View source for Interleukin-17 receptor

{{Pfam_box
| Symbol = IL17R
| Name = Interleukin-17 receptor
| image = 
| width =
| caption = 
| InterPro= IPR013568
| SMART=
| PROSITE = 
| SCOP = 
| TCDB = 
| OPM family= 
| OPM protein= 
| Pfam= PF08357
| PDB=
| Membranome superfamily= 8
}}

{{infobox protein
| Name = [[IL17RA|interleukin 17 receptor A]]
| caption = Crystal structure of a complex of IL-17RA bound to IL-17F in a 1:2 stoichiometry.<ref name="pmid19838198">{{PDB|3JVF}}; {{cite journal |vauthors=Ely LK, Fischer S, Garcia KC | title = Structural basis of receptor sharing by interleukin 17 cytokines | journal = Nat. Immunol. | volume = 10 | issue = 12 | pages = 1245–51 |date=December 2009 | pmid = 19838198 | pmc = 2783927 | doi = 10.1038/ni.1813 | url = | issn = }}</ref>
| image = 5JVF.pdb.jpg 
| width = 
| HGNCid = 5985
| Symbol = [[IL17RA]]
| AltSymbols = IL17R, CDw217
| EntrezGene = 23765
| OMIM = 605461
| RefSeq = NM_014339
| UniProt = Q96F46
| PDB = 
| ECnumber = 
| Chromosome = 22
| Arm = q
| Band = 11.1
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[IL17RB|interleukin 17 receptor B]]
| caption = 
| image = 
| width = 
| HGNCid = 18015
| Symbol = [[IL17RB]]
| AltSymbols = IL17BR
| EntrezGene = 55540
| OMIM = 605458
| RefSeq = NM_172234
| UniProt = Q9NRM6
| PDB = 
| ECnumber = 
| Chromosome = 3
| Arm = p
| Band = 21.1
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[IL17RC|interleukin 17 receptor C]]
| caption = 
| image = 
| width = 
| HGNCid = 18358
| Symbol = [[IL17RC]]
| AltSymbols = IL17-RL
| EntrezGene = 84818
| OMIM = 610925
| RefSeq = NM_032732
| UniProt = Q8NAC3
| PDB = 
| ECnumber = 
| Chromosome = 3
| Arm = p
| Band = 25.3
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[Interleukin 17 receptor D]]
| caption = 
| image = 
| width = 
| HGNCid = 17616
| Symbol = IL17RD
| AltSymbols = SEF, IL17RLM, FLJ35755, IL-17RD
| EntrezGene = 54756
| OMIM = 606807
| RefSeq = NM_017563
| UniProt = Q8NFM7
| PDB = 
| ECnumber = 
| Chromosome = 3
| Arm = p
| Band = 21.1
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[interleukin 17 receptor E]]
| caption = 
| image = 
| width = 
| HGNCid = 18439
| Symbol = IL17RE
| AltSymbols = FLJ23658
| EntrezGene = 132014
| OMIM = 
| RefSeq = NM_153480
| UniProt = Q8NFR9
| PDB = 
| ECnumber = 
| Chromosome = 3
| Arm = p
| Band = 25.3
| LocusSupplementaryData = 
}}
{{infobox protein
| Name = [[Interleukin 17 receptor E-like]]
| caption = 
| image = 
| width = 
| HGNCid = 33808
| Symbol = IL17REL
| AltSymbols = 
| EntrezGene = 400935
| OMIM = 
| RefSeq = NM_001001694
| UniProt = Q6ZVW7
| PDB = 
| ECnumber = 
| Chromosome = 22
| Arm = q
| Band = 13.33
| LocusSupplementaryData = 
}}
'''Interleukin-17 receptor''' (IL-17R) is a [[cytokine receptor]] which binds [[interleukin 17A]].<ref name="pmid9367539">{{cite journal |vauthors=Yao Z, Spriggs MK, Derry JM, Strockbine L, Park LS, VandenBos T, Zappone JD, Painter SL, Armitage RJ | title = Molecular characterization of the human interleukin (IL)-17 receptor | journal = Cytokine | volume = 9 | issue = 11 | pages = 794–800 | year = 1997 | pmid = 9367539 | doi = 10.1006/cyto.1997.0240 }}</ref> Functional IL-17R is a heteromeric complex consisting of at least [[IL17RA]] and [[IL17RC]].<ref name="pmid16785495">{{cite journal |vauthors=Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J | title = Cutting edge: interleukin 17 signals through a heteromeric receptor complex | journal = J. Immunol. | volume = 177 | issue = 1 | pages = 36–9 | year = 2006 | pmid = 16785495 | doi = 10.4049/jimmunol.177.1.36| issn = | url = http://www.jimmunol.org/cgi/content/abstract/177/1/36 }}</ref>

