Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPN33IU)

• DOT Name: Cytokine receptor-like factor 2 (CRLF2)
• Synonyms: Cytokine receptor-like 2; IL-XR; Thymic stromal lymphopoietin protein receptor; TSLP receptor
• Gene Name: CRLF2
• UniProt ID: CRLF2_HUMAN
• PDB ID: 5J11; 5J12
• Pfam ID: PF21605 ; PF21604
• Sequence:
  MGRLVLLWGAAVFLLGGWMALGQGGAAEGVQIQIIYFNLETVQVTWNASKYSRTNLTFHY
  RFNGDEAYDQCTNYLLQEGHTSGCLLDAEQRDDILYFSIRNGTHPVFTASRWMVYYLKPS
  SPKHVRFSWHQDAVTVTCSDLSYGDLLYEVQYRSPFDTEWQSKQENTCNVTIEGLDAEKC
  YSFWVRVKAMEDVYGPDTYPSDWSEVTCWQRGEIRDACAETPTPPKPKLSKFILISSLAI
  LLMVSLLLLSLWKLWRVKKFLIPSVPDPKSIFPGLFEIHQGNFQEWITDTQNVAHLHKMA
  GAEQESGPEEPLVVQLAKTEAESPRMLDPQTEEKEASGGSLQLPHQPLQGGDVVTIGGFT
  FVMNDRSYVAL
• Function: Receptor for thymic stromal lymphopoietin (TSLP). Forms a functional complex with TSLP and IL7R which is capable of stimulating cell proliferation through activation of STAT3 and STAT5. Also activates JAK2. Implicated in the development of the hematopoietic system.
• Tissue Specificity: Expressed in heart, skeletal muscle, kidney and adult and fetal liver. Primarily expressed in dendrites and monocytes. Weakly expressed in T-cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: Interleukin-7 signaling (R-HSA-1266695)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Cytokine receptor-like factor 2 (CRLF2).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cytokine receptor-like factor 2 (CRLF2).	[2]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Cytokine receptor-like factor 2 (CRLF2).	[3]

References

• [1] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [2] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [3] Toxicity of nickel ions and comprehensive analysis of nickel ion-associated gene expression profiles in THP-1 cells. Mol Med Rep. 2015 Sep;12(3):3273-3278. doi: 10.3892/mmr.2015.3878. Epub 2015 Jun 3.