Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVVI8ER)

• DOT Name: Interleukin-17 receptor A (IL17RA)
• Synonyms: IL-17 receptor A; IL-17RA; CDw217; CD antigen CD217
• Gene Name: IL17RA
• Related Disease:
  Crohn disease
  Psoriatic arthritis
  Type-1 diabetes
  Adenocarcinoma
  Advanced cancer
  Autism spectrum disorder
  Autoimmune disease
  Bone osteosarcoma
  Brain ischaemia
  Candidiasis
  Capillary malformation
  Cardiac failure
  Classic Hodgkin lymphoma
  Colitis
  Congestive heart failure
  Coronary atherosclerosis
  Coronary heart disease
  Gastric cancer
  Generalized pustular psoriasis
  Glioma
  Huntington disease
  Immunodeficiency 51
  Influenza
  Malignant glioma
  Multiple sclerosis
  Neoplasm
  Nervous system inflammation
  Non-alcoholic fatty liver disease
  Non-small-cell lung cancer
  Osteosarcoma
  Squamous cell carcinoma
  Stomach cancer
  Systemic sclerosis
  Tuberculosis
  Chronic obstructive pulmonary disease
  Chronic renal failure
  Head-neck squamous cell carcinoma
  Rheumatoid arthritis
  Chronic mucocutaneous candidiasis
  Arthritis
  Asthma
  Bladder cancer
  Colorectal carcinoma
  Prostate cancer
  Prostate carcinoma
  Psoriasis
  Thyroid gland papillary carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: I17RA_HUMAN
• PDB ID: 3JVF; 4HSA; 4NUX; 5N9B; 5NAN; 7UWL; 7UWM; 7UWN; 7ZAN
• Pfam ID: PF16556 ; PF16578 ; PF08357
• Sequence:
  MGAARSPPSAVPGPLLGLLLLLLGVLAPGGASLRLLDHRALVCSQPGLNCTVKNSTCLDD
  SWIHPRNLTPSSPKDLQIQLHFAHTQQGDLFPVAHIEWTLQTDASILYLEGAELSVLQLN
  TNERLCVRFEFLSKLRHHHRRWRFTFSHFVVDPDQEYEVTVHHLPKPIPDGDPNHQSKNF
  LVPDCEHARMKVTTPCMSSGSLWDPNITVETLEAHQLRVSFTLWNESTHYQILLTSFPHM
  ENHSCFEHMHHIPAPRPEEFHQRSNVTLTLRNLKGCCRHQVQIQPFFSSCLNDCLRHSAT
  VSCPEMPDTPEPIPDYMPLWVYWFITGISILLVGSVILLIVCMTWRLAGPGSEKYSDDTK
  YTDGLPAADLIPPPLKPRKVWIIYSADHPLYVDVVLKFAQFLLTACGTEVALDLLEEQAI
  SEAGVMTWVGRQKQEMVESNSKIIVLCSRGTRAKWQALLGRGAPVRLRCDHGKPVGDLFT
  AAMNMILPDFKRPACFGTYVVCYFSEVSCDGDVPDLFGAAPRYPLMDRFEEVYFRIQDLE
  MFQPGRMHRVGELSGDNYLRSPGGRQLRAALDRFRDWQVRCPDWFECENLYSADDQDAPS
  LDEEVFEEPLLPPGTGIVKRAPLVREPGSQACLAIDPLVGEEGGAAVAKLEPHLQPRGQP
  APQPLHTLVLAAEEGALVAAVEPGPLADGAAVRLALAGEGEACPLLGSPGAGRNSVLFLP
  VDPEDSPLGSSTPMASPDLLPEDVREHLEGLMLSLFEQSLSCQAQGGCSRPAMVLTDPHT
  PYEEEQRQSVQSDQGYISRSSPQPPEGLTEMEEEEEEEQDPGKPALPLSPEDLESLRSLQ
  RQLLFRQLQKNSGWDTMGSESEGPSA
• 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. Receptor for IL17F. Binds to IL17A with higher affinity than to IL17F. Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC. Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC. 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. Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi. 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. 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. 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. Receptor for IL17C as part of a heterodimeric complex with IL17RE ; (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.
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  IL-17 sig.ling pathway (hsa04657)
  Alcoholic liver disease (hsa04936)
• Reactome Pathway:
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Interleukin-17 signaling (R-HSA-448424)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Crohn disease	DIS2C5Q8	Definitive	Genetic Variation	[1]
Psoriatic arthritis	DISLWTG2	Definitive	Biomarker	[2]
Type-1 diabetes	DIS7HLUB	Definitive	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Autism spectrum disorder	DISXK8NV	Strong	Altered Expression	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Brain ischaemia	DIS9Q4RT	Strong	Biomarker	[9]
Candidiasis	DISIRYMU	Strong	Biomarker	[10]
Capillary malformation	DISR6ZSG	Strong	Genetic Variation	[11]
Cardiac failure	DISDC067	Strong	Genetic Variation	[12]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[13]
Colitis	DISAF7DD	Strong	Biomarker	[14]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[12]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[15]
Coronary heart disease	DIS5OIP1	Strong	Biomarker	[15]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[16]
Generalized pustular psoriasis	DISTSNLR	Strong	Biomarker	[17]
Glioma	DIS5RPEH	Strong	Biomarker	[18]
Huntington disease	DISQPLA4	Strong	Altered Expression	[13]
Immunodeficiency 51	DISSNV1N	Strong	Autosomal recessive	[19]
Influenza	DIS3PNU3	Strong	Altered Expression	[20]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[21]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[22]
Neoplasm	DISZKGEW	Strong	Biomarker	[23]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[22]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Genetic Variation	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[4]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[16]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[26]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[27]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[28]
Chronic renal failure	DISGG7K6	moderate	Genetic Variation	[29]
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[30]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[27]
Chronic mucocutaneous candidiasis	DISPSGYF	Supportive	Autosomal dominant	[19]
Arthritis	DIST1YEL	Limited	Biomarker	[31]
Asthma	DISW9QNS	Limited	Biomarker	[32]
Bladder cancer	DISUHNM0	Limited	Biomarker	[33]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[23]
Prostate cancer	DISF190Y	Limited	Biomarker	[34]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[34]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[35]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Genetic Variation	[36]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[33]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[33]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Interleukin-17 receptor A (IL17RA).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interleukin-17 receptor A (IL17RA).	[41]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Interleukin-17 receptor A (IL17RA).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interleukin-17 receptor A (IL17RA).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-17 receptor A (IL17RA).	[40]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Interleukin-17 receptor A (IL17RA).	[42]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-17 receptor A (IL17RA).	[43]

References

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