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Tclin Interleukin-17 receptor A

Receptor for IL17A (PubMed:17911633, PubMed:9367539). Receptor for IL17F (PubMed:19838198, PubMed:17911633). Binds to IL17A with higher affinity than to IL17F (PubMed:17911633). Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (PubMed:16785495). Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (PubMed:18684971). Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848). Activation of IL17RA leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1, CXCL8/IL8 and IL6 (PubMed:16785495, PubMed:17911633, PubMed:18684971).

Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]

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Property Summary

NCBI Gene PubMed Count 68
PubMed Score 107.64
PubTator Score 90.32

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Disease Target Count
Plaque psoriasis 14

Expression

  Differential Expression (13)

Disease log2 FC p
hepatocellular carcinoma 1.200 3.0e-05
pancreatic cancer 1.200 5.5e-03
osteosarcoma -3.230 4.9e-05
astrocytoma 1.300 3.8e-03
glioblastoma 1.300 1.6e-04
tuberculosis 1.500 5.0e-04
pediatric high grade glioma 1.100 4.0e-05
group 3 medulloblastoma -1.400 2.3e-03
pilocytic astrocytoma 1.300 1.5e-08
pancreatic carcinoma 1.200 5.5e-03
lung carcinoma -1.500 6.8e-25
ovarian cancer 1.400 5.6e-06
pituitary cancer -1.300 3.8e-04

Synonym

Accession Q96F46 O43844 Q20WK1 IL-17 receptor A
Symbols CD217
IL17R
CANDF5
CDw217
IL-17RA
hIL-17R

Gene

IL17RA

PDB

3JVF   4HSA   4NUX  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (16)

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 GO Function (1)

 GO Component (3)

 GO Process (8)

 Compartment GO Term (17)

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 MGI Phenotype (7)

 HCA RNA Cell Line (56)

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 CSPA Cell Line (23)

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Pathway (11)

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Protein-protein Interaction (60)

IL17A   IL17RC   IL17RE   IL17RB   ACAD11   DYNC2H1   IQGAP3   KIAA1671   SMG8   RPS6KA3   RPS6KA2   RPS6KA1   MAP7D2   ZNF318   ICE2   FAM208A   YEATS2   RICTOR   NCOR1   BCOR   PPIP5K2   BRIP1   HTT   TUBA4A   DDX11   DDX11L8   MCM8   CCDC88A   LRIF1   CBWD1   SIMC1   PLCH1   TUBB1   EIF4E2   ZBTB33   GTSE1   ZNF644   ANKHD1   NR3C1   ESPL1   TBL1XR1   TBL1X   GSG2   BCAS3   TTF2   HDAC3   ZNHIT6   KIAA0586   C5orf34   USP54   TRPS1   MAP7   HAUS5   MKS1   TBCD   C15orf39   C14orf80   SIK2   PLEKHA5   PKN3  

Drug (1)

No structure for brodalumab

brodalumab
pKd 9.20

Ligand (1)

Structure of CHEMBL2086760

CHEMBL2086760
pIC50 7.60

Gene RIF (54)