A number of additional variants exist including [[IL17RB]],<ref name="pmid10815801">{{cite journal |vauthors=Tian E, Sawyer JR, Largaespada DA, Jenkins NA, Copeland NG, Shaughnessy JD | title = Evi27 encodes a novel membrane protein with homology to the IL17 receptor | journal = Oncogene | volume = 19 | issue = 17 | pages = 2098–109 | year = 2000 | pmid = 10815801 | doi = 10.1038/sj.onc.1203577 }}</ref> which binds preferentially [[Interleukin 17|IL17B]] and [[Interleukin 25|IL17E]].<ref name="pmid10749887">{{cite journal |vauthors=Shi Y, Ullrich SJ, Zhang J, Connolly K, Grzegorzewski KJ, Barber MC, Wang W, Wathen K, Hodge V, Fisher CL, Olsen H, Ruben SM, Knyazev I, Cho YH, Kao V, Wilkinson KA, Carrell JA, Ebner R | title = A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity | journal = J. Biol. Chem. | volume = 275 | issue = 25 | pages = 19167–76 | year = 2000 | pmid = 10749887 | doi = 10.1074/jbc.M910228199 }}</ref><ref name="pmid11058597">{{cite journal |vauthors=Lee J, Ho WH, Maruoka M, Corpuz RT, Baldwin DT, Foster JS, Goddard AD, Yansura DG, Vandlen RL, Wood WI, Gurney AL | title = IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1 | journal = J. Biol. Chem. | volume = 276 | issue = 2 | pages = 1660–4 | year = 2001 | pmid = 11058597 | doi = 10.1074/jbc.M008289200 }}</ref> A total of five members of the family have been identified.<ref name="pmid19016708">{{cite journal |vauthors=Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K |title=Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin |journal=Br. J. Dermatol. |volume=160 |issue=2 |pages=319–24 |date=February 2009 |pmid=19016708 |doi=10.1111/j.1365-2133.2008.08902.x |url=}}</ref> The first identified member, IL-17RA is located on human chromosome 22.

==Evolution==

There are two IL17Rs (IL17RA and IL17RD) in the genome of the basal chordate ''[[Amphioxus]]''.<ref name="pmid21732179">{{cite journal |vauthors=Wu B, Jin M, Zhang Y, Wei T, Bai Z | title = Evolution of the IL17 receptor family in chordates: a new subfamily IL17REL | journal = Immunogenetics | volume = 63| issue = 12| pages = 835–45|date=July 2011 | pmid = 21732179 | doi = 10.1007/s00251-011-0554-4 }}</ref> After two rounds of whole genome duplications, these two IL17R genes expanded into five early vertebrate IL17R genes, IL17RA to IL17RE. Two (IL17RA and IL17RD) are found in most vertebrates, whereas the other three (IL17RB, ILR17RC and IL17RE) have undergone some losses in vertebrates during evolution.

== Structure ==

IL-17RA is the founding member of a new IL-17R(A-E) subfamily of cytokine receptors. IL-17RA is by far the largest member of the family and has the largest cytoplasmic tail of the family. This cytoplasmic tail provides docking sites for numerous signaling intermediates. IL-17RA is composed of both [[alpha helix|alpha helices]] and [[beta sheet]]s and has [[fibronectin]] domains, [[beta barrel|beta-sandwich]] domains, and [[ectodomain]]s.<ref name="pmid19575028">{{cite journal | author = Gaffen SL | title = Structure and signalling in the IL-17 receptor family | journal = Nat. Rev. Immunol. | volume = 9 | issue = 8 | pages = 556–67 |date=August 2009 | pmid = 19575028 | pmc = 2821718 | doi = 10.1038/nri2586 }}</ref>

==Distribution==
IL-17 RA has been observed at high levels in certain tissues such as: haematopoietic, bone marrow, thymus, and spleen tissue. IL-17 RA is also normally found in low levels in colon, small intestine, and lung tissues.<ref name="pmid20012905"/>

==Expression and regulation==
IL-17RA is expressed in CD8+ T cells, and upregulated by IL-15 and IL-21.<ref name="pmid20012905"/> IL-17RA may be internalised after binding IL-17A.<ref name="pmid20012905"/>

IL-17RC expression is low in haematopoietic tissues and high in non-immune cells of the prostate, liver, kidney, thyroid and joints.<ref name="pmid20012905"/>

== Clinical significance ==
{{as of |2010}} IL-17A neutralizing antibodies have the potential for the treatment of autoimmune diseases in humans. It also may soon be used for protection against [[periodontal]] bone loss as it is currently being tested in mice. IL-17 RA has been observed at high levels in people undergoing treatment for cardiac fibroblasts and in certain tissues such as: haematopoietic, bone marrow, thymus, and spleen tissue.<ref name="pmid20012905">{{cite journal |vauthors=Ho AW, Gaffen SL | title = IL-17RC: a partner in IL-17 signaling and beyond | journal = Semin Immunopathol | volume = 32 | issue = 1 | pages = 33–42 |date=March 2010 | pmid = 20012905 | pmc = 2837117 | doi = 10.1007/s00281-009-0185-0 }}</ref>

===As therapy targets===
Approved anti-IL17(R) drugs include : [[Brodalumab]] (Siliq), an antibody to the receptor, approved for [[psoriasis]].
[[Ixekizumab]], approved for plaque psoriasis, is an antibody to IL-17 itself (rather than the receptor).

==See also==
* [[T helper 17 cell]]
* [[IL-17 family]]

==References==
{{Reflist|2}}

==External links==
* {{MeshName|Receptors,+Interleukin-17}}
* 'http://www.rcsb.org/pdb/explore/explore.do?structureId=3JVF'

{{Cytokine receptors}}
{{Interleukin receptor modulators}}

[[Category:IL17 family cytokine receptors]]