Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
3  structures 28  species 0  interactions 77  sequences 2  architectures

Family: IL7 (PF01415)

Summary: Interleukin 7/9 family

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...

Interleukin Edit Wikipedia article

Interleukins are a group of cytokines (secreted proteins and signaling molecules) that were first seen to be expressed by white blood cells (leukocytes).[1]

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.

Interleukin receptors on astrocytes in the hippocampus are also known to be involved in the development of spatial memories in mice.[2]

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, "Heidikine"). This decision was taken during a meeting in Interlaken (Switzerland).

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, though (the term was coined by Dr Vern Paetkau, University of Victoria;[3] it has since been found that interleukins are produced by a wide variety of body cells.

Common families of interleukins

Interleukin 1

Interleukin 1 / 18
3LTQ.pdb.png
Crystallographic structure of human interleukin 1B.[4]
Identifiers
Symbol IL1
Pfam PF00340
InterPro IPR000975
SMART SM00125
PROSITE PDOC00226
SCOP 1i1b
SUPERFAMILY 1i1b

Interleukin 1 alpha and interleukin 1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis.[5] 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.[6] 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.[7] The receptors can both bind all three forms of IL-1 (IL-1 alpha, IL-1 beta and IL-1RA).

The crystal structures of IL1A and IL1B[8] 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.[9] The beta-sheets are arranged in 3 similar lobes around a central axis, 6 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 IL-1 receptor type I 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.[10][11] 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 receptor, the mice exhibit normal hippocampal-dependent memory function, and partial restoration of Long-term potentiation.[10]

Interleukin 2

Interleukin 2
Identifiers
Symbol Interleukin-2
Pfam PF00715
InterPro IPR000779
SMART SM00189
PROSITE PDOC00349

T Lymphocytes regulate the growth and differentiation of T cells and certain B cells through the release of secreted protein factors.[12] 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,[13] as a growth factor and antibody production stimulant.[14] The protein is secreted as a single glycosylated polypeptide, and cleavage of a signal sequence is required for its activity.[13] 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).[14]

Interleukin 3

Interleukin 3
Identifiers
Symbol Interleukin_3
Pfam PF02059
InterPro IPR002183

Interleukin 3 (IL3) is a cytokine that regulates blood-cell production by controlling the production, differentiation and function of granulocytes and macrophages.[15][16] The protein, which exists in vivo as a monomer, is produced in activated T cells and mast cells,[15][16] and is activated by the cleavage of an N-terminal signal sequence.[16]

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.[16] 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.[16]

Interleukin 4

Interleukin 4
Identifiers
Symbol Interleukin_4
Pfam PF02059
InterPro IPR002183

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

Interleukin 5
Identifiers
Symbol Interleukin_5
Pfam PF02025
InterPro IPR000186

Interleukin 5 (IL5), also known as eosinophil differentiation factor (EDF), is a lineage-specific cytokine for eosinophilpoiesis.[17][18] It regulates eosinophil growth and activation,[17] and thus plays an important role in diseases associated with increased levels of eosinophils, including asthma.[18] IL5 has a similar overall fold to other cytokines (e.g., IL2, IL4 and GCSF),[18] 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.[18][19] The monomers are held together by 2 interchain disulphide bonds.[19]

Interleukin 6

Interleukin 6/G-CSF/MGF
Identifiers
Symbol IL6_MGF_GCSF
Pfam PF00489
InterPro IPR003573
SMART SM00126
PROSITE PDOC00227

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.[20] It plays an essential role in the final differentiation of B cells into IG-secreting cells, as well as inducing myeloma/plasmacytoma growth, nerve cell differentiation, and, in hepatocytes, acute-phase reactants.[20][21]

A number of other cytokines may be grouped with IL6 on the basis of sequence similarity.[20][21][22] 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.[22] 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 contains four conserved cysteine residues involved in two disulphide bonds:.[22] They have a compact, globular fold (similar to other interleukins), stabilised by the 2 disulphide bonds. One half of the structure is dominated by a 4-alpha-helix bundle with a left-handed twist;[23] the helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet. The fourth alpha-helix is important to the biological activity of the molecule.[21]

