the extracellular portion of the membrane receptors.
Both IL-1 receptors (CD121a/IL1R1, CD121b/IL1R2) appear to be well conserved in evolution, and map to the same chromosomal location. The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1 receptor antagonist).
The crystal structures of IL1A and IL1B have been solved, showing them to share the same 12-stranded beta-sheet structure as both the heparin binding growth factors and the Kunitz-type soybean trypsin inhibitors. The beta-sheets are arranged in 4 similar lobes around a central axis, 8 strands forming an anti-parallel beta-barrel. Several regions, especially the loop between strands 4 and 5, have been implicated in receptor binding.
Molecular cloning of the Interleukin 1 Beta converting enzyme is generated by the proteolytic cleavage of an inactive precursor molecule. A complementary DNA encoding protease that carries out this cleavage has been cloned. Recombinant expression enables cells to process precursor Interleukin 1 Beta to the mature form of the enzyme.
Interleukin 1 also plays a role in the Central Nervous System. Research indicates that mice with a genetic deletion of the type I IL-1 receptor display markedly impaired hippocampal-dependent memory functioning and Long-term potentiation, although memories that do not depend on the integrity of the hippocampus seem to be spared. However, when mice with this genetic deletion have wild-type neural precursor cells injected into their hippocampus and these cells are allowed to mature into astrocytes containing the interleukin-1 receptors, the mice exhibit normal hippocampal-dependent memory function, and partial restoration of long-term potentiation.
T lymphocytes regulate the growth and differentiation of T cells and certain B cells through the release of secreted protein factors. These factors, which include interleukin 2 (IL2), are secreted by lectin- or antigen-stimulated T cells, and have various physiological effects. IL2 is a lymphokine that induces the proliferation of responsive T cells. In addition, it acts on some B cells, via receptor-specific binding, as a growth factor and antibody production stimulant. The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity. Solution NMR suggests that the structure of IL2 comprises a bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly defined loops. Residues in helix A, and in the loop region between helices A and B, are important for receptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF).
Interleukin 3 (IL3) is a cytokine that regulates hematopoiesis by controlling the production, differentiation and function of granulocytes and macrophages. The protein, which exists in vivo as a monomer, is produced in activated T cells and mast cells, and is activated by the cleavage of an N-terminal signal sequence.
IL3 is produced by T lymphocytes and T-cell lymphomas only after stimulation with antigens, mitogens, or chemical activators such as phorbol esters. However, IL3 is constitutively expressed in the myelomonocytic leukaemia cell line WEHI-3B. It is thought that the genetic change of the cell line to constitutive production of IL3 is the key event in development of this leukaemia.
Interleukin 4 (IL4) is produced by CD4+ T cells specialized in providing help to B cells to proliferate and to undergo class switch recombination and somatic hypermutation. Th2 cells, through production of IL-4, have an important function in B-cell responses that involve class switch recombination to the IgG1 and IgE isotypes.
Interleukin 5 (IL5), also known as eosinophil differentiation factor (EDF), is a lineage-specific cytokine for eosinophilpoiesis. It regulates eosinophil growth and activation, and thus plays an important role in diseases associated with increased levels of eosinophils, including asthma. IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF), but while these exist as monomeric structures, IL5 is a homodimer. The fold contains an anti-parallel 4-alpha-helix bundle with a left handed twist, connected by a 2-stranded anti-parallel beta-sheet. The monomers are held together by 2 interchain disulphide bonds.
Interleukin 6 (IL6), also referred to as B-cell stimulatory factor-2 (BSF-2) and interferon beta-2, is a cytokine involved in a wide variety of biological functions. It plays an essential role in the final differentiation of B cells into immunoglobulin-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation, and, in hepatocytes, acute-phase reactants.
A number of other cytokines may be grouped with IL6 on the basis of sequence similarity. These include granulocyte colony-stimulating factor (GCSF) and myelomonocytic growth factor (MGF). GCSF acts in hematopoiesis by affecting the production, differentiation, and function of 2 related white cell groups in the blood. MGF also acts in hematopoiesis, stimulating proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.
Cytokines of the IL6/GCSF/MGF family are glycoproteins of about 170 to 180 amino acid residues that contain four conserved cysteine residues involved in two disulphide bonds. They have a compact, globular fold (similar to other interleukins), stabilised by the two disulphide bonds. One half of the structure is dominated by a 4-alpha-helix bundle with a left-handed twist; the helices are anti-parallel, with two overhand connections, which fall into a double-stranded anti-parallel beta-sheet. The fourth alpha-helix is important to the biological activity of the molecule.
