Interleukin-17 receptor

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interleukin 17 receptor A
5JVF.pdb.jpg
Crystal structure of a complex of IL-17RA bound to IL-17F in a 1:2 stoichiometry.[1]
Identifiers
Symbol IL17RA
Alt. symbols IL17R, CDw217
Entrez 23765
HUGO 5985
OMIM 605461
RefSeq NM_014339
UniProt Q96F46
Other data
Locus Chr. 22 q11.1
interleukin 17 receptor B
Identifiers
Symbol IL17RB
Alt. symbols IL17BR
Entrez 55540
HUGO 18015
OMIM 605458
RefSeq NM_172234
UniProt Q9NRM6
Other data
Locus Chr. 3 p21.1
interleukin 17 receptor C
Identifiers
Symbol IL17RC
Alt. symbols IL17-RL
Entrez 84818
HUGO 18358
OMIM 610925
RefSeq NM_032732
UniProt Q8NAC3
Other data
Locus Chr. 3 p25.3
interleukin 17 receptor D
Identifiers
Symbol IL17RD
Alt. symbols SEF, IL17RLM, FLJ35755, IL-17RD
Entrez 54756
HUGO 17616
OMIM 606807
RefSeq NM_017563
UniProt Q8NFM7
Other data
Locus Chr. 3 p21.1
interleukin 17 receptor E
Identifiers
Symbol IL17RE
Alt. symbols FLJ23658
Entrez 132014
HUGO 18439
RefSeq NM_153480
UniProt Q8NFR9
Other data
Locus Chr. 3 p25.3
interleukin 17 receptor E-like
Identifiers
Symbol IL17REL
Entrez 400935
HUGO 33808
RefSeq NM_001001694
UniProt Q6ZVW7
Other data
Locus Chr. 22 q13.33

Interleukin-17 receptor (IL-17R) is a cytokine receptor which binds interleukin 17A.[2] Functional IL-17R is a heteromeric complex consisting of at least IL17RA and IL17RC.[3]

A number of additional variants exist including IL17RB,[4] which binds preferentially IL17B and IL17E.[5][6] A total of five members of the family have been identified.[7] The first identified member, IL-17RA is located on human chromosome 22.

Evolution[edit]

There are two IL17Rs (IL17RA and IL17RD) in the genome of the basal chordate Amphioxus.[8] 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[edit]

IL-17A and IL-17RA are founding members of a new subfamily receptors A-F. 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 helices and beta sheets and has fibronectin domains, beta-sandwich domains, and ectodomains.[9]

Clinical significance[edit]

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. IL-17 RA is also normally found in low levels in colon, small intestine, and lung tissues.[10]

See also[edit]

References[edit]

  1. ^ PDB 3JVF; Ely LK, Fischer S, Garcia KC (December 2009). "Structural basis of receptor sharing by interleukin 17 cytokines". Nat. Immunol. 10 (12): 1245–51. doi:10.1038/ni.1813. PMC 2783927. PMID 19838198. 
  2. ^ Yao Z, Spriggs MK, Derry JM, Strockbine L, Park LS, VandenBos T, Zappone JD, Painter SL, Armitage RJ (1997). "Molecular characterization of the human interleukin (IL)-17 receptor". Cytokine 9 (11): 794–800. doi:10.1006/cyto.1997.0240. PMID 9367539. 
  3. ^ Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006). "Cutting edge: interleukin 17 signals through a heteromeric receptor complex". J. Immunol. 177 (1): 36–9. PMID 16785495. 
  4. ^ Tian E, Sawyer JR, Largaespada DA, Jenkins NA, Copeland NG, Shaughnessy JD (2000). "Evi27 encodes a novel membrane protein with homology to the IL17 receptor". Oncogene 19 (17): 2098–109. doi:10.1038/sj.onc.1203577. PMID 10815801. 
  5. ^ 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 (2000). "A novel cytokine receptor-ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity". J. Biol. Chem. 275 (25): 19167–76. doi:10.1074/jbc.M910228199. PMID 10749887. 
  6. ^ Lee J, Ho WH, Maruoka M, Corpuz RT, Baldwin DT, Foster JS, Goddard AD, Yansura DG, Vandlen RL, Wood WI, Gurney AL (2001). "IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1". J. Biol. Chem. 276 (2): 1660–4. doi:10.1074/jbc.M008289200. PMID 11058597. 
  7. ^ Johansen C, Usher PA, Kjellerup RB, Lundsgaard D, Iversen L, Kragballe K (February 2009). "Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin". Br. J. Dermatol. 160 (2): 319–24. doi:10.1111/j.1365-2133.2008.08902.x. PMID 19016708. 
  8. ^ Wu B, Jin M, Zhang Y, Wei T, Bai Z (July 2011). "Evolution of the IL17 receptor family in chordates: a new subfamily IL17REL". Immunogenetics 63 (12): 835–45. doi:10.1007/s00251-011-0554-4. PMID 21732179. 
  9. ^ Gaffen SL (August 2009). "Structure and signalling in the IL-17 receptor family". Nat. Rev. Immunol. 9 (8): 556–67. doi:10.1038/nri2586. PMC 2821718. PMID 19575028. 
  10. ^ Ho AW, Gaffen SL (March 2010). "IL-17RC: a partner in IL-17 signaling and beyond". Semin Immunopathol 32 (1): 33–42. doi:10.1007/s00281-009-0185-0. PMC 2837117. PMID 20012905. 

External links[edit]