Interleukins 7 and 9

Interleukin 7/interleukin 9
Identifiers
Symbol Interleukin_7_9
Pfam PF01415
InterPro IPR000226
PROSITE PDOC00228

Interleukin 7 (IL-7)[24] is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages. Interleukin 9 (IL-9)[25] is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T cells. Interleukin 7 and 9 seems to be evolutionary related.[26]

Interleukin 8

Main article: Interleukin 8

Interleukin 10

Interleukin 10
Identifiers
Symbol Interleukin_10
Pfam PF00726
InterPro IPR000098
SMART SM00188
PROSITE PDOC00450

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.[27] 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.[28] a protein that has antiproliferative properties in human melanoma cells. Mda-7 contains only two of the four cysteines of IL-10.

Interleukin 11

Interleukin 11
Identifiers
Symbol IL11
Pfam PF07400
InterPro IPR010873

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.[29] Family members seem to be restricted to mammals.

Interleukin 12

Interleukin 12 alpha subunit
Identifiers
Symbol IL12
Pfam PF03039
InterPro IPR004281

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[30][31] 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.[32][33]

Interleukin 13

Interleukin 13
Identifiers
Symbol Interleukin_13
Pfam PF03487
InterPro IPR003634

Interleukin 13 (IL-13) is a pleiotropic cytokine that may be important in the regulation of the inflammatory and immune responses.[34] 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.[35]

Interleukin 15

Interleukin 15
Identifiers
Symbol Interleukin_15
Pfam PF02372
InterPro IPR003443

Interleukin 15 (IL-15) is a cytokine that possesses a variety of biological functions, including stimulation and maintenance of cellular immune responses.[36] 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

Interleukin 17
Identifiers
Symbol IL17
Pfam PF06083
InterPro IPR010345

Interleukin 17 (IL-17) is a potent proinflammatory cytokine produced by activated memory T cells.[37] The IL-17 family is thought to represent a distinct signalling system that appears to have been highly conserved across vertebrate evolution.[37]

List of human interleukins

A list of interleukins:

Name Source [38] Target receptors[38][39] Target cells[38] Function[38]
IL-1 macrophages, B cells, monocytes,[40] dendritic cells [40] CD121a/IL1R1, CD121b/IL1R2 T helper cells co-stimulation [40]
B cells maturation & proliferation [40]
NK cells activation[40]
macrophages, endothelium, other inflammation,[40] small amounts induce acute phase reaction, large amounts induce fever
IL-2 Th1-cells CD25/IL2RA, CD122/IL2RB, CD132/IL2RG activated[40] 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,[40] mast cells, NK cells, endothelium, eosinophils CD123/IL3RA, CD131/IL3RB hematopoietic stem cells differentiation and proliferation of myeloid progenitor cells [40] to e.g. erythrocytes, granulocytes
mast cells growth and histamine release[40]
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.[40] Important role in allergic response (IgE)
T cells proliferation[40]
endothelium
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[40]
B cells activation [40]
mast cells
Th1 cells inhibits Th1 cytokine production (IFN-γ, TNF-β, IL-2)
Th2 cells Stimulation
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 [40] T cells, differentiation into Cytotoxic T cells with IL-2,[40]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 CDw218a/IL18R1 Th1 cells, NK cells Induces production of IFNγ, ↑ NK cell activity
IL-19 - IL20R -
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.[30] 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,[30] 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