Interleukins 7 and 9
|Interleukin 7/interleukin 9|
Interleukin 7 (IL-7) is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages. Interleukin 9 (IL-9) is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T cells. Interleukin 7 and 9 seem to be evolutionary related.
Interleukin 10 (IL-10) is a protein that inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF, and GM-CSF produced by activated macrophages and by helper T cells. In structure, IL-10 is a protein of about 160 amino acids that contains four conserved cysteines involved in disulphide bonds. IL-10 is highly similar to the Human herpesvirus 4 (Epstein-Barr virus) BCRF1 protein, which inhibits the synthesis of gamma-interferon and to Equid herpesvirus 2 (Equine herpesvirus 2) protein E7. It is also similar, but to a lesser degree, with human protein mda-7. a protein that has antiproliferative properties in human melanoma cells. Mda-7 contains only two of the four cysteines of IL-10.
Interleukin 11 (IL-11) 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.
|Interleukin 12 alpha subunit|
Interleukin 12 (IL-12) is a disulphide-bonded heterodimer consisting of a 35kDa alpha subunit and a 40kDa beta subunit. It is involved in the stimulation and maintenance of Th1 cellular immune responses, including the normal host defence against various intracellular pathogens, such as Leishmania, Toxoplasma, Measles virus, and Human immunodeficiency virus 1 (HIV). IL-12 also has an important role in enhancing the cytotoxic function of NK cells and role in pathological Th1 responses, such as in inflammatory bowel disease and multiple sclerosis. Suppression of IL-12 activity in such diseases may have therapeutic benefit. On the other hand, administration of recombinant IL-12 may have therapeutic benefit in conditions associated with pathological Th2 responses.
Interleukin 13 (IL-13) is a pleiotropic cytokine that may be important in the regulation of the inflammatory and immune responses. It inhibits inflammatory cytokine production and synergises with IL-2 in regulating interferon-gamma synthesis. The sequences of IL-4 and IL-13 are distantly related.
Interleukin 15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses. IL-15 stimulates the proliferation of T lymphocytes, which requires interaction of IL-15 with components of IL-2R, including IL-2R beta and probably IL-2R gamma, but not IL-2R alpha.
Interleukin 17 (IL-17) is a potent proinflammatory cytokine produced by activated memory T cells. The IL-17 family is thought to represent a distinct signalling system that appears to have been highly conserved across vertebrate evolution.
List of human interleukins
|Name||Source ||Target receptors||Target cells||Function|
|IL-1||macrophages, B cells, monocytes, dendritic cells ||CD121a/IL1R1, CD121b/IL1R2||T helper cells||co-stimulation |
|B cells||maturation & proliferation |
|macrophages, endothelium, other||inflammation, small amounts induce acute phase reaction, large amounts induce fever|
|IL-2||Th1-cells||CD25/IL2RA, CD122/IL2RB, CD132/IL2RG||activated T cells and B cells, NK cells, macrophages, oligodendrocytes||stimulates growth and differentiation of T cell response. Can be used in immunotherapy to treat cancer or suppressed for transplant patients. Has also been used in clinical trials (ESPIRIT. Stalwart) to raise CD4 counts in HIV positive patients.|
|IL-3||activated T helper cells, mast cells, NK cells, endothelium, eosinophils||CD123/IL3RA, CD131/IL3RB||hematopoietic stem cells||differentiation and proliferation of myeloid progenitor cells  to e.g. erythrocytes, granulocytes|
|mast cells||growth and histamine release|
|IL-4||Th2 cells, just activated naive CD4+ cell, memory CD4+ cells, mast cells, macrophages||CD124/IL4R, CD132/IL2RG||activated B cells||proliferation and differentiation, IgG1 and IgE synthesis. Important role in allergic response (IgE)|
|endothelium||increase expression of vascular cell adhesion molecule (VCAM-1) promoting adhesion of lymphocytes.|
