Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGEZR0L)

• DOT Name: Cytokine receptor common subunit beta (CSF2RB)
• Synonyms: CDw131; GM-CSF/IL-3/IL-5 receptor common beta subunit; CD antigen CD131
• Gene Name: CSF2RB
• Related Disease:
  Surfactant metabolism dysfunction, pulmonary, 5
  Hereditary pulmonary alveolar proteinosis
• UniProt ID: IL3RB_HUMAN
• PDB ID: 1C8P; 1EGJ; 1GH7; 2GYS; 2NA8; 2NA9; 4NKQ; 5DWU
• Pfam ID: PF21460
• Sequence:
  MVLAQGLLSMALLALCWERSLAGAEETIPLQTLRCYNDYTSHITCRWADTQDAQRLVNVT
  LIRRVNEDLLEPVSCDLSDDMPWSACPHPRCVPRRCVIPCQSFVVTDVDYFSFQPDRPLG
  TRLTVTLTQHVQPPEPRDLQISTDQDHFLLTWSVALGSPQSHWLSPGDLEFEVVYKRLQD
  SWEDAAILLSNTSQATLGPEHLMPSSTYVARVRTRLAPGSRLSGRPSKWSPEVCWDSQPG
  DEAQPQNLECFFDGAAVLSCSWEVRKEVASSVSFGLFYKPSPDAGEEECSPVLREGLGSL
  HTRHHCQIPVPDPATHGQYIVSVQPRRAEKHIKSSVNIQMAPPSLNVTKDGDSYSLRWET
  MKMRYEHIDHTFEIQYRKDTATWKDSKTETLQNAHSMALPALEPSTRYWARVRVRTSRTG
  YNGIWSEWSEARSWDTESVLPMWVLALIVIFLTIAVLLALRFCGIYGYRLRRKWEEKIPN
  PSKSHLFQNGSAELWPPGSMSAFTSGSPPHQGPWGSRFPELEGVFPVGFGDSEVSPLTIE
  DPKHVCDPPSGPDTTPAASDLPTEQPPSPQPGPPAASHTPEKQASSFDFNGPYLGPPHSR
  SLPDILGQPEPPQEGGSQKSPPPGSLEYLCLPAGGQVQLVPLAQAMGPGQAVEVERRPSQ
  GAAGSPSLESGGGPAPPALGPRVGGQDQKDSPVAIPMSSGDTEDPGVASGYVSSADLVFT
  PNSGASSVSLVPSLGLPSDQTPSLCPGLASGPPGAPGPVKSGFEGYVELPPIEGRSPRSP
  RNNPVPPEAKSPVLNPGERPADVSPTSPQPEGLLVLQQVGDYCFLPGLGPGPLSLRSKPS
  SPGPGPEIKNLDQAFQVKKPPGQAVPQVPVIQLFKALKQQDYLSLPPWEVNKPGEVC
• Function: Cell surface receptor that plays a role in immune response and controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells. Acts by forming an heterodimeric receptor through interaction with different partners such as IL3RA, IL5RA or CSF2RA. In turn, participates in various signaling pathways including interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor/CSF2 pathways. In unstimulated conditions, interacts constitutively with JAK1 and ligand binding leads to JAK1 stimulation and subsequent activation of the JAK-STAT pathway.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Apoptosis (hsa04210)
  JAK-STAT sig.ling pathway (hsa04630)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  RAF/MAP kinase cascade (R-HSA-5673001)
  Surfactant metabolism (R-HSA-5683826)
  Defective CSF2RB causes SMDP5 (R-HSA-5688849)
  Defective CSF2RA causes SMDP4 (R-HSA-5688890)
  Interleukin receptor SHC signaling (R-HSA-912526)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Surfactant metabolism dysfunction, pulmonary, 5	DISS44AR	Moderate	Autosomal recessive	[1]
Hereditary pulmonary alveolar proteinosis	DISQC53I	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Cytokine receptor common subunit beta (CSF2RB).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytokine receptor common subunit beta (CSF2RB).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytokine receptor common subunit beta (CSF2RB).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cytokine receptor common subunit beta (CSF2RB).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Cytokine receptor common subunit beta (CSF2RB).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Cytokine receptor common subunit beta (CSF2RB).	[7]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cytokine receptor common subunit beta (CSF2RB).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cytokine receptor common subunit beta (CSF2RB).	[9]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Cytokine receptor common subunit beta (CSF2RB).	[10]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB. J Med Genet. 2011 Mar;48(3):205-9. doi: 10.1136/jmg.2010.082586. Epub 2010 Nov 12.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4578-83.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.