References

  1. ^ 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 3390169. PMID 21106488. 
  2. ^ Ben Menachem-Zidon, Ofra; Avi Avital; Yair Ben-Menahem; Inbal Goshen; Tirzah Kreisel; Eli M. Shmueli; Menahem Segal; Tamir Ben Hur; Raz Yirmiya (17 November 2010). "Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling". Brain, Behaviour, and Immunity 25: 1008–1016. doi:10.1016/j.bbi.2010.11.007. 
  3. ^ Khadka, A (2014). "Interleukins in Therapeutics". PharmaTutor 2 (4): 67–72. 
  4. ^ PDB 3LTQ; Barthelmes K, Reynolds AM, Peisach E, Jonker HR, DeNunzio NJ, Allen KN, Imperiali B, Schwalbe H (February 2011). "Engineering encodable lanthanide-binding tags into loop regions of proteins". J. Am. Chem. Soc. 133 (4): 808–19. doi:10.1021/ja104983t. PMC 3043167. PMID 21182275. 
  5. ^ Sims JE, March CJ, Cosman D, Widmer MB, MacDonald HR, McMahan CJ, Grubin CE, Wignall JM, Jackson JL, Call SM (July 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. 
  6. ^ Liu C, Hart RP, Liu XJ, Clevenger W, Maki RA, De Souza EB (August 1996). "Cloning and characterization of an alternatively processed human type II interleukin-1 receptor mRNA". J. Biol. Chem. 271 (34): 20965–72. doi:10.1074/jbc.271.34.20965. PMID 8702856. 
  7. ^ McMahan CJ, Slack JL, Mosley B, Cosman D, Lupton SD, Brunton LL, Grubin CE, Wignall JM, Jenkins NA, Brannan CI (October 1991). "A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types". EMBO J. 10 (10): 2821–32. PMC 452992. PMID 1833184. 
  8. ^ Priestle JP, Schär HP, Grütter MG (December 1989). "Crystallographic refinement of interleukin 1 beta at 2.0 A resolution". Proc. Natl. Acad. Sci. U.S.A. 86 (24): 9667–71. doi:10.1073/pnas.86.24.9667. PMC 298562. PMID 2602367. 
  9. ^ Murzin AG, Lesk AM, Chothia C (January 1992). "beta-Trefoil fold. Patterns of structure and sequence in the Kunitz inhibitors interleukins-1 beta and 1 alpha and fibroblast growth factors". J. Mol. Biol. 223 (2): 531–43. doi:10.1016/0022-2836(92)90668-A. PMID 1738162. 
  10. ^ a b Ben Menachem-Zidon O, Avital A, Ben-Menahem Y, Goshen I, Kreisel T, Shmueli EM, Segal M, Ben Hur T, Yirmiya R (July 2011). "Astrocytes support hippocampal-dependent memory and long-term potentiation via interleukin-1 signaling". Brain Behav. Immun. 25 (5): 1008–16. doi:10.1016/j.bbi.2010.11.007. PMID 21093580. 
  11. ^ 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. 
  12. ^ Arai K, Yokota T, Arai N, Lee F, Rennick D, Mosmann T (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". Proc. Natl. Acad. Sci. U.S.A. 82 (1): 68–72. doi:10.1073/pnas.82.1.68. PMC 396972. PMID 3918306. 
  13. ^ a b Gillis S, Cerretti DP, McKereghan K, Larsen A, Cantrell MA, Anderson D, Cosman D, Baker PE (1986). "Cloning, sequence, and expression of bovine interleukin 2". Proc. Natl. Acad. Sci. U.S.A. 83 (10): 3223–3227. doi:10.1073/pnas.83.10.3223. PMC 323485. PMID 3517854. 
  14. ^ a b Driscoll PC, Campbell ID, Mott HR, Boyd J, Cooke RM, Weir MP (1992). "Secondary structure of human interleukin 2 from 3D heteronuclear NMR experiments". Biochemistry 31 (33): 7741–7744. doi:10.1021/bi00148a040. PMID 1510960. 
  15. ^ a b Dorssers L, Burger H, Bot F, Delwel R, Lowenberg B, Wagemaker G, Geurts van Kessel AH (1987). "Characterization of a human multilineage-colony-stimulating factor cDNA clone identified by a conserved noncoding sequence in mouse interleukin-3". Gene 55 (1): 115–124. doi:10.1016/0378-1119(87)90254-X. PMID 3497843. 
  16. ^ a b c d e Ymer S, Tucker WQ, Sanderson CJ, Campbell HD, Young IG, Hapel AJ (1985). "Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene". Nature 317 (6034): 255–258. doi:10.1038/317255a0. PMID 2413359. 
  17. ^ a b Tucker WQ, Sanderson CJ, Campbell HD, Young IG, Hort Y, Martinson ME, Mayo G, Clutterbuck EJ (1987). "Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5)". Proc. Natl. Acad. Sci. U.S.A. 84 (19): 6629–6633. doi:10.1073/pnas.84.19.6629. PMC 299136. PMID 3498940. 
  18. ^ a b c d Proudfoot AE, Wells TN, Milburn MV, Hassell AM, Lambert MH, Jordan SR, Graber P (1993). "A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5". Nature 363 (6425): 172–176. doi:10.1038/363172a0. PMID 8483502. 