PMID Text
26667835 IL17F and IL17RA polymorphisms modulate susceptibility to cerebral malaria(CM) and provide evidence that IL-17F protects against CM.
26607704 IL-17 receptor A and adenosine deaminase 2 deficiency due to deletion mutations was found in siblings with chronic mucocutaneous candidiasis and chronic systemic inflammation.
26451724 The data indicate that the genetic variants of rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA may not play a role in the pathogenesis of preeclampsia in Chinese Han women.
26356122 expression of immunoreactivity for IL-17A, IL-17RA, IL-17E, and IL-17F was significantly elevated in prostatic tissue from benign prostatic hyperplasia and prostate cancer compared with that in controls
26347322 Identified the IL17RA rs4819554 SNP as a risk factor for psoriasis.
26261590 Increased expression of IL-17RA plays an important role in gastric cancer progression, migration and prognosis.
26228109 High IL-17RA expression is associated with Intrahepatic Cholangiocarcinoma.
26198032 In vitro, CSE stimulation significantly increased IL-17F and IL-17R in 16HBE (2.5%) and A549 (5%) while IL-17A and IL-17F in PBMC (10%). IL-17A and CSE stimulation, rather than CSE or rhIL-17A alone, increased proliferation in 16HBE and apoptosis in A549
26123260 The presence of IL7R polymorphisms seems to be related to severe liver disease in HIV/hepatitis c virus coinfected patients.
25935436 Both genetic variants of IL-17R (rs882643 and rs2241049) were associated with PGD. This confirms a genetic predisposition toward PGD and suggests a role of IL-17 in driving neutrophilia in PGD.
25636567 genetic polymorphism is associated with a reduced renal filtration rate, and with the risk of developing end stage renal disease in healthy elderly from Spain
25484349 IL17RA polymorphisms, but not those of IL17, can influence both the development and the bilaterality of papillary thyroid carcinoma
24916639 IL-17R was almost exclusively expressed by endothelial cells, not by myeloma cells in the masses of skeletal extramedullary disease patients.
24816115 Interleukin-17 receptor A crystal structure shows that the downstream motif of IL-17RA SEFIR together with helix alpha C could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.
24780906 IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor
24263024 Genetic variation in interleukin-17 receptor A is functionally associated with chronic rejection after lung transplantation.
24247484 The increased IL-25 levels in plasma and the expression of IL-17RA and IL-17RB on eosinophils in allergic asthma patients suggests that IL-25 may activate eosinophils during allergic inflammation.
24166352 Whereas no association was found between the alternative splicing SNP, rs6897932, and multiple sclerosis, a significant link was found between the promoter single nucleotide polymorphism, rs11567685, and the disease.
24084331 Data show that the interleukin (IL)-17 receptor IL-17RA variant is generated by spliced out of exon 11 encoding the transmembrane region in a variety of tissues.
23852838 polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis.
23695682 crystal structures of homodimeric IL-17A and its complex with IL-17RA, are reported.
23501056 Our data indicates that serum IL-17 levels are significantly increased in intractable Graves disease and affected thyrocytes show functional IL-17R expression.
23334598 protein levels of IL-17 and IL-17R positively correlated with the frequency of seizures in focal cortical dysplasias patients patients.
23220496 Data suggest that the interleukin 17 receptor A (IL17RA) minor alleles of the three single nucleotide polymorphisms (SNP) may decrease the risk of Aspirin Exacerbated Respiratory Disease (AERD) via attenuation of IL17RA gene expression.
23192273 IL-17A/IL-17RA interaction promoted the metastasis of OS in nude mice.
23147652 Two polymorphisms within the IL17E and IL17RA genes are associated with ESRD independent of age and sex.
22955875 Il-17R SNPs were not associated with psoriatic arthritis susceptibility in northern Italians.
22909235 Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis.
22898922 Data show that IL-17RA, IL-17RC, IL-22R1, ERK1/2 MAPK and NF-kappaB pathways are involved in Th17 cytokine-induced proliferation.
22484243 IFN-alpha could be associated with the expansion of IL-7Ralpha(low) CD45RA(+) EM CD8(+) T cells in the CMV-uninfected elderly
21894442 Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3; demonstrate the functional significance of IL-17RA in psoriatic arthritis
21530504 IL-17/IL-17RA signaling plays an important role in myocardial collagen metabolism in hypertension-induced diastolic dysfunction.
21279695 mRNA levels of IL-17, IL-17R and MMP-9 were also higher in the invasive group than in the non-invasive group in human pituitary adenomas.
21145111 Human periodontal ligament fibroblasts are a target of Th17, and that IL-17 appears to up-regulate the expression of IL-23 p19 via a homeostatic mechanism involving Akt-, p38 MAPK-, and ERK 1/2-dependent NF-kappaB signalling versus the JNK/AP-1 pathway.
20729198 an extended SEFIR domain is required for il-17RA-mediated signal transduction.
20503287 Observational study of gene-disease association. (HuGE Navigator)
20237496 Observational study of gene-disease association. (HuGE Navigator)
19258923 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19244213 IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain.
19235914 significant association between Crohn disease and the widely replicated IL23R variants is only seen in the presence of IL17A or IL17RA variants
18768888 IL-17RA plays a functional role in the human IL-25 receptor complex in vitro that is independent of IL-17A.
18684971 Interleukin (IL)-17A activity is inhibited by the IL-17RA receptor, and a combination of soluble IL-17RA/IL-17RC receptors is required for inhibition of heterodimeric IL-17F/IL-17A activity.
18348982 IL-2 and IL-15 differentially regulate PI3K and IL-17RA
18097068 IL-17A-induced IL-6, IL-8, and CCL20 secretion was dependent on both IL-17RA and IL-17RC, which are overexpressed in RA patients.
17876645 IL-17 contributes to osteoclastic bone resoption in RA patients.
17703412 Observational study of gene-disease association. (HuGE Navigator)
17456598 structure-function analysis of a IL-17 superfamily receptor reveals important differences in IL-17RA compared with IL-1/TLR receptors
17346928 This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6.
16874957 IL-17 may have an important role in the occurrence of nasal polyps by specific combination with IL-17R and over-expression in nasal polyps.
16805377 Both IL-17 and IL-17R displayed specific bands in nasal polyps and turbinates, but the bands of IL-17 and IL-17R in nasal polyps were stronger than those in turbinates.
16785495 The biologic activity of IL-17 is dependent on a complex composed of receptors IL-17RA and IL-17RC.
16533341 In this JEG-3 cell model of human trophoblast, the IL-17 receptor may have a regulatory role in trophoblast invasion.
15972674 cell membrane IL-17R is required for signaling by both IL-17A and IL-17F
11966773 Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis

AA Sequence 

MGAARSPPSAVPGPLLGLLLLLLGVLAPGGASLRLLDHRALVCSQPGLNCTVKNSTCLDDSWIHPRNLTP      1 - 70
SSPKDLQIQLHFAHTQQGDLFPVAHIEWTLQTDASILYLEGAELSVLQLNTNERLCVRFEFLSKLRHHHR     71 - 140
RWRFTFSHFVVDPDQEYEVTVHHLPKPIPDGDPNHQSKNFLVPDCEHARMKVTTPCMSSGSLWDPNITVE    141 - 210
TLEAHQLRVSFTLWNESTHYQILLTSFPHMENHSCFEHMHHIPAPRPEEFHQRSNVTLTLRNLKGCCRHQ    211 - 280
VQIQPFFSSCLNDCLRHSATVSCPEMPDTPEPIPDYMPLWVYWFITGISILLVGSVILLIVCMTWRLAGP    281 - 350
GSEKYSDDTKYTDGLPAADLIPPPLKPRKVWIIYSADHPLYVDVVLKFAQFLLTACGTEVALDLLEEQAI    351 - 420
SEAGVMTWVGRQKQEMVESNSKIIVLCSRGTRAKWQALLGRGAPVRLRCDHGKPVGDLFTAAMNMILPDF    421 - 490
KRPACFGTYVVCYFSEVSCDGDVPDLFGAAPRYPLMDRFEEVYFRIQDLEMFQPGRMHRVGELSGDNYLR    491 - 560
SPGGRQLRAALDRFRDWQVRCPDWFECENLYSADDQDAPSLDEEVFEEPLLPPGTGIVKRAPLVREPGSQ    561 - 630
ACLAIDPLVGEEGGAAVAKLEPHLQPRGQPAPQPLHTLVLAAEEGALVAAVEPGPLADGAAVRLALAGEG    631 - 700
EACPLLGSPGAGRNSVLFLPVDPEDSPLGSSTPMASPDLLPEDVREHLEGLMLSLFEQSLSCQAQGGCSR    701 - 770
PAMVLTDPHTPYEEEQRQSVQSDQGYISRSSPQPPEGLTEMEEEEEEEQDPGKPALPLSPEDLESLRSLQ    771 - 840
RQLLFRQLQKNSGWDTMGSESEGPSA                                                841 - 866
//

Text Mined References (71)

