Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6M0F70)

• DOT Name: Interleukin-2 receptor subunit beta (IL2RB)
• Synonyms: IL-2 receptor subunit beta; IL-2R subunit beta; IL-2RB; High affinity IL-2 receptor subunit beta; Interleukin-15 receptor subunit beta; p70-75; p75; CD antigen CD122
• Gene Name: IL2RB
• Related Disease: Immunodeficiency 63 with lymphoproliferation and autoimmunity
• UniProt ID: IL2RB_HUMAN
• PDB ID: 2B5I; 2ERJ; 3QAZ; 4GS7; 5M5E; 6E8K; 7S2S
• Pfam ID: PF18707
• Sequence:
  MAAPALSWRLPLLILLLPLATSWASAAVNGTSQFTCFYNSRANISCVWSQDGALQDTSCQ
  VHAWPDRRRWNQTCELLPVSQASWACNLILGAPDSQKLTTVDIVTLRVLCREGVRWRVMA
  IQDFKPFENLRLMAPISLQVVHVETHRCNISWEISQASHYFERHLEFEARTLSPGHTWEE
  APLLTLKQKQEWICLETLTPDTQYEFQVRVKPLQGEFTTWSPWSQPLAFRTKPAALGKDT
  IPWLGHLLVGLSGAFGFIILVYLLINCRNTGPWLKKVLKCNTPDPSKFFSQLSSEHGGDV
  QKWLSSPFPSSSFSPGGLAPEISPLEVLERDKVTQLLLQQDKVPEPASLSSNHSLTSCFT
  NQGYFFFHLPDALEIEACQVYFTYDPYSEEDPDEGVAGAPTGSSPQPLQPLSGEDDAYCT
  FPSRDDLLLFSPSLLGGPSPPSTAPGGSGAGEERMPPSLQERVPRDWDPQPLGPPTPGVP
  DLVDFQPPPELVLREAGEEVPDAGPREGVSFPWSRPPGQGEFRALNARLPLNTDAYLSLQ
  ELQGQDPTHLV
• Function: Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Endocytosis (hsa04144)
  PI3K-Akt sig.ling pathway (hsa04151)
  JAK-STAT sig.ling pathway (hsa04630)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Measles (hsa05162)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway:
  Interleukin-15 signaling (R-HSA-8983432)
  Interleukin-2 signaling (R-HSA-9020558)
  Interleukin receptor SHC signaling (R-HSA-912526)
  RAF/MAP kinase cascade (R-HSA-5673001)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency 63 with lymphoproliferation and autoimmunity	DISVNIQ0	Strong	Autosomal recessive	[1]

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-2 receptor subunit beta (IL2RB).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Interleukin-2 receptor subunit beta (IL2RB).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Interleukin-2 receptor subunit beta (IL2RB).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[6]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[7]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Interleukin-2 receptor subunit beta (IL2RB).	[11]
Choline	DM5D9YK	Investigative	Choline affects the expression of Interleukin-2 receptor subunit beta (IL2RB).	[12]

References

• [1] [Anthroposophic medicine]. Tidsskr Nor Laegeforen. 1986 Feb 20;106(5):426-31.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [5] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [6] Glucocorticoid-mediated inhibition of interleukin-2 receptor alpha and -beta subunit expression by human T cells. Immunopharmacology. 1994 Jan-Feb;27(1):43-55. doi: 10.1016/0162-3109(94)90006-x.
• [7] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [8] Ouabain induces inhibition of the progression phase in human T-cell proliferation. J Cell Physiol. 1995 Nov;165(2):246-53. doi: 10.1002/jcp.1041650205.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not. Am J Clin Nutr. 2007 Jul;86(1):230-9. doi: 10.1093/ajcn/86.1.230.