|IL-5||Th2 cells, mast cells, eosinophils||CD125/IL5RA, CD131/IL3RB||eosinophils||production|
|B cells||differentiation, IgA production|
|IL-6||macrophages, Th2 cells, B cells, astrocytes, endothelium||CD126/IL6RA, CD130/IR6RB||activated B cells||differentiation into plasma cells|
|plasma cells||antibody secretion|
|hematopoietic stem cells||differentiation|
|T cells, others||induces acute phase reaction, hematopoiesis, differentiation, inflammation|
|IL-7||Bone marrow stromal cells and thymus stromal cells||CD127/IL7RA, CD132/IL2RG||pre/pro-B cell, pre/pro-T cell, NK cells||differentiation and proliferation of lymphoid progenitor cells, involved in B, T, and NK cell survival, development, and homeostasis, ↑proinflammatory cytokines|
|IL-8 or CXCL8||macrophages, lymphocytes, epithelial cells, endothelial cells||CXCR1/IL8RA, CXCR2/IL8RB/CD128||neutrophils, basophils, lymphocytes||Neutrophil chemotaxis|
|IL-9||Th2 cells, specifically by CD4+ helper cells||CD129/IL9R||T cells, B cells||Potentiates IgM, IgG, IgE, stimulates mast cells|
|IL-10||monocytes, Th2 cells, CD8+ T cells, mast cells, macrophages, B cell subset||CD210/IL10RA, CDW210B/IL10RB||macrophages||cytokine production|
|B cells||activation |
|Th1 cells||inhibits Th1 cytokine production (IFN-γ, TNF-β, IL-2)|
|IL-11||bone marrow stroma||IL11RA||bone marrow stroma||acute phase protein production, osteoclast formation|
|IL-12||dendritic cells, B cells, T cells, macrophages||CD212/IL12RB1, IR12RB2||activated  T cells,||differentiation into Cytotoxic T cells with IL-2, ↑ IFN-γ, TNF-α, ↓ IL-10|
|NK cells||↑ IFN-γ, TNF-α|
|IL-13||activated Th2 cells, mast cells, NK cells||IL13R||TH2-cells, B cells, macrophages||Stimulates growth and differentiation of B cells (IgE), inhibits TH1-cells and the production of macrophage inflammatory cytokines (e.g. IL-1, IL-6), ↓ IL-8, IL-10, IL-12|
|IL-14||T cells and certain malignant B cells||activated B cells||controls the growth and proliferation of B cells, inhibits Ig secretion|
|IL-15||mononuclear phagocytes (and some other cells), especially macrophages following infection by virus(es)||IL15RA||T cells, activated B cells||Induces production of Natural killer cells|
|IL-16||lymphocytes, epithelial cells, eosinophils, CD8+ T cells||CD4||CD4+ T cells (Th-cells)||CD4+ chemoattractant|
|IL-17||T helper 17 cells (Th17)||CDw217/IL17RA, IL17RB||epithelium, endothelium, other||osteoclastogenesis, angiogenesis, ↑ inflammatory cytokines|
|IL-18||macrophages m,v,v,lkj,vn,||CDw218a/IL18R1||Th1 cells, NK cells||Induces production of IFNγ, ↑ NK cell activity|
|IL-20||Activated keratinocytes and monocytes||IL20R||regulates proliferation and differentiation of keratinocytes|
|IL-21||activated T helper cells, NKT cells||IL21R||All lymphocytes, dendritic cells||costimulates activation and proliferation of CD8+ T cells, augment NK cytotoxicity, augments CD40-driven B cell proliferation, differentiation and isotype switching, promotes differentiation of Th17 cells|
|IL-22||T helper 17 cells (Th17)||IL22R||Production of defensins from epithelial cells. Activates STAT1 and STAT3 and increases production of acute phase proteins such as serum amyloid A, Alpha 1-antichymotrypsin and haptoglobin in hepatoma cell lines|
|IL-23||macrophages, dendritic cells||IL23R||Maintenance of IL-17 producing cells, increases angiogenesis but reduces CD8 T-cell infiltration|
|IL-24||melanocytes, keratinocytes, monocytes, T cells||IL20R||Plays important roles in tumor suppression, wound healing and psoriasis by influencing cell survival, inflammatory cytokine expression.|
|IL-25||T Cells, mast cells, eosinophils, macrophages, mucosal epithelial cells||LY6E||Induces the production IL-4, IL-5 and IL-13, which stimulate eosinophil expansion|
|IL-26||T cells, monocytes||IL20R1||Enhances secretion of IL-10 and IL-8 and cell surface expression of CD54 on epithelial cells|
|IL-27||macrophages, dendritic cells||IL27RA||Regulates the activity of B lymphocyte and T lymphocytes|
