IL17RA (interleukin 17 receptor A)

Gene

• Entrez ID: 23765
• Gene name: Interleukin 17 receptor A
• Gene symbol: IL17RA
• Synonyms: CANDF5, CD217, CDw217, IL-17RA, IL17R, IMD51, hIL-17R
• Chromosome: 22
• Chromosome location: 22q11.1
• Summary: 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs201128237	T>C	Likely-pathogenic	Splice donor variant
rs387906913	C>T	Pathogenic	Stop gained, coding sequence variant
rs778624945	C>A,T	Pathogenic	Synonymous variant, coding sequence variant, stop gained
rs1057518744	->GGAGATGGTGGAGAGCA	Pathogenic	Frameshift variant, coding sequence variant
rs1057518745	C>G,T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs1057518746	C>-	Pathogenic	Frameshift variant, coding sequence variant
rs1057518747	CCAGA>-	Pathogenic	Frameshift variant, coding sequence variant
rs1057519079	G>A	Pathogenic	Coding sequence variant, missense variant
rs1601340933	->ACCT	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019991	hsa-miR-375	Microarray	20215506
MIRT049271	hsa-miR-92a-3p	CLASH	23622248
MIRT450048	hsa-miR-3978	PAR-CLIP	22100165
MIRT450049	hsa-miR-6807-5p	PAR-CLIP	22100165
MIRT450050	hsa-miR-7160-5p	PAR-CLIP	22100165
MIRT450051	hsa-miR-7854-3p	PAR-CLIP	22100165
MIRT450052	hsa-miR-6134	PAR-CLIP	22100165
MIRT450053	hsa-miR-6823-3p	PAR-CLIP	22100165
MIRT450054	hsa-miR-2114-3p	PAR-CLIP	22100165
MIRT450055	hsa-miR-7162-3p	PAR-CLIP	22100165
MIRT450056	hsa-miR-135b-5p	PAR-CLIP	22100165
MIRT450057	hsa-miR-135a-5p	PAR-CLIP	22100165
MIRT450058	hsa-miR-4662b	PAR-CLIP	22100165
MIRT450059	hsa-miR-4647	PAR-CLIP	22100165
MIRT450060	hsa-miR-4426	PAR-CLIP	22100165
MIRT631777	hsa-miR-498	HITS-CLIP	23824327
MIRT631778	hsa-miR-5001-3p	HITS-CLIP	23824327
MIRT631779	hsa-miR-4279	HITS-CLIP	23824327
MIRT631780	hsa-miR-4772-3p	HITS-CLIP	23824327
MIRT631781	hsa-miR-3653-5p	HITS-CLIP	23824327
MIRT631782	hsa-miR-10b-3p	HITS-CLIP	23824327
MIRT631783	hsa-miR-5571-5p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002250	Process	Adaptive immune response	IEA
GO:0005515	Function	Protein binding	IPI	21993848, 23695682, 24120361, 28827714, 32353859, 33060197
GO:0005576	Component	Extracellular region	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	NAS	9367539
GO:0006954	Process	Inflammatory response	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	NAS	9367539
GO:0030368	Function	Interleukin-17 receptor activity	IBA	21873635
GO:0030368	Function	Interleukin-17 receptor activity	NAS	9367539
GO:0032747	Process	Positive regulation of interleukin-23 production	IDA	21145111
GO:0032755	Process	Positive regulation of interleukin-6 production	IMP	21350122
GO:0045087	Process	Innate immune response	IEA
GO:0072537	Process	Fibroblast activation	IDA	21145111
GO:0097400	Process	Interleukin-17-mediated signaling pathway	IMP	21350122
GO:0097400	Process	Interleukin-17-mediated signaling pathway	TAS
GO:2000340	Process	Positive regulation of chemokine (C-X-C motif) ligand 1 production	IMP	21350122

Other IDs

• MIM: 605461
• HGNC: 5985
• e!Ensembl: ENSG00000177663

Protein

• UniProt ID: Q96F46
• Protein name: Interleukin-17 receptor A (IL-17 receptor A) (IL-17RA) (CDw217) (CD antigen CD217)
• Protein function: Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. 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). Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16785495, PubMed:24120361, PubMed:17911633, PubMed:18684971, PubMed:21350122). Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (By similarity). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity). Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (By similarity). Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848). ; (Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway.
• PDB: 3JVF, 4HSA, 4NUX, 5N9B, 5NAN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16556	IL17R_fnIII_D1	48 → 198	Interleukin-17 receptor, fibronectin-III-like domain 1	Domain
  PF16578	IL17R_fnIII_D2	199 → 303		Domain
  PF08357	SEFIR	378 → 536	SEFIR domain	Family

• Sequence:

  MGAARSPPSAVPGPLLGLLLLLLGVLAPGGASLRLLDHRALVCSQPGLNCTVKNSTCLDD
  SWIHPRNLTPSSPKDLQIQLHFAHTQQGDLFPVAHIEWTLQTDASILYLEGAELSVLQLN
  TNERLCVRFEFLSKLRHHHRRWRFTFSHFVVDPDQEYEVTVHHLPKPIPDGDPNHQSKNF
  LVPDCEHARMKVTTPCMSSGSLWDPNITVETLEAHQLRVSFTLWNESTHYQILLTSFPHM
  ENHSCFEHMHHIPAPRPEEFHQRSNVTLTLRNLKGCCRHQVQIQPFFSSCLNDCLRHSAT
  VSCPEMPDTPEPIPDYMPLWVYWFITGISILLVGSVILLIVCMTWRLAGPGSEKYSDDTK
  YTDGLPAADLIPPPLKPRKVWIIYSADHPLYVDVVLKFAQFLLTACGTEVALDLLEEQAI
  SEAGVMTWVGRQKQEMVESNSKIIVLCSRGTRAKWQALLGRGAPVRLRCDHGKPVGDLFT
  AAMNMILPDFKRPACFGTYVVCYFSEVSCDGDVPDLFGAAPRYPLMDRFEEVYFRIQDLE
  MFQPGRMHRVGELSGDNYLRSPGGRQLRAALDRFRDWQVRCPDWFECENLYSADDQDAPS
  LDEEVFEEPLLPPGTGIVKRAPLVREPGSQACLAIDPLVGEEGGAAVAKLEPHLQPRGQP
  APQPLHTLVLAAEEGALVAAVEPGPLADGAAVRLALAGEGEACPLLGSPGAGRNSVLFLP
  VDPEDSPLGSSTPMASPDLLPEDVREHLEGLMLSLFEQSLSCQAQGGCSRPAMVLTDPHT
  PYEEEQRQSVQSDQGYISRSSPQPPEGLTEMEEEEEEEQDPGKPALPLSPEDLESLRSLQ
  RQLLFRQLQKNSGWDTMGSESEGPSA

• Sequence length: 866