Interleukin-17 receptor

interleukin 17 receptor A
	File:5JVF.pdb.jpg Crystal structure of a complex of IL-17RA bound to IL-17F in a 1:2 stoichiometry.
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

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Interleukin-17 receptor
Identifiers
Symbol	IL17R
Pfam	PF08357
InterPro	IPR013568
Membranome	8
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

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

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

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 helices and beta sheets and has fibronectin domains, beta-sandwich domains, and ectodomains.^[9]

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.^[10]

Expression and regulation

IL-17RA is expressed in CD8+ T cells, and upregulated by IL-15 and IL-21.^[10] IL-17RA may be internalised after binding IL-17A.^[10]

IL-17RC expression is low in haematopoietic tissues and high in non-immune cells of the prostate, liver, kidney, thyroid and joints.^[10]

Clinical significance

As of 2010^[update] 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.^[10]

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).

References

↑ 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.
↑ 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.
↑ 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. doi:10.4049/jimmunol.177.1.36. PMID 16785495.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 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

Receptors,+Interleukin-17 at the US National Library of Medicine Medical Subject Headings (MeSH)
'http://www.rcsb.org/pdb/explore/explore.do?structureId=3JVF'

[pmid19838198-1] 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.

[pmid9367539-2] 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.

[pmid16785495-3] 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. doi:10.4049/jimmunol.177.1.36. PMID 16785495.

[pmid10815801-4] 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.

[pmid10749887-5] 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.

[pmid11058597-6] 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.

[pmid19016708-7] 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.

[pmid21732179-8] 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.

[pmid19575028-9] 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.

[pmid20012905-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 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.

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