|IL-28||-||IL28R||Plays a role in immune defense against viruses|
|IL-29||-||Plays a role in host defenses against microbes|
|IL-30||-||Forms one chain of IL-27|
|IL-31||Th2 cells||IL31RA||May play a role in inflammation of the skin|
|IL-32||-||Induces monocytes and macrophages to secrete TNF-α, IL-8 and CXCL2|
|IL-33||-||Induces helper T cells to produce type 2 cytokine|
|IL-35||regulatory T cells||Suppression of T helper cell activation|
|IL-36||-||Regulates DC and T cell responses|
INNs for pharmaceutical analogues and derivatives
|Endogenous form name||Pharmaceutical form INN suffix||INNs|
|interleukin-2 (IL-2)||-leukin||adargileukin alfa, aldesleukin, celmoleukin, denileukin diftitox, pegaldesleukin, teceleukin, tucotuzumab celmoleukin|
|interleukin-3 (IL-3)||-plestim||daniplestim, muplestim|
|interleukin-6 (IL-6)||-exakin||atexakin alfa|
|interleukin-12 (IL-12)||-dodekin||edodekin alfa|
|interleukin-13 (IL-13)||-tredekin||cintredekin besudotox|
- Brocker C, Thompson D, Matsumoto A, Nebert DW, Vasiliou V (Oct 2010). "Evolutionary divergence and functions of the human interleukin (IL) gene family". Human Genomics. 5 (1): 30–55. doi:10.1186/1479-7364-5-1-30. PMC . PMID 21106488.
- Ben Menachem-Zidon O, Avital A, Ben-Menahem Y, Goshen I, Kreisel T, Shmueli EM, Segal M, Ben Hur T, Yirmiya R (Jul 2011). "Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling". Brain, Behavior, and Immunity. 25 (5): 1008–16. doi:10.1016/j.bbi.2010.11.007. PMID 21093580.
- di Giovine FS, Duff GW (Jan 1990). "Interleukin 1: the first interleukin". Immunology Today. 11 (1): 13–20. doi:10.1016/0167-5699(90)90005-t. PMID 2405873.
- Schindler R, Dinarello CA (1990). "Interleukin 1". In Habenicht A. Growth Factors, Differentiation Factors, and Cytokines. Berlin, Heidelberg: Springer. doi:10.1007/978-3-642-74856-1_7. ISBN 978-3-642-74856-1.
- "Revised nomenclature for antigen-nonspecific T cell proliferation and helper factors". Journal of Immunology. 123 (6): 2928–9. Dec 1979. PMID 91646.
- "Engineering encodable lanthanide-binding tags into loop regions of proteins". Journal of the American Chemical Society. 133 (4): 808–19. doi:10.1021/ja104983t. PMC . PMID 21182275.; Barthelmes K, Reynolds AM, Peisach E, Jonker HR, DeNunzio NJ, Allen KN, Imperiali B, Schwalbe H (Feb 2011).
- Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM (Jul 1988). "cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily". Science. 241 (4865): 585–9. doi:10.1126/science.2969618. PMID 2969618.
- Liu C, Hart RP, Liu XJ, Clevenger W, Maki RA, De Souza EB (Aug 1996). "Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA". The Journal of Biological Chemistry. 271 (34): 20965–72. doi:10.1074/jbc.271.34.20965. PMID 8702856.
- McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI (Oct 1991). "A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types". The EMBO Journal. 10 (10): 2821–32. PMC . PMID 1833184.
- Priestle JP, Schär HP, Grütter MG (Dec 1989). "Crystallographic refinement of interleukin 1 beta at 2.0 A resolution". Proceedings of the National Academy of Sciences of the United States of America. 86 (24): 9667–71. doi:10.1073/pnas.86.24.9667. PMC . PMID 2602367.
- Murzin AG, Lesk AM, Chothia C (Jan 1992). "beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors". Journal of Molecular Biology. 223 (2): 531–43. doi:10.1016/0022-2836(92)90668-A. PMID 1738162.
- Avital A, Goshen I, Kamsler A, Segal M, Iverfeldt K, Richter-Levin G, Yirmiya R (2003). "Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity". Hippocampus. 13 (7): 826–34. doi:10.1002/hipo.10135. PMID 14620878.
- Yokota T, Arai N, Lee F, Rennick D, Mosmann T, Arai K (Jan 1985). "Use of a cDNA expression vector for isolation of mouse interleukin 2 cDNA clones: expression of T-cell growth-factor activity after transfection of monkey cells". Proceedings of the National Academy of Sciences of the United States of America. 82 (1): 68–72. doi:10.1073/pnas.82.1.68. PMC . PMID 3918306.