  19. ^ a b Proudfoot AE, Turcatti G, Davies JG, Wingfield PT (1991). "Human interleukin-5 expressed in Escherichia coli: assignment of the disulfide bridges of the purified unglycosylated protein". FEBS Lett. 283 (1): 61–64. doi:10.1016/0014-5793(91)80553-F. PMID 2037074. 
  20. ^ a b c Hirano T, Harada H, Nakajima K, Iwamatsu A, Yasukawa K, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Koyama K (1986). "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin". Nature 324 (6092): 73–76. doi:10.1038/324073a0. PMID 3491322. 
  21. ^ a b c Heinrich PC, Rose-John S, Lutticken C, Kruttgen A, Moller C (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 Lett. 282 (2): 265–267. doi:10.1016/0014-5793(91)80491-K. PMID 2037043. 
  22. ^ a b c Clogston CL, Boone TC, Crandall BC, Mendiaz EA, Lu HS (1989). "Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor". Arch. Biochem. Biophys. 272 (1): 144–151. doi:10.1016/0003-9861(89)90205-1. PMID 2472117. 
  23. ^ Cook WJ, Bugg CE, Walter MR, Ealick SE, Zhao BG, Reichert P, Nagabhushan TL, Trotta PP, Cameron Jr RP, Walter Jr RL (1992). "Crystal structure of recombinant human interleukin-4". J. Biol. Chem. 267 (28): 20371–20376. PMID 1400355. 
  24. ^ Henney CS (1989). "Interleukin 7: effects on early events in lymphopoiesis". Immunol. Today 10 (5): 170–173. doi:10.1016/0167-5699(89)90175-8. PMID 2663018. 
  25. ^ Renauld JC, Goethals A, Houssiau F, Merz H, Van Roost E, Van Snick J (1990). "Human P40/IL-9. Expression in activated CD4+ T cells, genomic organization, and comparison with the mouse gene". J. Immunol. 144 (11): 4235–4241. PMID 1971295. 
  26. ^ Paul WE, Boulay JL (1993). "Hematopoietin sub-family classification based on size, gene organization and sequence homology". Curr. Biol. 3 (9): 573–581. doi:10.1016/0960-9822(93)90002-6. PMID 15335670. 
  27. ^ Wlodawer A, Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J (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. 
  28. ^ Jiang H, Lin JJ, Goldstein NI, Fisher PB, Su ZZ (1995). "Subtraction hybridization identifies a novel melanoma differentiation associated gene, mda-7, modulated during human melanoma differentiation, growth and progression". Oncogene 11 (12): 2477–2486. PMID 8545104. 
  29. ^ Leng SX, Elias JA (1997). "Interleukin-11". Int. J. Biochem. Cell Biol. 29 (8–9): 1059–1062. doi:10.1016/S1357-2725(97)00017-4. PMID 9416001. 
  30. ^ a b c Abbas AK, Lichtman AH, Pillai S (2012). Cellular and molecular immunology (7th ed. ed.). Philadelphia: Elsevier/Saunders. ISBN 1437715281. 
  31. ^ Zhang C, Zhang J, Niu J, Zhou Z, Zhang J, Tian Z (2008). "Interleukin-12 improves cytotoxicity of natural killer cells via upregulated expression of NKG2D". Hum. Immunol. 69 (8): 490–500. doi:10.1016/j.humimm.2008.06.004. PMID 18619507. 
  32. ^ Park AY, Scott P (2001). "Il-12: keeping cell-mediated immunity alive". Scand. J. Immunol. 53 (6): 529–532. doi:10.1046/j.1365-3083.2001.00917.x. PMID 11422900. 
  33. ^ Presky DH, Gately MK, Gubler U, Renzetti LM, Magram J, Stern AS, Adorini L (1998). "The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses". Annu. Rev. Immunol. 16: 495–521. doi:10.1146/annurev.immunol.16.1.495. PMID 9597139. 
  34. ^ Minty A, Chalon P, Dumont X, Kaghad M, Labit C, Leplatois P, Liauzun P, Miloux B, Derocq JM, Guillemot JC (1993). "Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses". Nature 362 (6417): 248–250. doi:10.1038/362248a0. PMID 8096327. 
  35. ^ 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.
  36. ^ Arena A, Merendino RA, Bonina L, Iannello D, Stassi G, Mastroeni P (2000). "Role of IL-15 on monocytic resistance to human herpesvirus 6 infection". New Microbiol. 23 (2): 105–112. PMID 10872679. 
  37. ^ a b Gurney AL, Aggarwal S (2002). "IL-17: prototype member of an emerging cytokine family". J. Leukoc. Biol. 71 (1): 1–8. PMID 11781375. 
  38. ^ a b c d 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
  39. ^ Noosheen Alaverdi & David Sehy (2007-05-01). "Cytokines - Master Regulators of the Immune System". eBioscience. Retrieved 2008-02-28. 
  40. ^ a b c d e f g h i j k l m n o p Cytokine tutorial, The University of Arizona

