Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOX3D1D)

• DOT Name: Interleukin-10 receptor subunit alpha (IL10RA)
• Synonyms: IL-10 receptor subunit alpha; IL-10R subunit alpha; IL-10RA; CDw210a; Interleukin-10 receptor subunit 1; IL-10R subunit 1; IL-10R1; CD antigen CD210
• Gene Name: IL10RA
• Related Disease:
  Arthritis
  Atopic dermatitis
  Benign prostatic hyperplasia
  Bladder cancer
  Chronic myelomonocytic leukaemia
  Colitis
  Colorectal carcinoma
  Cryohydrocytosis
  Enterocolitis
  Hepatitis B virus infection
  Idiopathic thrombocytopenic purpura
  Immunodeficiency
  Inflammatory bowel disease
  Inflammatory bowel disease 28
  Leprosy
  Liver cirrhosis
  Lung neoplasm
  Lymphoma, non-Hodgkin, familial
  Mental disorder
  Neoplasm
  Nephritis
  Non-hodgkin lymphoma
  Obesity
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Rheumatoid arthritis
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Visceral leishmaniasis
  Adult lymphoma
  Brain neoplasm
  Classic Hodgkin lymphoma
  Crohn disease
  High blood pressure
  Lupus nephritis
  Lymphoma
  Pediatric lymphoma
  Plasma cell myeloma
  Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
  Tuberculosis
  Ankylosing spondylitis
  B-cell neoplasm
  Chronic obstructive pulmonary disease
  Hepatitis C virus infection
  Malaria
  Metastatic malignant neoplasm
• UniProt ID: I10R1_HUMAN
• PDB ID: 1J7V; 1LQS; 1Y6K; 1Y6M; 1Y6N; 5IXI; 6X93
• Pfam ID: PF01108
• Sequence:
  MLPCLVVLLAALLSLRLGSDAHGTELPSPPSVWFEAEFFHHILHWTPIPNQSESTCYEVA
  LLRYGIESWNSISNCSQTLSYDLTAVTLDLYHSNGYRARVRAVDGSRHSNWTVTNTRFSV
  DEVTLTVGSVNLEIHNGFILGKIQLPRPKMAPANDTYESIFSHFREYEIAIRKVPGNFTF
  THKKVKHENFSLLTSGEVGEFCVQVKPSVASRSNKGMWSKEECISLTRQYFTVTNVIIFF
  AFVLLLSGALAYCLALQLYVRRRKKLPSVLLFKKPSPFIFISQRPSPETQDTIHPLDEEA
  FLKVSPELKNLDLHGSTDSGFGSTKPSLQTEEPQFLLPDPHPQADRTLGNREPPVLGDSC
  SSGSSNSTDSGICLQEPSLSPSTGPTWEQQVGSNSRGQDDSGIDLVQNSEGRAGDTQGGS
  ALGHHSPPEPEVPGEEDPAAVAFQGYLRQTRCAEEKATKTGCLEEESPLTDGLGPKFGRC
  LVDEAGLHPPALAKGYLKQDPLEMTLASSGAPTGQWNQPTEEWSLLALSSCSDLGISDWS
  FAHDLAPLGCVAAPGGLLGSFNSDLVTLPLISSLQSSE
• Function: Cell surface receptor for the cytokine IL10 that participates in IL10-mediated anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Upon binding to IL10, induces a conformational change in IL10RB, allowing IL10RB to bind IL10 as well. In turn, the heterotetrameric assembly complex, composed of two subunits of IL10RA and IL10RB, activates the kinases JAK1 and TYK2 that are constitutively associated with IL10RA and IL10RB respectively. These kinases then phosphorylate specific tyrosine residues in the intracellular domain in IL10RA leading to the recruitment and subsequent phosphorylation of STAT3. Once phosphorylated, STAT3 homodimerizes, translocates to the nucleus and activates the expression of anti-inflammatory genes. In addition, IL10RA-mediated activation of STAT3 inhibits starvation-induced autophagy.
• Tissue Specificity: Primarily expressed in hematopoetic cells including B-cells, T-cells, NK cells, monocytes and macrophages. Not expressed in non-hematopoetic cells such as fibroblasts or endothelial cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  JAK-STAT sig.ling pathway (hsa04630)
  Toxoplasmosis (hsa05145)
  Tuberculosis (hsa05152)
  Human cytomegalovirus infection (hsa05163)
• Reactome Pathway: Interleukin-10 signaling (R-HSA-6783783)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Strong	Genetic Variation	[1]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[2]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[5]
Colitis	DISAF7DD	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Cryohydrocytosis	DISMQHL3	Strong	Genetic Variation	[8]
Enterocolitis	DISYACTL	Strong	Genetic Variation	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[10]
Idiopathic thrombocytopenic purpura	DISFKGJU	Strong	Genetic Variation	[5]
Immunodeficiency	DIS093I0	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[12]
Inflammatory bowel disease 28	DISWKAPR	Strong	Autosomal recessive	[1]
Leprosy	DISAA4UI	Strong	Biomarker	[13]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[8]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[14]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[15]
Mental disorder	DIS3J5R8	Strong	Biomarker	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Nephritis	DISQZQ70	Strong	Biomarker	[18]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[15]
Obesity	DIS47Y1K	Strong	Genetic Variation	[19]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[19]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[20]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[21]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Visceral leishmaniasis	DISTKEYK	Strong	Therapeutic	[23]
Adult lymphoma	DISK8IZR	moderate	Genetic Variation	[24]
Brain neoplasm	DISY3EKS	moderate	Altered Expression	[25]
Classic Hodgkin lymphoma	DISV1LU6	moderate	Genetic Variation	[24]
Crohn disease	DIS2C5Q8	moderate	Genetic Variation	[26]
High blood pressure	DISY2OHH	moderate	Biomarker	[27]
Lupus nephritis	DISCVGPZ	moderate	Altered Expression	[28]
Lymphoma	DISN6V4S	moderate	Genetic Variation	[24]
Pediatric lymphoma	DIS51BK2	moderate	Genetic Variation	[24]
Plasma cell myeloma	DIS0DFZ0	moderate	Genetic Variation	[29]
Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome	DISB2Y7L	Supportive	Autosomal recessive	[30]
Tuberculosis	DIS2YIMD	Disputed	Genetic Variation	[31]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[32]
B-cell neoplasm	DISVY326	Limited	Genetic Variation	[33]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Genetic Variation	[34]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[35]
Malaria	DISQ9Y50	Limited	Genetic Variation	[36]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[25]

13 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-10 receptor subunit alpha (IL10RA).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[40]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[42]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[43]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[37]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[37]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[44]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Interleukin-10 receptor subunit alpha (IL10RA).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[43]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Interleukin-10 receptor subunit alpha (IL10RA).	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Interleukin-10 receptor subunit alpha (IL10RA).	[41]

References

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