- Cerretti DP, McKereghan K, Larsen A, Cantrell MA, Anderson D, Gillis S, Cosman D, Baker PE (May 1986). "Cloning, sequence, and expression of bovine interleukin 2". Proceedings of the National Academy of Sciences of the United States of America. 83 (10): 3223–7. doi:10.1073/pnas.83.10.3223. PMC . PMID 3517854.
- Mott HR, Driscoll PC, Boyd J, Cooke RM, Weir MP, Campbell ID (Aug 1992). "Secondary structure of human interleukin 2 from 3D heteronuclear NMR experiments". Biochemistry. 31 (33): 7741–4. doi:10.1021/bi00148a040. PMID 1510960.
- Dorssers L, Burger H, Bot F, Delwel R, Geurts van Kessel AH, Löwenberg B, Wagemaker G (1987). "Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3". Gene. 55 (1): 115–24. doi:10.1016/0378-1119(87)90254-X. PMID 3497843.
- Ymer S, Tucker WQ, Sanderson CJ, Hapel AJ, Campbell HD, Young IG (1985). "Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene". Nature. 317 (6034): 255–8. doi:10.1038/317255a0. PMID 2413359.
- Campbell HD, Tucker WQ, Hort Y, Martinson ME, Mayo G, Clutterbuck EJ, Sanderson CJ, Young IG (Oct 1987). "Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5)". Proceedings of the National Academy of Sciences of the United States of America. 84 (19): 6629–33. doi:10.1073/pnas.84.19.6629. PMC . PMID 3498940.
- Milburn MV, Hassell AM, Lambert MH, Jordan SR, Proudfoot AE, Graber P, Wells TN (May 1993). "A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5". Nature. 363 (6425): 172–6. doi:10.1038/363172a0. PMID 8483502.
- Proudfoot AE, Davies JG, Turcatti G, Wingfield PT (May 1991). "Human interleukin-5 expressed in Escherichia coli: assignment of the disulfide bridges of the purified unglycosylated protein". FEBS Letters. 283 (1): 61–4. doi:10.1016/0014-5793(91)80553-F. PMID 2037074.
- Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A (1986). "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin". Nature. 324 (6092): 73–6. doi:10.1038/324073a0. PMID 3491322.
- Lütticken C, Krüttgen A, Möller C, Heinrich PC, Rose-John S (May 1991). "Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6". FEBS Letters. 282 (2): 265–7. doi:10.1016/0014-5793(91)80491-K. PMID 2037043.
- Clogston CL, Boone TC, Crandall BC, Mendiaz EA, Lu HS (Jul 1989). "Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor". Archives of Biochemistry and Biophysics. 272 (1): 144–51. doi:10.1016/0003-9861(89)90205-1. PMID 2472117.
- Walter MR, Cook WJ, Zhao BG, Cameron RP, Ealick SE, Walter RL, Reichert P, Nagabhushan TL, Trotta PP, Bugg CE (Oct 1992). "Crystal structure of recombinant human interleukin-4". The Journal of Biological Chemistry. 267 (28): 20371–6. PMID 1400355.
- Henney CS (May 1989). "Interleukin 7: effects on early events in lymphopoiesis". Immunology Today. 10 (5): 170–3. doi:10.1016/0167-5699(89)90175-8. PMID 2663018.
- Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J (Jun 1990). "Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene". Journal of Immunology. 144 (11): 4235–41. PMID 1971295.
- Boulay JL, Paul WE (Sep 1993). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Current Biology. 3 (9): 573–81. doi:10.1016/0960-9822(93)90002-6. PMID 15335670.
- Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A (Jun 1995). "Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma". Structure. 3 (6): 591–601. doi:10.1016/S0969-2126(01)00193-9. PMID 8590020.
- Jiang H, Lin JJ, Su ZZ, Goldstein NI, Fisher PB (Dec 1995). "Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression". Oncogene. 11 (12): 2477–86. PMID 8545104.
- Leng SX, Elias JA (1997). "Interleukin-11". The International Journal of Biochemistry & Cell Biology. 29 (8-9): 1059–62. doi:10.1016/S1357-2725(97)00017-4. PMID 9416001.
- Abbas AK, Lichtman AH, Pillai S (2012). Cellular and molecular immunology (7th ed.). Philadelphia: Elsevier/Saunders. ISBN 1437715281.