PMID Year Title
26667835 2015 The IL17F and IL17RA Genetic Variants Increase Risk of Cerebral Malaria in Two African Populations.
26607704 2016 IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation.
26451724 2015 Role of IL-17 Variants in Preeclampsia in Chinese Han Women.
26356122 2015 Expression of IL-17A, E, and F and their receptors in human prostatic cancer: Comparison with benign prostatic hyperplasia.
26347322 2015 Association between single nucleotide polymorphisms IL17RA rs4819554 and IL17E rs79877597 and Psoriasis in a Spanish cohort.
26261590 2015 Increased chemokine receptor IL-17RA expression is associated with poor survival in gastric cancer patients.
26228109 2015 Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma.
26198032 2015 Cigarette smoke affects IL-17A, IL-17F and IL-17 receptor expression in the lung tissue: Ex vivo and in vitro studies.
26123260 2015 Association between IL7R polymorphisms and severe liver disease in HIV/HCV coinfected patients: a cross-sectional study.
25935436 2015 Interleukin-17 receptor polymorphism predisposes to primary graft dysfunction after lung transplantation.
25636567 2015 Association between the IL17RA rs4819554 polymorphism and reduced renal filtration rate in the Spanish RENASTUR cohort.
25484349 2015 Association between interleukin 17/interleukin 17 receptor gene polymorphisms and papillary thyroid cancer in Korean population.
25130324 2014 A genome-wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus.
24916639 2014 Interleukin-17 receptor expression on vascular endothelial cells of masses of skeletal extramedullary disease in myeloma patients.
24816115 2014 Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved ?-helix for Act1 binding and IL-17 signaling.
24780906 2014 Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker: implications for age-related macular degeneration.
24263024 2013 Genetic variation in interleukin-17 receptor A is functionally associated with chronic rejection after lung transplantation.
24247484 2014 IL-25 and IL-25 receptor expression on eosinophils from subjects with allergic asthma.
24166352 2014 The promoter SNP, but not the alternative splicing SNP, is linked to multiple sclerosis among Jordanian patients.
24084331 2013 Identification of a soluble isoform of human IL-17RA generated by alternative splicing.
23852838 2013 Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.
23695682 2013 Crystal structures of interleukin 17A and its complex with IL-17 receptor A.
23501056 2013 Functional interleukin-17 receptor A are present in the thyroid gland in intractable Graves disease.
23334598 2013 The interleukin 17 system in cortical lesions in focal cortical dysplasias.
23220496 2013 Association of single nucleotide polymorphisms on Interleukin 17 receptor A (IL17RA) gene with aspirin hypersensitivity in asthmatics.
23192273 2013 IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23147652 2012 Gene polymorphisms of interleukin-17 and interleukin-17 receptor are associated with end-stage kidney disease.
22955875 2013 IL-23A, IL-23R, IL-17A and IL-17R polymorphisms in different psoriatic arthritis clinical manifestations in the northern Italian population.
22909235 2013 Gene-gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population.
22898922 2012 Th17-associated cytokines promote human airway smooth muscle cell proliferation.
22484243 2012 The relationship of cytomegalovirus (CMV) infection with circulatory IFN-? levels and IL-7 receptor ? expression on CD8+ T cells in human aging.
21993848 2011 IL-17C regulates the innate immune function of epithelial cells in an autocrine manner.
21894442 2012 IL-17 receptor and its functional significance in psoriatic arthritis.
21530504 2011 Lentivirus mediated IL-17R blockade improves diastolic cardiac function in spontaneously hypertensive rats.
21350122 2011 Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity.
21279695 2011 The expression of interleukin (IL)-17 and IL-17 receptor and MMP-9 in human pituitary adenomas.
21145111 2011 IL-17R activation of human periodontal ligament fibroblasts induces IL-23 p19 production: Differential involvement of NF-?B versus JNK/AP-1 pathways.
20729198 2010 SEF/IL-17R (SEFIR) is not enough: an extended SEFIR domain is required for il-17RA-mediated signal transduction.
20503287 2010 Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
19838198 2009 Structural basis of receptor sharing by interleukin 17 cytokines.
19258923 2009 Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes.
19244213 2009 IL-17 receptor signaling inhibits C/EBPbeta by sequential phosphorylation of the regulatory 2 domain.
19235914 2009 Genetic epistasis of IL23/IL17 pathway genes in Crohn's disease.
18768888 2008 Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities.
18684971 2008 The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex.
18348982 2008 Differential regulation of the IL-17 receptor by gammac cytokines: inhibitory signaling by the phosphatidylinositol 3-kinase pathway.
18097068 2008 IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR+ CXC chemokine expression in synoviocytes and are overexpressed in rheumatoid blood.
17911633 2007 Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F.
17876645 2007 Associations between HLA-DRB1, RANK, RANKL, OPG, and IL-17 genotypes and disease severity phenotypes in Japanese patients with early rheumatoid arthritis.
17703412 2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes.
17456598 2007 Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression.
17346928 2007 Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6.
16874957 2005 [Expression and significance of interleukin-17 and its receptor in nasal polyps].
16805377 2006 Expression profile of immune-associated genes in nasal polyps.
16785495 2006 Cutting edge: interleukin 17 signals through a heteromeric receptor complex.
16533341 2006 The effect of interleukin-17 on the proliferation and invasion of JEG-3 human choriocarcinoma cells.
15972674 2005 Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15461802 2004 A genome annotation-driven approach to cloning the human ORFeome.
15340161 2004 Signal peptide prediction based on analysis of experimentally verified cleavage sites.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12772186 2003 Expression and function of pro-inflammatory interleukin IL-17 and IL-17 receptor in normal, benign hyperplastic, and malignant prostate.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11966773 2002 Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis.
11706037 2002 Soluble and transmembrane isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer.
11381032 2001 Analysis of the cat eye syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere.
11371660 2001 High in vivo expression of interleukin-17 receptor in synovial endothelial cells and chondrocytes from arthritis patients.
10591208 1999 The DNA sequence of human chromosome 22.
9367539 1997 Molecular characterization of the human interleukin (IL)-17 receptor.