External links

This article incorporates text from the public domain Pfam and InterPro IPR000779

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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 7/9 family Provide feedback

IL-7 is a cytokine that acts as a growth factor for early lymphoid cells of both B- and T-cell lineages. IL-9 is a multi-functional cytokine that, although originally described as a T-cell growth factor, its function in T-cell response remains unclear.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000226

Interleukin-7 (IL-7) [PUBMED:2663018] is a cytokine that serves as a growth factor for early lymphoid cells of both B- and T-cell lineages. Interleukin-9 (IL-9) [PUBMED:1971295] is a cytokine that supports IL-2 independent and IL-4 independent growth of helper T-cells. Interleukin-7 and -9 seems to be evolutionary related [PUBMED:15335670].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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.

  Seed
(7)
Full
(77)
Representative proteomes NCBI
(73)
Meta
(0)
RP15
(2)
RP35
(2)
RP55
(2)
RP75
(23)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(7)
Full
(77)
Representative proteomes NCBI
(73)
Meta
(0)
RP15
(2)
RP35
(2)
RP55
(2)
RP75
(23)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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.

  Seed
(7)
Full
(77)
Representative proteomes NCBI
(73)
Meta
(0)
RP15
(2)
RP35
(2)
RP55
(2)
RP75
(23)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

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...

Trees

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.

Curation View help on the curation process

Seed source: SMART
Previous IDs: none
Type: Family
Author: Ponting CP, Schultz J, Bork P
Number in seed: 7
Number in full: 77
Average length of the domain: 111.60 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 85.17 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.3
Noise cut-off 20.4 20.8
Model length: 129
Family (HMM) version: 11
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

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.

Structures

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 IL7 domain has been found. There are 3 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.

Loading structure mapping...