- Zhang C, Zhang J, Niu J, Zhou Z, Zhang J, Tian Z (Aug 2008). "Interleukin-12 improves cytotoxicity of natural killer cells via upregulated expression of NKG2D". Human Immunology. 69 (8): 490–500. doi:10.1016/j.humimm.2008.06.004. PMID 18619507.
- Park AY, Scott P (Jun 2001). "Il-12: keeping cell-mediated immunity alive". Scandinavian Journal of Immunology. 53 (6): 529–32. doi:10.1046/j.1365-3083.2001.00917.x. PMID 11422900.
- Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, Presky DH (1998). "The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses". Annual Review of Immunology. 16: 495–521. doi:10.1146/annurev.immunol.16.1.495. PMID 9597139.
- Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B (Mar 1993). "Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses". Nature. 362 (6417): 248–50. doi:10.1038/362248a0. PMID 8096327.
- Seyfizadeh, N., Seyfizadeh, N., Babaloo, Z. (2014). "Interleukin-13 as an Important Mediator: A Review on its Roles in Some Human Diseases", Iranian Journal of Allergy, Asthma and Immunology, In Press.
- Arena A, Merendino RA, Bonina L, Iannello D, Stassi G, Mastroeni P (Apr 2000). "Role of IL-15 on monocytic resistance to human herpesvirus 6 infection". The New Microbiologica. 23 (2): 105–12. PMID 10872679.
- Aggarwal S, Gurney AL (Jan 2002). "IL-17: prototype member of an emerging cytokine family". Journal of Leukocyte Biology. 71 (1): 1–8. PMID 11781375.
- Unless else specified in boxes, then ref is: Lippincott's Illustrated Reviews: Immunology. Paperback: 384 pages. Publisher: Lippincott Williams & Wilkins; (July 1, 2007). Language: English. ISBN 0-7817-9543-5. ISBN 978-0-7817-9543-2. Page 68
- Noosheen Alaverdi; David Sehy (2007-05-01). "Cytokines - Master Regulators of the Immune System" (PDF). eBioscience. Archived from the original (PDF) on 2006-03-15. Retrieved 2008-02-28.
- Cytokine tutorial, The University of Arizona Archived 2008-02-02 at the Wayback Machine.
- Kotowicz K, Callard RE, Friedrich K, Matthews DJ, Klein N (Dec 1996). "Biological activity of IL-4 and IL-13 on human endothelial cells: functional evidence that both cytokines act through the same receptor". Int Immunol. 8 (12): 1915–25. doi:10.1093/intimm/8.12.1915. PMID 8982776.
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.
Interleukin 2 Provide feedback
No Pfam abstract.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR000779T-Lymphocytes regulate the growth and differentiation of certain lymphopoietic and haemopoietic cells through the release of various secreted protein factors [PUBMED:3918306]. These factors, which include interleukin-2 (IL2), are secreted by lectin- or antigen-stimulated T-cells, and have various physiological effects. IL2 is a lymphokine that induces the proliferation of responsive T-cells. In addition, it acts on some B-cells, via receptor-specific binding [PUBMED:3517854], as a growth factor and antibody production stimulant [PUBMED:1510960]. The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity [PUBMED:3517854]. Solution NMR suggests that the structure of IL2 comprises a bundle of 4 helices (termed A-D), flanked by 2 shorter helices and several poorly-defined loops. Residues in helix A, and in the loop region between helices A and B, are important for receptor binding. Secondary structure analysis has suggested similarity to IL4 and granulocyte-macrophage colony stimulating factor (GMCSF) [PUBMED:1510960].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||extracellular region (GO:0005576)|
|Molecular function||growth factor activity (GO:0008083)|
|interleukin-2 receptor binding (GO:0005134)|
|Biological process||immune response (GO:0006955)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
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 29 members:CNTF CSF-1 EPO_TPO Flt3_lig GCSF GM_CSF Hormone_1 IFN-gamma IL10 IL11 IL12 IL13 IL15 IL2 IL22 IL23 IL28A IL3 IL34 IL4 IL5 IL6 IL7 Interferon Leptin LIF_OSM PRF SCF TSLP
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...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
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_709 (release 2.1)|
|Number in seed:||14|
|Number in full:||55|
|Average length of the domain:||138.00 aa|
|Average identity of full alignment:||69 %|
|Average coverage of the sequence by the domain:||93.75 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||17|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
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.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There are 7 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 IL2 domain has been found. There are 56 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 sequence.
Loading structure mapping...