Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT07XAZF)

• DOT Name: GDNF family receptor alpha-3 (GFRA3)
• Synonyms: GDNF receptor alpha-3; GDNFR-alpha-3; GFR-alpha-3
• Gene Name: GFRA3
• UniProt ID: GFRA3_HUMAN
• PDB ID: 2GH0; 6Q2S
• Pfam ID: PF02351
• Sequence:
  MVRPLNPRPLPPVVLMLLLLLPPSPLPLAAGDPLPTESRLMNSCLQARRKCQADPTCSAA
  YHHLDSCTSSISTPLPSEEPSVPADCLEAAQQLRNSSLIGCMCHRRMKNQVACLDIYWTV
  HRARSLGNYELDVSPYEDTVTSKPWKMNLSKLNMLKPDSDLCLKFAMLCTLNDKCDRLRK
  AYGEACSGPHCQRHVCLRQLLTFFEKAAEPHAQGLLLCPCAPNDRGCGERRRNTIAPNCA
  LPPVAPNCLELRRLCFSDPLCRSRLVDFQTHCHPMDILGTCATEQSRCLRAYLGLIGTAM
  TPNFVSNVNTSVALSCTCRGSGNLQEECEMLEGFFSHNPCLTEAIAAKMRFHSQLFSQDW
  PHPTFAVMAHQNENPAVRPQPWVPSLFSCTLPLILLLSLW
• Function: Receptor for the glial cell line-derived neurotrophic factor, ARTN (artemin). Mediates the artemin-induced autophosphorylation and activation of the RET receptor tyrosine kinase.
• Tissue Specificity: Widely expressed in adult and fetus which exhibit a similar pattern. Essentially not expressed in the central nervous system, but highly expressed in several sensory and sympathetic ganglia of the peripheral nervous system. Moderate expression in many non-neuronal tissues, particularly those of the digestive and urogenital systems, but high expression in stomach and appendix. Several types of glandular tissues show low expression. Very low or no expression detected in the hematopoietic system.
• Reactome Pathway:
  RET signaling (R-HSA-8853659)
  RAF/MAP kinase cascade (R-HSA-5673001)

Molecular Interaction Atlas (MIA) of This DOT

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 GDNF family receptor alpha-3 (GFRA3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of GDNF family receptor alpha-3 (GFRA3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Aspirin increases the expression of GDNF family receptor alpha-3 (GFRA3).	[2]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of GDNF family receptor alpha-3 (GFRA3).	[3]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of GDNF family receptor alpha-3 (GFRA3).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of GDNF family receptor alpha-3 (GFRA3).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of GDNF family receptor alpha-3 (GFRA3).	[7]

References

• [1] 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.
• [2] 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.
• [3] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.